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Sample records for voltage feedback loop

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

    PubMed Central

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

    2014-01-01

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

  2. Monitoring Digital Closed-Loop Feedback Systems

    NASA Technical Reports Server (NTRS)

    Katz, Richard; Kleyner, Igor

    2011-01-01

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

  3. UWB communication receiver feedback loop

    DOEpatents

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

    2007-12-04

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

  4. Three loop balanced bridge feedback pointing control

    NASA Technical Reports Server (NTRS)

    Lurie, Boris J.

    1988-01-01

    The balanced bridge feedback (BBF) technique developed in communication engineering is applied to the multiloop pointing control problem. Using colocated sensors, BBF decouples the motor loop from the mechanical plant and increases the feedback bandwidth in the motor and plant loops.

  5. Nested feedback loops in gene regulation

    NASA Astrophysics Data System (ADS)

    Mengel, Benedicte; Krishna, Sandeep; Jensen, Mogens H.; Trusina, Ala

    2012-01-01

    Protein activities may exhibit oscillations which often occur due to the existence of a negative feedback loop with an effective time delay. Many biological systems are, however, not limited to one feedback loop but consist of multiple loops on different regulatory levels. Here, we analyze the properties of oscillations generated by one fast feedback nested within a slower feedback. An example of such a regulatory structure is the NF-?B signaling system. The nuclear-cytoplasmic shuttling of NF-?B is characterized by single cell oscillations of the nuclear concentration with a time period of around 1-2 h. The NF-?B network contains several feedback loops modulating the overall response of NF-?B activity. While the role of the local I?B? feedback is known to drive the oscillations, the precise role of the up-stream negative feedback loops remains to be elucidated. Using NF-?B-inspired model loops we find that the design based on nested feedback loops allows for independent control of the oscillation period. Based on these results, we predict that by adjusting the expression level of A20, Cezanne, or other proteins functioning up-stream of IKK, for example, by siRNA, the oscillation period can be changed by up to a factor 2.

  6. Recurrent Feedback Loops in Associative Learning.

    PubMed

    Person, Abigail L; Khodakhah, Kamran

    2016-02-01

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

  7. 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.

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

    SciTech Connect

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

    1989-07-01

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

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

    ERIC Educational Resources Information Center

    Wehlburg, Catherine M.

    2007-01-01

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

  10. 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 10M?, 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.

  11. 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

  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. 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-?m 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 ?A. The line regulation and load regulation are improved to 0.1 mV/V and 3.4 ?V/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 ?s respectively.

  14. Creating the feedback loop: closed-loop neurostimulation.

    PubMed

    Hebb, Adam O; Zhang, Jun Jason; Mahoor, Mohammad H; Tsiokos, Christos; Matlack, Charles; Chizeck, Howard Jay; Pouratian, Nader

    2014-01-01

    Current DBS therapy delivers a train of electrical pulses at set stimulation parameters. This open-loop design is effective for movement disorders, but therapy may be further optimized by a closed loop design. The technology to record biosignals has outpaced our understanding of their relationship to the clinical state of the whole person. Neuronal oscillations may represent or facilitate the cooperative functioning of brain ensembles, and may provide critical information to customize neuromodulation therapy. This review addresses advances to date, not of the technology per se, but of the strategies to apply neuronal signals to trigger or modulate stimulation systems. PMID:24262909

  15. A SQUID gradiometer module with wire-wound pickup antenna and integrated voltage feedback circuit

    NASA Astrophysics Data System (ADS)

    Zhang, Guofeng; Zhang, Yi; Zhang, Shulin; Krause, Hans-Joachim; Wang, Yongliang; Liu, Chao; Zeng, Jia; Qiu, Yang; Kong, Xiangyan; Dong, Hui; Xie, Xiaoming; Offenhusser, Andreas; Jiang, Mianheng

    2012-10-01

    The performance of the direct readout schemes for dc SQUID, Additional Positive Feedback (APF), noise cancellation (NC) and SQUID bootstrap circuit (SBC), have been studied in conjunction with planar SQUID magnetometers. In this paper, we examine the NC technique applied to a niobium SQUID gradiometer module with an Nb wire-wound antenna connecting to a dual-loop SQUID chip with an integrated voltage feedback circuit for suppression of the preamplifier noise contribution. The sensitivity of the SQUID gradiometer module is measured to be about 1 fT/(cm ?Hz) in the white noise range in a magnetically shielded room. Using such gradiometer, both MCG and MEG signals are recorded.

  16. Feedback control of electrode offset voltage during functional electrical stimulation.

    PubMed

    Chu, Jun-Uk; Song, Kang-Il; Shon, Ahnsei; Han, Sungmin; Lee, Soo Hyun; Kang, Ji Yoon; Hwang, Dosik; Suh, Jun-Kyo Francis; Choi, Kuiwon; Youn, Inchan

    2013-08-15

    Control of the electrode offset voltage is an important issue related to the processes of functional electrical stimulation because excess charge accumulation over time damages both the tissue and the electrodes. This paper proposes a new feedback control scheme to regulate the electrode offset voltage to a predetermined reference value. The electrode offset voltage was continuously monitored using a sample-and-hold (S/H) circuit during stimulation and non-stimulation periods. The stimulation current was subsequently adjusted using a proportional-integral (PI) controller to minimise the error between the reference value and the electrode offset voltage. During the stimulation period, the electrode offset voltage was maintained through the S/H circuit, and the PI controller did not affect the amplitude of the stimulation current. In contrast, during the non-stimulation period, the electrode offset voltage was sampled through the S/H circuit and rapidly regulated through the PI controller. The experimental results obtained using a nerve cuff electrode showed that the electrode offset voltage was successfully controlled in terms of the performance specifications, such as the steady- and transient-state responses and the constraint of the controller output. Therefore, the proposed control scheme can potentially be used in various nerve stimulation devices and applications requiring control of the electrode offset voltage. PMID:23685268

  17. Coupled feedback loops govern bistability properties in gene networks

    NASA Astrophysics Data System (ADS)

    Tiwari, Abhinav; Igoshin, Oleg

    2011-03-01

    Positive feedback is a necessary component for network bistability - the simplest design being a positive autoregulatory circuit. Then why some biological systems have multiple feedback loops? We hypothesize that the presence of multiple additively or multiplicatively coupled feedback loops affects the net cooperativity of the system, thereby influencing the possibility of bistability. We find that additively coupled feedback loops in the MprAB-SigE-RseA network in mycobacteria do not lead to bistability. Only the inclusion of post-translational regulation of SigE by RseA makes the system robustly bistable. In general we find that if two one-feedback networks are individually monostable, then only multiplicative coupling can generate bistability in the combined circuit. We analytically perform pair-wise controlled comparisons between the autoregulation circuit, additively and multiplicatively coupled two-gene circuits that reveal neither of the circuits has an advantage with regards to bistability range. We numerically validate our results by employing Monte Carlo parameter sampling for the comparisons.

  18. 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.

  19. 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.

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

    PubMed Central

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

    2014-01-01

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

  1. 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.

  2. Quantized optical mode in a phase-switching feedback loop

    NASA Astrophysics Data System (ADS)

    Tomilin, V. A.; Il'ichov, L. V.

    2015-02-01

    We investigate the steady state of quantized monochromatic cavity mode excited by coherent pumping and placed in a feedback loop that changes the mode phase by ? upon each detection of the photon that left the cavity. Such type of feedback is used for fighting decoherence of Schrbinger cat states. Results of numerical calculations of the Glauber P-function for different detunings of mode frequency from pumping frequency are presented. Qualitative explanation for certain peculiarities of the behavior of the P-function is provided. We also suggest a simplified model that gives accurate description of the behavior of the system in the case where external coherent pumping is far detuned from the cavity eigenfrequency.

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

    NASA Astrophysics Data System (ADS)

    Tiwari, Abhinav; Igoshin, Oleg A.

    2012-10-01

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

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

    PubMed Central

    Tiwari, Abhinav; Igoshin, Oleg A.

    2012-01-01

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

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

    PubMed

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

    2012-06-01

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

  6. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2016-02-01

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

  8. Practical Loop-Shaping Design of Feedback Control Systems

    NASA Technical Reports Server (NTRS)

    Kopasakis, George

    2010-01-01

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

  9. 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.

  10. Interlinking positive and negative feedback loops creates a tunable motif in gene regulatory networks

    NASA Astrophysics Data System (ADS)

    Tian, Xiao-Jun; Zhang, Xiao-Peng; Liu, Feng; Wang, Wei

    2009-07-01

    Positive and negative feedback loops are often coupled to perform various functions in gene regulatory networks, acting as bistable switches, oscillators, and excitable devices. It is implied that such a system with interlinked positive and negative feedback loops is a flexible motif that can modulate itself among various functions. Here, we developed a minimal model for the system and systematically explored its dynamics and performance advantage in response to stimuli in a unifying framework. The system indeed displays diverse behaviors when the strength of feedback loops is changed. First, the system can be tunable from monostability to bistability by increasing the strength of positive feedback, and the bistability regime is modulated by the strength of negative feedback. Second, the system undergoes transitions from bistability to excitability and to oscillation with increasing the strength of negative feedback, and the reverse conversion occurs by enhancing the strength of positive feedback. Third, the system is more flexible than a single feedback loop; it can produce robust larger-amplitude oscillations over a wider stimulus regime compared with a single time-delayed negative feedback loop. Furthermore, the tunability of the system depends mainly on the topology of coupled feedback loops but less on the exact parameter values or the mode of interactions between model components. Thus, our results interpret why such a system represents a tunable motif and can accomplish various functions. These also suggest that coupled feedback loops can act as toolboxes for engineering diverse functional circuits in synthetic biology.

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

    PubMed

    Pnicaud, Luc

    2010-01-01

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

  12. 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

  13. 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)…

  14. 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)

  15. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2009-01-01

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

  17. 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

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

    NASA Astrophysics Data System (ADS)

    Bhalla, Upinder S.; Iyengar, Ravi

    2001-03-01

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

  19. 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.

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

    NASA Astrophysics Data System (ADS)

    Sayed, Mahmoud A.; Takeshita, Takaharu

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

  1. 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.

  2. 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

  3. 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

  4. 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,

  5. 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,…

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

    SciTech Connect

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

    2001-01-16

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

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

    DOE PAGESBeta

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

    2015-12-01

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

  8. 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.

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

    ERIC Educational Resources Information Center

    O'Donnell, Kerri

    2011-01-01

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

  10. 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…

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

    NASA Technical Reports Server (NTRS)

    Thompson, P. M.

    1979-01-01

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

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

    NASA Technical Reports Server (NTRS)

    Heyman, J. S. (Inventor)

    1982-01-01

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

  13. Channel cytoplasmic loops alter voltage-dependent sodium channel activation in an isoform-specific manner.

    PubMed

    Bennett, E S

    2001-09-01

    1. The isoform-specific functional role of cytoplasmic structures of two voltage-gated sodium channel isoforms, the human cardiac channel (hH1) and the adult human skeletal muscle channel (hSkM1) was investigated through functional comparison of chimeras. 2. The voltage of half-activation (V(a)) for hH1 was shifted by > 20 mV in the hyperpolarised direction following internal papain treatment ('papain sensitive'), while V(a) for hSkM1 was unaffected ('papain insensitive'). 3. The hH1 region(s) responsible for this papain sensitivity was localised by testing a series of hH1/hSkM1 chimeras in which combinations of the large hH1 cytoplasmic loops joining the four transmembrane domains replaced analogous hSkM1 loops. Various chimeras were used to determine the smallest subset of loops that converted fully the papain-insensitive hSkM1 into a papain-sensitive channel. Then three converse chimeras were tested in which hSkM1 loops replaced hH1 loops to determine the smallest subset of loops necessary and sufficient to convert the papain-sensitive hH1 into a papain-insensitive channel. 4. Functional studies of this inclusive set of chimeras indicate that the first two cytoplasmic loops of the cardiac sodium channel that join domain I to II (loop A), and domain II to III (loop B), are both necessary, and together are sufficient to produce a papain-induced hyperpolarising shift in the voltage at which channels activate. When both loops are present (wild-type hH1 and the chimera hSkM1AB), V(a) for the channel shifts in the hyperpolarised direction by > 20 mV with papain treatment. When the analogous hSkM1 loops are present (wild-type hSkM1 and the chimera hH1AB), V(a) for the channel is not sensitive to treatment with papain. For channels that contain only one of the two hH1 loops, the effect of papain on V(a) is intermediary. 5. Experiments performed in the absence of papain showed that the activation voltages of the double loop chimeras, hSkM1AB and hH1AB, were shifted significantly from V(a) for hSkM1 and V(a) for hH1, respectively, indicating that these loops directly alter channel activation voltage. The resulting shifts in V(a) were in opposing directions, suggesting that cytoplasmic control of activation voltage is isoform specific. V(a) for hSkM1AB was about 20 mV more depolarised than V(a) for hSkM1, and V(a) for hH1AB was about 9 mV more negative than V(a) for hH1. 6. These data are the first to indicate isoform-specific cytoplasmic regions of the voltage-gated sodium channel that directly and differently alter the voltage of channel activation. PMID:11533130

  14. 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.

  15. 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

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

    ERIC Educational Resources Information Center

    Donovan, Pam

    2014-01-01

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

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

    ERIC Educational Resources Information Center

    Donovan, Pam

    2014-01-01

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

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

    PubMed

    Lou, Yi; Clay, Sharon A; Davis, Adam S; Dille, Anita; Felix, Joel; Ramirez, Analiza H M; Sprague, Christy L; Yannarell, Anthony C

    2014-05-01

    Feedback loops involving soil microorganisms can regulate plant populations. Here, we hypothesize that microorganisms are most likely to play a role in plant-soil feedback loops when they possess an affinity for a particular plant and the capacity to consistently affect the growth of that plant for good or ill. We characterized microbial communities using whole-community DNA fingerprinting from multiple "home-and-away" experiments involving giant ragweed (Ambrosia trifida L.) and common sunflower (Helianthus annuus L.), and we looked for affinity-effect relationships in these microbial communities. Using canonical ordination and partial least squares regression, we developed indices expressing each microorganism's affinity for ragweed or sunflower and its putative effect on plant biomass, and we used linear regression to analyze the relationship between microbial affinity and effect. Significant linear affinity-effect relationships were found in 75 % of cases. Affinity-effect relationships were stronger for ragweed than for sunflower, and ragweed affinity-effect relationships showed consistent potential for negative feedback loops. The ragweed feedback relationships indicated the potential involvement of multiple microbial taxa, resulting in strong, consistent affinity-effect relationships in spite of large-scale microbial variability between trials. In contrast, sunflower plant-soil feedback may involve just a few key players, making it more sensitive to underlying microbial variation. We propose that affinity-effect relationship can be used to determine key microbial players in plant-soil feedback against a low "signal-to-noise" background of complex microbial datasets. PMID:24402363

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

    PubMed

    Barnes, Richard; Lehman, Clarence

    2013-06-01

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

  20. 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…

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

    ERIC Educational Resources Information Center

    Hokayem, Hayat; Ma, Jingjing; Jin, Hui

    2015-01-01

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

  2. 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

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

    PubMed Central

    Ito, Sosuke; Sagawa, Takahiro

    2015-01-01

    Signal transduction in living cells is vital to maintain life itself, where information transfer in noisy environment plays a significant role. In a rather different context, the recent intensive research on Maxwell's demon'a feedback controller that utilizes information of individual moleculeshave 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 informationthermodynamics link. PMID:26099556

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

    NASA Astrophysics Data System (ADS)

    Ito, Sosuke; Sagawa, Takahiro

    2015-06-01

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

  5. Stepper Motor Current Control With Cascaded Voltage-Time Integral Control Loop

    NASA Astrophysics Data System (ADS)

    Kreid, Fritz; Wurz, Johann

    2011-10-01

    In recent years the product specifications in the area of space borne motor drives show a growing need for motor drive electronics with increasing performance requirements. New drive concepts are needed for stepper motor applications like high resolution pointing and positioning systems with precise torque requirements and the need for smooth operation to achieve high mechanical endurance of the system. This paper presents a constant frequency switched mode drive circuit for bipolar stepper motors. In contrast to many industrial ICs where the phase current is regulated directly with a single control loop, a cascaded control system with an inner voltage control loop and an outer current control loop is used. This concept offers high control loop stability and four-quadrant current mode operation for improved smoothness of the motor rotation. The work was supported by the Austrian Space Applications Programme (ASAP-6) which was initiated by the Austrian Federal Ministry for Transport, Innovation and Technology (FFG project Number 819707).

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

    PubMed

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

    2015-04-20

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

  7. 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.

  8. Exact offset voltage cancellation of sensitive IRFPA microbolometers by a novel feedback readout circuit

    NASA Astrophysics Data System (ADS)

    Mang, Ou-Yang; Lee, Tzong-sheng; Hsieh, Yao-Fang; Huang, Ting-Wei

    2009-08-01

    A new feedback readout circuit of microbolometers for sensing radiant power is proposed in this paper. Due to excellent thermal characteristics of microstructure on infrared application recently, the readout circuits of the microsensors would not concern the responsivity only, but should also take offset voltage cancellation, digitalization, and signal-to-noise ratio under considerations. Although Wheatstone bridge readout circuit has been widely used in resistive thermal sensor readout for several decades, its nonlinear output voltage acting as the offset voltage still perplex us, as well as its digitalization and signal-to-noise ratio could be unsatisfied for microbolometer applications. Hence, we present the feedback readout which could optimize the key factors simultaneously and increase the responsivity without any layout modification of the bridge structure on Infrared Focal Plane Array (IRFPA) microbolometer chip. The results revealed that the balanced parameter, frequency, equal to 0.5 would be the best condition for these requirements instead of the balanced parameter equal to unity by intuition traditionally. Compared to traditional Wheatstone bridge readout circuit, the feedback readout circuit would improve the responsivity of 2.86 times, immunize the offset voltage exactly, obtain a very large OVRR, and reduce the noise of the readout circuit of 5.6 dB. These significantly important results will improve significantly the performance of the readout circuit, and speed up the commercialization of infrared focal plane array of microbolometers.

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

    NASA Astrophysics Data System (ADS)

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

    2015-12-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2014-12-01

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

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

    NASA Astrophysics Data System (ADS)

    Han, Wang; Lin, Tan

    2016-02-01

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

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

    PubMed

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

    2015-03-01

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

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

    NASA Technical Reports Server (NTRS)

    Steadman, Karl N.; Gupta, Inder J.; Walton, Eric K.

    1990-01-01

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

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

    NASA Technical Reports Server (NTRS)

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

    1990-01-01

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

  15. 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.

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

    PubMed

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

    2015-07-01

    CD147 is a novel cancer biomarker that has been confirmed to be overexpressed in ovarian carcinoma, which is significantly associated with poor prognosis. Although the Sp1 protein regulates the expression level of CD147, it remains unclear whether Sp1 phosphorylation plays a role in this regulation. A dual-luciferase assay revealed that T453 and T739 mutations decreased the activity of Sp1 binding to the promoter of CD147, followed by a decrease in CD147 mRNA and protein expression. Western blot analysis showed that CD147 promoted Sp1 phosphorylation at T453 and T739 through the PI3K/AKT and MAPK/ERK pathways. In addition, blocking the Sp1-CD147 positive feedback loop reduced the invasion ability of HO-8910pm cells. Immunohistochemical staining showed that the components of the feedback loop were overexpressed in ovarian cancer tissues. The correlation analysis revealed a significant correlation between phospho-Sp1 (T453), phospho-Sp1 (T739) and CD147 expression levels, with correlation coefficients of r=0.477 and r=0.461, respectively. Collectively, our results suggest that a Sp1-CD147 positive feedback loop plays a critical role in the invasion ability of ovarian cancer cells. PMID:25998266

  17. 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

  18. 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.

  19. 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

  20. Short and long sympathetic-sensory feedback loops in white fat.

    PubMed

    Ryu, Vitaly; Bartness, Timothy J

    2014-06-15

    We previously demonstrated white adipose tissue (WAT) innervation using the established WAT retrograde sympathetic nervous system (SNS)-specific transneuronal viral tract tracer pseudorabies virus (PRV152) and showed its role in the control of lipolysis. Conversely, we demonstrated WAT sensory innervation using the established anterograde sensory system (SS)-specific transneuronal viral tracer, the H129 strain of herpes simplex virus-1, with sensory nerves showing responsiveness with increases in WAT SNS drive. Several brain areas were part of the SNS outflow to and SS inflow from WAT between these studies suggesting SNS-SS feedback loops. Therefore, we injected both PRV152 and H129 into inguinal WAT (IWAT) of Siberian hamsters. Animals were perfused on days 5 and 6 postinoculation after H129 and PRV152 injections, respectively, and brains, spinal cords, sympathetic, and dorsal root ganglia (DRG) were processed for immunohistochemical detection of each virus across the neuroaxis. The presence of H129+PRV152-colocalized neurons (~50%) in the spinal segments innervating IWAT suggested short SNS-SS loops with significant coinfections (>60%) in discrete brain regions, signifying long SNS-SS loops. Notably, the most highly populated sites with the double-infected neurons were the medial part of medial preoptic nucleus, medial preoptic area, hypothalamic paraventricular nucleus, lateral hypothalamus, periaqueductal gray, oral part of the pontine reticular nucleus, and the nucleus of the solitary tract. Collectively, these results strongly indicate the neuroanatomical reality of the central SNS-SS feedback loops with short loops in the spinal cord and long loops in the brain, both likely involved in the control of lipolysis or other WAT pad-specific functions. PMID:24717676

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

    NASA Astrophysics Data System (ADS)

    Wang, Junwei; Zhou, Tianshou

    2010-06-01

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

  2. Anatomy of a negative feedback loop: the case of I?B?.

    PubMed

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

    2015-09-01

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

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

    NASA Astrophysics Data System (ADS)

    Gaspari, Massimo

    2015-08-01

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

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

    NASA Astrophysics Data System (ADS)

    Gaspari, Massimo

    2015-08-01

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

  5. 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.

