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1

Analysis and design of a multiple feedback loop control strategy for single-phase voltage-source UPS inverters  

SciTech Connect

This paper presents the analysis and design of a multiple feedback loop control scheme for single-phase voltage-source uninterruptible power supply (UPS) inverters with an L-C filter. The control scheme is based on sensing the current in the capacitor of the load filter and using it in an inner feedback loop. An outer voltage feedback loop is also incorporated to ensure that the load voltage is sinusoidal and well regulated. A general state-space averaged model of the UPS system is first derived and used to establish the steady-steady quiescent point. A linearized small signal dynamic model is then developed from the system general model using perturbation and small-signal approximation. The linearized system model is employed to examine the incremental dynamics of the power circuit and select appropriate feedback variables for stable operation of the closed-loop UPS system. Experimental verification of a laboratory model of the UPS system under the proposed closed-loop operation is provided for both linear and nonlinear loads. It is shown that the control scheme offers improved performance measures over existing schemes. It is simple to implement and capable of producing nearly perfect sinusoidal load voltage waveform at moderate switching frequency and reasonable size of filter parameters. Furthermore, the scheme has excellent dynamic response and high voltage utilization of the dc source.

Abdel-Rahim, N.M.; Quaicoe, J.E. [Memorial Univ. of Newfoundland, St. Johns, Newfoundland (Canada). Faculty of Engineering and Applied Science] [Memorial Univ. of Newfoundland, St. Johns, Newfoundland (Canada). Faculty of Engineering and Applied Science

1996-07-01

2

Climate Feedback Loops  

NSDL National Science Digital Library

This is the seventh of nine lessons in the 'Visualizing and Understanding the Science of Climate Change' website. This lesson addresses climate feedback loops and how these loops help drive and regulate Earth's unique climate system.

Researchers, King'S C.

3

Feedback loops with electrically driven microcantilevers  

NASA Astrophysics Data System (ADS)

The electronic feedback used with microcantilevers (?CLs) to obtain their best performances requires a precise driving method to exert on them a force proportional to an electrical signal. One of these methods is Electrostatic Driving (ED) easily achieved on ?CLs placed some mm apart from a conductive surface. This easy appearance of ED is the reason to find it unexpectedly, coming from electrical fields not properly shielded, in setups designed for other driving as Magnetic Driving (MD). When feedback loops designed for MD suffers from this ED contamination due to an unshielded solenoid for example, the tight phase control of the driving is lost. As a result, self-oscillation of the loop does not take place at f 0, the resonance frequency of the ?CL, or an appealing shift in the resonance frequency from f 0 without feedback to f FB=f 0+/-?f with feedback appears in non-oscillating loops. A feedback force proportional to the displacement (DF) or to the speed (SF) of ?CLs has been studied and it is demonstrated that SF sets an apparent temperature for the thermal motion of a ?CL without changing its native f 0 (a desired feature for high stability ?CL-based oscillating sensors) whereas the f FB+/-f 0 produced by DF allows an electrical tuning of f FB very useful for ?CL-based Voltage Controlled Oscillators.

Malo, Javier; Izpura, José-Ignacio

2007-06-01

4

Monitoring Digital Closed-Loop Feedback Systems  

NASA Technical Reports Server (NTRS)

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.

Katz, Richard; Kleyner, Igor

2011-01-01

5

UWB communication receiver feedback loop  

DOEpatents

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.

Spiridon, Alex (Palo Alto, CA); Benzel, Dave (Livermore, CA); Dowla, Farid U. (Castro Valley, CA); Nekoogar, Faranak (San Ramon, CA); Rosenbury, Erwin T. (Castro Valley, CA)

2007-12-04

6

The ionospheric outflow feedback loop  

NASA Astrophysics Data System (ADS)

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

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

2014-08-01

7

Design of low-voltage high performance CMOS-Current feedback amplifier using indirect feedback compensated Op-Amp  

Microsoft Academic Search

In this paper low-voltage high performance CMOS current feedback amplifier is designed using indirect feedback compensated operational amplifier and the results are compared with the existing topology. The operational-amplifier used has the open loop gain of 101.8 dB with 25 ns settling time, unity gain bandwidth 169.8 MHz, phase margin 70° with rail to rail output swing. The CMOS-current feedback

R. K. Nandwana; M. Arrawatia; N. Goel

2009-01-01

8

Feedback Loops Shape Cellular Signals in Space and Time  

PubMed Central

Positive and negative feedback loops are common regulatory elements in biological signaling systems. We discuss core feedback motifs that have distinct roles in shaping signaling responses in space and time. We also discuss approaches to experimentally investigate feedback loops in signaling systems.

Brandman, Onn; Meyer, Tobias

2009-01-01

9

Linear State Feedback, Quadratic Weights, and Closed Loop Eigenstructures.  

National Technical Information Service (NTIS)

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 multiva...

P. M. Thompson

1979-01-01

10

Closing the Feedback Loop Is Not Enough: The Assessment Spiral  

ERIC Educational Resources Information Center

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…

Wehlburg, Catherine M.

2007-01-01

11

Noise in transcription negative feedback loops: simulation and experimental analysis  

Microsoft Academic Search

Negative feedback loops have been invoked as a way to control and decrease transcriptional noise. Here, we have built three circuits to test the effect of negative feedback loops on transcriptional noise of an autoregulated gene encoding a transcription factor (TF) and a downstream gene (DG), regulated by this TF. Experimental analysis shows that self-repression decreases noise compared to expression

Yann Dublanche; Konstantinos Michalodimitrakis; Nico Kümmerer; Mathilde Foglierini; Luis Serrano

2006-01-01

12

Delaying instability and voltage collapse in power systems using SVCs with washout filter-aided feedback  

Microsoft Academic Search

This paper introduces washout filter-aided feedback in the design of static var compensator (SVC) control to increase the range of stable operation of a power system susceptible to voltage collapse. The use of such a control automatically maintains the open-loop steady state operating conditions. In contrast to static state feedback designs, washout-filter based designs are more efficient because no control

Mohamed S. Saad; Munther A. Hassouneh; Eyad H. Abed; Abdel-Aty Edris

2005-01-01

13

Loop-voltage tomography in tokamaks using transient synchrotron radiation  

SciTech Connect

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.

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

1989-07-01

14

Different effects of redundant feedback loops on a bistable switch.  

PubMed

Bistable switches have important roles in cellular decision-making processes. Bistability can be the consequence of positive or double-negative feedback loops. Although necessary, such feedback is not sufficient for bistability, which also requires nonlinearity. Nonlinearity can be provided by synergy of multiple feedback loops or by an ultrasensitive response within a single feedback loop. However, these two possibilities are not mutually exclusive; a combination of them is also possible. Here we analyze a biochemical regulatory network that controls a crucial cell cycle transition in all eukaryotic cells and contains multiple redundant feedback loops and nonlinearity. We show in this realistic biological example that two redundant feedback loops have different effects on the position of one of the saddle-node bifurcations of the system, which determines where the system switches. This illustrates that even though the roles of positive and double-negative feedbacks have been regarded as equivalent, the difference in their architectures can lead to differences in their effects on the system. We speculate that this conclusion could be general for other bistable systems with redundant feedback loops. PMID:21198132

Domingo-Sananes, Maria Rosa; Novak, Bela

2010-12-01

15

Digital Phase-Locked Loop With Phase And Frequency Feedback  

NASA Technical Reports Server (NTRS)

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

Thomas, J. Brooks

1991-01-01

16

Virtual grasping: closed-loop force control using electrotactile feedback.  

PubMed

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

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

2014-01-01

17

Virtual Grasping: Closed-Loop Force Control Using Electrotactile Feedback  

PubMed Central

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.

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

2014-01-01

18

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

NASA Astrophysics Data System (ADS)

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.

Han, Wang; Maomao, Sun

2014-04-01

19

Creating the feedback loop: closed-loop neurostimulation.  

PubMed

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

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

2014-01-01

20

Optical bistability in nonlinear system with two loops of feedback  

NASA Astrophysics Data System (ADS)

A model of nonlinear optical system surrounded by two loops of feedback is investigated. The cell with the vapor of rubidium ? - type atoms is taken in the capacity of nonlinear element. Two modes of near-resonant electromagnetic field interacting with the cell are involved in the feedback. Two-dimensional optical bistability domain in location of input field intensities is obtained and dependence of its form and magnitude from the system parameters (photon detunings, feedback factor etc.) is investigated. "Input -output" relations corresponding to different trajectories in the bistability domain are obtained. Cross-hysteresis is studied.

Miroshnichenko, George P.; Trifanov, Alexander I.

2010-09-01

21

Analysis of Feedback Systems with a Multipower Open Loop Chain.  

National Technical Information Service (NTIS)

The report analyses the input-output behavior of feedback systems whose open loop map can be modeled by an operator, K, defined on a Hilbert space. In particular, attention is focused on the case where K is multipower, bounded, and strictly causal. The an...

R. M. DeSantis W. A. Porter

1973-01-01

22

Reduced Complexity Decision Feedback Equalization for Digital Subscriber Loops  

Microsoft Academic Search

Decision feedback equalizers (DFEs) are widely used in modern local network digital transmission systems to remove the intersymbol interference caused by slowly decaying pulse tails. A gradient descent algorithm for adapting a coefficient to model the slowly decaying portion of the tail is described. An equalization strategy is described that exploits prior knowledge of the nature of the subscriber loop

Gavin Young

1991-01-01

23

The Effect of Insulin Feedback on Closed Loop Glucose Control  

PubMed Central

Context: Initial studies of closed-loop proportional integral derivative control in individuals with type 1 diabetes showed good overnight performance, but with breakfast meal being the hardest to control and requiring supplemental carbohydrate to prevent hypoglycemia. Objective: The aim of this study was to assess the ability of insulin feedback to improve the breakfast-meal profile. Design and Setting: We performed a single center study with closed-loop control over approximately 30 h at an inpatient clinical research facility. Patients: Eight adult subjects with previously diagnosed type 1 diabetes participated. Intervention: Subjects received closed-loop insulin delivery with supplemental carbohydrate as needed. Main Outcome Measures: Outcome measures were plasma insulin concentration, model-predicted plasma insulin concentration, 2-h postprandial and 3- to 4-h glucose rate-of-change following breakfast after 1 d of closed-loop control, and the need for supplemental carbohydrate in response to nadir hypoglycemia. Results: Plasma insulin levels during closed loop were well correlated with model predictions (R = 0.86). Fasting glucose after 1 d of closed loop was not different from nighttime target (118 ± 9 vs. 110 mg/dl; P = 0.38). Two-hour postbreakfast glucose was 132 ± 16 mg/dl with stable values 3–4 h after the meal (0.03792 ± 0.0884 mg/dl · min, not different from 0; P = 0.68) and at target (97 ± 6 mg/dl, not different from 90; P = 0.28). Three subjects required supplemental carbohydrates after breakfast on d 2 of closed loop. Conclusions/Interpretation: Insulin feedback can be implemented using a model estimate of concentration. Proportional integral derivative control with insulin feedback can achieve a desired breakfast response but still requires supplemental carbohydrate to be delivered in some instances. Studies assessing more optimal control configurations and safeguards need to be conducted.

Palerm, Cesar C.; Kurtz, Natalie; Voskanyan, Gayane; Roy, Anirban; Paz, Sachiko; Kandeel, Fouad R.

2011-01-01

24

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

PubMed

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

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

2014-03-01

25

Control of breathing by interacting pontine and pulmonary feedback loops  

PubMed Central

The medullary respiratory network generates respiratory rhythm via sequential phase switching, which in turn is controlled by multiple feedbacks including those from the pons and nucleus tractus solitarii; the latter mediates pulmonary afferent feedback to the medullary circuits. It is hypothesized that both pontine and pulmonary feedback pathways operate via activation of medullary respiratory neurons that are critically involved in phase switching. Moreover, the pontine and pulmonary control loops interact, so that pulmonary afferents control the gain of pontine influence of the respiratory pattern. We used an established computational model of the respiratory network (Smith et al., 2007) and extended it by incorporating pontine circuits and pulmonary feedback. In the extended model, the pontine neurons receive phasic excitatory activation from, and provide feedback to, medullary respiratory neurons responsible for the onset and termination of inspiration. The model was used to study the effects of: (1) “vagotomy” (removal of pulmonary feedback), (2) suppression of pontine activity attenuating pontine feedback, and (3) these perturbations applied together on the respiratory pattern and durations of inspiration (TI) and expiration (TE). In our model: (a) the simulated vagotomy resulted in increases of both TI and TE, (b) the suppression of pontine-medullary interactions led to the prolongation of TI at relatively constant, but variable TE, and (c) these perturbations applied together resulted in “apneusis,” characterized by a significantly prolonged TI. The results of modeling were compared with, and provided a reasonable explanation for, multiple experimental data. The characteristic changes in TI and TE demonstrated with the model may represent characteristic changes in the balance between the pontine and pulmonary feedback control mechanisms that may reflect specific cardio-respiratory disorders and diseases.

Molkov, Yaroslav I.; Bacak, Bartholomew J.; Dick, Thomas E.; Rybak, Ilya A.

2013-01-01

26

Integration of a short-loop SLIC in a low-voltage submicron BiCMOS technology  

Microsoft Academic Search

This paper presents the high-voltage building blocks of a short-loop subscriber line interface circuit (SLIC), implemented in a 5 V 0.8 ?m BiCMOS technology using fully compatible high-voltage MOS transistors. The presented circuits include a 30 V class-AB line driver, a 30 V fully differential preamplifier, and a novel common-mode feedback circuit. Using a floating-current-mirror technique, the line driver features

R. Aliahmad; C. Andre; T. Salama

1998-01-01

27

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

NASA Technical Reports Server (NTRS)

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.

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

1992-01-01

28

AC loop voltages and MHD stability in RFP plasmas  

NASA Astrophysics Data System (ADS)

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

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

2012-10-01

29

Closed loop kinesthetic feedback for postural control rehabilitation.  

PubMed

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

Verite, Fabien; Bachta, Wael; Morel, Guillaume

2014-01-01

30

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

NASA Astrophysics Data System (ADS)

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.

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

2009-07-01

31

Practical Loop-Shaping Design of Feedback Control Systems  

NASA Technical Reports Server (NTRS)

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.

Kopasakis, George

2010-01-01

32

Rotating transformation and resonant control based feedback control strategy for dynamic voltage restorer system  

Microsoft Academic Search

Dynamic voltage restorer (DVR) has been demonstrated to be a very effective mechanism to deal with key voltage-quality disturbances. Although the dynamic response requirement for voltage sag could be satisfied by a feedforward control strategy, the voltage-quality requirement and zero-error tracking need an advanced feedback control strategy. This paper proposes a d-q transformation and proportional-resonant (PR) control based feedback control

S. Guo; D. Liu

2010-01-01

33

Desert dust suppressing precipitation: A possible desertification feedback loop  

PubMed Central

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.

Rosenfeld, Daniel; Rudich, Yinon; Lahav, Ronen

2001-01-01

34

KAYAK-? modulates circadian transcriptional feedback loops in Drosophila pacemaker neurons  

PubMed Central

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

Ling, Jinli; Dubruille, Raphaelle; Emery, Patrick

2012-01-01

35

Overcoming Software Fragility with Interacting Feedback Loops and Reversible Phase Transitions  

Microsoft Academic Search

Programs are fragile for many reasons, including software errors, partial failures, and network problems. One way to make software more robust is to design it from the start as a set of interacting feedback loops. Studying and using feedback loops is an old idea that dates back at least to Norbert Wiener's work on Cybernetics. Up to now almost all

Peter Van Roy

2008-01-01

36

Interlinked Fast and Slow Positive Feedback Loops Drive Reliable Cell Decisions  

NASA Astrophysics Data System (ADS)

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

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

2005-10-01

37

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

PubMed

A PID controller is widely used to control industrial processes that are mostly open loop stable or unstable. Selection of proper feedback structure and controller tuning helps to improve the performance of the loop. In this paper a double-feedback loop/method is used to achieve stability and better performance of the process. The internal feedback is used for stabilizing the process and the outer loop is used for good setpoint tracking. An internal model controller (IMC) based PID method is used for tuning the outer loop controller. Autotuning based on relay feedback or the Ziegler-Nichols method can be used for tuning an inner loop controller. A tuning parameter (?) that is used to tune IMC-PID is used as a time constant of a setpoint filter that is used for reducing the peak overshoot. The method has been tested successfully on many low order processes. PMID:22494496

Vijayan, V; Panda, Rames C

2012-07-01

38

Manipulation of peripheral neural feedback loops alters human corticomuscular coherence  

PubMed Central

Sensorimotor EEG shows ?20 Hz coherence with contralateral EMG. This could involve efferent and/or afferent components of the sensorimotor loop. We investigated the pathways responsible for coherence genesis by manipulating nervous conduction delays using cooling. Coherence between left sensorimotor EEG and right EMG from three hand and two forearm muscles was assessed in healthy subjects during the hold phase of a precision grip task. The right arm was then cooled to 10°C for ?90 min, increasing peripheral motor conduction time (PMCT) by ?35% (assessed by F-wave latency). EEG and EMG recordings were repeated, and coherence recalculated. Control recordings revealed a heterogeneous subject population. In 6/15 subjects (Group A), the corticomuscular coherence phase increased linearly with frequency, as expected if oscillations were propagated along efferent pathways from cortex to muscle. The mean corticomuscular conduction delay for intrinsic hand muscles calculated from the phase–frequency regression slope was 10.4 ms; this is smaller than the delay expected for conduction over fast corticospinal pathways. In 8/15 subjects (Group B), the phase showed no dependence with frequency. One subject showed both Group A and Group B patterns over different frequency ranges. Following cooling, averaged corticomuscular coherence was decreased in Group A subjects, but unchanged for Group B, even though both groups showed comparable slowing of nervous conduction. The delay calculated from the slope of the phase–frequency regression was increased following cooling. However, the size of this increase was around twice the rise in PMCT measured using the F-wave (regression slope 2.33, 95% confidence limits 1.30–3.36). Both afferent and efferent peripheral nerves will be slowed by similar amounts following cooling. The change in delay calculated from the coherence phase therefore better matches the rise in total sensorimotor feedback loop time caused by cooling, rather than just the change in the efferent limb. A model of corticomuscular coherence which assumes that only efferent pathways contribute cannot be reconciled to these results. The data rather suggest that afferent feedback pathways may also play a role in the genesis of corticomuscular coherence.

Riddle, C Nicholas; Baker, Stuart N

2005-01-01

39

A closed-loop analysis of the tubuloglomerular feedback mechanism.  