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

    PubMed

    Yousaf, Saqib; Qin, Shiyin

    2015-12-01

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

  7. Fine-tuning of Voltage Sensitivity of the Kv1.2 Potassium Channel by Interhelix Loop Dynamics*

    PubMed Central

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

    2013-01-01

    Many proteins function by changing conformation in response to ligand binding or changes in other factors in their environment. Any change in the sequence of a protein, for example during evolution, which alters the relative free energies of the different functional conformations changes the conditions under which the protein will function. Voltage-gated ion channels are membrane proteins that open and close an ion-selective pore in response to changes in transmembrane voltage. The charged S4 transmembrane helix transduces changes in transmembrane voltage into a change in protein internal energy by interacting with the rest of the channel protein through a combination of non-covalent interactions between adjacent helices and covalent interactions along the peptide backbone. However, the structural basis for the wide variation in the V50 value between different voltage-gated potassium channels is not well defined. To test the role of the loop linking the S3 helix and the S4 helix in voltage sensitivity, we have constructed a set of mutants of the rat Kv1.2 channel that vary solely in the length and composition of the extracellular loop that connects S4 to S3. We evaluated the effect of these different loop substitutions on the voltage sensitivity of the channel and compared these experimental results with molecular dynamics simulations of the loop structures. Here, we show that this loop has a significant role in setting the precise V50 of activation in Kv1 family channels. PMID:23413033

  8. 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.

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

    NASA Astrophysics Data System (ADS)

    Joo, Jaewook

    2010-03-01

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

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

    PubMed

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

    2012-03-01

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed

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

    2012-07-01

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

  13. 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.

  14. 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

  15. 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 our ongoing research on developmental patterning.

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

    PubMed Central

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

    2014-01-01

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

  17. 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.

  18. 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

  19. 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.

  20. Quality-factor amplification in piezoelectric MEMS resonators applying an all-electrical feedback loop

    NASA Astrophysics Data System (ADS)

    Manzaneque, T.; Hernando-Garca, J.; Ababneh, A.; Schwarz, P.; Seidel, H.; Schmid, U.; Snchez-Rojas, J. L.

    2011-02-01

    An all-electrical velocity feedback control to enhance the quality factor of piezoelectric aluminium nitride (AlN)-based microcantilevers and microbridges was implemented. Two alternatives to obtain a velocity-proportional signal were demonstrated depending on the top electrode configuration. For a straightforward electrode design in one-port configuration (i.e. self-actuation and self-sensing), a velocity signal, proportional to the piezoelectric current, was used in the feedback loop by cancelling out the dielectric current electronically. For top electrodes allowing a two-port configuration (i.e. one for actuation and one for sensing), the piezoelectric current is directly extracted and its relationship with velocity is analysed taking the symmetry of the modal shape into account. Standard operational amplifier-based configurations for the feedback circuits were implemented on a printed circuit board. Quality factors were determined from the transient electrical response of the devices. Comparable results were obtained from the displacement spectrum applying a laser Doppler vibrometer. Quality factors as high as 2 105, corresponding to an enhancement factor of about 200, were achieved in air for the lowest gain margin achievable before the circuit becomes unstable, making this kind of device more competitive for mass sensor applications due to enhanced spectral resolution.

  1. Activation of TGF-?1-CD147 positive feedback loop in hepatic stellate cells promotes liver fibrosis.

    PubMed

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

    2015-01-01

    Activation of hepatic stellate cells (HSCs) by transforming growth factor-?1 (TGF-?1) initiates HBV-associated fibrogenesis. The mechanism of TGF-?1 modulating HSC activation is not fully uncovered. We hypothesized a positive feedback signaling loop of TGF-?1-CD147 promoting liver fibrogenesis by activation of HSCs. Human HSC cell line LX-2 and spontaneous liver fibrosis model derived from HBV transgenic mice were used to evaluate the activation of molecules in the signaling loop. Wound healing and cell contraction assay were performed to detect the CD147-overexpressed HSC migration and contraction. The transcriptional regulation of CD147 by TGF-?1/Smad4 was determined using dual-luciferase reporter assay and chromatin immunoprecipitation. We found that a positive reciprocal regulation between TGF-?1 and CD147 mediated HSC activation. CD147 over-expression promoted HSC migration and accelerated TGF-?1-induced cell contraction. Phosphorylation of Smad2 and Smad3 in cooperation with Smad4 mediated the TGF-?1-regulated CD147 expression. Smad4 activated the transcription by direct interaction with CD147 promoter. Meanwhile, CD147 modulated the activated phenotype of HSCs through the ERK1/2 and Sp1 which up-regulated ?-SMA, collagen I, and TGF-?1 synthesis. These findings indicate that TGF-?1-CD147 loop plays a key role in regulating the HSC activation and combination of TGF-? receptor inhibitor and anti-CD147 antibody might be promised to reverse fibrogenesis. PMID:26559755

  2. Activation of TGF-?1-CD147 positive feedback loop in hepatic stellate cells promotes liver fibrosis

    PubMed Central

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

    2015-01-01

    Activation of hepatic stellate cells (HSCs) by transforming growth factor-?1 (TGF-?1) initiates HBV-associated fibrogenesis. The mechanism of TGF-?1 modulating HSC activation is not fully uncovered. We hypothesized a positive feedback signaling loop of TGF-?1-CD147 promoting liver fibrogenesis by activation of HSCs. Human HSC cell line LX-2 and spontaneous liver fibrosis model derived from HBV transgenic mice were used to evaluate the activation of molecules in the signaling loop. Wound healing and cell contraction assay were performed to detect the CD147-overexpressed HSC migration and contraction. The transcriptional regulation of CD147 by TGF-?1/Smad4 was determined using dual-luciferase reporter assay and chromatin immunoprecipitation. We found that a positive reciprocal regulation between TGF-?1 and CD147 mediated HSC activation. CD147 over-expression promoted HSC migration and accelerated TGF-?1-induced cell contraction. Phosphorylation of Smad2 and Smad3 in cooperation with Smad4 mediated the TGF-?1-regulated CD147 expression. Smad4 activated the transcription by direct interaction with CD147 promoter. Meanwhile, CD147 modulated the activated phenotype of HSCs through the ERK1/2 and Sp1 which up-regulated ?-SMA, collagen I, and TGF-?1 synthesis. These findings indicate that TGF-?1-CD147 loop plays a key role in regulating the HSC activation and combination of TGF-? receptor inhibitor and anti-CD147 antibody might be promised to reverse fibrogenesis. PMID:26559755

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

    PubMed Central

    Mller, 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 metaloxidesemiconductor (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. 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.

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

    PubMed

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

    2016-03-01

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

  6. A MicroRNA-BDNF Negative Feedback Signaling Loop in Brain: Implications for Alzheimer's Disease.

    PubMed

    Keifer, Joyce; Zheng, Zhaoqing; Ambigapathy, Ganesh

    2015-01-01

    MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression posttranscriptionally by interfering with translation of their target mRNAs. Typically, miRNAs bind to the 3' UTRs of mRNAs to induce repression or degradation. Neurotrophins are growth factors in brain required for neuronal survival, synapse formation, and plasticity mechanisms. Neurotrophins are not only regulated by miRNAs, but they in turn regulate miRNA expression. Accumulating data indicate there is a regulatory negative feedback loop between one ubiquitous neurotrophin, brain-derived neurotrophic factor (BDNF), and miRNAs. That is, while BDNF treatment stimulates neuronal miRNA expression, miRNAs generally function to inhibit expression of BDNF. This negative feedback loop is maintained in a state of equilibrium in normal cells. However, in Alzheimer's Disease (AD), a progressive neurodegenerative disorder resulting in memory loss and eventually dementia that is characterized by reduced levels of BDNF in brain, the balance between BDNF and miRNA is shifted toward inhibitory control by miRNAs. Here, we will briefly review the evidence for a positive action of BDNF on miRNA expression and a negative action of miRNAs on BDNF. We propose that the reduction in BDNF that occurs in the AD brain is the result of two independent mechanisms: 1) a failure in the proteolytic conversion of BDNF precursor protein to its functional mature form, and 2) inhibition of BDNF gene expression by miRNAs. The role of miRNAs in BDNF regulation should be considered when developing BDNF-based therapeutic treatments for AD. PMID:26456533

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

    PubMed Central

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

    2014-01-01

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

  8. 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.

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

    PubMed

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

    2015-09-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2012-01-01

    Circadian clocks synchronise biological processes with the day/night cycle, using molecular mechanisms that include interlocked, transcriptional feedback loops. Recent experiments identified the evening complex (EC) as a repressor that can be essential for gene expression rhythms in plants. Integrating the EC components in this role significantly alters our mechanistic, mathematical model of the clock gene circuit. Negative autoregulation of the EC genes constitutes the clock's evening loop, replacing the hypothetical component Y. The EC explains our earlier conjecture that the morning gene PSEUDO-RESPONSE REGULATOR 9 was repressed by an evening gene, previously identified with TIMING OF CAB EXPRESSION1 (TOC1). Our computational analysis suggests that TOC1 is a repressor of the morning genes LATE ELONGATED HYPOCOTYL and CIRCADIAN CLOCK ASSOCIATED1 rather than an activator as first conceived. This removes the necessity for the unknown component X (or TOC1mod) from previous clock models. As well as matching timeseries and phase-response data, the model provides a new conceptual framework for the plant clock that includes a three-component repressilator circuit in its complex structure. PMID:22395476

  12. 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

  13. 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

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

    PubMed

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

    2015-06-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2015-05-01

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

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

    PubMed

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

    2015-05-15

    We investigated the capability of obtaining atomic resolution surface potential images by frequency-modulation Kelvin probe force microscopy (FM-KPFM) without bias voltage feedback. We theoretically derived equations representing the relationship between the contact potential difference and the frequency shift (?f) of an oscillating cantilever. For the first time, we obtained atomic resolution images and site-dependent spectroscopic curves for ?f and VLCPD on a Si (111)-7נ7 surface. FM-KPFM without bias voltage feedback does not involve the influence of the FM-KPFM controller because it has no deviation from a parabolic dependence of ?f on the dc-bias voltage. It is particularly suitable for investigation on molecular electronics and organic photovoltaics, because electron or ion movement induced by dc bias is avoided and the electrochemical reactions are inhibited. PMID:25895740

  17. 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)

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

    PubMed

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

    2016-02-01

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

  19. 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.

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

    PubMed

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

    2002-11-01

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

  1. 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

  2. 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

  3. 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%.

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

    NASA Technical Reports Server (NTRS)

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

    1989-01-01

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

  5. A negative feedback loop involving small RNAs accelerates Vibrio choleraes transition out of quorum-sensing mode

    PubMed Central

    Svenningsen, Sine L.; Waters, Christopher M.; Bassler, Bonnie L.

    2008-01-01

    Quorum sensing is a cell-to-cell communication process that allows bacteria to measure their population numbers and to synchronously alter gene expression in response to changes in cell population density. At the core of the Vibrio cholerae quorum-sensing signal transduction pathway lie four redundant small RNAs (sRNAs), named the Quorum Regulatory RNAs (Qrr14). Expression of qrr14 is cell population density-dependent due to a requirement for the quorum-sensing controlled phosphorylated response regulator LuxO-P, which is abundant only at low cell population density. When expressed, Qrr14 repress translation of HapR, the master quorum-sensing transcription factor. Here we show a negative feedback loop in which HapR activates transcription of the qrr genes, which indirectly leads to hapR repression. Efficient feedback activation of the qrr genes requires the simultaneous presence of LuxO-P (present only at low cell population density) and HapR (present only at high cell population density). For this reason, the feedback loop does not influence quorum sensing at steady-state low or high cell population density. However, LuxO-P and HapR are simultaneously present immediately following the switch from high to low cell density conditions. In this state, the HapR feedback loop dramatically accelerates V. choleraes transition from the high to the low cell density mode. PMID:18198339

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

    SciTech Connect

    Iizuka, Katsumi; Horikawa, Yukio

    2008-09-12

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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

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

    2009-01-01

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

  9. 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

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

    PubMed Central

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

    2012-01-01

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

  11. 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

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

    PubMed

    Reed, Phil

    2016-03-01

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

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

    PubMed

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

    2015-07-01

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

  14. Positive feedback loop of hepatoma-derived growth factor and ?-catenin promotes carcinogenesis of colorectal cancer

    PubMed Central

    Li, Hui; Zhen, Tiantian; Xie, Wenlin; Zhang, Fenfen; Yang, Yang; Han, Anjia

    2015-01-01

    To clarify the role of hepatoma-derived growth factor (HDGF) and ?-catenin in carcinogenesis of colorectal cancer (CRC), our results showed that high HDGF expression was found in CRC cells and tissues and significantly related to histological differentiation (p = 0.035) and lymph node metastasis (p = 0.000). Significant positive correlation between HDGF expression and ?-catenin abnormal expression was found in CRC tissues. High HDGF and lymph node metastasis were the strong independent prognostic indicators for reduced overall survival in CRC patients. HDGF knockdown dramatically inhibited cellular proliferation, migration, invasion, and tumorigenesis, both in vitro and in vivo, but induced G1 phase arrest and apoptosis in CRC cells. HDGF knock-down dramatically suppressed ?-catenin and its down-stream genes expression in CRC cells. Intriguingly, ?-catenin knock-down dramatically suppressed HDGF expression in CRC cells. Human recombinant Wnt3a and DKK1 treatment increased and decreased HDGF, ?-catenin, c-Myc, cyclin D1, MMP9, and phos-GSK-3? (Ser9) protein expression in nuclear and cytoplasmic fraction of CRC cells upon ?-catenin knock-down, respectively. Three HDGF-binding elements in ?-catenin promoter were found and specific for transcriptional activation of ?-catenin in CRC cells. In conclusion, our results first suggest that HDGF and ?-catenin interacts as a positive feedback loop, which plays an important role in carcinogenesis and progression of CRC. PMID:26296979

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

    PubMed

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

    2016-03-01

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

  16. Intronic promoter-mediated feedback loop regulates bean PvSR2 gene expression.

    PubMed

    Yang, Wanning; Bei, Xiujuan; Liu, Meng; Qi, Xiaoting

    2015-08-01

    Intronic promoter usage is a widespread regulatory mechanism for increasing the diversity of gene expression regulation. However, its trans-acting mechanisms that modulate host gene expression are poorly characterized. We previously showed that bean (Phaseolus vulgaris) stress-related gene 2 (PvSR2) produces a metal-responsive element (MRE)-binding transcription factor (PvMTF-1) by using an intronic promoter. Interestingly, a functional MRE resides within the upstream PvSR2 promoter, implying that PvMTF-1 is likely to regulate its host gene expression via this MRE. Through DNA-protein interaction studies combined with an analysis of expression of PvMTF-1 in bean leaves, we now report that PvMTF-1 binds to this MRE and thereby up-regulates PvSR2 expression, thus constituting a positive regulatory feedback loop. Our findings provide evidence for a trans-acting mechanism of an intronic promoter in host gene expression, hence, adding a new layer of complexity in intronic promoter-mediated gene regulation. This study may also contribute to the understanding of the intron-mediated regulation of gene expression in trans. PMID:26079876

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

    PubMed Central

    Wang, Qian; Whim, Matthew D.

    2013-01-01

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

  18. 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

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

    PubMed

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

    2015-10-01

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

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

    PubMed Central

    Moes, Michle; Le Bchec, 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

  1. Investigating the functional implications of reinforcing feedback loops in transcriptional regulatory networks.

    PubMed

    Li, Yue; Liang, Cheng; Easterbrook, Steve; Luo, Jiawei; Zhang, Zhaolei

    2014-12-01

    Transcription factors (TFs) and microRNAs (miRNAs) can jointly regulate transcriptional networks in the form of recurrent circuits or motifs. A motif can be divided into a feedforward loop (FFL) and a feedback loop (FBL). Incoherent FFLs have been the recent focus due to their potential to dampen gene expression noise in maintaining physiological norms. However, a cell is not only able to manage noise but also able to exploit it during development or tumorigenesis to initiate radical transformation such as cell differentiation or metastasis. A plausible mechanism may involve reinforcing FBLs (rFBLs), which amplify changes to a sufficient level in order to complete the state transition. To study the behaviour of rFBLs, we developed a novel theoretical framework based on biochemical kinetics. The proposed rFBL follows a parsimonious design, involving two TFs and two miRNAs. A simulation study based on our model suggested that a system with rFBLs is robust to only a certain level of fluctuation but prone to a complete paradigm shift when the change exceeds a threshold level. To investigate the natural occurrence of rFBLs, we performed a rigorous network motif analysis using a recently available TF/miRNA regulatory network from the Encyclopedia of DNA Elements (ENCODE). Our analysis suggested that the rFBL is significantly depleted in the observed network. Nonetheless, we identified 9 rFBL instances. Among them, we found a double-rFBL involving three TFs SUZ12/BCLAF1/ZBTB33 and three miRNAs miR-9/19a/129-5p, which together serve as an intriguing toggle switch between nerve development and telomere maintenance. Additionally, we investigated the interactions implicated in the rFBLs using expression profiles of cancer patients from The Cancer Genome Atlas (TCGA). Together, we provided a novel and comprehensive view of the profound impacts of rFBLs and highlighted several TFs and miRNAs as the leverage points for potential therapeutic targets in cancers due to their eminent roles in the identified rFBLs. PMID:25286350

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

    PubMed

    Zamora-Chimal, Criseida; Santilln, Moiss; Rodrguez-Gonzlez, Jess

    2012-10-01

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

  3. 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

  4. ASDTIC - A feedback control innovation.

    NASA Technical Reports Server (NTRS)

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

    1972-01-01

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

  5. ASDTIC: A feedback control innovation

    NASA Technical Reports Server (NTRS)

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

    1972-01-01

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

  6. 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 ?-oxo-aldehydes into the corresponding ?-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

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

    PubMed

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

    2010-05-21

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

  8. 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

  9. Nodule Inception creates a long-distance negative feedback loop involved in homeostatic regulation of nodule organ production.

    PubMed

    Soyano, Takashi; Hirakawa, Hideki; Sato, Shusei; Hayashi, Makoto; Kawaguchi, Masayoshi

    2014-10-01

    Autoregulatory negative-feedback loops play important roles in fine-balancing tissue and organ development. Such loops are composed of short-range intercellular signaling pathways via cell-cell communications. On the other hand, leguminous plants use a long-distance negative-feedback system involving root-shoot communication to control the number of root nodules, root lateral organs that harbor symbiotic nitrogen-fixing bacteria known as rhizobia. This feedback system, known as autoregulation of nodulation (AON), consists of two long-distance mobile signals: root-derived and shoot-derived signals. Two Lotus japonicus CLAVATA3/endosperm surrounding region (CLE)-related small peptides, CLE root signal1 (CLE-RS1) and CLE-RS2, function as root-derived signals and are perceived by a shoot-acting AON factor, the hypernodulation aberrant root formation1 (HAR1) receptor protein, an ortholog of Arabidopsis CLAVATA1, which is responsible for shoot apical meristem homeostasis. This peptide-receptor interaction is necessary for systemic suppression of nodulation. How the onset of nodulation activates AON and how optimal nodule numbers are maintained remain unknown, however. Here we show that an RWP-RK-containing transcription factor, nodule inception (NIN), which induces nodule-like structures without rhizobial infection when expressed ectopically, directly targets CLE-RS1 and CLE-RS2. Roots constitutively expressing NIN systemically repress activation of endogenous NIN expression in untransformed roots of the same plant in a HAR1-dependent manner, leading to systemic suppression of nodulation and down-regulation of CLE expression. Our findings provide, to our knowledge, the first molecular evidence of a long-distance autoregulatory negative-feedback loop that homeostatically regulates nodule organ formation. PMID:25246578

  10. Contribution of the ROS-p53 feedback loop in thuja-induced apoptosis of mammary epithelial carcinoma cells.

    PubMed

    Saha, Shilpi; Bhattacharjee, Pushpak; Mukherjee, Shravanti; Mazumdar, Minakshi; Chakraborty, Samik; Khurana, Anil; Nayak, Debadatta; Manchanda, Rajkumar; Chakrabarty, Rathin; Das, Tanya; Sa, Gaurisankar

    2014-04-01

    The adverse side-effects associated with chemotherapy during cancer treatment have shifted considerable focus towards therapies that are targeted but devoid of toxic side-effects. In the present study, the antitumorigenic activity of thuja, the bioactive derivative of the medicinal plant Thuja occidentalis, was evaluated, and the molecular mechanisms underlying thuja-induced apoptosis of functional p53-expressing mammary epithelial carcinoma cells were elucidated. Our results showed that thuja successfully induced apoptosis in functional p53-expressing mammary epithelial carcinoma cells. Abrogation of intracellular reactive oxygen species (ROS), prevention of p53-activation, knockdown of p53 or inhibition of its functional activity significantly abridged ROS generation. Notably, under these conditions, thuja-induced breast cancer cell apoptosis was reduced, thereby validating the existence of an ROS-p53 feedback loop. Elucidating this feedback loop revealed bi-phasic ROS generation as a key mediator of thuja-induced apoptosis. the first phase of ROS was instrumental in ensuring activation of p53 via p38MAPK and its nuclear translocation for transactivation of Bax, which induced a second phase of mitochondrial ROS to construct the ROS-p53 feedback loop. Such molecular crosstalk induced mitochondrial changes i) to maintain and amplify the thuja signal in a positive self-regulatory feedback manner; and ii) to promote the mitochondrial death cascade through cytochrome c release and caspase-driven apoptosis. These results open the horizon for developing a targeted therapy by modulating the redox status of functional p53-expressing mammary epithelial carcinoma cells by thuja. PMID:24482097

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

    SciTech Connect

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

    2014-03-28

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

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

    PubMed

    Cunningham, John P; Nuyujukian, Paul; Gilja, Vikash; Chestek, Cindy A; Ryu, Stephen I; Shenoy, Krishna V

    2011-04-01

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

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

    PubMed Central

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

    2014-01-01

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

  14. Interleukin 6 promotes endometrial cancer growth through an autocrine feedback loop involving ERK-NF-?B 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-?B) and extra-cellular signal-regulated kinase (ERK). Importantly, activation of ERK was upstream of the NF-?B 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-?B pathway as a critical mediator of IL-6 production, implying IL-6 to be an important therapeutic target in endometrial carcinoma. PMID:24582558

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

    PubMed

    Yue, Jicheng; Ben Messaoud, Nabil; Lpez, Jos 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

  16. 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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  18. 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

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

    NASA Technical Reports Server (NTRS)

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

    1974-01-01

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

  20. 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.