PubMed

The tubuloglomerular feedback (TGF) mechanism is of importance in the regulation of glomerular filtration rate (GFR). A second mechanism of potential importance is the change in proximal pressure caused by a change, for example, in the rate of proximal fluid reabsorption. The quantitative contributions of these two mechanisms to the regulation of GFR and the late proximal flow rate are not known. To determine the regulatory efficiency of these two mechanisms, the late proximal flow rate was perturbed by microperfusion with artificial tubular fluid in halothane-anesthetized Sprague-Dawley rats. The resulting changes in late proximal flow rate were measured by pulse injection of rhodamine dextran. Fluorescence was excited by means of a He-Ne laser. Bolus velocity was measured by videomicroscopy. Tubular pressure was measured by the servonulling method. The microperfusion rate was varied from -15 to 20 nl/min in steps of 5 nl/min. The open-loop gain (OLG) was 3.1 (range 1.5-9.9, n = 13) at the unperturbed tubular flow rate, and decreased as the tubular flow rate was either increased or decreased. The proximal pressure increased by 0.21 +/- 0.03 mmHg per unit increase in late proximal flow rate (nl/min). By use of a mathematical model of the glomerulus, it is estimated that under the present experimental conditions the pressure increase contributes 8% (range 3-15%) of the OLG. It is concluded that, for small perturbations around the operating point, TGF accounts for most of the regulation of GFR and the late proximal flow rate, with changes in the proximal pressure of lesser importance. Furthermore, under closed-loop conditions the operating point for the TGF mechanism is at or close to the point of maximal sensitivity. PMID:1951720

Holstein-Rathlou, N H

1991-11-01

40

Application of Reset Voltage Feedback for Droop Minimization in the Unidirectional Current Pulse Transformer  

Microsoft Academic Search

This paper investigates the application of reset voltage feedback for reducing errors due to droop in the signal derived from a current transformer sensing unidirectional current pulses in switched-mode power converter applications. Droop is minimised by applying a correcting voltage in series with the transformer's output terminals during the current pulse. The magnitude of the correcting voltage is based on

Neville McNeill; Narendra K. Gupta; Steve G. Burrow; Derrick Holliday; Phil H. Mellor

2008-01-01

41

Parameter Derivation of Type2 Discrete-Time Phase-Locked Loops Containing Feedback Delays  

Microsoft Academic Search

Modern implementations of discrete-time phase-locked loops (DT-PLLs) often contain delayed feedback. The delays are usually a side effect to pipelining, filtering, or other inner-loop mechanisms. Each delay increases the order of the system by introducing an additional pole to the closed-loop transfer function and, in many cases, makes the traditional type-2 loop equations obsolete. This brief describes how the second-order

Joey Wilson; Andrew Nelson; Behrouz Farhang-Boroujeny

2009-01-01

42

Loop voltage, inductance, and impurity ion velocity in toroidal discharges  

NASA Astrophysics Data System (ADS)

Strong co-current drift and substantial heating of impurity ions were reported in some early (˜1960) toroidal devices with low magnetic field B and high loop voltage, VL (Sceptre and ZETA in Britain and Al'fa in Russia). High frequency spikes in VL suggest rapid changes in the discharge inductance; VL should be treated as the sum of resistive [IR] and inductive [d(LI)/dt] terms. Experimental data can be used to estimate the resistive and inductive contributions. High-energy electrons and (impurity and hydrogenic) ions were observed, but the average energies were a few tens of eV. Calculations using a 1-D momentum equation with a toroidal electric field as driver and slowing in Coulomb collisions and inelastic processes yield impurity ion (average) drift velocities and apparent temperature (drift driven by voltage spikes) that are consistent with spectroscopic observations on Al'fa. These early experiments contrast with modern tokamaks, which are comparatively quiescent and usually have relatively higher toroidal B and lower VL. On the other hand, ZETA was a precursor of the reversed field pinch (RFP), some of whose characteristics seem related to their high VL. Toroidal drift ("rotation") velocities for tokamaks and RFPs can be calculated in the same way.

McNeill, D. H.

2009-03-01

43

A Non-invasive Technique for Configuring Low Level RF Feedback Loops in PEP-II  

SciTech Connect

The RF system of the PEP-II collider uses two fast feedback loops around each klystron and set of cavities. These loops reduce the impedance of the fundamental mode of the accelerating cavities seen by the beam, and are necessary to reduce the growth rates of longitudinal modes within the RF system bandwidth. Operation of the accelerator at high beam currents is very sensitive to the configuration of the low-level RF feedback loops. There are 7 loop control parameters that strongly influence the stability of the feedback loops and the achieved level of longitudinal impedance reduction. Diagnostic techniques for the analysis of the RF feedback via closed-loop system transfer function measurements will be presented. The model is fit to the measured closed-loop transfer function data and the extracted parameters are then used to calculate optimal tuning and corrections to the loop control elements in the physical channel. These techniques allow fine-tuning of RF feedback with stored beam as well as diagnosis of misconfigured or malfunctioning elements of the system. Results from PEP-II operation will be presented to illustrate the techniques and their applications.

Teytelman, D; /SLAC

2005-06-22

44

Regulation of oscillation dynamics in biochemical systems with dual negative feedback loops  

PubMed Central

Feedback controls are central to cellular regulation. Negative-feedback mechanisms are well known to underline oscillatory dynamics. However, the presence of multiple negative-feedback mechanisms is common in oscillatory cellular systems, raising intriguing questions of how they cooperate to regulate oscillations. In this work, we studied the dynamical properties of a set of general biochemical motifs with dual, nested negative-feedback structures. We showed analytically and then confirmed numerically that, in these motifs, each negative-feedback loop exhibits distinctly different oscillation-controlling functions. The longer, outer feedback loop was found to promote oscillations, whereas the short, inner loop suppresses and can even eliminate oscillations. We found that the position of the inner loop within the coupled motifs affects its repression strength towards oscillatory dynamics. Bifurcation analysis indicated that emergence of oscillations may be a strict parametric requirement and thus evolutionarily tricky. Investigation of the quantitative features of oscillations (i.e. frequency, amplitude and mean value) revealed that coupling negative feedback provides robust tuning of the oscillation dynamics. Finally, we demonstrated that the mitogen-activated protein kinase (MAPK) cascades also display properties seen in the general nested feedback motifs. The findings and implications in this study provide novel understanding of biochemical negative-feedback regulation in a mixed wiring context.

Nguyen, Lan K.

2012-01-01

45

Dynamic Feedback and the Design of Closed-loop Drug Delivery Systems  

Microsoft Academic Search

A closed-loop drug delivery system is constructed in which external negative feed- back is used to regulate the dynamics of a time-delayed negative feedback mechanism which regulates hormone concentration. This results in a control system composed of two time-delayed negative feedback loops arranged in parallel. Stability regions in pa- rameter space and the location of steady states are determined for

John Milton; Sue Ann Campbell; Jacques Belair

46

Performance improvement of the dynamic voltage restorer with closed-loop load voltage and current-mode control  

Microsoft Academic Search

The performance of a dynamic voltage restorer (DVR) in improving the quality of power supply is examined. It is shown that the existing open-loop control strategy used in the DVR to regulate load voltage can produce poorly damped response due to the presence of the switching harmonic filter in the restorer. Damping is shown to be improved if the proposed

Mahinda Vilathgamuwa; A. A. D. Ranjith Perera; S. S. Choi

2002-01-01

47

Design of a State Feedback Controller for Series Voltage Sag Compensators  

Microsoft Academic Search

Voltage sags have become a major power quality issue encountered by industries in recent years. The voltage sag compensator, based on the transformer-coupled series-connected voltage source inverter, is among the most cost-effective solution to protect sensitive loads. Many voltage sag compensators adopt open-loop control strategies to increase the response speed for the sag compensation. But the L-C filter installed at

Po-Tai Cheng; Chia-Long Ni; Jhao-Ming Chen

2007-01-01

48

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

SciTech Connect

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.

Alexeff, I.; Rader, M. [Univ. of Tennessee, Knoxville, TN (United States)

1995-05-01

49

A Non-Invasive Technique for Configuring Low Level RF Feedback Loops in PEP-II  

Microsoft Academic Search

The RF system of the PEP-II collider uses two fast feedback loops around each klystron and set of cavities. These loops reduce the impedance of the fundamental mode of the accelerating cavities seen by the beam, and are necessary to reduce the growth rates of longitudinal modes within the RF system bandwidth. Operation of the accelerator at high beam currents

D. Teytelman

2005-01-01

50

Model-based vibration suppression in piezoelectric tube scanners through induced voltage feedback  

Microsoft Academic Search

The operation speed and tracking accuracy of piezoelectric tube actuators in scanning probe microscopy is significantly reduced due to the excitation of the scanner eigenfrequencies by the driving voltages. Feedback control is a suitable method for vibration suppression but suffers from the required additional sensor equipment and high cost for generation of a displacement feedback signal. Operating the piezotube in

Johannes Maess; Andrew J. Fleming; F. Allgower

2008-01-01

51

Coherent beam combination of two nanosecond fiber amplifiers by an all-optical feedback loop.  