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

    PubMed

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

    2016-01-01

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

  2. 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

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

    NASA Astrophysics Data System (ADS)

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

    1997-05-01

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

  4. Voltage-biased superconducting transition-edge bolometer with strong electrothermal feedback operated at 370 mK

    SciTech Connect

    Lee, S.; 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{sub c}{approximately}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{sub 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{times}10{sup {minus}17} W/{radical}()Hz was measured for a thermal conductance G{approximately}4.7{times}10{sup {minus}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. {copyright} 1998 Optical Society of America

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

    PubMed

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

    2015-04-01

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

  6. 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.

  7. 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.

  8. 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

  9. 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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

    Osorio-Zambrano, William F.; Davey, Scott

    2015-01-01

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

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

    PubMed

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

    2015-09-01

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

  13. A positive feedback loop between Gli1 and tyrosine kinase Hck amplifies shh signaling activities in medulloblastoma

    PubMed Central

    Shi, X; Zhan, X; Wu, J

    2015-01-01

    Sonic hedgehog (Shh) signaling is critical during normal development, and the abnormal activation of the Shh pathway is involved in many human cancers. As a target gene of the Shh pathway and as a transcription activator downstream of Shh signaling, Gli1 autoregulates and increases Shh signaling output. Gli1 is one of the key oncogenic factors in Shh-induced tumors such as medulloblastoma. Gli1 is posttranslationally modified, but the nature of the active form of Gli1 was unclear. Here we identified a Src family kinase Hck as a novel activator of Gli1. In Shh-responsive NIH3T3 cells, Hck interacts with Gli1 and phosphorylates multiple tyrosine residues in Gli1. Gli1-mediated target gene activation was significantly enhanced by Hck with both kinase activity-dependent and -independent mechanisms. We provide evidence showing that Hck disrupts the interaction between Gli1 and its inhibitor Sufu. In both NIH3T3 cells and cerebellum granule neuron precursors, the Hck gene is also a direct target of Gli1. Therefore, Gli1 and Hck form a positive feedback loop that amplifies Shh signaling transcription outcomes. In Shh-induced medulloblastoma, Hck is highly expressed and Gli1 is tyrosine phosphorylated, which may enhance the tumorigenic effects of the Gli1 oncogene. RNAi-mediated inhibition of Hck expression significantly repressed medulloblastoma cell growth. In summary, a novel positive feedback loop contributes to maximal Gli1 oncogenic activities in Shh-induced tumors such as medulloblastoma. PMID:26619401

  14. 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

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

    PubMed Central

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

    1978-01-01

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

  16. 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.

  17. 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

  18. 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.

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

    SciTech Connect

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

    2015-01-13

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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  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

    DOEpatents

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

    1992-01-01

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

  3. Closing the Loop: The Impact of Student Feedback on Students' Subsequent Learning. Research Report Series.

    ERIC Educational Resources Information Center

    Powney, Janet; Hall, Stuart

    Higher education institutions in the United Kingdom (UK) use a variety of ways to collect views from students about the quality of their educational experiences and suggestions for improvements. A small-scale study, funded by Higher Education Quality Council (QAA), explored how this feedback contributes to enhancing subsequent performance. Drawing

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

    PubMed

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

    2015-08-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2005-12-01

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

  6. 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.

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

    NASA Astrophysics Data System (ADS)

    Burkholder, Michael B.; Litster, Shawn

    2015-02-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2014-12-01

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

  9. PIV wave propagation investigation of non-linear losses through 90 degree bends in a thermoacoustic engine's feedback loop

    NASA Astrophysics Data System (ADS)

    Wee, S. T.; Hann, D. B.; Abakr, Yousif Abdalla; Riley, P.

    2012-06-01

    Thermoacoustic engine technology has recently been applied to renewable energy to convert heat energy into acoustic energy for the purpose of electricity generation. One of the vital components of the engine is its feedback loop which is sensitive to geometrical changes that can cause system losses. We previously postulated that a critical Acoustic Dean Number exist above which the Acoustic Power Transmission Loss increases drastically for a wave propagating though a bend. This paper investigates the wave propagation through the bend using Particle Image Velocimetry(PIV). This technique has not been used in this field of investigation and allows the flow visualization as well as the planar velocity field measurement of the system. The PIV results confirmed earlier pressure measurements that a critical Dean number does exist, and describes visualizations of the flows causing the losses.

  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 is that the resulting control law has an algebraic closed-form structure. The proposed method uses an optimal spatial statistical predictor called universal kriging to construct the surrogate model of a feedback controller, which is capable of quickly predicting an optimal control estimate based on current state (and time) information. With universal kriging, an approximation to the optimal feedback map is computed by conceptualizing a set of state-control samples from pre-computed extremals to be a particular realization of a jointly Gaussian spatial process. Feedback policies are computed for a variety of example dynamic optimization problems in order to evaluate the effectiveness of this methodology. This feedback synthesis approach is found to combine good numerical accuracy with low computational overhead, making it a suitable candidate for real-time applications. Particle swarm and universal kriging are combined for a capstone example, a near optimal, near-admissible, full-state feedback control law is computed and tested for the heat-load-limited atmospheric-turn guidance of an aeroassisted transfer vehicle. The performance of this explicit guidance scheme is found to be very promising; initial errors in atmospheric entry due to simulated thruster misfirings are found to be accurately corrected while closely respecting the algebraic state-inequality constraint.

  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 and the parameterisation approach that would be taken in each case is discussed. Preliminary findings in the case studies lend support to the conceptual theories outlined in the framework. It is envisioned that the application of this framework across study sites and gradients will aid in developing our understanding of the fundamental interactions and feedbacks in such complex human-hydrology systems, and allow hydrologists to improve social-ecological systems modelling through better representation of human feedbacks on hydrological processes.

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

    NASA Astrophysics Data System (ADS)

    Tiwari, Abhinav; Balzsi, Gbor; Gennaro, Maria Laura; Igoshin, Oleg A.

    2010-09-01

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

  14. 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

  15. 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

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

    PubMed Central

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

    2011-01-01

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

  17. 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

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

    PubMed Central

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

    2013-01-01

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

  19. 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.

  20. 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

  1. 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.

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

    PubMed Central

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

    2014-01-01

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

  3. 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

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

    NASA Astrophysics Data System (ADS)

    Murray, A. B.

    2014-12-01

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

  5. 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.

  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. 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.

  8. 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.

  9. PER/TIM-mediated amplification, gene dosage effects and temperature compensation in an interlocking-feedback loop model of the Drosophila circadian clock.

    PubMed

    Ruoff, Peter; Christensen, Melinda K; Sharma, Vijay K

    2005-11-01

    We have analysed a first-order kinetic representation of a interlocking-feedback loop model for the Drosophila circadian clock. In this model, the transcription factor Drosophila CLOCK (dCLK) which activates the clock genes period (per) and timeless (tim) is subjected to positive and negative regulations by the proteins 'PAR Domain Protein 1' (PDP1) and VRILLE (VRI), whose transcription is activated by dCLK. The PER/TIM complex binds to dCLK and in this way reduces the activity of dCLK. The results of our simulations suggest that the positive and negative feedback loops of Pdp1 and vri are essential for the overall oscillations. Although self sustained oscillations can be obtained without per/tim, the model shows that the PER/TIM complex plays an important role in amplification and stabilization of the oscillations generated by the Pdp1/vri positive/negative feedback loops. We further show that in contrast to a single (per/tim) negative feedback loop oscillator, the interlocking-feedback loop model can readily account for the effect of gene dosages of per, vri, and Pdp1 on the period length. Calculations of phase resetting on a temperature compensated version of the model shows good agreement with experimental phase response curves for high and low temperature pulses. Also, the partial losses of temperature compensation in perS and perL mutants can be described, which are related to decreased stabilities of the PER/TIM complex in perS and the stronger/more stable inhibitory complex between dCLK and PER/TIM in perL, respectively. The model shows (somewhat surprisingly) poor entrainment properties, especially under extended light/dark (L/D) cycles, which suggests that parts of the L/D tracking or sensing system are not well represented. PMID:15935389

  10. Dynamics of a Minimal Model of Interlocked Positive and Negative Feedback Loops of Transcriptional Regulation by cAMP-Response Element Binding Proteins

    PubMed Central

    Song, Hao; Smolen, Paul; Av-Ron, Evyatar; Baxter, Douglas A.; Byrne, John H.

    2007-01-01

    cAMP-response element binding (CREB) proteins are involved in transcriptional regulation in a number of cellular processes (e.g., neural plasticity and circadian rhythms). The CREB family contains activators and repressors that may interact through positive and negative feedback loops. These loops can be generated by auto- and cross-regulation of expression of CREB proteins, via CRE elements in or near their genes. Experiments suggest that such feedback loops may operate in several systems (e.g., Aplysia and rat). To understand the functional implications of such feedback loops, which are interlocked via cross-regulation of transcription, a minimal model with a positive and negative loop was developed and investigated using bifurcation analysis. Bifurcation analysis revealed diverse nonlinear dynamics (e.g., bistability and oscillations). The stability of steady states or oscillations could be changed by time delays in the synthesis of the activator (CREB1) or the repressor (CREB2). Investigation of stochastic fluctuations due to small numbers of molecules of CREB1 and CREB2 revealed a bimodal distribution of CREB molecules in the bistability region. The robustness of the stable HIGH and LOW states of CREB expression to stochastic noise differs, and a critical number of molecules was required to sustain the HIGH state for days or longer. Increasing positive feedback or decreasing negative feedback also increased the lifetime of the HIGH state, and persistence of this state may correlate with long-term memory formation. A critical number of molecules was also required to sustain robust oscillations of CREB expression. If a steady state was near a deterministic Hopf bifurcation point, stochastic resonance could induce oscillations. This comparative analysis of deterministic and stochastic dynamics not only provides insights into the possible dynamics of CREB regulatory motifs, but also demonstrates a framework for understanding other regulatory processes with similar network architecture. PMID:17277187

  11. 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.

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

    PubMed

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

    2015-12-01

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

  13. 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

  14. 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 (?) cells. However, little is known about how insulin signaling feedback might influence neogenesis of ? 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 ? cell genes insulin and pdx1, and promoted ? cell fate at the expense of alpha cell fate. In addition, loss of insulin signaling promoted ? cell regeneration and destabilization of alpha cell character. These data indicate that insulin signaling constitutes a tunable mechanism for ? 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 ? cells. Furthermore, the extent of this differentiation was dependent on the function of the ? cell mass in the host. Altogether, our results indicate that modulation of insulin signaling will be crucial for the development of ? cell restoration therapies for diabetics; further clarification of the mechanisms of insulin signaling in ? cell progenitors will reveal therapeutic targets for both in vivo and in vitro ? cell generation. PMID:26658317

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2011-07-01

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

  17. Auxin and cytokinin regulate each other's levels via a metabolic feedback loop

    PubMed Central

    Jones, Brian

    2011-01-01

    The hormones auxin and cytokinin are key regulators of plant growth and development. As they are active at minute concentrations and regulate dynamic processes, cell and tissue levels of the hormones are finely controlled developmentally, diurnally, and in response to environmental variables. This fine control, along with a regulation of the capacity to respond ensures that the appropriate type, duration and intensity of responses are elicited. We have recently discovered that cytokinin and auxin regulate the synthesis of each other, demonstrating a mechanism for mutual feed back and feed forward control of auxin and cytokinin levels. This regulatory loop could be important for many developmental processes in plants, i.e., in fine-tuning plant hormone levels in the developing meristems of the root and shoot apex. These findings could also give a molecular explanation for earlier observations of auxin and cytokinin effects on cell cultures,1 where specific auxin and cytokinin ratios have been used to trigger different morphological events. PMID:21543904

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

    PubMed

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

    2015-03-01

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

  19. Oocyte polarity requires a Bucky ball-dependent feedback amplification loop

    PubMed Central

    Heim, Amanda E.; Hartung, Odelya; Rothhmel, Sophie; Ferreira, Elodie; Jenny, Andreas; Marlow, Florence L.

    2014-01-01

    In vertebrates, the first asymmetries are established along the animal-vegetal axis during oogenesis, but the underlying molecular mechanisms are poorly understood. Bucky ball (Buc) was identified in zebrafish as a novel vertebrate-specific regulator of oocyte polarity, acting through unknown molecular interactions. Here we show that endogenous Buc protein localizes to the Balbiani body, a conserved, asymmetric structure in oocytes that requires Buc for its formation. Asymmetric distribution of Buc in oocytes precedes Balbiani body formation, defining Buc as the earliest marker of oocyte polarity in zebrafish. Through a transgenic strategy, we determined that excess Buc disrupts polarity and results in supernumerary Balbiani bodies in a 3?UTR-dependent manner, and we identified roles for the buc introns in regulating Buc activity. Analyses of mosaic ovaries indicate that oocyte pattern determines the number of animal pole-specific micropylar cells that are associated with an egg via a close-range signal or direct cell contact. We demonstrate interactions between Buc protein and buc mRNA with two conserved RNA-binding proteins (RNAbps) that are localized to the Balbiani body: RNA binding protein with multiple splice isoforms 2 (Rbpms2) and Deleted in azoospermia-like (Dazl). Buc protein and buc mRNA interact with Rbpms2; buc and dazl mRNAs interact with Dazl protein. Cumulatively, these studies indicate that oocyte polarization depends on tight regulation of buc: Buc establishes oocyte polarity through interactions with RNAbps, initiating a feedback amplification mechanism in which Buc protein recruits RNAbps that in turn recruit buc and other RNAs to the Balbiani body. PMID:24496621

  20. 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/EBP?, 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

  1. 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.

  2. 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

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

    PubMed Central

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

    2014-01-01

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

  4. 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 ?-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

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

    SciTech Connect

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

    2008-05-23

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

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

    PubMed

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

    2013-12-01

    Heme oxygenase-1 (HMOX1) is a ubiquitously expressed inducible enzyme that degrades heme to carbon monoxide, biliverdin, and free iron ions. Since 1950, many studies have revealed the role of HMOX1 in reducing the impact of oxidative stress in many types of diseases, such as Alzheimer's disease, heart disease, and the development of tumors. These effects arise as a result of the removal of heme, the biological activities of the products of HMOX1 and the activity of HMOX1 itself. However, HMOX1 has some contradictory effects. The discovery of microRNAs (miRNAs) and their relationship with HMOX1 has provided a new direction for research in this field. Here, we discuss the role of a potential regulatory feedback loop between HMOX1 and miRNAs in pathological processes based on recently published data. We hope to describe a new mechanism for HMOX1 function based on miRNAs to address the contradictory results reported in the literature. PMID:23939757

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

    PubMed Central

    Crisp, Kevin M.; Muller, Kenneth J.

    2007-01-01

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

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

    PubMed

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

    2015-11-01

    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/GSK3? 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

  9. 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

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

    PubMed

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

    2015-12-15

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

  11. Elastin-derived peptides stimulate trophoblast migration and invasion: a positive feedback loop to enhance spiral artery remodelling.

    PubMed

    Desforges, Michelle; Harris, Lynda K; Aplin, John D

    2015-01-01

    Elastin breakdown in the walls of uterine spiral arteries during early pregnancy facilitates their transformation into dilated, high-flow, low-resistance channels. Elastin-derived peptides (EDP) can influence cell migration, invasion and protease activity, and so we hypothesized that EDP released during elastolysis promote extravillous trophoblast (EVT) invasion and further elastin breakdown. Treatment of the trophoblast cell line SGHPL4 with the elastin-derived matrikine VGVAPG (1 ?g/ml) significantly increased total elastase activity, promoted migration in a wound healing assay and increased invasion through Matrigel-coated transwells compared with vehicle control (0.1% DMSO) or the scrambled sequence VVGPGA. Furthermore, treatment of first-trimester placental villous explants with this EDP significantly increased both the area of trophoblast outgrowth and distance of migration away from the villous tips. Primary first-trimester cytotrophoblast exposed to VGVAPG (1 ?g/ml) for 30 min showed increased phosphorylation of endothelial nitric oxide synthase and activation of the mitogen activated protein kinase pathway, events also associated with tumour cell migration and invasion. These in vitro observations suggest liberation of bioactive EDP during induction of elastolysis in the uterine spiral arteries may orchestrate a positive feedback loop that promotes EVT invasion and further elastin breakdown, contributing to the process of vascular remodelling. PMID:25245255

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

    PubMed

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

    2016-01-01

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

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

    PubMed

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

    2015-09-01

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

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

    PubMed

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

    2014-04-10

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

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

    NASA Astrophysics Data System (ADS)

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

    2014-05-01

    Using satellite data in a hydrological model has long been occurring in modelling of hydrological processes, as a source of low cost regular data. The methods range from using satellite products as direct input, model validation, and data assimilation. However, the satellite data frequently face the missing value problem, whether due to the cloud cover or the limited temporal coverage. The problem could seriously affect its usefulness in hydrological model, especially if the model uses it as direct input, so data infilling becomes one of the important parts in the whole modelling exercise. In this research, actual evapotranspiration product from satellite is directly used as input into a spatially distributed hydrological model, and validated by comparing the catchment's end discharge with measured data. The instantaneous actual evapotranspiration is estimated from MODIS satellite images using a variation of the energy balance model for land (SEBAL). The eight-day cumulative actual evapotranspiration is then obtained by a temporal integration that uses the reference evapotranspiration calculated from meteorological data [1]. However, the above method cannot fill in a cell if the cell is constantly having no-data value during the eight-day periods. The hydrological model requires full set of data without no-data cells, hence, the no-data cells in the satellite's evapotranspiration map need to be filled in. In order to fills the no-data cells, an output of hydrological model is used. The hydrological model is firstly run with reference evapotranspiration as input to calculate discharge and actual evapotranspiration. The no-data cells in the eight-day cumulative map from the satellite are then filled in with the output of the first run of hydrological model. The final data is then used as input in a hydrological model to calculate discharge, thus creating a loop. The method is applied in the case study of Rijnland, the Netherlands where in the winter, cloud cover is persistent and leads to many no-data cells in the satellite products. The Rijnland area is a low-lying area with tight water system control. The satellite data is used as input in a SIMGRO model, a spatially distributed hydrological model that is able to handle the controlled water system and that is suitable for the low-lying areas in the Netherlands. The application in the Rijnland area gives overall a good result of total discharge. By using the method, the hydrological model is improved in term of spatial hydrological state, where the original model is only calibrated to discharge in one location. [1] Alexandridis, T.K., Cherif, I., Chemin, Y., Silleos, G.N., Stavrinos, E. & Zalidis, G.C. (2009). Integrated Methodology for Estimating Water Use in Mediterranean Agricultural Areas. Remote Sensing. 1

  16. 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.

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2015-05-01

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

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

    PubMed

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

    2015-10-20

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

  20. 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 510(6) ST4/pIKT-shPlk, PLK1 transcript levels in tumors were 62.518.6% 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

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

    PubMed Central

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

    2015-01-01

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

  2. 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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

    Seydel, U; Jans, D A

    1996-01-01

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

  5. 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.

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

    NASA Astrophysics Data System (ADS)

    Sai, Toru; Sugimoto, Yasuhiro

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

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

    NASA Astrophysics Data System (ADS)

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

    2006-05-01

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

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

    PubMed

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

    2016-03-01

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

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

    PubMed

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

    2016-01-29

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

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

    NASA Astrophysics Data System (ADS)

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

    2016-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  12. 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.

  13. 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

  14. 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.

  15. 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.

  16. A set of homology models of pore loop domain of six eukaryotic voltage-gated potassium channels Kv1.1-Kv1.6.

    PubMed

    Liu, Hsuan-Liang; Lin, Jin-Chung

    2004-05-15

    Homology models of the pore loop domain of six eukaryotic potassium channels, Kv1.1-Kv1.6, were generated based on the crystallographic structure of KcsA. The results of amino acid sequence alignment indicate that these Kv channels are composed of two structurally and functionally independent domains: the N-terminal 'voltage sensor' domain and the C-terminal 'pore loop' domain. The homology models reveal that the pore loop domains of these Kv channels exhibit similar folds to those of KcsA. The structural features and specific packing of aromatic residues around the selectivity filter of these Kv channels are nearly identical to those of KcsA, whereas most of the structural variations occur in the turret as well as in the inner and outer helices. The distribution of polar and nonpolar side chains on the surfaces of the KcsA and Kv channels reveals that they exhibit a segregation of side chains common to most integral membrane proteins. As the hydrogen bond between Glu71 and Asp80 in KcsA plays an important role in stabilizing the channel, the substituted Val residue in the Kv family corresponding to Glu71 of KcsA stabilizes the channel by making hydrophobic contact with Tyr residue from the signature sequence of the selectivity filter. The homology models of these Kv channels provide particularly attractive subjects for further structure-based studies. PMID:15103620

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed Central

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

    2015-01-01

    How nature discriminates sodium from calcium ions in eukaryotic channels has been difficult to resolve because they contain four homologous, but markedly different repeat domains. We glean clues from analyzing the changing pore region in sodium, calcium and NALCN channels, from single-cell eukaryotes to mammals. Alternative splicing in invertebrate homologs provides insights into different structural features underlying calcium and sodium selectivity. NALCN generates alternative ion selectivity with splicing that changes the high field strength (HFS) site at the narrowest level of the hourglass shaped pore where the selectivity filter is located. Alternative splicing creates NALCN isoforms, in which the HFS site has a ring of glutamates contributed by all four repeat domains (EEEE), or three glutamates and a lysine residue in the third (EEKE) or second (EKEE) position. Alternative splicing provides sodium and/or calcium selectivity in T-type channels with extracellular loops between S5 and P-helices (S5P) of different lengths that contain three or five cysteines. All eukaryotic channels have a set of eight core cysteines in extracellular regions, but the T-type channels have an infusion of 412 extra cysteines in extracellular regions. The pattern of conservation suggests a possible pairing of long loops in Domains I and III, which are bridged with core cysteines in NALCN, Cav, and Nav channels, and pairing of shorter loops in Domains II and IV in T-type channel through disulfide bonds involving T-type specific cysteines. Extracellular turrets of increasing lengths in potassium channels (Kir2.2, hERG, and K2P1) contribute to a changing landscape above the pore selectivity filter that can limit drug access and serve as an ion pre-filter before ions reach the pore selectivity filter below. Pairing of extended loops likely contributes to the large extracellular appendage as seen in single particle electron cryo-microscopy images of the eel Nav1 channel. PMID:26042044

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

    PubMed

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

    2015-01-01

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

  20. 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.