PubMed

A passive coherent beam combination of two nanosecond amplifiers is realized by using an all-optical feedback loop. The width of the combined pulses is 9.7 ns, and the pulse repetition frequency is 2.023 MHz. With the least mismatch between pulse period and time of the cavity round trip in our loop, the visibility of far-field coherent patterns is more than 71%. The dynamics of passive phase locking is studied, and the established time of phase locking of two pulsed amplifiers is at least 10 cavity round trips in the all-optical feedback loop. PMID:23041892

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

2012-09-15

52

The slow dynamics of postural sway are in the feedback loop  

PubMed Central

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

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

2009-01-01

53

Closed Loop Feedback of MHD Instabilities on DIII-D  

SciTech Connect

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.

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

2001-01-16

54

The exosome regulates circadian gene expression in a posttranscriptional negative feedback loop  

PubMed Central

Summary The eukaryotic circadian oscillators consist of autoregulatory negative feedback loops. However, little is known about the role of post-transcriptional regulation of RNA in circadian oscillators. In the Neurospora circadian negative feedback loop, FRQ and FRH form the FFC complex that represses frq transcription. Here we show that FFC also binds frq RNA and interacts with the exosome to regulate frq RNA decay. Consequently, frq RNA is robustly rhythmic as it is more stable when FRQ levels are low. Silencing of RRP44, the catalytic subunit of the exosome, elevates frq RNA levels and impairs clock function. In addition, rrp44 is a clock-controlled gene and a direct target of the WHITE COLLAR complex, and RRP44 controls the circadian expression of at least one ccg. Taken together, these results suggest that FFC and the exosome are part of a post-transcriptional negative feedback loop that regulates frq transcript levels and the circadian output pathway.

Guo, Jinhu; Cheng, Ping; Yuan, Haiyan; Liu, Yi

2009-01-01

55

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

NASA Technical Reports Server (NTRS)

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.

Thompson, P. M.

1979-01-01

56

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

NASA Astrophysics Data System (ADS)

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.

Sayed, Mahmoud A.; Takeshita, Takaharu

57

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

NASA Technical Reports Server (NTRS)

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

Stalford, Harold

1988-01-01

58

MICROBE SENSING, POSITIVE FEEDBACK LOOPS, AND THE PATHOGENESIS OF INFLAMMATORY DISEASES  

PubMed Central

Summary The molecular apparatus that protects us against infection can also injure us by causing autoimmune or autoinflammatory disease. It now seems that at times, defects within the sensing arm of innate immunity contribute to diseases of this type. The initiation of an immune response is often microbe dependent and, in many cases, Toll-like receptor (TLR) dependent. Positive feedback loops triggering immune activation may occur when TLR signaling pathways stimulate host cells in an unchecked manner. Or, immune activation may persist because of failure to eradicate an inciting infection. Or on occasion, endogenous DNA may trigger specific immune responses that beget further responses in a TLR-dependent autoamplification loop. Specific biochemical defects that cause loop-related autoimmunity have been revealed by random germline mutagenesis and by gene targeting. We have also developed some insight into critical points at which feedback loops can be interrupted.

Beutler, Bruce

2009-01-01

59

Asymmetric positive feedback loops reliably control biological responses  

PubMed Central

Positive feedback is a common mechanism enabling biological systems to respond to stimuli in a switch-like manner. Such systems are often characterized by the requisite formation of a heterodimer where only one of the pair is subject to feedback. This ASymmetric Self-UpREgulation (ASSURE) motif is central to many biological systems, including cholesterol homeostasis (LXR?/RXR?), adipocyte differentiation (PPAR?/RXR?), development and differentiation (RAR/RXR), myogenesis (MyoD/E12) and cellular antiviral defense (IRF3/IRF7). To understand why this motif is so prevalent, we examined its properties in an evolutionarily conserved transcriptional regulatory network in yeast (Oaf1p/Pip2p). We demonstrate that the asymmetry in positive feedback confers a competitive advantage and allows the system to robustly increase its responsiveness while precisely tuning the response to a consistent level in the presence of varying stimuli. This study reveals evolutionary advantages for the ASSURE motif, and mechanisms for control, that are relevant to pharmacologic intervention and synthetic biology applications.

Ratushny, Alexander V; Saleem, Ramsey A; Sitko, Katherine; Ramsey, Stephen A; Aitchison, John D

2012-01-01

60

Closed loop AC voltage generation using Harmonic Cancellation Technique  

Microsoft Academic Search

AC power supplies generated by means of an inverter are under very restrictive specifications regarding their AC output voltage THD, even when they are supplying both linear and nonlinear loads. The presence of the low frequency harmonic content due to nonlinear loads operation, greatly increase the THD of the AC power supply output voltage. Traditional state of the art techniques

I. Quesada; C. Lucena; C. Martinez; A. Lazaro; A. Barrado; R. Vazquez; I. Gonzalez; N. Herreros

2010-01-01

61

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

SciTech Connect

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

Kim, Yunseok [ORNL; Yang, J.-C. [University of California, Berkeley; Chu, Ying Hao [National Chiao Tung University, Hsinchu, Taiwan; Yu, Pu [University of California, Berkeley; Lu, X. [Xidian University, China; Jesse, Stephen [ORNL; Kalinin, Sergei V [ORNL

2012-01-01

62

Acceleration feedback of a CCD-based tracking loop for fast steering mirror  

NASA Astrophysics Data System (ADS)

In the control system of a CCD-based tracking loop for a fast steering mirror (FSM), the most effective method often employed to improve pointing performance is to increase high gain of the control system for a high bandwidth, which, however, usually suffers a great deal from a low CCD sampling rate and the mechanics of the FSM. Moreover, the amount of time delay engendered by sampling and data processing can significantly reduce the performance of a closed-loop system. Therefore, a tentative approach to the implementation of a CCD-based tracking control system with acceleration feedback is proposed. In theory, the position open loop is made of double integrators with a high bandwidth of the acceleration feedback loop; in fact, however, the acceleration open loop of the FSM response includes a quadratic differential, and it is very difficult to compensate a quadratic differential with an integral algorithm. To solve this problem, a novel acceleration closed system such as a bandpass filter is proposed. The position is reconstructed into a simple first-order filter instead of a third-order control system. In addition experimental results show that the acceleration feedback proposed here can effectively enhance the bandwidth of the closed-loop system and its trajectory tracking and pointing performance.

Tang, Tao; Huang, Yongmei; Fu, Chengyu; Liu, Shunfa

2009-01-01

63

Uninterruptible power supply multi-loop control employing digital predictive voltage and current regulators  

Microsoft Academic Search

A digital control technique for the inverter stage of uninterruptible power supplies (UPSs) is described, which is based on voltage and current predictive regulators. Its aim is to achieve a dead-beat dynamic response for the controlled variables (output voltage and inverter current). The controller maintains the advantageous conventional multi-loop structure and is capable of guaranteeing a high quality dynamic performance.

S. Buso; S. Fasolo; P. Mattavelli

2001-01-01

64

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

NASA Astrophysics Data System (ADS)

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

Pfeuty, Benjamin; Kaneko, Kunihiko

2009-12-01

65

Closed-loop adaptive voltage scaling controller for standard-cell ASICs  

Microsoft Academic Search

The paper describes a closed-loop controller for adaptive voltage scaling (AVS) where the supply voltage to a standard-cell ASIC is dynamically adjusted to the minimum value required for the desired system speed. The controller includes a clock generator that provides a low-jitter clock to the ASIC at all steady-state operating points and through transients. To speed up the voltage transient

Sandeep Dhar; Dragan Maksimovi?; Bruno Kranzen

2002-01-01

66

Voltage transient analysis of a PMSG wind power system using controller-hardware-in-the loops  

Microsoft Academic Search

This paper presents voltage transient analysis of a proposed 3MW permanent magnet synchronous generator (PMSG) wind power generation system (WPGS) using a real time digital simulator (RTDS). The WPGS that is modeled with real- time digital simulator (RTDS) and RSCAD simulators are characterized for voltage transient analysis. Furthermore, a newly actual controller-hardware-in-the-loop simulation (CHILS) is employed to analyze voltage transient

Chulsang Hwang; Gyeong-Hun Kim; Byeong-Mun Song; Kwang Y. Lee

2011-01-01

67

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

PubMed Central

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

2011-01-01

68

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

Microsoft Academic Search

Circadian rhythms provide organisms with an adaptive advantage, allowing them to regulate physiological and developmental events so that they occur at the most appropriate time of day. In plants, as in other eukaryotes, multiple transcriptional feedback loops are central to clock function. In one such feedback loop, the Myb-like transcription factors CCA1 and LHY directly repress expression of the pseudoresponse

Reetika Rawat; Nozomu Takahashi; Polly Yingshan Hsu; Matthew A. Jones; Jacob Schwartz; Michelle R. Salemi; Brett S. Phinney; Stacey L. Harmer

2011-01-01

69

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

Microsoft Academic Search

Theoretical analysis and numerical simulations of the magnetron operation with a feedback loop were performed assuming that the delay of the electromagnetic wave propagating in the loop is constant whereas the phase of the complex feedback reflection coefficient is varied. Results of simulations showed that, by a proper adjustment of the values of the time delay and phase of the

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

2012-01-01

70

Interlinked Dual-Time Feedback Loops can Enhance Robustness to Stochasticity and Persistence of Memory  

PubMed Central

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

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

2009-01-01

71

Baylor College of Medicine researchers determine that feedback loop maintains basal cell population  

Cancer.gov

Notch -- the protein that can help determine cell fate -- maintains a stable population of basal cells in the prostate through a positive feedback loop system with another key protein TGF beta (transforming growth factor beta), said Baylor College of Medicine researchers in the journal Cell Stem Cell.