  1. MicroRNA-30e* promotes human glioma cell invasiveness in an orthotopic xenotransplantation model by disrupting the NF-?B/I?B? negative feedback loop

    PubMed Central

    Jiang, Lili; Lin, Chuyong; Song, Libing; Wu, Jueheng; Chen, Baixue; Ying, Zhe; Fang, Lishan; Yan, Xiao; He, Mian; Li, Jun; Li, Mengfeng

    2011-01-01

    Constitutive activation of NF-?B is a frequent event in human cancers, playing important roles in cancer development and progression. In nontransformed cells, NF-?B activation is tightly controlled by I?Bs. I?Bs bind NF-?B in the cytoplasm, preventing it from translocating to the nucleus to modulate gene expression. Stimuli that activate NF-?B signaling trigger I?B degradation, enabling nuclear translocation of NF-?B. Among the genes regulated by NF-?B are those encoding the I?Bs, providing a negative feedback loop that limits NF-?B activity. How transformed cells override this NF-?B/I?B negative feedback loop remains unclear. Here, we report in human glioma cell lines that microRNA-30e* (miR-30e*) directly targets the I?B? 3?-UTR and suppresses I?B? expression. Overexpression of miR-30e* in human glioma cell lines led to hyperactivation of NF-?B and enhanced expression of NF-?Bregulated genes, which promoted glioma cell invasiveness in in vitro assays and in an orthotopic xenotransplantation model. These effects of miR-30e* were shown to be clinically relevant, as miR-30e* was found to be upregulated in primary human glioma cells and correlated with malignant progression and poor survival. Hence, miR-30e* provides an epigenetic mechanism that disrupts the NF-?B/I?B? loop and may represent a new therapeutic target and prognostic marker. PMID:22156201

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

    PubMed Central

    Rokavec, Matjaz; ner, Meryem Glfem; 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-6induced EMT and invasion. Furthermore, we identified the IL-6 receptor (IL-6R), which mediates IL-6dependent 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-6induced invasion and migration via miR-34adependent 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

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

    PubMed

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

    2016-03-01

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

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

    PubMed

    Hao, Lijie; Yang, Zhuoqin; Bi, Yuanhong

    2016-04-01

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

  5. High voltage DC power supply

    DOEpatents

    Droege, Thomas F.

    1989-01-01

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

  6. High voltage DC power supply

    DOEpatents

    Droege, T.F.

    1989-12-19

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

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

    PubMed

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

    2011-09-01

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

  8. 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.

  9. The role of dural sinus stenosis in idiopathic intracranial hypertension pathogenesis: the self-limiting venous collapse feedback-loop model.

    PubMed

    De Simone, R; Ranieri, A; Montella, S; Bilo, L; Cautiero, F

    2014-09-01

    In recent years the efficacy of endovascular venous stenting in idiopathic IIH treatment has been consistently reported, strongly suggesting that sinus stenosis should be viewed as a causative factor rather than a secondary phenomenon. We propose that in subjects carrying one or more collapsible segments of large cerebral venous collectors and exposed to a number of different promoting factors, sinus venous compression and cerebrospinal fluid (CSF) hypertension may influence each other in a circular way, leading to a new relatively stable venous/CSF pressures balance state at higher values. The mechanism relay on self-limiting venous collapse (SVC) feedback-loop between the CSF pressure, that compresses the sinus, and the consequent venous pressure rise, that increases the CSF pressure. The result is the "coupled" increase of both pressure values, a phenomenon not expected in presence of sufficiently rigid central veins. Once the maximum stretch of venous wall is reached the loop stabilize at higher venous/CSF pressure values and become self-sustaining, therefore persisting even after the ceasing of the promoting factor. Notably, the SVC is reversible provided an adequate perturbation is carried to whichever side of the loop such as sinus venous stenting, on one hand, and CSF diversion or even a single CSF withdrawal by lumbar puncture (LP), on the other. The SVC model predicts that any condition leading to an increase of either, cerebral venous pressure or CSF pressure may trigger the feedback loop in predisposed individuals. Migraine with and without aura, a disease sharing with IIH a much higher prevalence among women of childbearing age, is associated with waves of significant brain hyperperfusion. These may lead to the congestion of large cerebral venous collectors and could represent a common SVC promoting condition in susceptible individuals. The SVC model give reason of the high specificity and sensitivity of sinus stenosis as IIH predictor and of the multiplicity of the factors that have been found associated with IIH. Moreover it might explain why, among the sinus stenosis carriers, young and overweight women are at higher risk of developing the disease. Finally, the SVC model fully explain the enigmatic longstanding remissions that can be commonly observed after a single LP with CSF subtraction in IIH with or without papilledema. PMID:24867405

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

    PubMed

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

    2016-01-19

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

  11. BK channel activation by tungstate requires the ?1 subunit extracellular loop residues essential to modulate voltage sensor function and channel gating.

    PubMed

    Fernndez-Mario, Ana I; Valverde, Miguel A; Fernndez-Fernndez, Jos 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 ?1 or ?4 subunits. The BK activation by tungstate is Mg(2+)-dependent and promotes arterial vasodilation, but only in precontracted mouse arteries expressing ?1. In this study, we further explored how the ?1 subunit participates in tungstate activation of BK channels. Activation of heterologously expressed human BK??1 channels in inside-out patches is fully dependent on the Mg(2+) sensitivity of the BK ? channel subunit even at high (10?M) cytosolic Ca(2+) concentration. Alanine mutagenesis of ?1 extracellular residues Y74 or S104, which destabilize the active voltage sensor, greatly decreased the tungstate-induced left-shift of the BK??1 G-V curves in either the absence or presence of physiologically relevant cytosolic Ca(2+) levels (10?M). The weakened tungstate activation of the BK??1Y74A and BK??1S104A 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 ? channel subunit, around the Mg(2+) binding site. The role of ?1 in tungstate-induced channel activation seems to rely on its interaction with the BK ? 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

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

    PubMed

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

    2013-06-01

    The voltage-gated potassium channels KV7.2 and KV7.3 (KCNQ2/3 genes) play an important role in regulating neuronal excitability. More than 50 KCNQ2/3 mutations have been identified to cause an inherited form of epilepsy in newborns. For two of those (E119G and S122L) found in the S1-S2 region of KV7.2, we previously showed a decreased channel availability mainly at action potential subthreshold voltages caused by a slight depolarizing shift of the activation curve. Interestingly, recent studies revealed that a threonine residue within the S1-S2 loop, highly conserved among different classes of KV channels, is crucial for both their function and surface expression. To investigate the functional role of the homologous threonine residues in KV7.2 (T114) and KV7.3 (T144) channels, we replaced them with alanine and examined the electrophysiological properties using heterologous expression in CHO cells and whole cell patch clamping. Channels comprising mutant subunits yielded decreased potassium currents with slowed activation and accelerated deactivation kinetics. However, the most striking effect was a depolarizing shift in the voltage dependence of activation reaching +30mV upon co-expression of both mutant subunits. Potential interactions of T114 within the channel were analyzed by creating a 3D homology model of KV7.2 in an open state suggesting that this residue plays a central role in the formation of a stable interface between the S1-S2 and the S5 segment helices. This could be the explanation why substitution of the conserved threonine in KV7.2 and KV7.3 channels destabilizes the open and favors the closed state of these channels. PMID:23271449

  13. A PXR-Mediated Negative Feedback Loop Attenuates the Expression of CYP3A in Response to the PXR Agonist Pregnenalone-16?-Carbonitrile

    PubMed Central

    Bailey, Ian; Gibson, G. Gordon; Plant, Kathryn; Graham, Mark; Plant, Nick

    2011-01-01

    The nuclear receptor superfamily of ligand-activated transcription factors plays a central role in the regulation of cellular responses to chemical challenge. Nuclear receptors are activated by a wide range of both endogenous and exogenous chemicals, and their target genes include those involved in the metabolism and transport of the activating chemical. Such target gene activation, thus, acts to remove the stimulating xenobiotic or to maintain homeostatic levels of endogenous chemicals. Given the dual nature of this system it is important to understand how these two roles are balanced, such that xenobiotics are efficiently removed while not impacting negatively on homeostasis of endogenous chemicals. Using DNA microarray technology we have examined the transcriptome response of primary rat hepatocytes to two nuclear receptor ligands: Pregnenalone-16?-carbonitrile (PCN), a xenobiotic PXR agonist, and lithocholic acid, an endogenous mixed PXR/VDR/FXR agonist. We demonstrate that despite differences in the profile of activated nuclear receptors, transcriptome responses for these two ligands are broadly similar at lower concentrations, indicating a conserved general response. However, as concentrations of stimulating ligand rises, the transcriptome responses diverge, reflecting a need for specific responses to the two stimulating chemicals. Finally, we demonstrate a novel feed-back loop for PXR, whereby ligand-activation of PXR suppresses transcription of the PXR gene, acting to attenuate PXR protein expression levels at higher ligand concentrations. Through in silico simulation we demonstrate that this feed-back loop is an important factor to prevent hyperexpression of PXR target genes such as CYP3A and confirm these findings in vitro. This novel insight into the regulation of the PXR-mediated regulatory signal networks provides a potential mechanistic rationale for the robustness in steroid homeostasis within the cell. PMID:21311750

  14. TMEM16A and myocardin form a positive feedback loop that is disrupted by KLF5 during Ang II-induced vascular remodeling.

    PubMed

    Zhang, Xin-Hua; Zheng, Bin; Yang, Zhan; He, Ming; Yue, Ling-Yan; Zhang, Ruo-Nan; Zhang, Ming; Zhang, Wei; Zhang, Xuan; Wen, Jin-Kun

    2015-08-01

    The TMEM16A protein is an important component of Ca(2+)-dependent Cl(-) channels (CaCCs) in vascular smooth muscle cells. A recent study showed that TMEM16A inhibits angiotensin II-induced proliferation in rat basilar smooth muscle cells. However, whether and how TMEM16A is involved in vascular remodeling characterized by vascular smooth muscle cell proliferation remains largely unclear. In this study, luciferase reporter, Western blotting, and qRT-PCR assays were performed. The results suggested that myocardin promotes TMEM16A expression by forming a complex with serum response factor (SRF) on the TMEM16A promoter in human aortic smooth muscle cells (HASMCs). In turn, upregulated TMEM16A promotes expression of myocardin and vascular smooth muscle cell marker genes, thus forming a positive feedback loop that induces cell differentiation and inhibits cell proliferation. Angiotensin II inhibits TMEM16A expression via Krppel-like factor 5 (KLF5) in cultured HASMCs. Moreover, in vivo experiments show that infusion of angiotensin II into mice causes a marked reduction in TMEM16A expression and vascular remodeling, and angiotensin II-induced effects are largely reversed in KLF5 null (KLF5(-/-)) mice. KLF5 competes with SRF to interact with myocardin, thereby limiting myocardin binding to SRF and the synergistic activation of the TMEM16A promoter by myocardin and SRF. Our studies demonstrated that angiotensin II induces KLF5 expression and facilitates KLF5 association with myocardin to disrupt the myocardin-SRF complex, subsequently leading to inhibition of TMEM16A transcription. Blocking the positive feedback loop between myocardin and TMEM16A may be a novel therapeutic approach for vascular remodeling. PMID:26077572

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

    PubMed Central

    Rizzino, Angie

    2013-01-01

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

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

    PubMed

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

    2014-02-01

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

  17. 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) [1-5]. 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) [6], 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 negativefeedback 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

  18. 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.

  19. 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.

  20. 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.

  1. Senescence sensitivity of breast cancer cells is defined by positive feedback loop between CIP2A and E2F1

    PubMed Central

    Laine, Anni; Sihto, Harri; Come, Christophe; Rosenfeldt, Mathias T.; Zwolinska, Aleksandra; Niemel, Minna; Khanna, Anchit; Chan, Edward K.; Khri, Veli-Matti; Kellokumpu-Lehtinen, Pirkko-Liisa; Sansom, Owen J.; Evan, Gerard I.; Junttila, Melissa R.; Ryan, Kevin M.; Marine, Jean-Christophe; Joensuu, Heikki; Westermarck, Jukka

    2013-01-01

    Senescence induction contributes to cancer therapy responses and is crucial for p53-mediated tumor suppression. However, whether p53 inactivation actively suppresses senescence induction has been unclear. Here we demonstrate that E2F1 overexpression, due to p53 or p21 inactivation, promotes expression of human oncoprotein CIP2A, which in turn, by inhibiting PP2A activity, increases stabilizing serine 364 phosphorylation of E2F1. Several lines of evidence demonstrate that increased activity of E2F1-CIP2A feedback renders breast cancer cells resistant to senescence induction. Importantly, mammary tumorigenesis is impaired in a CIP2A deficient mouse model, and CIP2A deficient tumors display markers of senescence induction. Moreover, high CIP2A expression predicts for poor prognosis in a subgroup of breast cancer patients treated with senescence-inducing chemotherapy. Together these results implicate E2F1-CIP2A feedback loop as a key determinant of breast cancer cell sensitivity to senescence induction. It also constitutes a promising pro-senescence target for therapy of cancers with inactivated p53-p21 pathway. PMID:23306062

  2. Retinoic acid receptor and CNGA2 channel signaling are part of a regulatory feedback loop controlling axonal convergence and survival of olfactory sensory neurons

    PubMed Central

    ztokatli, Hande; Hrnberg, Maria; Berghard, Anna; Bohm, Staffan

    2012-01-01

    Little is known about the identities and functions of extracellular signaling molecules that work in concert with neuronal activity to regulate refinement and maintenance of the mouse olfactory sensory map. We show that expression of a dominant negative retinoic acid receptor (RAR) in olfactory sensory neurons (OSNs) increased the number of glomeruli that incorrectly contained OSN axons expressing different odorant receptors. This phenotype became apparent postnatally, coincided with increased cell death, and was preceded by increased Neuropilin-1 and reduced Kirrel-2 expressions. Kirrel-2-mediated cell adhesion influences odorant receptor-specific axonal convergence and is regulated by odorant receptor signaling via the olfactory cyclic nucleotide-gated (CNG) ion channel. Accordingly, we found that inhibited RAR function correlated with reduced CNG channel expression. Naris occlusion experiments and analysis of CNG channel-deficient mice further indicated that RAR-regulated CNG channel levels influenced the intrinsic neuronal activity required for cell survival in the absence of odor stimulation. Finally, we showed that CNG channel activity regulated expression of the retinoic acid-degrading enzyme Cyp26B1. Combined, these results identify a novel homeostatic feedback mechanism involving retinoic acid metabolism and CNG channel activity, which influences glomerular homogeneity and maintenance of precisely connected OSNs.ztokatli, H., Hrnberg, M., Berghard, A., Bohm, S. Retinoic acid receptor and CNGA2 channel signaling are part of a regulatory feedback loop controlling axonal convergence and survival of olfactory sensory neurons. PMID:22009938

  3. 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

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

    PubMed Central

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

    2015-01-01

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

  5. 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.

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

    PubMed

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

    2015-01-01

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

  7. Effects of finite feedback loop gain and bandwidth on stabilization of magnetohydrodynamic instabilities by an ``intelligent shell''

    NASA Astrophysics Data System (ADS)

    Jensen, T. H.; Garofalo, A. M.

    1999-07-01

    The "intelligent shell" [C. M. Bishop, Plasma Phys. Contr. Fusion 31, 1179 (1989)] utilizes a feedback system intended to make a resistive wall appear perfectly conducting to a plasma. It can thus be used for stabilizing modes of the plasma which are unstable when the plasma is surrounded by a resistive wall, but stable if the wall were perfectly conducting. Several concepts of magnetic confinement, such as reversed field pinches, spheromaks, and tokamaks may benefit from an intelligent shell. The paper addresses the question of the dependency of the stabilizing effect on the gain and bandwidth of the feedback circuits (assumed linear). A simple model for the phenomena involved is made and solved numerically for certain parameter values. A characteristic time of the model is a resistive time ? of the wall; the calculations suggest that an upper cutoff frequency of 50/? and sufficient gain provides a stabilization similar to that of ideal circuits with infinite bandwidth and gain. Under laboratory circumstances with ?10-3 s it is thus practical to obtain mass produced components which make the circuits as effective as ideal circuits.

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

    PubMed

    Sakurai, S; Williams, C M

    1989-08-01

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

  9. 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

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

    NASA Astrophysics Data System (ADS)

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

    2016-01-01

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

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

    PubMed

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

    2015-07-28

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

  12. Fast flux locked loop

    DOEpatents

    Ganther, Jr., Kenneth R. (Olathe, KS); Snapp, Lowell D. (Independence, MO)

    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.

  13. Mediation of Osteogenic Differentiation of Human Mesenchymal Stem Cells on Titanium Surfaces by a Wnt-Integrin Feedback Loop

    PubMed Central

    Olivares-Navarrete, Rene; Hyzy, Sharon L.; Park, Jung Hwa; Dunn, Ginger; Haithcock, David; Wasilewski, Christine; Boyan, Barbara D.; Schwartz, Zvi

    2012-01-01

    Peri-implant bone formation depends on the ability of mesenchymal cells to colonize the implant surface and differentiate into osteoblasts. Human mesenchymal stem cells (HMSCs) undergo osteoblastic differentiation on microstructured titanium (Ti) surfaces in the absence of exogenous factors, but the mechanisms are unknown. Wnt proteins are associated with an osteoblast phenotype, but how Wnt signaling regulates HMSC differentiation on microstructured Ti surfaces is not known. HMSCs were cultured on tissue culture polystyrene or Ti (PT [Sa=0.33?m, ?=96], SLA [Sa=2.5?m, ?=132], modSLA [hydrophilic-SLA]). Expression of calcium-dependent Wnt ligand WNT5A increased and canonical Wnt pathway ligands decreased on microstructured Ti in a time-dependent manner. Treatment of HMSCs with canonical ligand Wnt3a preserved the mesenchymal phenotype on smooth surfaces. Treatment with Wnt5a increased osteoblastic differentiation. Expression of integrins ITGA1, ITGA2, and ITGAV increased over time and correlated with increased WNT5A expression. Treatment of HMSCs with Wnt5a, but not Wnt3a, increased integrin expression. Regulation of integrin expression due to surface roughness and energy was ablated in WNT5A-knockdown HMSCs. This indicates that surface properties regulate stem cell fate and induce osteoblast differentiation via the Wnt calcium-dependent pathway. Wnt5a enhances osteogenesis through a positive feedback with integrins and local factor regulation, particularly though BMP signaling. PMID:21636130

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

    PubMed Central

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

    2015-01-01

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

  15. A feedback regulatory loop involving microRNA-9 and nuclear receptor TLX in neural stem cell fate determination.

    PubMed

    Zhao, Chunnian; Sun, GuoQiang; Li, Shengxiu; Shi, Yanhong

    2009-04-01

    MicroRNAs have been implicated as having important roles in stem cell biology. MicroRNA-9 (miR-9) is expressed specifically in neurogenic areas of the brain and may be involved in neural stem cell self-renewal and differentiation. We showed previously that the nuclear receptor TLX is an essential regulator of neural stem cell self-renewal. Here we show that miR-9 suppresses TLX expression to negatively regulate neural stem cell proliferation and accelerate neural differentiation. Introducing a TLX expression vector that is not prone to miR-9 regulation rescued miR-9-induced proliferation deficiency and inhibited precocious differentiation. In utero electroporation of miR-9 in embryonic brains led to premature differentiation and outward migration of the transfected neural stem cells. Moreover, TLX represses expression of the miR-9 pri-miRNA. By forming a negative regulatory loop with TLX, miR-9 provides a model for controlling the balance between neural stem cell proliferation and differentiation. PMID:19330006

  16. 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

  17. 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.

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

    PubMed

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

    2015-10-01

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

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2008-01-01

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

  1. 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

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

    PubMed

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

    2015-01-01

    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

  3. 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 proteinDNA 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 plantinsect coevolution and the adaptive radiation of angiosperms. PMID:22649271

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2013-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    SciTech Connect

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

    2010-05-28

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

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

    PubMed

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

    2016-01-01

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

  9. Widespread JNK-dependent alternative splicing induces a positive feedback loop through CELF2-mediated regulation of MKK7 during T-cell activation.