72

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

NASA Astrophysics Data System (ADS)

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.

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

2011-06-01

73

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

NASA Astrophysics Data System (ADS)

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

Jones, Lloyd E.; Sandberg, Richard D.

2011-12-01

74

Singleloop vs two-loop voltage and frequency control of isolated SEIG based RECS  

Microsoft Academic Search

Present investigation deals with the comparison of performance of a Generalized Impedance Controller (GIC) based 3-phase self excited induction generator (SEIG) terminal voltage and frequency regulator, having single and two-loop control, in an isolated wind\\/microhydro type renewable energy conversion system (RECS). Where, GIC is a PWM voltage source converter with dc-bus battery, having controlled four-quadrant equivalent impedance. Amplitude and frequency

J. K. Chatterjee; Priyesh J. Chauhan

2011-01-01

75

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

NASA Astrophysics Data System (ADS)

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

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

2012-01-01

76

Tubuloglomerular Feedback Signal Transduction in a Short Loop of Henle  

Microsoft Academic Search

In previous studies, we used a mathematical model of the thick ascending limb (TAL) to investigate nonlinearities in the tubuloglomerular\\u000a feedback (TGF) loop. That model does not represent other segments of the nephron, the water, and NaCl transport along which\\u000a may impact fluid flow rate and NaCl transport along the TAL. To investigate the extent to which those transport processes

Anita T. Layton; Aurélie Edwards

2010-01-01

77

HuR Inhibits Apoptosis by Amplifying Akt Signaling through a Positive Feedback Loop  

PubMed Central

Human antigen R (HuR) is a post-transcriptional regulator of gene expression that plays a key role in stabilizing mRNAs during cellular stress, leading to enhanced survival. HuR expression is tightly regulated through multiple transcription and post-transcriptional controls. Although HuR is known to stabilize a subset of mRNAs involved in cell survival, its role in the survival pathway of PI3-kinase/Akt signaling is unclear. Here, we show that in renal proximal tubule cells, HuR performs a central role in cell survival by amplifying Akt signaling in a positive feedback loop. Key to this feedback loop is HuR-mediated stabilization of mRNA encoding Grb10, an adaptor protein whose expression is critical for Akt activation. Stimulation of Akt by interaction with Grb10 then activates NF-?B, which further enhances HuR mRNA and protein expression. This feedback loop is active in unstressed cells, but its effects are increased during stress. Therefore, this study demonstrates a central role for HuR in Akt signaling and reveals a mechanism by which modest changes in HuR levels below or above normal may be amplified, potentially resulting in cell death or cellular transformation.

Singh, Mamata; Martinez, Alaina R.; Govindaraju, Suman; Lee, Beth S.

2012-01-01

78

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

PubMed Central

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

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

2010-01-01

79

Antagonistic feedback loops involving Rau and Sprouty in the Drosophila eye control neuronal and glial differentiation.  

PubMed

During development, differentiation is often initiated by the activation of different receptor tyrosine kinases (RTKs), which results in the tightly regulated activation of cytoplasmic signaling cascades. In the differentiation of neurons and glia in the developing Drosophila eye, we found that the proper intensity of RTK signaling downstream of fibroblast growth factor receptor (FGFR) or epidermal growth factor receptor required two mutually antagonistic feedback loops. We identified a positive feedback loop mediated by the Ras association (RA) domain-containing protein Rau that sustained Ras activity and counteracted the negative feedback loop mediated by Sprouty. Rau has two RA domains that together showed a binding preference for GTP (guanosine 5'-triphosphate)-loaded (active) Ras. Rau homodimerized and was found in large-molecular weight complexes. Deletion of rau in flies decreased the differentiation of retinal wrapping glia and induced a rough eye phenotype, similar to that seen in alterations of Ras signaling. Further, the expression of sprouty was repressed and that of rau was increased by the COUP transcription factor Seven-up in the presence of weak, but not constitutive, activation of FGFR. Together, our findings reveal another regulatory mechanism that controls the intensity of RTK signaling in the developing neural network in the Drosophila eye. PMID:24194583

Sieglitz, Florian; Matzat, Till; Yuva-Adyemir, Yeliz; Neuert, Helen; Altenhein, Benjamin; Klämbt, Christian

2013-11-01

80

Multiple feedback regulatory loops upon rat hypothalamic corticotropin-releasing hormone secretion. Potential clinical implications.  

PubMed Central

To examine whether the hypothalamic corticotropin-releasing hormone (CRH) neuron is regulated by CRH, by products of the proopiomelanocortin (POMC) gene, and/or by glucocorticoids, we used a rat hypothalamic organ culture system in which rat CRH secretion from single explanted hypothalami was evaluated by an RIA (iCRH) specific for rat CRH. The effects of graded concentrations of ovine CRH (oCRH), adrenocorticotropin hormone (ACTH), beta-endorphin (beta-EP), alpha-melanocyte-stimulating hormone (alpha-MSH), corticotropin-like intermediate lobe peptide (CLIP), ovine beta-lipotropin (ovine beta-LPH), and dexamethasone (DEX) upon unstimulated and serotonin- (5HT), acetylcholine- (ACh), and norepinephrine-(NE) stimulated CRH secretion were determined. oCRH and DEX inhibited unstimulated iCRH secretion with ID50 at the 10(-8) M range. ACTH had no detectable suppressive effect at 10(-8) M. oCRH, ACTH, and DEX inhibited 5HT-, ACh-, and NE-stimulated iCRH secretion in a dose-dependent fashion. beta-EP, alpha-MSH, and CLIP also inhibited 5HT-induced iCRH secretion. Of the latter peptides, the strongest inhibitor was beta-EP and the weakest was CLIP. Ovine beta-LPH had only a weak inhibitory effect on 5HT-induced iCRH secretion. Generally, the concentrations required for 50% suppression of neurotransmitter-stimulated iCRH secretion were significantly lower than those required for a similar suppression of unstimulated iCRH secretion. In conclusion, these data suggest the presence of multiple negative feedback loops involved in the regulation of the hypothalamic CRH neuron: an ultrashort CRH-mediated loop, a short, hypothalamic POMC-derived peptide loop, and a long, glucocorticoid-mediated negative feedback loop. The potency of these negative feedback loops may be determined by the state of activation of the CRH neuron.

Calogero, A E; Gallucci, W T; Gold, P W; Chrousos, G P

1988-01-01

81

Dynamics of a self-phase-locked nondegenerate optical parametric oscillator with nonsymmetric feedback loops  

NASA Astrophysics Data System (ADS)

We discuss the evolution of two-mode states of a self-phase-locked type-II nondegenerate optical parametric oscillator with homodyne-mediated quantum feedback. It is shown that different strengths of the feedback loops can simulate the effect of a squeezed thermal environment and lead additionally to the process of the parametric-down conversion for each mode. In the steady state regime all initial density matrices evolve towards a Gaussian equilibrium state. It is shown that the nonsymmetric feedback can further increase entanglement of the equilibrium state. Dynamical behaviour of intracavity entanglement for a number of initial states is investigated, and entanglement sudden death and birth phenomena, and a delay birth of entanglement are reported.

Olkiewicz, R.; ?aba, M.

2009-10-01

82

Positive feedback frequency compensation for low-voltage low-power three-stage amplifier  

Microsoft Academic Search

The use of a new frequency compensation scheme for a three-stage operational amplifier is presented. The use of a positive feedback compensation (PFC) is employed to improve frequency response when compared to nested Miller compensation. A set of design equations is derived to give insight into the sizing of the amplifier. In addition, some characteristics relevant to the low-voltage low-power

Joao Ramos; Michiel S. J. Steyaert

2004-01-01

83

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

PubMed Central

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 straightforward 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.

Dunlop, Mary J.; Keasling, Jay D.

2010-01-01

84

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

PubMed Central

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.

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

2012-01-01

85

Compensation Loop Design of a Photovoltaic System Based on Constant Voltage MPPT  

Microsoft Academic Search

This paper presents an approach to design a high performance compensation loop for a photovoltaic system based on constant voltage (CV) maximum power point tracking (MPPT) method, which is quite different from that of common DC\\/DC converter. The dynamic model of the power module, which is implemented by a Buck converter, is established using switch average model. Based on the

Ye Zhihao; Wu Xiaobo

2009-01-01

86

Stability of the Fast Voltage Control Loop in DC-DC Converters  

Microsoft Academic Search

This paper describes a method for stability analysis and design of a fast voltage loop in DC-DC converters. The method is based on the Popov criterion, which unifies tools for nonlinear system analysis with frequency domain analysis tools used in linear systems. This study establishes sufficient conditions for absolute stability of time-varying control systems. The proposed conditions extend in a

P. Dobra; L. Nagy-Kulcsar; M. Trusca; D. Moga; R. Balan

2006-01-01

87

An Fgf/Gremlin Inhibitory Feedback Loop Triggers Termination of Limb Bud Outgrowth  

PubMed Central

During organ formation and regeneration a proper balance between promoting and restricting growth is critical to achieve stereotypical size. Limb bud outgrowth is driven by signals in a positive feedback loop involving fibroblast growth factor (Fgf) genes, sonic hedgehog (Shh) and Gremlin1 (Grem1)1. Precise termination of these signals is essential to restrict limb bud size2–4. The current model predicts a sequence of signal termination consistent with that in chick limb buds4. Our finding that the sequence in mouse limb buds is different led us to explore alternative mechanisms. By analyzing compound mouse mutants defective in genes comprising the positive loop, we uncovered genetic evidence that FGF signaling can repress Grem1 expression, revealing a novel Fgf/Grem1 inhibitory loop. This repression occurs in both mouse and chick limb buds, and is dependent on high FGF activity. These data support a mechanism where the positive Fgf/Shh loop drives outgrowth and an increase in FGF signaling, which triggers the Fgf/Grem1 inhibitory loop. The inhibitory loop then operates to terminate outgrowth signals in the order observed in either mouse or chick limb buds. Our study unveils the concept of a self-promoting and self-terminating circuit that may be used to attain proper tissue size in a broad spectrum of developmental and regenerative settings.