    PubMed

    Martinez, Nicole M; Agosto, Laura; Qiu, Jinsong; Mallory, Michael J; Gazzara, Matthew R; Barash, Yoseph; Fu, Xiang-Dong; Lynch, Kristen W

    2015-10-01

    Alternative splicing is prevalent among genes encoding signaling molecules; however, the functional consequence of differential isoform expression remains largely unknown. Here we demonstrate that, in response to T-cell activation, the Jun kinase (JNK) kinase MAP kinase kinase 7 (MKK7) is alternatively spliced to favor an isoform that lacks exon 2. This isoform restores a JNK-docking site within MKK7 that is disrupted in the larger isoform. Consistently, we show that skipping of MKK7 exon 2 enhances JNK pathway activity, as indicated by c-Jun phosphorylation and up-regulation of TNF-?. Moreover, this splicing event is itself dependent on JNK signaling. Thus, MKK7 alternative splicing represents a positive feedback loop through which JNK promotes its own signaling. We further show that repression of MKK7 exon 2 is dependent on the presence of flanking sequences and the JNK-induced expression of the RNA-binding protein CELF2, which binds to these regulatory elements. Finally, we found that ?25% of T-cell receptor-mediated alternative splicing events are dependent on JNK signaling. Strikingly, these JNK-dependent events are also significantly enriched for responsiveness to CELF2. Together, our data demonstrate a widespread role for the JNK-CELF2 axis in controlling splicing during T-cell activation, including a specific role in propagating JNK signaling. PMID:26443849

  10. Reciprocal negative feedback loop between EZH2 and miR-101-1 contributes to miR-101 deregulation in hepatocellular carcinoma.

    PubMed

    Huang, Da; Wang, Xiaobei; Zhuang, Chunbo; Shi, Wuhe; Liu, Mu; Tu, Qiming; Zhang, Detai; Hu, Lihua

    2016-02-01

    Although the tumor suppressive role of miR-101 is well documented in hepatocellular carcinoma (HCC), how the expression of miR-101 itself is regulated remains elusive. In the present study, we demonstrated that the miR-101 precursor pre-miR-101-1 could be regulated by an important epigenetic regulator, the enhancer of zeste homolog 2 (EZH2). Reporter gene assays revealed that ectopic expression of EZH2 inhibited the transcriptional activities of miR-101-1 promoter. Subsequent analyses revealed that miR-101-1 directly represses the expression of EZH2, and miR-101-1 and EZH2 form a reciprocal negative feedback loop as indicated by the fact that ectopic mature miR-101 could induce endogenous pre-miR-101-1 expression. This mature miR-101-induced pre-miR-101 expression was specific to pre-miR-101-1 and depended on EZH2 activities. Moreover, our results also demonstrated that similar antitumor effects can be achieved either by ectopic miR-101 or EZH2 silencing in HCC cells. These findings show that elevated EZH2 contributes to miR-101 deregulation in HCC and highlight the coordinated role of miR-101 and EZH2 in hepatocarcinogenesis. PMID:26718325

  11. 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

  12. 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

  13. 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

  14. Evidence for ultra-short-loop feedback in ACTH-induced interrenal steroidogenesis in coho salmon: acute self-suppression of cortisol secretion in vitro.

    PubMed

    Bradford, C S; Fitzpatrick, M S; Schreck, C B

    1992-08-01

    Interrenal tissues from coho salmon (Oncorhynchus kisutch) were incubated in a defined medium under blood-gas atmosphere at 17 degrees. Rates of cortisol secretion by tissues incubated in media containing 50 mU/ml porcine-ACTH were initially much greater than those of resting tissues in hormone-free media, but after 3 to 6 hr returned to resting rates. The time course of cortisol accumulation in ACTH-containing media was the same when tissues were incubated in different volumes; the final concentrations of cortisol in these incubations were similar to each other and resembled peak in vivo concentrations in juvenile coho subjected to acute stress. Cortisol secretion rates of tissues sequentially transferred to fresh ACTH-containing media every 6 hr did not return to resting levels but remained elevated for at least 24 hr. Cortisol secretion in response to ACTH was attenuated or completely abolished in tissues incubated in media containing exogenous cortisol; this effect was reversible and dose-dependent. Our results suggest that in coho salmon, cortisol may exert ultra-short-loop negative feedback directly at the level of the interrenal gland to effect self-suppression. PMID:1327952

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

    PubMed Central

    Bastos, Ricardo Nunes; Cundell, Michael J.

    2014-01-01

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

  16. 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

  17. 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.

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

    PubMed Central

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

    2015-01-01

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

  19. Adaptor protein CRK induces epithelialmesenchymal 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 epithelialmesenchymal 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 epithelialmesenchymal 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. 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

  1. 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

  2. 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

  3. Nitric oxide initiates progression of human melanoma via a feedback loop mediated by apurinic/apyrimidinic endonuclease-1/redox factor-1, which is inhibited by resveratrol.

    PubMed

    Yang, Zhen; Yang, Sun; Misner, Bobbye J; Chiu, Rita; Liu, Feng; Meyskens, Frank L

    2008-12-01

    It is well recognized that nitric oxide (NO) is involved in tumor progression, including melanoma. Measurement of proliferative and metastatic capacity by MTS and Matrigel invasion assays, respectively, was done and showed that NO-treated melanoma cells exhibited a higher capacity compared with control, especially metastatic Lu1205 cells. Apurinic/apyrimidinic endonuclease-1/redox factor-1 (APE/Ref-1) is a multifunctional protein and its role in tumor biology has attracted considerable attention. To determine whether APE/Ref-1 plays a role in mediating NO stimulation of melanoma progression, we investigated the effect of DETA/NO on levels of APE/Ref-1 and related downstream targets [activator protein-1 (AP-1)/JunD, matrix metalloproteinase-1 (MMP-1), Bcl-2, and inducible nitric oxide synthase (iNOS)] by Western blot and reverse transcription-PCR analysis. Following DETA/NO treatment, APE/Ref-1 and other downstream molecules were induced. Knockdown of APE/Ref-1 or AP-1/JunD by specific small interfering RNA markedly reversed the induction by NO stress of target proteins. These results present evidence for the existence of a functional feedback loop contributing to progression and metastasis of melanoma cells. Resveratrol has been shown to be an APE/Ref-1 inhibitor and significant decreases in AP-1/JunD, MMP-1, Bcl-2, and iNOS protein levels occurred after exposure to resveratrol. This phenolic antioxidant may be an appropriate choice for combining with other compounds that develop resistance by up-regulation of these molecules. PMID:19074850

  4. Formononetin promotes proliferation that involves a feedback loop of microRNA-375 and estrogen receptor alpha in estrogen receptor-positive cells.

    PubMed

    Chen, Jian; Zhang, Xing; Wang, Yong; Ye, Yu; Huang, Zhaoquan

    2016-03-01

    Formononetin is an O-methylated isoflavone that is isolated from the root of Astragalus membranaceus, and it has antitumorigenic effects. Our previous studies found that formononetin triggered growth-inhibitory and apoptotic activities in MCF-7 breast cancer cells. To further investigate the potential effect of formononetin in promoting cell proliferation in estrogen receptor (ER)-positive cells, we used in vivo and in vitro studies to elucidate the possible mechanism. ER?-positive cells (HUVEC, MCF-7) were treated with formononetin. The CCK8 assay, Hoechst 33258, and flow cytometry were used to assess cell proliferation and apoptosis. mRNA levels of ER?, Bcl-2, and miR-375 were quantified using real-time polymerase chain reaction. ER?, p-Akt, and Bcl-2 expression was determined using Western blot. Compared with the control, low formononetin concentrations (2-6??M) stimulated ER?-positive cell proliferation (HUVEC, MCF-7). The more sensitive HUVEC cells were used to study the relevant signaling pathway. After treatment with formononetin, ER?, miR-375, p-Akt, and Bcl-2 expression was significantly upregulated. The proliferative effect of formononetin was also blocked by a miR-375 inhibitor or raloxifene pretreatment. Additionally, in the in vivo studies, uterine weight in ovariectomized mice treated with formononetin increased significantly, but the weight dramatically decreased with raloxifene or miR-375 inhibitor pretreatment before formononetin. This study demonstrated that formononetin promoted ER?-positive cell proliferation through miR-375 activation and this mechanism is possibly involving in a miR-375 and ER? feedback loop. 2015 Wiley Periodicals, Inc. PMID:25663261

  5. 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.

  6. Epithelial-mesenchymal transition and tumor suppression are controlled by a reciprocal feedback loop between ZEB1 and Grainyhead-like-2

    PubMed Central

    Cieply, Benjamin; Farris, Joshua; Denvir, James; Ford, Heide; Frisch, Steven M.

    2013-01-01

    Epithelial-mesenchymal transition (EMT) in carcinoma cells enhances malignant progression by promoting invasion and survival. EMT is induced by microenvironmental factors including TGF-? and Wnt agonists, and by the E-box-binding transcription factors Twist, Snail and ZEB. Grainyhead-like-2 (GRHL2), a member of the mammalian Grainyhead family of wound healing regulatory transcription factors, suppresses EMT and restores sensitivity to anoikis by repressing ZEB1 expression and inhibiting TGF-? signaling. In this study, we elucidate the functional relationship between GRHL2 and ZEB1 in EMT/MET and tumor biology. At least three homeodomain proteins, Six1, LBX1, and HoxA5, transactivated the ZEB1 promoter, in the case of Six1, through direct protein-promoter interaction. GRHL2 altered the Six1-DNA complex, inhibiting this transactivation. Correspondingly, GRHL2 expression prevented tumor initiation in xenograft assays, sensitized breast cancer cells to paclitaxel and suppressed the emergence of CD44highCD24low cells (defining the cancer stem cell phenotype in the cell type studied). GRHL2 was down-regulated in recurrent mouse tumors that had evolved to an oncogene-independent, EMT-like state, supporting a role for GRHL2 down-regulation in this phenotypic transition, modeling disease recurrence. The combination of TGF-? and Wnt activation repressed GRHL2 expression by direct interaction of ZEB1 with the GRHL2 promoter, inducing EMT. Together, our observations indicate that a reciprocal feedback loop between GRHL2 and ZEB1 controls epithelial vs. mesenchymal phenotypes and EMT-driven tumor progression. PMID:23943797

  7. 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

  8. Caspase-3 feedback loop enhances Bid-induced AIF/endoG and Bak activation in Bax and p53-independent manner

    PubMed Central

    Guo, W; Zhang, Y; Ling, Z; Liu, X; Zhao, X; Yuan, Z; Nie, C; Wei, Y

    2015-01-01

    Chemoresistance in cancer has previously been attributed to gene mutations or deficiencies. Bax or p53 deficiency can lead to resistance to cancer drugs. We aimed to find an agent to overcome chemoresistance induced by Bax or p53 deficiency. Here, we used immunoblot, flow-cytometry analysis, gene interference, etc. to show that genistein, a major component of isoflavone that is known to have anti-tumor activities in a variety of models, induces Bax/p53-independent cell death in HCT116 Bax knockout (KO), HCT116 p53 KO, DU145 Bax KO, or DU145 p53 KO cells that express wild-type (WT) Bak. Bak knockdown (KD) only partially attenuated genistein-induced apoptosis. Further results indicated that the release of AIF and endoG also contributes to genistein-induced cell death, which is independent of Bak activation. Conversely, AIF and endoG knockdown had little effect on Bak activation. Knockdown of either AIF or endoG alone could not efficiently inhibit apoptosis in cells treated with genistein, whereas an AIF, endoG, and Bak triple knockdown almost completely attenuated apoptosis. Next, we found that the Akt-Bid pathway mediates Bak-induced caspase-dependent and AIF- and endoG-induced caspase-independent cell death. Moreover, downstream caspase-3 could enhance the release of AIF and endoG as well as Bak activation via a positive feedback loop. Taken together, our data elaborate the detailed mechanisms of genistein in Bax/p53-independent apoptosis and indicate that caspase-3-enhanced Bid activation initiates the cell death pathway. Our results also suggest that genistein may be an effective agent for overcoming chemoresistance in cancers with dysfunctional Bax and p53. PMID:26469967

  9. 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

  10. p38/p53/miR-200a-3p feedback loop promotes oxidative stress-mediated liver cell death.

    PubMed

    Xiao, Yongtao; Yan, Weihui; Lu, Lina; Wang, Ying; Lu, Wei; Cao, Yi; Cai, Wei

    2015-01-01

    Although our previous studies have provided evidence that oxidative stress has an essential role in total parenteral nutrition (TPN)-associated liver injury, the mechanisms involved are incompletely understood. Here, we show the existence of crosstalk between the miR-200 family of microRNAs and oxidative stress. The members of the miR-200 family are markedly enhanced in hepatic cells by hydrogen peroxide (H2O2) treatment. The upregulation of miR-200-3p in turn modulates the H2O2-mediated oxidative stress response by targeting p38?. The enhanced expression of miR-200-3p mimics p38? deficiency and promotes H2O2-induced cell death. Members of the miR-200 family that are known to inhibit the epithelial to mesenchymal transition (EMT) are induced by the tumor suppressor p53. Here, we show that p53 phosphorylation at Ser 33 contributes to H2O2-induced miR-200s transcription. In addition, we show that p38? can directly phosphorylate p53 at serine 33 upon H2O2 exposure. Thus, we suggest that in liver cells, the oxidative stress-induced, p38?-mediated phosphorylation of p53 at Ser33 is essential for the functional regulation of oxidative stress-induced miR-200 transcription by p53. Collectively, our data indicate that the p53-dependent expression of miR-200a-3p promotes cell death by inhibiting a p38/p53/miR-200 feedback loop. PMID:25789565

  11. Demonstration and biological significance of a gastrin‐P21‐activated kinase 1 feedback loop in colorectal cancer cells

    PubMed Central

    Huynh, Nhi; Liu, Kevin H.; Yim, Mildred; Shulkes, Arthur; Baldwin, Graham S.; He, Hong

    2014-01-01

    Abstract Gastrins, including amidated gastrin17 and glycine‐extended gastrin17, are important growth factors in colorectal cancer (CRC). The p21‐activated kinase 1 (PAK1) plays key roles in cellular processes including proliferation, survival, and motility, and in cell transformation and tumor progression. PAK1 expression increases with the progression of CRC, and knockdown of PAK1 blocks CRC cell growth and metastasis both in vitro and in vivo. The aim of this study was to determine the interaction between PAK1 and gastrins in CRC cells. PAK1 expression and activation were assayed by Western blots, and concentrations of gastrin mRNA and peptides by real‐time PCR and radioimmunoassay, respectively. Proliferation of CRC cells was measured by 3H‐thymidine incorporation, and vascular endothelial growth factor (VEGF) secretion was measured by ELISA. Gastrins activated PAK1 via PI3K‐dependent pathways. Activated PAK1 in turn mediated gastrin‐stimulated activation of β‐catenin and VEGF secretion in CRC cells, as knockdown of PAK1 blocked stimulation of these cellular processes by gastrins. Downregulation of gastrin reduced the expression and activity of PAK1, but in contrast there was a compensatory increase in gastrins either when PAK1 was downregulated, or after treatment with a PAK inhibitor. Our results indicate that PAK1 is required for the stimulation of CRC cells by gastrins, and suggest the existence of an inhibitory feedback loop by which PAK1 downregulates gastrin production in CRC cells. PMID:24963032

  12. 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.

  13. [Study on double feedback current source for biologic impedance measurement].

    PubMed

    Wang, Chao; Wang, Xiangyu; Sun, Hongjun; Wang, Huaxiang

    2006-08-01

    A double feedback current source for biologic impedance measurement is designed in order to solve the problem on the poor constant-current characteristic under higher frequency and meet the request for the ability to eliminate the direct current signal. The voltage controlled current source based on the second generation current conveyor theory is presented, which has good output impedance and anti-direct current characteristics by using the direct current feedback unit and input buffer. The closed loop control of current amplitude is implemented by means of the direct digital synthesizer and multiplication demodulation technique, which improves the constant-current characteristic of the current source. PMID:17002089

  14. Optical voltage reference

    DOEpatents

    Rankin, Richard (Ammon, ID); Kotter, Dale (Bingham County, ID)

    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.

  15. 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.

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

    PubMed Central

    2014-01-01

    Background High androgen receptor (AR) level in primary tumour predicts increased prostate cancer (PCa)-specific mortality. Furthermore, activations of the AR, PI3K, mTOR, NF?B and Hedgehog (Hh) signaling pathways are involved in the fatal development of castration-resistant prostate cancer during androgen ablation therapy. MID1, a negative regulator of the tumor-suppressor PP2A, is known to promote PI3K, mTOR, NF?B and Hh signaling. Here we investigate the interaction of MID1 and AR. Methods AR and MID1 mRNA and protein levels were measured by qPCR, Western blot and immunohistochemistry. Co-immunoprecipitation followed by PCR and RNA-pull-down followed by Western blot was used to investigate protein-mRNA interaction, chromatin-immunoprecipitation followed by next-generation sequencing for identification of AR chromatin binding sites. AR transcriptional activity and activity of promoter binding sites for AR were analyzed by reporter gene assays. For knockdown or overexpression of proteins of interest prostate cancer cells were transfected with siRNA or expression plasmids, respectively. Results The microtubule-associated MID1 protein complex associates with AR mRNA via purine-rich trinucleotide repeats, expansions of which are known to correlate with ataxia and cancer. The level of MID1 directly correlates with the AR protein level in PCa cells. Overexpression of MID1 results in a several fold increase in AR protein and activity without major changes in mRNA-levels, whereas siRNA-triggered knockdown of MID1 mRNA reduces AR-protein levels significantly. Upregulation of AR protein by MID1 occurs via increased translation as no major changes in AR protein stability could be observed. AR on the other hand, regulates MID1 via several functional AR binding sites in the MID1 gene, and, in the presence of androgens, exerts a negative feedback loop on MID1 transcription. Thus, androgen withdrawal increases MID1 and concomitantly AR-protein levels. In line with this, MID1 is significantly over-expressed in PCa in a stage-dependent manner. Conclusion Promotion of AR, in addition to enhancement of the Akt-, NF?B-, and Hh-pathways by sustained MID1-upregulation during androgen deprivation therapy provides a powerful proliferative scenario for PCa progression into castration resistance. Thus MID1 represents a novel, multi-faceted player in PCa and a promising target to treat castration resistant prostate cancer. PMID:24913494

  17. Feedback Augmented Sub-Ranging (FASR) Quantizer

    NASA Technical Reports Server (NTRS)

    Guilligan, Gerard

    2012-01-01

    This innovation is intended to reduce the size, power, and complexity of pipeline analog-to-digital converters (ADCs) that require high resolution and speed along with low power. Digitizers are important components in any application where analog signals (such as light, sound, temperature, etc.) need to be digitally processed. The innovation implements amplification of a sampled residual voltage in a switched capacitor amplifier stage that does not depend on charge redistribution. The result is less sensitive to capacitor mismatches that cause gain errors, which are the main limitation of such amplifiers in pipeline ADCs. The residual errors due to mismatch are reduced by at least a factor of 16, which is equivalent to at least 4 bits of improvement. The settling time is also faster because of a higher feedback factor. In traditional switched capacitor residue amplifiers, closed-loop amplification of a sampled and held residue signal is achieved by redistributing sampled charge onto a feedback capacitor around a high-gain transconductance amplifier. The residual charge that was sampled during the acquisition or sampling phase is stored on two or more capacitors, often equal in value or integral multiples of each other. During the hold or amplification phase, all of the charge is redistributed onto one capacitor in the feedback loop of the amplifier to produce an amplified voltage. The key error source is the non-ideal ratios of feedback and input capacitors caused by manufacturing tolerances, called mismatches. The mismatches cause non-ideal closed-loop gain, leading to higher differential non-linearity. Traditional solutions to the mismatch errors are to use larger capacitor values (than dictated by thermal noise requirements) and/or complex calibration schemes, both of which increase the die size and power dissipation. The key features of this innovation are (1) the elimination of the need for charge redistribution to achieve an accurate closed-loop gain of two, (2) a higher feedback factor in the amplifier stage giving a higher closed-loop bandwidth compared to the prior art, and (3) reduced requirement for calibration. The accuracy of the new amplifier is mainly limited by the sampling networks parasitic capacitances, which should be minimized in relation to the sampling capacitors.

  18. 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

  19. Global Feedback Simulator

    SciTech Connect

    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.

  20. 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

  1. System Design as a Three-Phase Dual-Loop (TPDL) Process: Types of Knowledge-Applied Sources of Feedback, and Student Development as Independent Learners

    ERIC Educational Resources Information Center

    Barak, Moshe

    2010-01-01

    This study aimed at exploring how high school students deal with designing an information system, for example, for a small business or a medical clinic, the extent to which students develop as independent learners while working on their projects, and the factors that help or hinder fostering students' design skills. The three-phase dual-loop

  2. 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

  3. Steep Subthreshold Swing n- and p-Channel Operation of Bendable Feedback Field-Effect Transistors with p(+)-i-n(+) Nanowires by Dual-Top-Gate Voltage Modulation.

    PubMed

    Jeon, Youngin; Kim, Minsuk; Lim, Doohyeok; Kim, Sangsig

    2015-08-12

    In this study, we present the steep switching characteristics of bendable feedback field-effect transistors (FBFETs) consisting of p(+)-i-n(+) Si nanowires (NWs) and dual-top-gate structures. As a result of a positive feedback loop in the intrinsic channel region, our FBFET features the outstanding switching characteristics of an on/off current ratio of approximately 10(6), and point subthreshold swings (SSs) of 18-19 mV/dec in the n-channel operation mode and of 10-23 mV/dec in the p-channel operation mode. Not only can these devices operate in n- or p-channel modes, their switching characteristics can also be modulated by adjusting the gate biases. Moreover, the device maintains its steep SS characteristics, even when the substrate is bent. This study demonstrates the promising potential of bendable NW FBFETs for use as low-power components in integrated circuits or memory devices. PMID:26218327

  4. 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; Gull, 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

  5. 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.

  6. 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…

  7. 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

  8. Down-regulation of miR-129-5p via the Twist1-Snail feedback loop stimulates the epithelial-mesenchymal transition and is associated with poor prognosis in breast cancer

    PubMed Central

    Yu, Yue; Zhao, Ying; Sun, Xiao-Hu; Ge, Jie; Zhang, Bin; Wang, Xin; Cao, Xu-Chen

    2015-01-01

    The epithelial to mesenchymal transition (EMT) plays a pivotal role in breast cancer progression. We found that overexpression of miR-129-5p reversed EMT, whereas depletion of miR-129-5p induced EMT in breast cancer cells. We demonstrated that Twist1 is a direct target of miR-129-5p. Both Twist1 and Snail transcriptionally suppressed miR-129-5p expression. Levels of miR-129-5p were low in breast cancer tissues. miR-129-5p down-regulation correlated with advanced clinical stage and poor prognosis in patients with breast cancer. miR-129-5p expression negatively correlated with Twist1 and Snail expression. Thus, miR-129-5p down-regulation fosters EMT in breast cancer by increasing Twist1-Snail and activating a negative feedback loop. PMID:26460733

  9. 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.