Verheyden, Jamie M.; Sun, Xin

2010-01-01

88

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

PubMed

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

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

2012-12-01

89

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

PubMed

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

Ryu, Vitaly; Bartness, Timothy J

2014-06-15

90

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

NASA Astrophysics Data System (ADS)

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.

Wang, Junwei; Zhou, Tianshou

2010-06-01

91

Magnetic flux and gate voltage modulation of the current in a superconducting loop of ultra-small tunnel junctions  

Microsoft Academic Search

We have measured the current-voltage (I-V) characteristics of a loop of four superconducting tunnel junctions at low temperatures (T~50mK). In each branch of the loop, tunneling occurs through a small capacitance island (C?~1fF). In this geometry we can vary the magnetic flux Phi in the loop and the voltage Vg on gate electrodes, which have capacitance Cg to the small

Y. Harada; D. B. Haviland; C. D. Chen; P. Delsing; T. Claeson

1994-01-01

92

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

NASA Astrophysics Data System (ADS)

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

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

2012-07-01

93

The Per2 Negative Feedback Loop Sets the Period in the Mammalian Circadian Clock Mechanism  

PubMed Central

Processes that repeat in time, such as the cell cycle, the circadian rhythm, and seasonal variations, are prevalent in biology. Mathematical models can represent our knowledge of the underlying mechanisms, and numerical methods can then facilitate analysis, which forms the foundation for a more integrated understanding as well as for design and intervention. Here, the intracellular molecular network responsible for the mammalian circadian clock system was studied. A new formulation of detailed sensitivity analysis is introduced and applied to elucidate the influence of individual rate processes, represented through their parameters, on network functional characteristics. One of four negative feedback loops in the model, the Per2 loop, was uniquely identified as most responsible for setting the period of oscillation; none of the other feedback loops were found to play as substantial a role. The analysis further suggested that the activity of the kinases CK1? and CK1? were well placed within the network such that they could be instrumental in implementing short-term adjustments to the period in the circadian clock system. The numerical results reported here are supported by previously published experimental data.

Wilkins, A. Katharina; Barton, Paul I; Tidor, Bruce

2007-01-01

94

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

PubMed Central

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.

Harrison, Mary E.; Dunlop, Mary J.

2012-01-01

95

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

NASA Astrophysics Data System (ADS)

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.

Joo, Jaewook

2010-03-01

96

Establishment of a robust single axis of cell polarity by coupling multiple positive feedback loops  

PubMed Central

Establishment of cell polarity—or symmetry breaking—relies on local accumulation of polarity regulators. Although simple positive feedback is sufficient to drive symmetry breaking, it is highly sensitive to stochastic fluctuations typical for living cells. Here, by integrating mathematical modelling with quantitative experimental validations, we show that in the yeast Saccharomyces cerevisiae a combination of actin- and guanine nucleotide dissociation inhibitor-dependent recycling of the central polarity regulator Cdc42 is needed to establish robust cell polarity at a single site during yeast budding. The guanine nucleotide dissociation inhibitor pathway consistently generates a single-polarization site, but requires Cdc42 to cycle rapidly between its active and inactive form, and is therefore sensitive to perturbations of the GTPase cycle. Conversely, actin-mediated recycling of Cdc42 induces robust symmetry breaking but cannot restrict polarization to a single site. Our results demonstrate how cells optimize symmetry breaking through coupling between multiple feedback loops.

Freisinger, Tina; Klunder, Ben; Johnson, Jared; Muller, Nikola; Pichler, Garwin; Beck, Gisela; Costanzo, Michael; Boone, Charles; Cerione, Richard A.; Frey, Erwin; Wedlich-Soldner, Roland

2013-01-01

97

Buck-boost switched-capacitor DC-DC voltage regulator using delta-sigma control loop  

Microsoft Academic Search

This paper presents a delta-sigma control loop for a buck-boost DC-DC converter with fractional gains. The charge pump used to convert the input voltage acts as a D\\/A converter in the loop, and its output ripple is frequency shaped by the loop, which also provides the pulse frequency modulation needed for the conversion. Simulation results show that the delta-sigma loop

A. Rao; W. Mcintyre; J. Parry; Un-ku Moon; Gabor C. Temes

2002-01-01

98

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

NASA Astrophysics Data System (ADS)

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.

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

99

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

PubMed Central

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

Schiefelbein, John; Huang, Ling; Zheng, Xiaohua

2014-01-01

100

Runaway-loss induced negative and positive loop voltage spikes in the Aditya Tokamak  

NASA Astrophysics Data System (ADS)

Negative spikes followed by positive ones in the loop voltage signal during the discharge are observed in the Aditya Tokamak [S. B. Bhatt et al., Indian J. Pure Appl. Phys. 27, 710 (1989)]. These spikes are always accompanied by hard x-ray bursts caused by sudden loss of runaway electrons. The observed growth of m=3 mode seemed responsible for the losses of localized beams of runaway electrons (E?~1-5 MeV) from the plasma region around q=3 magnetic surface. The movement of these runaway electrons during their extraction from inside the plasma induces both positive and negative electric fields at those locations. In this paper, a one-dimensional toroidal electric field diffusion model is used to estimate the induced electric field at the plasma boundary, which matches quite well with the observed spikes in loop voltage in both magnitude as well as its temporal evolution.

Paradkar, Bhooshan; Ghosh, J.; Chattopadhyay, P. K.; Tanna, R. L.; Raju, D.; Bhatt, S. B.; Rao, C. V. S.; Joisa, Sankar; Banerjee, Santanu; Manchanda, R.; Gupta, C. N.; Saxena, Y. C.; Aditya Team

2010-09-01

101

Runaway-loss induced negative and positive loop voltage spikes in the Aditya Tokamak  

SciTech Connect

Negative spikes followed by positive ones in the loop voltage signal during the discharge are observed in the Aditya Tokamak [S. B. Bhatt et al., Indian J. Pure Appl. Phys. 27, 710 (1989)]. These spikes are always accompanied by hard x-ray bursts caused by sudden loss of runaway electrons. The observed growth of m=3 mode seemed responsible for the losses of localized beams of runaway electrons (E{sub {gamma}{approx}1}-5 MeV) from the plasma region around q=3 magnetic surface. The movement of these runaway electrons during their extraction from inside the plasma induces both positive and negative electric fields at those locations. In this paper, a one-dimensional toroidal electric field diffusion model is used to estimate the induced electric field at the plasma boundary, which matches quite well with the observed spikes in loop voltage in both magnitude as well as its temporal evolution.

Paradkar, Bhooshan; Ghosh, J.; Chattopadhyay, P. K.; Tanna, R. L.; Raju, D.; Bhatt, S. B.; Rao, C. V. S.; Joisa, Sankar; Banerjee, Santanu; Manchanda, R.; Gupta, C. N.; Saxena, Y. C. [Institute for Plasma Research, Bhat, Gandhinagar 382428 (India)

2010-09-15

102

A high speed and low power voltage controlled ring oscillator for phase locked loop circuits  

Microsoft Academic Search

This paper presents the design of a high speed and low power voltage controlled ring oscillator. The proposed design is suitable for phase locked loop circuits. The ring oscillator operates at 5GHz and designed by 0.13 ?m CMOS technology. Seven stages of inverters are built to construct the oscillator, forming 126 bit vectors. The frequency is controlled by a tri-state

A. A. Alsharef; M. J. Taghizadeh. Marvast; M. A. Mohd. Ali; H. Sanusi

2011-01-01

103

Better Bet-Hedging with coupled positive and negative feedback loops  

NASA Astrophysics Data System (ADS)

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

Narula, Jatin; Igoshin, Oleg

2011-03-01

104

A c-Myc-MicroRNA functional feedback loop affects hepatocarcinogenesis.  

PubMed

c-Myc (Myc) plays an important role in normal liver development and tumorigenesis. We show here that Myc is pathologically activated in and essential for promoting human hepatocellular carcinoma (HCC). Myc induces HCC through a novel, microRNA (miRNA)-mediated feedback loop comprised of miR-148a-5p, miR-363-3p, and ubiquitin-specific protease 28 (USP28). Myc directly binds to conserved regions in the promoters of the two miRNAs and represses their expression. miR-148a-5p directly targets and inhibits Myc, whereas miR-363-3p destabilizes Myc by directly targeting and inhibiting USP28. Inhibition of miR-148a-5p or miR-363-3p induces hepatocellular tumorigenesis by promoting G1 to S phase progression, whereas activation of them has the opposite effects. The Myc-miRNA feedback loop is dysregulated in human HCC. Conclusion: These results define miR-148a-5p and miR-363-3p as negative regulators of Myc, thus revealing their heretofore unappreciated roles in hepatocarcinogenesis. (HEPATOLOGY 2013;57:2378-2389). PMID:23389829

Han, Han; Sun, Dan; Li, Wenjuan; Shen, Hongxing; Zhu, Yahui; Li, Chen; Chen, Yuxing; Lu, Longfeng; Li, Wenhua; Zhang, Jinxiang; Tian, Yuan; Li, Youjun

2013-06-01

105

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

PubMed

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

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

2013-08-01

106

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

NASA Technical Reports Server (NTRS)

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.