  10. 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.

  11. 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.

  12. E-beam high voltage switching power supply

    DOEpatents

    Shimer, Daniel W. (Danville, CA); Lange, Arnold C. (Livermore, CA)

    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.

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

    PubMed Central

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

    2015-01-01

    Background HCV replication in persistently infected cell culture remains resistant to IFN-α/RBV combination treatment, whereas IFN-λ1 induces viral clearance. The antiviral mechanisms by which IFN-λ1 induces sustained HCV clearance have not been determined. Aim To investigate the mechanisms by which IFN-λ clears HCV replication in an HCV cell culture model. Methods IFN-α sensitive (S3-GFP) and resistant (R4-GFP) cells were treated with equivalent concentrations of either IFN-α or IFN-λ. The relative antiviral effects of IFN-α and IFN-λ1 were compared by measuring the HCV replication, quantification of HCV-GFP expression by flow cytometry, and viral RNA levels by real time RT-PCR. Activation of Jak-Stat signaling, interferon stimulated gene (ISG) expression, and miRNA-122 transcription in S3-GFP and R4-GFP cells were examined. Results We have shown that IFN-λ1 induces HCV clearance in IFN-α resistant and sensitive replicon cell lines in a dose dependent manner through Jak-Stat signaling, and induces STAT 1 and STAT 2 activation, ISRE-luciferase promoter activation and ISG expression. Stat 3 activation is also involved in IFN-λ1 induced antiviral activity in HCV cell culture. IFN-λ1 induced Stat 3 phosphorylation reduces the expression of hepatocyte nuclear factor 4 alpha (HNF4α) through miR-24 in R4-GFP cells. Reduced expression of HNF4α is associated with decreased expression of miR-122 resulting in an anti-HCV effect. Northern blot analysis confirms that IFN-λ1 reduces miR-122 levels in R4-GFP cells. Our results indicate that IFN-λ1 activates the Stat 3-HNF4α feedback inflammatory loop to inhibit miR-122 transcription in HCV cell culture. Conclusions In addition to the classical Jak–Stat antiviral signaling pathway, IFN-λ1 inhibits HCV replication through the suppression of miRNA-122 transcription via an inflammatory Stat 3–HNF4α feedback loop. Inflammatory feedback circuits activated by IFNs during chronic inflammation expose non-responders to the risk of hepatocellular carcinoma. PMID:26657215

  14. 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…

  15. Model-based feedback control of a microfluidic electroporation system

    NASA Astrophysics Data System (ADS)

    Ghadami, M.; Mahjoob, M. J.; Shagoshtasbi, H.; Lee, Y.-K.

    2013-12-01

    This paper describes new model-based feedback control method used for a single-cell microfluidic electroporation (EP) system. For this purpose, a new four-state nonlinear model has been developed to describe dynamics of a micro-channel electroporation system. EP measured current response is then used to verify the efficiency of the proposed new EP model. Consequently, two feedback control methods, namely, proportional-integral-derivative controller and model predictive controller have been applied to regulate the key states (i.e. transmembrane voltage (Vm) and nano-electropore radius (r)) in the EP model. Numerical simulations of static and dynamic responses of the two critical states, Vm and r, show that feedback control can improve the cell viability and EP efficiency compared to the open-loop system. In the experimental phase, a fabricated micro-EP chip with integrated Coulter counter is used to define the cell-size-dependent parameters of the EP model and electroporation of HeLa cells. In this phase, the EP model is also inserted into LabView software's environment to estimate the value of transmembrane voltage during the experiment. Variation of the external applied voltage derived from experimental result was in good adaptation with its equivalent theoretical values.

  16. Integrated optical phase locked loop.

    SciTech Connect

    Lentine, Anthony L.; Kim, Jungwon; Trotter, Douglas Chandler; DeRose, Christopher T.; Kartner, Franz X.; Byun, Hyunil; Nejadmalayeri, Amir H.; Watts, Michael R.; Zortman, William A.

    2010-12-01

    A silicon photonics based integrated optical phase locked loop is utilized to synchronize a 10.2 GHz voltage controlled oscillator with a 509 MHz mode locked laser, achieving 32 fs integrated jitter over 300 kHz bandwidth.

  17. A positive feedback loop of p53/miR-19/TP53INP1 modulates pancreatic cancer cell proliferation and apoptosis.

    PubMed

    Wang, Xiaofang; Wang, Lei; Mo, Qingjiang; Jia, Ankui; Dong, Yuqian; Wang, Guoqiang

    2016-01-01

    Pancreatic cancer is a common malignancy whose prognosis and treatment of pancreatic cancer is extremely poor, with only 20% of patients reaching two years of survival. Previous findings have shown that the tumor suppressor p53 is involved in the development of various types of cancer, including pancreatic cancer. Additionally, p53 is able to activate TP53INP1 transcription by regulating several phenotypes of cancer cells. Using gain and loss-of-function assays, the aim of the present study was to examine the relationships between miR-19a/b and cancer development as well as potential underlying mechanisms. The results showed that miR-19a/b identified a positive feedback regulation of p53/TP53INP1 axis. Additionally, p53 upregulated the TP53INP1 level in pancreatic cancer cells. However, overexpressed miR-19a/b partially restored the TP53 function in the pancreatic cancer cells while miR-19a/b downregulated TP53INP1 protein by directly targeting 3'UTR of its mRNA at the post-transcriptional level. In addition, the patient tissues identified that the miR-19a/b level in pancreatic cancer tissues was conversely correlated with TP53 and TP53INP1 expression. The results provide evidence for revealing the molecular mechanism involved in the development of pancreatic cancer and may be useful in the identification of new therapeutic targets for pancreatic cancer. PMID:26531836

  18. Retinoic acid receptor and CNGA2 channel signaling are part of a regulatory feedback loop controlling axonal convergence and survival of olfactory sensory neurons.

    PubMed

    ztokatli, Hande; Hrnberg, Maria; Berghard, Anna; Bohm, Staffan

    2012-02-01

    Little is known about the identities and functions of extracellular signaling molecules that work in concert with neuronal activity to regulate refinement and maintenance of the mouse olfactory sensory map. We show that expression of a dominant negative retinoic acid receptor (RAR) in olfactory sensory neurons (OSNs) increased the number of glomeruli that incorrectly contained OSN axons expressing different odorant receptors. This phenotype became apparent postnatally, coincided with increased cell death, and was preceded by increased Neuropilin-1 and reduced Kirrel-2 expressions. Kirrel-2-mediated cell adhesion influences odorant receptor-specific axonal convergence and is regulated by odorant receptor signaling via the olfactory cyclic nucleotide-gated (CNG) ion channel. Accordingly, we found that inhibited RAR function correlated with reduced CNG channel expression. Naris occlusion experiments and analysis of CNG channel-deficient mice further indicated that RAR-regulated CNG channel levels influenced the intrinsic neuronal activity required for cell survival in the absence of odor stimulation. Finally, we showed that CNG channel activity regulated expression of the retinoic acid-degrading enzyme Cyp26B1. Combined, these results identify a novel homeostatic feedback mechanism involving retinoic acid metabolism and CNG channel activity, which influences glomerular homogeneity and maintenance of precisely connected OSNs. PMID:22009938

  19. LIM Homeobox 8 (Lhx8) Is a Key Regulator of the Cholinergic Neuronal Function via a Tropomyosin Receptor Kinase A (TrkA)-mediated Positive Feedback Loop*

    PubMed Central

    Tomioka, Takeyasu; Shimazaki, Takuya; Yamauchi, Toshihiko; Oki, Toru; Ohgoh, Makoto; Okano, Hideyuki

    2014-01-01

    Basal forebrain cholinergic neurons play an important role in cognitive functions such as learning and memory, and they are affected in several neurodegenerative diseases, including Alzheimer disease and Down syndrome. Despite their functional importance, the molecular mechanisms of functional maturation and maintenance of these cholinergic neurons after the differentiation stage have not been fully elucidated. This study demonstrates that the LIM homeobox 8 (Lhx8) transcription factor regulates cholinergic function in rat septal cholinergic neurons in primary cultures from E18.5 embryos and in the adult brain. Lhx8 expression modulated tropomyosin receptor kinase A (TrkA) expression in septal cholinergic neurons in vitro and in vivo, resulting in regulated acetylcholine release as an index of cholinergic function. In addition, Lhx8 expression and function were regulated by nerve growth factor (NGF), and the effect of NGF was potentiated by Lhx8-induced TrkA expression. Together, our findings suggest that positive feedback regulation between Lhx8, TrkA, and NGF is an important regulatory mechanism for cholinergic functions of the septum. PMID:24265310

  20. Brain-midgut cross-talk and autocrine metabolastat via the sNPF/CCAP negative feed-back loop in the American cockroach, Periplaneta americana.

    PubMed

    Mikani, Azam; Watari, Yasuhiko; Takeda, Makio

    2015-12-01

    Immunohistochemical reactivities against short neuropeptide F (sNPF-ir) and crustacean cardioactive peptide (CCAP-ir) were detected in both the brain-subesophageal ganglion (Br-SOG) and midgut epithelial cells of the male American cockroach, Periplaneta americana. Four weeks of starvation increased the number of sNPF-ir cells and decreased the CCAP-ir cells in the Br-SOG, whereas refeeding reversed these effects. The contents of sNPF in the Br-SOG, midgut and hemolymph titer decreased in response to an injection of CCAP into the hemocoel of normally fed male cockroaches, while CCAP titers/contents decreased in response to an injection of sNPF. The results of a double-labeling experiment demonstrated that sNPF-ir co-existed in CCAP-ir cells in the pars intercerebralis (PI), dorsolateral region of protocerebrum (DL), deutocerebrum (De) and SOG. sNPF-ir and CCAP-ir were also colocalized in the midgut. sNPF and CCAP are neuropeptides and midgut factors that interact with each other. Since the two peptides are known to be secreted by identical cells that affect each other, this constitutes autocrine negative feedback regulation for a quick response to food accessibility/inaccessibility. These peptides not only constitute the switch in the digestive mechanism but also couple digestive adaptation with behavior. A CCAP injection suppressed locomotor activity when cockroaches were starved, whereas sNPF activated it when they were fed. PMID:26178071

  1. Feedback & Objectives

    ERIC Educational Resources Information Center

    Butterworth, James R.

    1975-01-01

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

  2. 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.

  3. 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

  4. Role of histone deacetylase 3 in ankylosing spondylitis via negative feedback loop with microRNA-130a and enhancement of tumor necrosis factor-1? expression in peripheral blood mononuclear cells.

    PubMed

    Jiang, Ya; Wang, Lin

    2016-01-01

    The present study was performed to investigate the molecular mechanism of ankylosing spondylitis (AS). The interaction between micro (mi)RNA?130a and its target tumor necrosis factor (TNF)?1? and histone deactylase (HDAC)3 was assessed in peripheral blood mononuclear cells (PBMCs) from AS patients. Increased HDAC3 and decreased miRNA?130a levels were observed in PBMCs from AS patients. HDAC3 knockdown or HDAC3 inhibition promoted the expression of miRNA?130a, and HDAC3 was recruited to the promoter region of the gene encoding miRNA?130a in PBMCs. In addition, miR?130a overexpression led to a decrease, whereas miR?130a inhibition led to an increase of TNF?1? expression in PBMCs. Furthermore, HDAC3 knockdown or HDAC3 inhibition was associated with simultaneous upregulation of the expression of miR?130a and downregulation of the expression of TNF?1? in PBMCs. These results indicated that HDAC3 was involved in the regulation of the underlying molecular mechanism of AS by forming a negative feedback loop with miR-130a and enhancement of TNF-1? expression. PMID:26531724

  5. Role of histone deacetylase 3 in ankylosing spondylitis via negative feedback loop with microRNA-130a and enhancement of tumor necrosis factor-1α expression in peripheral blood mononuclear cells

    PubMed Central

    JIANG, YA; WANG, LIN

    2016-01-01

    The present study was performed to investigate the molecular mechanism of ankylosing spondylitis (AS). The interaction between micro (mi)RNA-130a and its target tumor necrosis factor (TNF)-1α and histone deactylase (HDAC)3 was assessed in peripheral blood mononuclear cells (PBMCs) from AS patients. Increased HDAC3 and decreased miRNA-130a levels were observed in PBMCs from AS patients. HDAC3 knockdown or HDAC3 inhibition promoted the expression of miRNA-130a, and HDAC3 was recruited to the promoter region of the gene encoding miRNA-130a in PBMCs. In addition, miR-130a overexpression led to a decrease, whereas miR-130a inhibition led to an increase of TNF-1α expression in PBMCs. Furthermore, HDAC3 knockdown or HDAC3 inhibition was associated with simultaneous upregulation of the expression of miR-130a and downregulation of the expression of TNF-1α in PBMCs. These results indicated that HDAC3 was involved in the regulation of the underlying molecular mechanism of AS by forming a negative feedback loop with miR-130a and enhancement of TNF-1α expression. PMID:26531724

  6. Strategies for effective feedback.

    PubMed

    Kritek, Patricia A

    2015-04-01

    Provision of regular feedback to trainees on clinical performance by supervising providers is increasingly recognized as an essential component of undergraduate and graduate health sciences education; however, many individuals have not been formally trained in this pedagogical skill. At the bedside or in the clinic, effective performance feedback can be accomplished by following four key steps. Begin by setting expectations that incorporate the trainee's personal goals and external objectives. Delineate how and when you will provide feedback to the learner. Next, directly observe the trainee's performance. This can be challenging while engaged on a busy clinical service, but a focus on discrete activities or interactions (e.g., family meeting, intravascular volume assessment using bedside ultrasound, or obtaining informed consent) is helpful. The third step is to plan and prioritize the feedback session. Feedback is most effective when given in a timely fashion and delivered in a safe environment. Limit the issues addressed because learners often disengage if confronted with too many deficiencies. Finally, when delivering feedback, begin by listening to the trainee's self-evaluation and then take a balanced approach. Describe in detail what the trainee does well and discuss opportunities for improvement with emphasis on specific, modifiable behaviors. The feedback loop is completed with a plan for follow-up reassessment. Through the use of these relatively simple practices, both the trainee and teacher can have a more productive learning experience. PMID:25723379

  7. Feedback sine wave driver design for ultrasonic transducers

    NASA Astrophysics Data System (ADS)

    Schweitzer, P.; Tisserand, E.; Hamed, A.; Andra, J.; Coutard, F.

    2009-07-01

    The optimal sinusoidal excitation of an ultrasonic transducer requests a knowledge of the frequency and the impedance of the used ceramic. These parameters, that vary during the application, depend on the characteristics of the transducer but also on the acoustic load of the propagation medium. In the search for an adaptive excitation, we propose the design of a digital generator assuring the functions of automatic tuning and impedance matching. The design uses the Butterworth-Van Dycke model of pizoelectric ceramics. The method of determination and identification of the model parameters is presented and applied on three different transducers. The negative feedback of the generator is carried out by the signal measured on the transducers. The dynamic voltage being very variable, the output resistor of the driver is controlled by transducer impedance. This feedback control allows the stability of the output voltage to a constant value whatever the frequency and the medium is. A Simulink^circledR model of the regulation loop shows that the frequency tuning could be realized by exploiting the command signal of the driver resistance. The precision and the stability of the feedback system are tested for frequencies between 1 to 3 MHz.

  8. 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.

  9. Voltage Sensor

    NASA Technical Reports Server (NTRS)

    1996-01-01

    Under a Lewis Research Center Small Business Innovation Research contract, SRICO, Inc. developed a fiber optic voltage sensor to measure voltage in electronic systems in spacecraft. The sensor uses glass and light to sense and transmit electricity, and is relatively safe and accurate. SRICO then commercialized the sensor for measurement of electric field and voltage in applications such as electric power systems and hazardous environments, lightning detection, and fiber optic communication systems.

  10. 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)

  11. Solid state high-voltage pulser operates with low supply voltage

    NASA Technical Reports Server (NTRS)

    Milberger, W. E.

    1968-01-01

    High speed klystron cathode pulser requires low voltage to generate high-voltage pulses. Broadband video transformers are wound in two configurations - /1/ transmission line, multifilar toroids and /2/ loop coupling toroids. The circuit adapts to generate high-speed, high-voltage, high-stability power pulses at megawatt levels.

  12. A positive feedback loop of IL-21 signaling provoked by homeostatic CD4+CD25- T cell expansion is essential for the development of arthritis in autoimmune K/BxN mice.

    PubMed

    Jang, Eunkyeong; Cho, Sin-Hye; Park, Hyunjoo; Paik, Doo-Jin; Kim, Jung Mogg; Youn, Jeehee

    2009-04-15

    Rheumatoid arthritis is a joint-specific autoimmune inflammatory disease of unknown etiology. The K/BxN mouse is a model of rheumatoid arthritis that is thought to be mainly due to autoantibody-mediated inflammatory responses. We showed previously that homeostatic proliferation of autoreactive CD4(+) T cells is required for disease initiation in the K/BxN mice. In this study, we show that the homeostatically proliferating CD4(+)CD25(-) T cells produce IL-21. We generated IL-21R-deficient (IL-21R(-/-)) K/BxN mice and found that these mice were completely refractory to the development of spontaneous arthritis. They contained fewer CD4(+) T cells with a reduced proportion of homeostatically proliferating cells, fewer follicular Th cells, and, surprisingly, more Th17 cells than their control counterparts. They also failed to develop IgG1(+) memory B cells and autoantigen-specific IgG1 Ab-secreting cells. IL-21 induced expression of receptor activator of NF-kappaB ligand (RANKL) a regulator of osteoclastogenesis, and few RANKL-expressing infiltrates were found in the synovia of IL-21R(-/-) K/BxN mice. Thus, our results demonstrate that IL-21 forms a positive feedback autocrine loop involving homeostatically activated CD4(+) cells and that it plays an essential role in the development of autoimmune arthritis by mechanisms dependent on follicular Th cell development, autoreactive B cell maturation, and RANKL induction but independent of Th17 cell function. Consistent with this, in vivo administration of soluble the IL-21R-Fc fusion protein delayed the onset and progression of arthritis. Our findings suggest that effective targeting of IL-21-mediated processes may be useful in treating autoimmune arthritis. PMID:19342640

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

    PubMed Central

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

    2014-01-01

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

  14. 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.

  15. Modular high voltage power supply for chemical analysis

    DOEpatents

    Stamps, James F. (Livermore, CA); Yee, Daniel D. (Dublin, CA)

    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.

  16. Modular high voltage power supply for chemical analysis

    DOEpatents

    Stamps, James F. (Livermore, CA); Yee, Daniel D. (Dublin, CA)

    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.

  17. Modular high voltage power supply for chemical analysis

    DOEpatents

    Stamps, James F. (Livermore, CA); Yee, Daniel D. (Dublin, CA)

    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.

  18. 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.

  19. Design and Construction of Low Cost High Voltage dc Power Supply for Constant Power Operation

    NASA Astrophysics Data System (ADS)

    Kumar, N. S.; Jayasankar, V.

    2013-06-01

    Pulsed load applications like laser based systems need high voltage dc power supplies with better regulation characteristics. This paper presents the design, construction and testing of dc power supply with 1 kV output at 300 W power level. The designed converter has half bridge switched mode power supply (SMPS) configuration with 20 kHz switching. The paper covers the design of half bridge inverter, closed loop control, High frequency transformer and other related electronics. The designed power supply incorporates a low cost OPAMP based feedback controller which is designed using small signal modelling of the converter. The designed converter was constructed and found to work satisfactorily as per the specifications.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. Pulsed feedback defers cellular differentiation.

    PubMed

    Levine, Joe H; Fontes, Michelle E; Dworkin, Jonathan; Elowitz, Michael B

    2012-01-01

    Environmental signals induce diverse cellular differentiation programs. In certain systems, cells defer differentiation for extended time periods after the signal appears, proliferating through multiple rounds of cell division before committing to a new fate. How can cells set a deferral time much longer than the cell cycle? Here we study Bacillus subtilis cells that respond to sudden nutrient limitation with multiple rounds of growth and division before differentiating into spores. A well-characterized genetic circuit controls the concentration and phosphorylation of the master regulator Spo0A, which rises to a critical concentration to initiate sporulation. However, it remains unclear how this circuit enables cells to defer sporulation for multiple cell cycles. Using quantitative time-lapse fluorescence microscopy of Spo0A dynamics in individual cells, we observed pulses of Spo0A phosphorylation at a characteristic cell cycle phase. Pulse amplitudes grew systematically and cell-autonomously over multiple cell cycles leading up to sporulation. This pulse growth required a key positive feedback loop involving the sporulation kinases, without which the deferral of sporulation became ultrasensitive to kinase expression. Thus, deferral is controlled by a pulsed positive feedback loop in which kinase expression is activated by pulses of Spo0A phosphorylation. This pulsed positive feedback architecture provides a more robust mechanism for setting deferral times than constitutive kinase expression. Finally, using mathematical modeling, we show how pulsing and time delays together enable "polyphasic" positive feedback, in which different parts of a feedback loop are active at different times. Polyphasic feedback can enable more accurate tuning of long deferral times. Together, these results suggest that Bacillus subtilis uses a pulsed positive feedback loop to implement a "timer" that operates over timescales much longer than a cell cycle. PMID:22303282

  5. 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.

  6. 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.

  7. 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

  8. 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.

  9. 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.)

  10. 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.

  11. 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.

  12. Feedback Regulation and Its Efficiency in Biochemical Networks

    NASA Astrophysics Data System (ADS)

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

    2016-01-01

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

  13. High-voltage circuits for power management on 65 nm CMOS

    NASA Astrophysics Data System (ADS)

    Pashmineh, S.; Killat, D.

    2015-11-01

    This paper presents two high-voltage circuits used in power management, a switching driver for buck converter with optimized on-resistance and a low dropout (LDO) voltage regulator with 2-stacked pMOS pass devices. The circuit design is based on stacked MOSFETs, thus the circuits are technology independent. High-voltage drivers with stacked devices suffer from slow switching characteristics. In this paper, a new concept to adjust gate voltages of stacked transistors is introduced for reduction of on-resistance. According to the theory, a circuit is proposed that drives 2 stacked transistors of a driver. Simulation results show a reduction of the on-resistance between 27 and 86 % and a reduction of rise and fall times between 16 and 83 % with a load capacitance of 150 pF at various supply voltages, compared to previous work. The concept can be applied to each high-voltage driver that is based on a number (N) of stacked transistors. The high voltage compatibility of the low drop-out voltage regulator (LDO) is established by a 2-stacked pMOS transistors as pass device controlled by two regulators: an error amplifier and a 2nd amplifier adjusting the division of the voltages between the two pass transistors. A high GBW and good DC accuracy in line and load regulation is achieved by using 3-stage error amplifiers. To improve stability, two feedback loops are utilized. In this paper, the 2.5 V I/O transistors of the TSMC 65 nm CMOS technology are used for the circuit design.

  14. 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.

  15. 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.

  16. Studies Of Positive-Position-Feedback Control

    NASA Technical Reports Server (NTRS)

    Fanson, James L.; Caughey, Thomas K.

    1992-01-01

    Report discusses theoretical and experimental studies of positive-position-feedback control for suppressing vibrations in large flexible structures. Positive-position-feedback control involves placement of actuators and sensors on structure; control voltages applied to actuators in response to outputs of sensors processed via compensator algorithm. Experiments demonstrate feasibility of suppressing vibrations by positive position feedback, and spillover of vibrational energy into uncontrolled modes has stabilizing effect if control gain sufficiently small.

  17. 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.

  18. Comparison of the domain and frequency domain state feedbacks

    SciTech Connect

    Zhang, S.Y.

    1986-01-01

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

  19. 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.

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

    PubMed

    ilingiro?lu, U?ur; ?pek, 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 ?m CMOS technology. PMID:23893206

  1. Development of scalable frequency and power Phase-Locked Loop in 130 nm CMOS technology

    NASA Astrophysics Data System (ADS)

    Firlej, M.; Fiutowski, T.; Idzik, M.; Moroń, J.; Świentek, K.

    2014-02-01

    The design and measurements results of a prototype very low power Phase-Locked Loop (PLL) ASIC for applications in readout systems of particle physics detectors are presented. The PLL was fabricated in 130 nm CMOS technology. It was designed and simulated for frequency range 10 MHz-3.5 GHz. Four division factors i.e. 6, 8, 10 and 16 were implemented in the PLL feedback loop. The main PLL block-voltage controlled oscillator (VCO) should work in 16 frequency ranges/modes, switched either manually or automatically. Preliminary measurements done in frequency range 20 MHz-1.6 GHz showed that the ASIC is functional and generates proper clock signal. The automatic VCO mode switching, one of the main design goals, was positively verified. Power consumption of around 0.6 mW was measured at 1 GHz for a division factor equal to 10.

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

    PubMed

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

    2016-01-01

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

  3. Reversed field pinch operation with intelligent shell feedback control in EXTRAP T2R

    NASA Astrophysics Data System (ADS)

    Brunsell, P. R.; Kuldkepp, M.; Menmuir, S.; Cecconello, M.; Hedqvist, A.; Yadikin, D.; Drake, J. R.; Rachlew, E.

    2006-11-01

    Discharges in the thin shell reversed field pinch (RFP) device EXTRAP T2R without active feedback control are characterized by growth of non-resonant m = 1 unstable resistive wall modes (RWMs) in agreement with linear MHD theory. Resonant m = 1 tearing modes (TMs) exhibit initially fast rotation and the associated perturbed radial fields at the shell are small, but eventually TMs wall-lock and give rise to a growing radial field. The increase in the radial field at the wall due to growing RWMs and wall-locked TMs is correlated with an increase in the toroidal loop voltage, which leads to discharge termination after 3-4 wall times. An active magnetic feedback control system has been installed in EXTRAP T2R. A two-dimensional array of 128 active saddle coils (pair-connected into 64 independent m = 1 coils) is used with intelligent shell feedback control to suppress the m = 1 radial field at the shell. With feedback control, active stabilization of the full toroidal spectrum of 16 unstable m = 1 non-resonant RWMs is achieved, and TM wall locking is avoided. A three-fold extension of the pulse length, up to the power supply limit, is observed. Intelligent shell feedback control is able to maintain the plasma equilibrium for 10 wall times, with plasma confinement parameters sustained at values comparable to those obtained in thick shell devices of similar size.

  4. 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.

  5. Reversing Quantum Trajectories with Analog Feedback

    NASA Astrophysics Data System (ADS)

    de Lange, G.; Rist, D.; Tiggelman, M. J.; Eichler, C.; Tornberg, L.; Johansson, G.; Wallraff, A.; Schouten, R. N.; DiCarlo, L.

    2014-02-01

    We demonstrate the active suppression of transmon qubit dephasing induced by dispersive measurement, using parametric amplification and analog feedback. By real-time processing of the homodyne record, the feedback controller reverts the stochastic quantum phase kick imparted by the measurement on the qubit. The feedback operation matches a model of quantum trajectories with a measurement efficiency ??0.5, consistent with the result obtained by postselection. We overcome the bandwidth limitations of the amplification chain by numerically optimizing the signal processing in the feedback loop and provide a theoretical model explaining the optimization result.

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

    PubMed

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

    2012-01-01

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

  7. 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 systems abilities for conducting closed-loop, multichannel interfacing experiments. PMID:23346047

  8. Rogowski Loop design for NSTX

    SciTech Connect

    McCormack, B.; Kaita, R.; Kugel, H.; Hatcher, R.

    2000-01-06

    The Rogowski Loop is one of the most basic diagnostics for tokamak operations. On the National Spherical Torus Experiment (NSTX), the plasma current Rogowski Loop had the constraints of the very limited space available on the center stack, 5,000 volt isolation, flexibility requirements as it remained a part of the Center Stack assembly after the first phase of operation, and a +120 C temperature requirement. For the second phase of operation, four Halo Current Rogowski Loops under the Center Stack tiles will be installed having +600 C and limited space requirements. Also as part of the second operational phase, up to ten Rogowski Loops will installed to measure eddy currents in the Passive Plate support structures with +350 C, restricted space, and flexibility requirements. This presentation will provide the details of the material selection, fabrication techniques, testing, and installation results of the Rogowski Loops that were fabricated for the high temperature operational and bakeout requirements, high voltage isolation requirements, and the space and flexibility requirements imposed upon the Rogowski Loops. In the future operational phases of NSTX, additional Rogowski Loops could be anticipated that will measure toroidal plasma currents in the vacuum vessel and in the Passive Plate assemblies.

  9. Loop-to-loop coupling.

    SciTech Connect

    Warne, Larry Kevin; Lucero, Larry Martin; Langston, William L.; Salazar, Robert Austin; Coleman, Phillip Dale; Basilio, Lorena I.; Bacon, Larry Donald

    2012-05-01

    This report estimates inductively-coupled energy to a low-impedance load in a loop-to-loop arrangement. Both analytical models and full-wave numerical simulations are used and the resulting fields, coupled powers and energies are compared. The energies are simply estimated from the coupled powers through approximations to the energy theorem. The transmitter loop is taken to be either a circular geometry or a rectangular-loop (stripline-type) geometry that was used in an experimental setup. Simple magnetic field models are constructed and used to estimate the mutual inductance to the receiving loop, which is taken to be circular with one or several turns. Circuit elements are estimated and used to determine the coupled current and power (an equivalent antenna picture is also given). These results are compared to an electromagnetic simulation of the transmitter geometry. Simple approximate relations are also given to estimate coupled energy from the power. The effect of additional loads in the form of attached leads, forming transmission lines, are considered. The results are summarized in a set of susceptibility-type curves. Finally, we also consider drives to the cables themselves and the resulting common-to-differential mode currents in the load.

  10. 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.

  11. 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.

  12. Loop Input.

    ERIC Educational Resources Information Center

    Woodward, Tessa

    2003-01-01

    Discusses loop input, a specific type of experiential teacher training process that involves an alignment of the process and content of learning. This concept has gradually gained ground in English language teacher training since 1986 when the term was coined. (Author/VWL)

  13. 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.

  14. Low power, scalable multichannel high voltage controller

    DOEpatents

    Stamps, James Frederick (Livermore, CA); Crocker, Robert Ward (Fremont, CA); Yee, Daniel Dadwa (Dublin, CA); Dils, David Wright (Fort Worth, TX)

    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.

  15. Low power, scalable multichannel high voltage controller

    DOEpatents

    Stamps, James Frederick (Livermore, CA); Crocker, Robert Ward (Fremont, CA); Yee, Daniel Dadwa (Dublin, CA); Dils, David Wright (Fort Worth, TX)

    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.

  16. 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.

  17. Scanning mutagenesis of the I-II loop of the Cav2.2 calcium channel identifies residues Arginine 376 and Valine 416 as molecular determinants of voltage dependent G protein inhibition

    PubMed Central

    2010-01-01

    Direct interaction with the ? subunit of the heterotrimeric G protein complex causes voltage-dependent inhibition of N-type calcium channels. To further characterize the molecular determinants of this interaction, we performed scanning mutagenesis of residues 372-387 and 410-428 of the N-type channel ?1 subunit, in which individual residues were replaced by either alanine or cysteine. We coexpressed wild type G?1?2 subunits with either wild type or point mutant N-type calcium channels, and voltage-dependent, G protein-mediated inhibition of the channels (VDI) was assessed using patch clamp recordings. The resulting data indicate that Arg376 and Val416 of the ?1 subunit, residues which are surface-exposed in the presence of the calcium channel ? subunit, contribute significantly to the functional inhibition by G?1. To further characterize the roles of Arg376 and Val416 in this interaction, we performed secondary mutagenesis of these residues, coexpressing the resulting mutants with wild type G?1?2 subunits and with several isoforms of the auxiliary ? subunit of the N-type channel, again assessing VDI using patch clamp recordings. The results confirm the importance of Arg376 for G protein-mediated inhibition and show that a single amino acid substitution to phenylalanine drastically alters the abilities of auxiliary calcium channel subunits to regulate G protein inhibition of the channel. PMID:20181083

  18. Scanning mutagenesis of the I-II loop of the Cav2.2 calcium channel identifies residues Arginine 376 and Valine 416 as molecular determinants of voltage dependent G protein inhibition.

    PubMed

    Tedford, Hugo W; Kisilevsky, Alexandra E; Vieira, Lucienne B; Varela, Diego; Chen, Lina; Zamponi, Gerald W

    2010-01-01

    Direct interaction with the beta subunit of the heterotrimeric G protein complex causes voltage-dependent inhibition of N-type calcium channels. To further characterize the molecular determinants of this interaction, we performed scanning mutagenesis of residues 372-387 and 410-428 of the N-type channel alpha1 subunit, in which individual residues were replaced by either alanine or cysteine. We coexpressed wild type Gbeta1gamma2 subunits with either wild type or point mutant N-type calcium channels, and voltage-dependent, G protein-mediated inhibition of the channels (VDI) was assessed using patch clamp recordings. The resulting data indicate that Arg376 and Val416 of the alpha1 subunit, residues which are surface-exposed in the presence of the calcium channel beta subunit, contribute significantly to the functional inhibition by Gbeta1. To further characterize the roles of Arg376 and Val416 in this interaction, we performed secondary mutagenesis of these residues, coexpressing the resulting mutants with wild type Gbeta1gamma2 subunits and with several isoforms of the auxiliary beta subunit of the N-type channel, again assessing VDI using patch clamp recordings. The results confirm the importance of Arg376 for G protein-mediated inhibition and show that a single amino acid substitution to phenylalanine drastically alters the abilities of auxiliary calcium channel subunits to regulate G protein inhibition of the channel. PMID:20181083

  19. 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.

  20. 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.

  1. Feedback: Breakfast of Champions.

    ERIC Educational Resources Information Center

    Justman, Jeffrey J.

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

  2. 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

  3. 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.

  4. 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

  5. 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.

  6. 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.

  7. 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.

  8. Beam-based Feedback Testing and Simulations for the SLC Linac

    SciTech Connect

    Hendrickson, Linda

    2000-09-05

    Beam-based feedback systems were a key element in the successful operation of the Stanford Linear Collider (SLC) but the performance was not optimal. Some limitations were incomplete communication between the feedback loops, slow correctors, and constraints on the placement of feedback devices. Recent beam experiments and simulations have improved understanding of feedback performance characteristics, and increased confidence in designing feedback systems for the Next Linear Collider (NLC).

  9. Feedback regulation in cell signalling: Lessons for cancer therapeutics.

    PubMed

    Nguyen, Lan K; Kholodenko, Boris N

    2016-02-01

    The notion of feedback is fundamental for understanding signal transduction networks. Feedback loops attenuate or amplify signals, change the network dynamics and modify the input-output relationships between the signal and the target. Negative feedback provides robustness to noise and adaptation to perturbations, but as a double-edged sword can prevent effective pathway inhibition by a drug. Positive feedback brings about switch-like network responses and can convert analog input signals into digital outputs, triggering cell fate decisions and phenotypic changes. We show how a multitude of protein-protein interactions creates hidden feedback loops in signal transduction cascades. Drug treatments that interfere with feedback regulation can cause unexpected adverse effects. Combinatorial molecular interactions generated by pathway crosstalk and feedback loops often bypass the block caused by targeted therapies against oncogenic mutated kinases. We discuss mechanisms of drug resistance caused by network adaptations and suggest that development of effective drug combinations requires understanding of how feedback loops modulate drug responses. PMID:26481970

  10. 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.

  11. 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.

  12. RF feedback simulation results for PEP-II

    SciTech Connect

    Tighe, R.; Corredoura, P.

    1995-06-01

    A model of the RF feedback system for PEP-II has been developed to provide time-domain simulation and frequency-domain analysis of the complete system. The model includes the longitudinal beam dynamics, cavity fundamental resonance, feedback loops, and the nonlinear klystron operating near saturation. Transients from an ion clearing gap and a reference phase modulation from the longitudinal feedback system are also studied. Growth rates are predicted and overall system stability examined.

  13. 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.

  14. 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

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. Offset quadrature communications with decision-feedback carrier synchronization

    NASA Technical Reports Server (NTRS)

    Simon, M. K.; Smith, J. G.

    1974-01-01

    In order to accommodate a quadrature amplitude-shift-keyed (QASK) signal, Simon and Smith (1974) have modified the decision-feedback loop which tracks a quadrature phase-shift-keyed (QPSK). In the investigation reported approaches are considered to modify the loops in such a way that offset QASK signals can be tracked, giving attention to the special case of an offset QPSK. The development of the stochastic integro-differential equation of operation for a decision-feedback offset QASK loop is discussed along with the probability density function of the phase error process.

  20. 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.

  1. 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.

  2. 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)

  3. 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.

  4. Causal Loop Analysis of coastal geomorphological systems

    NASA Astrophysics Data System (ADS)

    Payo, Andres; Hall, Jim W.; French, Jon; Sutherland, James; van Maanen, Barend; Nicholls, Robert J.; Reeve, Dominic E.

    2016-03-01

    As geomorphologists embrace ever more sophisticated theoretical frameworks that shift from simple notions of evolution towards single steady equilibria to recognise the possibility of multiple response pathways and outcomes, morphodynamic modellers are facing the problem of how to keep track of an ever-greater number of system feedbacks. Within coastal geomorphology, capturing these feedbacks is critically important, especially as the focus of activity shifts from reductionist models founded on sediment transport fundamentals to more synthesist ones intended to resolve emergent behaviours at decadal to centennial scales. This paper addresses the challenge of mapping the feedback structure of processes controlling geomorphic system behaviour with reference to illustrative applications of Causal Loop Analysis at two study cases: (1) the erosion-accretion behaviour of graded (mixed) sediment beds, and (2) the local alongshore sediment fluxes of sand-rich shorelines. These case study examples are chosen on account of their central role in the quantitative modelling of geomorphological futures and as they illustrate different types of causation. Causal loop diagrams, a form of directed graph, are used to distil the feedback structure to reveal, in advance of more quantitative modelling, multi-response pathways and multiple outcomes. In the case of graded sediment bed, up to three different outcomes (no response, and two disequilibrium states) can be derived from a simple qualitative stability analysis. For the sand-rich local shoreline behaviour case, two fundamentally different responses of the shoreline (diffusive and anti-diffusive), triggered by small changes of the shoreline cross-shore position, can be inferred purely through analysis of the causal pathways. Explicit depiction of feedback-structure diagrams is beneficial when developing numerical models to explore coastal morphological futures. By explicitly mapping the feedbacks included and neglected within a model, the modeller can readily assess if critical feedback loops are included.

  5. Cardiac arrhythmias and degradation into chaotic behavior prevention using feedback control

    NASA Astrophysics Data System (ADS)

    Uzelac, Ilija; Sidorov, Veniamin; Wikswo, John; Gray, Richard

    2012-02-01

    During normal heart rhythm, cardiac cells behave as a set of oscillators with a distribution of phases but with the same frequency. The heart as a dynamical system in a phase space representation can be modeled as a set of oscillators that have closed overlapping orbits with the same period. These orbits are not stable and in the case of disruption of the cardiac rhythm, such as due to premature beats, the system will have a tendency to leave its periodic unstable orbits. If these orbits become attracted to phase singularities, their disruption may lead to chaotic behavior, which appears as a life-threating ventricular fibrillation. By using closed-loop feedback in the form of an adjustable defibrillation shock, any drift from orbits corresponding to the normal rhythm can be corrected by forcing the system to maintain its orbits. The delay through the feedback network coincides with the period of normal heart beats. To implement this approach we developed a 1 kW arbitrary waveform voltage-to-current converter with a 1 kHz bandwidth driven by a photodiode system that records an optical electrocardiogram and provides a feedback signal in real time. Our goal is to determine whether our novel method to defibrillate the heart will require much lower energies than are currently utilized in single shock defibrillators.

  6. 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.

  7. 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.

  8. 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

  9. 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.

  10. Improving Low Voltage Ride Through Capability of Wind Generators Using Dynamic Voltage Restorer

    NASA Astrophysics Data System (ADS)

    Sivasankar, Gangatharan; Suresh Kumar, Velu

    2014-08-01

    The increasing wind power integration with power grid has forced the situation to improve the reliability of wind generators for stable operation. One important problem with induction generator based wind farm is its low ride through capability to the grid voltage disturbance. Any disturbance such as voltage dip may cause wind farm outages. Since wind power contribution is in predominant percentage, such outages may lead to stability problem. The proposed strategy is to use dynamic voltage controller (DVR) to compensate the voltage disturbance. The DVR provides the wind generator the ability to remain connected in grid and improve the reliability. The voltage dips due to symmetrical and unsymmetrical faults are considered for analysis. The vector control scheme is employed for fault compensation which uses software phase locked loop scheme and park dq0 transformation technique. Extensive simulation results are included to illustrate the control and operation of DVR.

  11. Delayed feedback of sampled higher derivatives.

    PubMed

    Insperger, Tamas; Stepan, Gabor; Turi, Janos

    2010-01-28

    Systems where the present rate of change of the state depends on the past values of the higher rates of change of the state are described by so-called advanced functional differential equations (AFDEs). In an AFDE, the highest derivative of the state-space coordinate appears with delayed argument only. The corresponding linearized equations are always unstable with infinitely many unstable poles, and are rarely related to practical applications due to their inherently implicit nature. In this paper, one of the simplest AFDEs, a linear scalar first-order system, is considered with the delayed feedback of the second derivative of the state in the presence of sampling in the feedback loop (i.e. in the case of digital control). It is shown that sampling of the feedback may stabilize the originally infinitely unstable system for certain parameter combinations. The result explains the stable behaviour of certain dynamical systems with feedback delay in the highest derivative. PMID:20008412

  12. Transient Voltage Recorder

    NASA Astrophysics Data System (ADS)

    Medelius, Pedro J.; Simpson, Howard J.

    2002-09-01

    A voltage transient recorder can detect lightning induced transient voltages. The recorder detects a lightning induced transient voltage and adjusts input amplifiers to accurately record transient voltage magnitudes. The recorder stores voltage data from numerous monitored channels, or devices. The data is time stamped and can be output in real time, or stored for later retrieval. The transient recorder, in one embodiment, includes an analog-to-digital converter and a voltage threshold detector. When an input voltage exceeds a pre-determined voltage threshold, the recorder stores the incoming voltage magnitude and time of arrival. The recorder also determines if its input amplifier circuits clip the incoming signal or if the incoming signal is too low. If the input data is clipped or too low, the recorder adjusts the gain of the amplifier circuits to accurately acquire subsequent components of the lightning induced transients.

  13. 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.

  14. An intensity ratio of interlocking loops determines circadian period length

    PubMed Central

    Yan, Jie; Shi, Guangsen; Zhang, Zhihui; Wu, Xi; Liu, Zhiwei; Xing, Lijuan; Qu, Zhipeng; Dong, Zhen; Yang, Ling; Xu, Ying

    2014-01-01

    Circadian clocks allow organisms to orchestrate the daily rhythms in physiology and behaviors, and disruption of circadian rhythmicity can profoundly affect fitness. The mammalian circadian oscillator consists of a negative primary feedback loop and is associated with some auxiliary loops. This raises the questions of how these interlocking loops coordinate to regulate the period and maintain its robustness. Here, we focused on the REV-ERB?/Cry1 auxiliary loop, consisting of Rev-Erb?/ROR-binding elements (RORE) mediated Cry1 transcription, coordinates with the negative primary feedback loop to modulate the mammalian circadian period. The silicon simulation revealed an unexpected rule: the intensity ratio of the primary loop to the auxiliary loop is inversely related to the period length, even when post-translational feedback is fixed. Then we measured the mRNA levels from two loops in 10-mutant mice and observed the similar monotonic relationship. Additionally, our simulation and the experimental results in human osteosarcoma cells suggest that a coupling effect between the numerator and denominator of this intensity ratio ensures the robustness of circadian period and, therefore, provides an efficient means of correcting circadian disorders. This ratio rule highlights the contribution of the transcriptional architecture to the period dynamics and might be helpful in the construction of synthetic oscillators. PMID:25122753

  15. 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.