Thompson, P. M.

1980-01-01

107

Simulations of Saccade Curvature by Models That Place Superior Colliculus Upstream From the Local Feedback Loop  

PubMed Central

When humans or monkeys are asked to make saccades to visual targets accompanied by one or more distractors, the two dimensional trajectory of the saccade will sometimes display significant curvature. Port and Wurtz used dual electrode recordings to show that this phenomenon is associated with activity at more than one site in superior colliculus (SC). The timing and initial direction of the curvature could be predicted by computing a weighted vector average of the normalized activity of the two neurons. As these authors noted, however, this approach does not result in correct predictions of the final direction of curved saccades. We show that the final direction of these movements can be predicted by taking into account the brain stem saccade generator and the local feedback loop. If the output of SC is computed as a weighted vector average of the saccades requested by the activated sites, and this collicular output is interpreted by downstream structures as desired displacement, existing models that place SC upstream from the local feedback loop can generate realistic saccade trajectories, including the final direction. We propose that saccade curvature is the result of a change in the relative level of activity at the two sites, which the brain stem saccade generator interprets as a change in desired displacement.

Walton, Mark M. G.; Sparks, David L.; Gandhi, Neeraj J.

2013-01-01

108

Fourier analysis and systems identification of the p53 feedback loop  

PubMed Central

A key circuit in the response of cells to damage is the p53–mdm2 feedback loop. This circuit shows sustained, noisy oscillations in individual human cells following DNA breaks. Here, we apply an engineering approach known as systems identification to quantify the in vivo interactions in the circuit on the basis of accurate measurements of its power spectrum. We obtained oscillation time courses of p53 and Mdm2 protein levels from several hundred cells and analyzed their Fourier spectra. We find characteristic spectra with distinct low-frequency components that are well-described by a third-order linear model with white noise. The model identifies the sign and strength of the known interactions, including a negative feedback loop between p53 and its upstream regulator. It also implies that noise can trigger and maintain the oscillations. The model also captures the power spectra of p53 dynamics without DNA damage. Parameters such as noise amplitudes and protein lifetimes are estimated. This approach employs natural biological noise as a diagnostic that stimulates the system at many frequencies at once. It seems to be a useful way to find the in vivo design of circuits and may be applied to other systems by monitoring their power spectrum in individual cells.

Geva-Zatorsky, Naama; Dekel, Erez; Batchelor, Eric; Lahav, Galit; Alon, Uri

2010-01-01

109

A wide-range phase-locked loop using a range-programmable voltage-controlled oscillator  

Microsoft Academic Search

A wide-range phase-locked loop incorporating a range-programmable voltage-controlled oscillator was developed for clock generation without an additional frequency synthesizer. Breaking down the original inverter into several smaller ones and re-combining them paralleled could extend the output frequency range effectively, and operate more efficiently. Using TSMC 1P3M 0.6 ?m CMOS technology, the proposed phase-locked loop at a supply voltage of 3.3

R. R.-B. Sheen; O. T.-C. Chen

2000-01-01

110

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

SciTech Connect

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

Aloisi, G. [Department of Chemistry, University of Florence, Via della Lastruccia 3, Sesto Fiorentino, Firenze I 50019 (Italy); Bacci, F.; Carla, M.; Dolci, D.; Lanzi, L. [Department of Physics, University of Florence, Via G. Sansone 1, I 50019 Sesto Fiorentino, Firenze I 50019 (Italy)

2008-11-15

111

Concise review: two negative feedback loops place mesenchymal stem/stromal cells at the center of early regulators of inflammation.  

PubMed

Recent data demonstrated that MSCs can be activated by proinflammatory signals to introduce two negative feedback loops into the generic pathway of inflammation. In one loop, the activated MSCs secrete PGE2 that drives resident macrophages with an M1 proinflammatory phenotype toward an M2 anti-inflammatory phenotype. In the second loop, the activated MSCs secrete TSG-6 that interacts with CD44 on resident macrophages to decrease TLR2/NF?-B signaling and thereby decrease the secretion of proinflammatory mediators of inflammation. The PGE2 and TSG-6 negative feedback loops allow MSCs to serve as regulators of the very early phases of inflammation. These and many related observations suggest that the MSC-like cells found in most tissues may be part of the pantheon of cells that protect us from foreign invaders, tissue injury, and aging. PMID:23681848

Prockop, Darwin J

2013-10-01

112

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

PubMed Central

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

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

2012-01-01

113

Human UDP-glucuronosyltransferases: feedback loops between substrates and ligands of their transcription factors.  

PubMed

Expression profiles of human adult and fetal hepatic and intestinal UDP-glucuronosyltransferases (UGTs), information about their endo- and xenobiotic substrates, and their transcriptional regulation suggests regulatory circuits between some UGT substrates and ligands of their transcription factors. For examples: (i) bilirubin is solely conjugated by UGT1A1 and activates its transcription factors Ah receptor, PXR and CAR. (ii) Hepatotoxic lithocholic acid (LCA) is oxidized to hyodeoxycholic acid, the latter conjugated by UGT2B4 and UGT2B7. LCA is also an agonist of FXR and PPAR?, which are controlling these UGTs. (iii) Similar feedback loops possibly exist between some eicosanoids, PPAR? and UGTs. (iv) Regulatory circuits may also have evolved between dietary polyphenols, which are efficient substrates of UGTs and activators of the Ah receptor. Although many newly developed drugs are conjugated by promiscuous UGTs, the discussed regulatory circuits may provide hints to evolutionary important UGT substrates. PMID:22820246

Bock, Karl Walter

2012-10-15

114

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

NASA Astrophysics Data System (ADS)

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

Krishna, Sandeep

2008-03-01

115

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

PubMed Central

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

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

2012-01-01

116

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

PubMed

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

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

2013-11-01

117

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

PubMed Central

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

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

2014-01-01

118

A Negative Feedback Loop Mediated by STAT3 Limits Human Th17 Responses.  

PubMed

The transcription factor STAT3 is critically required for the differentiation of Th17 cells, a T cell subset involved in various chronic inflammatory diseases. In this article, we report that STAT3 also drives a negative-feedback loop that limits the formation of IL-17-producing T cells within a memory population. By activating human memory CD4(+)CD45RO(+) T cells at a high density (HiD) or a low density (LoD) in the presence of the pro-Th17 cytokines IL-1?, IL-23, and TGF-?, we observed that the numbers of Th17 cells were significantly higher under LoD conditions. Assessment of STAT3 phosphorylation revealed a more rapid and stronger STAT3 activation in HiD cells than in LoD cells. Transient inhibition of active STAT3 in HiD cultures significantly enhanced Th17 cell numbers. Expression of the STAT3-regulated ectonucleotidase CD39, which catalyzes ATP hydrolysis, was higher in HiD, than in LoD, cell cultures. Interestingly, inhibition of CD39 ectonucleotidase activity enhanced Th17 responses under HiD conditions. Conversely, blocking the ATP receptor P2X7 reduced Th17 responses in LoD cultures. These data suggest that STAT3 negatively regulates Th17 cells by limiting the availability of ATP. This negative-feedback loop may provide a safety mechanism to limit tissue damage by Th17 cells during chronic inflammation. Furthermore, our results have relevance for the design of novel immunotherapeutics that target the STAT3-signaling pathway, because inhibition of this pathway may enhance, rather than suppress, memory Th17 responses. PMID:24973454

Purvis, Harriet A; Anderson, Amy E; Young, David A; Isaacs, John D; Hilkens, Catharien M U

2014-08-01

119

Feedback loops and temporal misalignment in component-based hydrologic modeling  

NASA Astrophysics Data System (ADS)

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.

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

2011-12-01

120

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

SciTech Connect

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

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

2004-03-19

121

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

PubMed Central

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.

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

2013-01-01

122

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

PubMed

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

Servedio, Maria R; Saetre, Glenn-Peter

2003-07-22

123

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

SciTech Connect

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)

Venediktov, Vladimir Yu; Ivanova, Natalya L; Freigang, N N [Research Center 'Vavilov State Optical Institute', St.Petersburg (Russian Federation); Laskin, V A [St. Petersburg State University, St. Petersburg (Russian Federation)

2009-10-31

124

A Positive Feedback Loop between Mesenchymal-like Cancer Cells and Macrophages Is Essential to Breast Cancer Metastasis.  