  16. Preventing Feedback Fizzle

    ERIC Educational Resources Information Center

    Brookhart, Susan M.

    2012-01-01

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

  17. 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

  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. 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.

  20. Quantum feedback experiments with atoms and cavities

    NASA Astrophysics Data System (ADS)

    Raimond, Jean-Michel

    2012-06-01

    Quantum feedback transposes the usual feedback loop concept into the quantum world. A measurement performed on the system by the sensor is used by a controller to infer the system's state and to steer it towards the target by the action of the actuator. This scheme has to face a fundamental difficulty, since the measurement changes the system's state. This back-action makes quantum feedback algorithms more complex than their classical counterparts. We report the first successful operation of a repeated quantum feedback loop [1]. It prepares photon number states (from 0 to 4 photons) on-demand in a superconducting microwave cavity and subsequently reverses the effect of decoherence-induced quantum jumps. The quantum sensors are circular Rydberg atoms, performing a Quantum Non Demolition (QND) measurement of the cavity field. Information they provide is used by the controller (real-time computer) to estimate the field state. The controller determines the amplitude of a coherent displacement leading the cavity closer to the target This displacement is performed by a microwave source acting as the actuator. Iterations of this loop rapidly drive the cavity towards the prescribed target. When it is reached, the actuator idles. It resumes operation when atomic detections indicate that a photon has been lost, or that a thermal photon has appeared. The feedback compensates for these quantum jumps and rapidly restores the field in the target state. In a variant of the experiment, we use quantum actuators, resonant atoms that feed photons back in the cavity when they get lost. This more efficient scheme allows us to stabilize higher photon numbers. These experiments are a first step towards the use of quantum feedback to protect fragile quantum resources. We also consider an alternative route towards state protection based on reservoir engineering [2]. [4pt] [1] C. Sayrin et al. Nature (London) 477, 73 (2011)[0pt] [2] A. Sarlette et al. Phys. Rev. Lett. 107, 010402 (2011)

  1. Numerical investigation of the nonlinear dynamics of a hybrid acousto-optic Bragg cell with a variable feedback gain

    NASA Astrophysics Data System (ADS)

    Chatterjee, Monish R.; Zhou, Hao

    2014-09-01

    Since around 1979, the operation of an acousto-optic Bragg cell under positive first-order feedback via amplification and delay in the loop has been studied extensively by several groups [1-3]. In recent work, the analysis of the nonlinear dynamics (NLD) of the system was extended to include bistable maps and Lyapunov exponents, and application of the chaos for signal encryption and decryption for uniform plane waves. The present work originated with the problem of a variable photodetector aperture opening relative to the first-order light. This potentially complex problem is simplified by assuming instead a variable feedback gain ( ? ~ (t)), which leads to considerably different NLD. This paper examines initially the NLD versus the (DC) bias voltage for different variable- ? ~ conditions, including slow and fast rates of change of the gain with time in relation to the feedback delay. It is found that the response depends critically on the rate of rise of the feedback gain, and also that the resulting chaotic regimes are generally significantly different from those for fixed values of ? ~ . We have generated constant feedback gain and the variable feedback gain (t) chaos characteristics of the hybrid A-O network. Chaos as an equivalent carrier has been used to encrypt messages for both fixed and variable ? ~ . The transmitted signal is detected from the encrypted carrier using a heterodyne method, using a slave Bragg cell with matched keys to generate local chaos followed by a low pass filter and a phase inverter. Results between variable- and fixed-gain systems are compared in terms of advantages and disadvantages.

  2. 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.

  3. 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.

  4. Enhancement of field squeezing using coherent feedback

    SciTech Connect

    Gough, J. E.; Wildfeuer, S.

    2009-10-15

    The theory of quantum feedback networks has recently been developed with the aim of showing how quantum input-output components may be connected together so as to control, stabilize, or enhance the performance of one of the subcomponents. In this paper, we show how the degree to which an idealized component (a degenerate parametric amplifier in the strong-coupling regime) can squeeze input fields may be enhanced by placing the component in loop in a simple feedback mechanism involving a beam splitter. We study the spectral properties of output fields, placing particular emphasis on the elastic and inelastic components of the power density.

  5. 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.

  6. 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.

  7. 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.

  8. Probabilistic models for feedback systems.

    SciTech Connect

    Grace, Matthew D.; Boggs, Paul T.

    2011-02-01

    In previous work, we developed a Bayesian-based methodology to analyze the reliability of hierarchical systems. The output of the procedure is a statistical distribution of the reliability, thus allowing many questions to be answered. The principal advantage of the approach is that along with an estimate of the reliability, we also can provide statements of confidence in the results. The model is quite general in that it allows general representations of all of the distributions involved, it incorporates prior knowledge into the models, it allows errors in the 'engineered' nodes of a system to be determined by the data, and leads to the ability to determine optimal testing strategies. In this report, we provide the preliminary steps necessary to extend this approach to systems with feedback. Feedback is an essential component of 'complexity' and provides interesting challenges in modeling the time-dependent action of a feedback loop. We provide a mechanism for doing this and analyze a simple case. We then consider some extensions to more interesting examples with local control affecting the entire system. Finally, a discussion of the status of the research is also included.

  9. Convection and the Soil-Moisture Precipitation Feedback

    NASA Astrophysics Data System (ADS)

    Schar, C.; Froidevaux, P.; Keller, M.; Schlemmer, L.; Langhans, W.; Schmidli, J.

    2014-12-01

    The soil moisture - precipitation (SMP) feedback is of key importance for climate and climate change. A positive SMP feedback tends to amplify the hydrological response to external forcings (and thereby fosters precipitation and drought extremes), while a negative SMP feedback tends to moderate the influence of external forcings (and thereby stabilizes the hydrological cycle). The sign of the SMP feedback is poorly constrained by the current literature. Theoretical, modeling and observational studies partly disagree, and have suggested both negative and positive feedback loops. Can wet soil anomalies indeed result in either an increase or a decrease of precipitation (positive or negative SMP feedback, respectively)? Here we investigate the local SMP feedback using real-case and idealized convection-resolving simulations. An idealized simulation strategy is developed, which is able to replicate both signs of the feedback loop, depending on the environmental parameters. The mechanism relies on horizontal soil moisture variations, which may develop and intensify spontaneously. The positive expression of the feedback is associated with the initiation of convection over dry soil patches, but the convective cells then propagate over wet patches, where they strengthen and preferentially precipitate. The negative feedback may occur when the wind profile is too weak to support the propagation of convective features from dry to wet areas. Precipitation is then generally weaker and falls preferentially over dry patches. The results highlight the role of the mid-tropospheric flow in determining the sign of the feedback. A key element of the positive feedback is the exploitation of both low convective inhibition (CIN) over dry patches (for the initiation of convection), and high CAPE over wet patches (for the generation of precipitation). The results of this study will also be discussed in relation to climate change scenarios that exhibit large biases in surface temperature and interannual variability over mid-latitude summer climates, both over Europe and North America. It is argued that parameterized convection may contribute towards such biases by overemphasizing a positive SMP feedback.

  10. Voltage monitoring system

    NASA Technical Reports Server (NTRS)

    Canicatti, C. L. (inventor)

    1975-01-01

    A description is given of a system for monitoring the voltage at a remote location and determining when the voltage exceeds upper and lower levels. The system includes transmission lines for transmitting the voltage back to a central station and applying such to an amplifier having a pair of outputs. One of the outputs of the amplifier is applied to an oscillograph. The other output is fed through an isolation transformer, a full wave rectifier, to a pair of unijunctional transistor circuits for producing pulses when the voltage exceeds or drops below a predetermined level. These pulses, in turn, energize a relay which turns on the oscillograph for recording the voltages being monitored.

  11. 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.

  12. 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.

  13. The fast correction coil feedback control system

    SciTech Connect

    Coffield, F.; Caporaso, G.; Zentler, J.M.

    1989-01-01

    A model-based feedback control system has been developed to correct beam displacement errors in the Advanced Test Accelerator (ATA) electron beam accelerator. The feedback control system drives an X/Y dipole steering system that has a 40-MHz bandwidth and can produce {+-}300-Gauss-cm dipole fields. A simulator was used to develop the control algorithm and to quantify the expected performance in the presence of beam position measurement noise and accelerator timing jitter. The major problem to date has been protecting the amplifiers from the voltage that is inductively coupled to the steering bars by the beam. 3 refs., 8 figs.

  14. 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…

  15. Feedbacks in human-landscape systems

    NASA Astrophysics Data System (ADS)

    Chin, Anne

    2015-04-01

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

  16. Internal and external feedback circuits for skilled forelimb movement

    PubMed Central

    Azim, Eiman; Fink, Andrew J.P.; Jessell, Thomas M.

    2015-01-01

    Skilled motor behavior emerges from interactions between efferent neural pathways that induce muscle contraction and feedback systems that report and refine movement. Two broad classes of feedback projections modify motor output, one from the periphery and a second that originates within the central nervous system. The mechanisms through which these pathways influence movement remain poorly understood, however. Here we discuss recent studies that delineate spinal circuitry that binds external and internal feedback pathways to forelimb motor behavior. A spinal presynaptic inhibitory circuit regulates the strength of external feedback, promoting limb stability during goal-directed reaching. A distinct excitatory propriospinal circuit conveys copies of motor commands to the cerebellum, establishing an internal feedback loop that rapidly modulates forelimb motor output. The behavioral consequences of manipulating these two circuits reveal distinct controls on motor performance, and provide an initial insight into feedback strategies that underlie skilled forelimb movement. PMID:25699987

  17. Remote feedback stabilization of tokamak instabilities

    SciTech Connect

    Sen, A.K. )

    1994-05-01

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

  18. Coronal Loop Database

    NASA Astrophysics Data System (ADS)

    Scott, Jason; Martens, P.

    2006-06-01

    We have created a database of all coronal loops for which we have been able to find measurements in the published open literature, from Skylab to TRACE. The loops and a set of their physical parameters are stored in the form of an IDL structure. The physical parameters considered are: the loop half length, the electron density of the loop, and the loop temperature. The studies that produced the physical parameters along with their observing instruments are recorded in the database as well. Correlations of pressure vs. temperature and heating rates vs. loop length are investigated. Instrumental selection effects are also considered. The loop parameters and correlations derived from the loop database are then compared to theoretical and numerical models for scaling laws and heating rates.This work is supported by NASA GSRP fellowship NNG05GK64H

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

    PubMed Central

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

    2015-01-01

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

  20. 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

  1. A transformer coupled semiconductor bridge igniter for low voltage ignition from a high voltage source

    NASA Astrophysics Data System (ADS)

    Bickes, R. W., Jr.; Schlobohm, S. L.

    Some missile systems have high voltage, short (less than 1 microsec) current pulses available for ignition of the missile's rocket motor. Such high voltage systems are desirable for enhanced safety considerations. However, application of high voltage firing pulses to conventional 1-omega bridgewire igniters can result in a detonation in the igniter rather than a well controlled burn. We present in this paper a concept proposed by Eglin Air Force Base for converting the high voltage (2 kV) firing signal pulse to the appropriate low voltage (less than 50 V) and low energy (approximately 1.5 mJ) input required for semiconductor bridge, SCB, igniters. The Eglin concept makes use of a pot core transformer to step down the input voltage. Our transformer is a Ferroxcube pot core (10 mil air gap) with a 50-turn primary and 1-turn secondary. In our prototype design, the 1-turn secondary is a Kapton-laminated copper loop with the SCB directly bonded to the ends of the copper loop. The igniter assembly consist of the primary spool and secondary loop mounted in the pot core transformer with a hole, which serves as the charge holder for the igniter material, drilled in one of the pot core halves and positioned directly over the SCB. The igniter material is pressed into the charge holder against the SCB. Application of a 2 kV (less than 1 microsec) pulse to the primary, produces a 40-V signal in the secondary that functions the SCB and ignites the explosive material. In addition to the 2-kV all-fire ignition requirement, the ignition system must be able to withstand 500-V no-fire signals and electrostatic discharge, ESD inputs. We will discuss in this paper various design configurations of this component and their output and also the ability of this concept to successfully withstand the no-fire and ESD inputs.

  2. Developing Sustainable Feedback Practices

    ERIC Educational Resources Information Center

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

    2011-01-01

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

  3. Chromaticity Feedback at RHIC

    SciTech Connect

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

    2010-05-23

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

  4. Passage Feedback with IRIS.

    ERIC Educational Resources Information Center

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

    2001-01-01

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

  5. Preventing Feedback Fizzle

    ERIC Educational Resources Information Center

    Brookhart, Susan M.

    2012-01-01

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

  6. Generalized modal analysis for closed-loop piezoelectric devices

    NASA Astrophysics Data System (ADS)

    Giraud-Audine, Christophe; Giraud, Frédéric; Amberg, Michel; Lemaire-Semail, Betty

    2015-08-01

    Stress in a piezoelectric material can be controlled by imposing an electrical field. Thanks to feedback, this electrical field can be a function of some strain-related measurement so as to confer on the piezoelectric device a closed-loop macroscopic behaviour. In this paper we address the modelling of such a system by extending the modal decomposition methods to account for the closed loop. To do so, the boundary conditions are modified to include the electrical feedback circuit, hence allowing a closed-loop modal analysis. A case study is used to illustrate the theory and to validate it. The main advantage of the method is that design issues such as the coupling factor of the device and closed-loop stability are simultaneously captured.

  7. Closed-Loop Optogenetic Brain Interface.

    PubMed

    Pashaie, Ramin; Baumgartner, Ryan; Richner, Thomas J; Brodnick, Sarah K; Azimipour, Mehdi; Eliceiri, Kevin W; Williams, Justin C

    2015-10-01

    This paper presents a new approach for implementation of closed-loop brain-machine interface algorithms by combining optogenetic neural stimulation with electrocorticography and fluorescence microscopy. We used a new generation of microfabricated electrocorticography (micro-ECoG) devices in which electrode arrays are embedded within an optically transparent biocompatible substrate that provides optical access to the brain tissue during electrophysiology recording. An optical setup was designed capable of projecting arbitrary patterns of light for optogenetic stimulation and performing fluorescence microscopy through the implant. For realization of a closed-loop system using this platform, the feedback can be taken from electrophysiology data or fluorescence imaging. In the closed-loop systems discussed in this paper, the feedback signal was taken from the micro-ECoG. In these algorithms, the electrophysiology data are continuously transferred to a computer and compared with some predefined spatial-temporal patterns of neural activity. The computer which processes the data also readjusts the duration and distribution of optogenetic stimulating pulses to minimize the difference between the recorded activity and the predefined set points so that after a limited period of transient response the recorded activity follows the set points. Details of the system design and implementation of typical closed-loop paradigms are discussed in this paper. PMID:26011877

  8. Remote Robot Control With High Force-Feedback Gain

    NASA Technical Reports Server (NTRS)

    Kim, Won S.

    1993-01-01

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

  9. RF feedback simulation for the PEP-II B Factory

    SciTech Connect

    Tighe, R.

    1994-06-01

    A model, of the beam and RF system for PEP-11 has been developed to allow both time-domain simulation and frequency-domain analysis of the complete system. The model includes the full set of feedback loops and nonlinear elements such as the beam and klystron. The model may be used to predict beam and feedback stability in the presence of nonlinearities through time-domain simulation as well as system frequency response about a given operating point.

  10. A programmable gain amplifier with a DC offset calibration loop for a direct-conversion WLAN transceiver

    NASA Astrophysics Data System (ADS)

    Qianqian, Lei; Min, Lin; Zhiming, Chen; Yin, Shi

    2011-04-01

    A high-linearity PGA (programmable gain amplifier) with a DC offset calibration loop is proposed. The PGA adopts a differential degeneration structure to vary voltage gain and uses the closed-loop structure including the input op-amps to enhance the linearity. A continuous time feedback based DC offset calibration loop is also designed to solve the DC offset problem. This PGA is fabricated by TSMC 0.13 ?m CMOS technology. The measurements show that the receiver PGA (RXPGA) provides a 64 dB gain range with a step of 1 dB, and the transmitter PGA (TXPGA) covers a 16 dB gain. The RXPGA consumes 18 mA and the TXPGA consumes 7 mA (I and Q path) under a 3.3 V supply. The bandwidth of the multi-stage PGA is higher than 20 MHz. In addition, the DCOC (DC offset cancellation) circuit shows 10 kHz of HPCF (high pass cutoff frequency) and the DCOC settling time is less than 0.45 ?s.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  12. Extracellular matrix proteins: a positive feedback loop in lung fibrosis?

    PubMed

    Blaauboer, Marjolein E; Boeijen, Fee R; Emson, Claire L; Turner, Scott M; Zandieh-Doulabi, Behrouz; Hanemaaijer, Roeland; Smit, Theo H; Stoop, Reinout; Everts, Vincent

    2014-02-01

    Lung fibrosis is characterized by excessive deposition of extracellular matrix. This not only affects tissue architecture and function, but it also influences fibroblast behavior and thus disease progression. Here we describe the expression of elastin, type V collagen and tenascin C during the development of bleomycin-induced lung fibrosis. We further report in vitro experiments clarifying both the effect of myofibroblast differentiation on this expression and the effect of extracellular elastin on myofibroblast differentiation. Lung fibrosis was induced in female C57Bl/6 mice by bleomycin instillation. Animals were sacrificed at zero to five weeks after fibrosis induction. Collagen synthesized during the week prior to sacrifice was labeled with deuterium. After sacrifice, lung tissue was collected for determination of new collagen formation, microarray analysis, and histology. Human lung fibroblasts were grown on tissue culture plastic or BioFlex culture plates coated with type I collagen or elastin, and stimulated to undergo myofibroblast differentiation by 0-10 ng/ml transforming growth factor (TGF)?1. mRNA expression was analyzed by quantitative real-time PCR. New collagen formation during bleomycin-induced fibrosis was highly correlated to gene expression of elastin, type V collagen and tenascin C. At the protein level, elastin, type V collagen and tenascin C were highly expressed in fibrotic areas as seen in histological sections of the lung. Type V collagen and tenascin C were transiently increased. Human lung fibroblasts stimulated with TGF?1 strongly increased gene expression of elastin, type V collagen and tenascin C. The extracellular presence of elastin increased gene expression of the myofibroblastic markers ? smooth muscle actin and type I collagen. The extracellular matrix composition changes dramatically during the development of lung fibrosis. The increased levels of elastin, type V collagen and tenascin C are probably the result of increased expression by fibroblastic cells; reversely, elastin influences myofibroblast differentiation. This suggests a reciprocal interaction between fibroblasts and the extracellular matrix composition that could enhance the development of lung fibrosis. PMID:24291458

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

    NASA Astrophysics Data System (ADS)

    Schultz, Colin

    2014-03-01

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

  14. Regulation of pollen tube polarity: Feedback loops rule

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  15. Better Safe than Sorry: Interlinked Feedback Loops for Robust Mitophagy.

    PubMed

    Manford, Andrew G; Rape, Michael

    2015-10-01

    In this issue of Molecular Cell, Heo et al. (2015) uncover a new mechanism of signal amplification during mitophagy through cooperative regulation of the TBK1 kinase and autophagy receptors. PMID:26431022

  16. A Feedback Loop Model of Postmerger Performance: Customers and Competitors.

    ERIC Educational Resources Information Center

    Bastien, David T.

    1994-01-01

    Offers a case study of a merger of two local theaters. Finds that organizational change causes customers to change vendors; the announcement of a merger fuels efforts by competitors to "steal" market share; and organizational change leads to more organizational change. (SR)

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

    DOEpatents

    Eres, D.; Sharp, J.W.

    1996-07-30

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

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

    DOEpatents

    Eres, Djula; Sharp, Jeffrey W.

    1996-01-01

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

  19. ANTENNAL FEEDBACK LOOP REGULATES PHEROMONE RELEASE IN BEETLES

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Regulation of pheromone release is critical for intraspecific communication and avoidance of predators release is critical for intraspecific communication and avoidance of predators or parasites dependent on such messages. Pheromone production is under endocrine control in insects (1,2). However, ...

  20. Feedbacks in human-landscape systems.

    PubMed

    Chin, Anne; Florsheim, Joan L; Wohl, Ellen; Collins, Brian D

    2014-01-01

    This article identifies key questions and challenges for geomorphologists in investigating coupled feedbacks in human-landscape systems. While feedbacks occur in the absence of human influences, they are also altered by human activity. Feedbacks are a key element to understanding human-influenced geomorphic systems in ways that extend our traditional approach of considering humans as unidirectional drivers of change. Feedbacks have been increasingly identified in Earth-environmental systems, with studies of coupled human-natural systems emphasizing ecological phenomena in producing emerging concepts for social-ecological systems. Enormous gaps or uncertainties in knowledge remain with respect to understanding impact-feedback loops within geomorphic systems with significant human alterations, where the impacted geomorphic systems in turn affect humans. Geomorphology should play an important role in public policy by identifying the many diffuse and subtle feedbacks of both local- and global-scale processes. This role is urgent, while time may still be available to mitigate the impacts that limit the sustainability of human societies. Challenges for geomorphology include identification of the often weak feedbacks that occur over varied time and space scales ranging from geologic time to single isolated events and very short time periods, the lack of available data linking impact with response, the identification of multiple thresholds that trigger feedback mechanisms, the varied tools and metrics needed to represent both physical and human processes, and the need to collaborate with social scientists with expertise in the human causes of geomorphic change, as well as the human responses to such change. PMID:23592016