PubMed

The close vicinity of cancer cells undergoing epithelial-mesenchymal transition (EMT) and tumor-associated macrophages (TAMs) at the invasive front of tumors suggests that these two cell type may mutually interact. We show that mesenchymal-like breast cancer cells activate macrophages to a TAM-like phenotype by GM-CSF. Reciprocally, CCL18 from TAMs induces cancer cell EMT, forming a positive feedback loop, in coculture systems and humanized mice. Inhibition of GM-CSF or CCL18 breaks this loop and reduces cancer metastasis. High GM-CSF expression in breast cancer samples is associated with more CCL18(+) macrophages, cancer cell EMT, enhanced metastasis, and reduced patient survival. These findings suggest that a positive feedback loop between GM-CSF and CCL18 is important in breast cancer metastasis. PMID:24823638

Su, Shicheng; Liu, Qiang; Chen, Jingqi; Chen, Jianing; Chen, Fei; He, Chonghua; Huang, Di; Wu, Wei; Lin, Ling; Huang, Wei; Zhang, Jin; Cui, Xiuying; Zheng, Fang; Li, Haiyan; Yao, Herui; Su, Fengxi; Song, Erwei

2014-05-12

125

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

PubMed

We have investigated an all-optical set/reset and latching operation using a monolithically integrated InP-based semiconductor optical amplifier type Mach-Zehnder interferometer with a feedback loop. In simulation, operation conditions when both set and reset are possible was estimated for input light pulse with a FWHM of 31 and 12.5 ps, and the tolerance of the CW probe light and feedback loop loss becomes large with increasing the input light pulse power. In addition, the loop length could be longer than the distance of the light propagating in one bit pulse because of the longer carrier recovery time than one bit time duration. Moreover, we successfully achieved set/reset operation with 34- and 18-ps wide set/reset pulses. PMID:23262871

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

2012-12-10

126

An open-loop feedback control approach to point-to-point control of linear continuous-time time-invariant dynamic systems  

Microsoft Academic Search

A combination of the classical frequency-domain and modern state-space approaches is employed to obtain an open-loop feedback control for a special class of control systems known as point-to-point (or terminal) control systems. The entire set of solution to the two-point-boundary-value problems is obtained. It is shown that the open-loop feedback control is equivalent to a linear state feedback control with

Hassan Hamidi-Hashemi; Mohsen H. Hashemi

1992-01-01

127

System Identification from Closed-Loop Data with Known Output Feedback Dynamics.  

National Technical Information Service (NTIS)

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, whic...

M. Phan J. Juang L. G. Horta R. W. Longman

1992-01-01

128

A negative feedback loop involving small RNAs accelerates Vibrio cholerae's transition out of quorum-sensing mode  

PubMed Central

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 (Qrr1–4). Expression of qrr1–4 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, Qrr1–4 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. cholerae’s transition from the high to the low cell density mode.

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

2008-01-01

129

Controlling thread formation during tipstreaming through an active feedback control loop.  

PubMed

Microscale tipstreaming is a hydrodynamic phenomenon capable of producing submicron sized droplets within a microfluidic device. The tipstreaming process results in the drawing of a thin thread from a highly curved interface and occurs as a result of interfacial surfactant concentration gradients that develop due to elongational flows generated within flow focusing geometries. However, in conventional microfluidic devices, the thread formation is periodically interrupted by the formation of larger primary droplets. This study presents an active feedback control loop capable of eliminating the production of primary droplets and producing a continuous thread, and therefore a continuous droplet stream. A proportional controller is used to successfully control the position of the interface and generate a continuous thread. A derivative component is incorporated in an attempt to increase controller stability, but this component is found to be ineffective. Analysis of the tip position as a function of time is performed to determine the optimal proportional gain constant and set point value for the proportional controller that minimize fluctuations in the produced droplet sizes. The generation of a continuous thread facilitates the use of tipstreaming in several applications, including nanoparticle synthesis, chemical detection, and enzyme activity studies. PMID:24100760

Moyle, Todd M; Walker, Lynn M; Anna, Shelley L

2013-12-01

130

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

PubMed

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

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

2012-04-01

131

Macrophage migration inhibitory factor is involved in a positive feedback loop increasing aromatase expression in endometriosis.  

PubMed

Immune-endocrine interplay may play a major role in the pathogenesis of endometriosis. In the present study, we have investigated the interaction between macrophage migration inhibitory factor (MIF), a major pro-inflammatory and growth-promoting factor markedly expressed in active endometriotic lesions, and estradiol (E(2)) in ectopic endometrial cells. Our data showed a significant increase of MIF protein secretion and mRNA expression in endometriotic cells in response to E(2). MIF production was blocked by Fulvestrant, an estrogen receptor (ER) antagonist, and induced by ER? and ER? selective agonists propyl-pyrazole-triol (PPT) and diarylpropionrile (DPN), respectively, thus demonstrating a specific receptor-mediated effect. Cell transfection with MIF promoter construct showed that E(2) significantly stimulates MIF promoter activity. Interestingly, our data further revealed that MIF reciprocally stimulates aromatase protein and mRNA expression via a posttranscriptional mRNA stabilization mechanism, that E(2) itself can upregulate aromatase expression, and that inhibition of endogenous MIF, using MIF specific siRNA, significantly inhibits E(2)-induced aromatase. Thus, the present study revealed the existence of a local positive feedback loop by which estrogen acts directly on ectopic endometrial cells to upregulate the expression of MIF, which, in turn, displays the capability of inducing the expression of aromatase, the key and rate-limiting enzyme for estrogen synthesis. Such interplay may have a considerable impact on the development of endometriosis. PMID:22759564

Veillat, Véronique; Sengers, Valérie; Metz, Christine N; Roger, Thierry; Leboeuf, Mathieu; Mailloux, Jacques; Akoum, Ali

2012-09-01

132

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

PubMed Central

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.

Wang, Qian; Whim, Matthew D.

2013-01-01

133

Noise-induced dynamics in the mixed-feedback-loop network motif  

NASA Astrophysics Data System (ADS)

In this paper, we present a stochastic model for the mixed-feedback loop (MFL), a motif found in integrated cellular networks of transcription regulation and protein-protein interaction. Previous bifurcation analysis indicates that this motif can serve as a bistable switch or a clock. We investigate how extrinsic and intrinsic noise affects its dynamic behaviors systematically. We find that this motif can exploit noise to enrich its dynamical performance. When the MFL is in the bistable region, under fluctuation of extrinsic noise, the MFL system can switch from one steady state to the other and meanwhile one protein’s production is amplified for more than three orders of magnitude. Further, from an engineering perspective, this noise-based switch and amplifier for gene expression is very easy to control. Without extrinsic noise, spontaneous transition between states occurs as the consequence of intrinsic noise. Such a switch is controlled by the parameters and system size. On the other hand, intrinsic noise can induce sustained stochastic oscillation when the corresponding deterministic system does not oscillate. Such stochastic oscillation shows the best performance at an optimal noise level, indicating the occurrence of intrinsic noise stochastic resonance which can contribute to the robustness of this oscillator. When considering the effects of extrinsic noise near bifurcation points, a similar phenomenon of extrinsic noise stochastic resonance is unveiled.

Li, Difei; Li, Chunguang

2008-01-01

134

A mutually inhibitory feedback loop between the 20S proteasome and its regulator, NQO1.  

PubMed

NAD(P)H:quinone-oxidoreductase-1 (NQO1) is a cytosolic enzyme that catalyzes the reduction of various quinones using flavin adenine dinucleotide (FAD) as a cofactor. NQO1 has been also shown to rescue proteins containing intrinsically unstructured domains, such as p53 and p73, from degradation by the 20S proteasome through an unknown mechanism. Here, we studied the nature of interaction between NQO1 and the 20S proteasome. Our study revealed a double negative feedback loop between NQO1 and the 20S proteasome, whereby NQO1 prevents the proteolytic activity of the 20S proteasome and the 20S proteasome degrades the apo form of NQO1. Furthermore, we demonstrate, both in vivo and in vitro, that NQO1 levels are highly dependent on FAD concentration. These observations suggest a link between 20S proteolysis and the metabolic cellular state. More generally, the results may represent a regulatory mechanism by which associated cofactors dictate the stability of proteins, thus coordinating protein levels with the metabolic status. PMID:22793692

Moscovitz, Oren; Tsvetkov, Peter; Hazan, Nimrod; Michaelevski, Izhak; Keisar, Hodaya; Ben-Nissan, Gili; Shaul, Yosef; Sharon, Michal

2012-07-13

135

Transcription of the Geminin gene is regulated by a negative-feedback loop  

PubMed Central

Geminin performs a central function in regulating cellular proliferation and differentiation in development and also in stem cells. Of interest, down-regulation of Geminin induces gene transcription regulated by E2F, indicating that Geminin is involved in regulation of E2F-mediated transcriptional activity. Because transcription of the Geminin gene is reportedly regulated via an E2F-responsive region (E2F-R) located in the first intron, we first used a reporter vector to examine the effect of Geminin on E2F-mediated transcriptional regulation. We found that Geminin transfection suppressed E2F1- and E2F2-mediated transcriptional activation and also mildly suppressed such activity in synergy with E2F5, 6, and 7, suggesting that Geminin constitutes a negative-feedback loop for the Geminin promoter. Of interest, Geminin also suppressed nuclease accessibility, acetylation of histone H3, and trimethylation of histone H3 at lysine 4, which were induced by E2F1 overexpression, and enhanced tri­methylation of histone H3 at lysine 27 and monoubiquitination of histone H2A at lysine 119 in E2F-R. However, Geminin5EQ, which does not interact with Brahma or Brg1, did not suppress accessibility to nuclease digestion or transcription but had an overall dominant-negative effect. These findings suggest that E2F-mediated activation of Geminin transcription is negatively regulated by Geminin through the inhibition of chromatin remodeling.

Ohno, Yoshinori; Saeki, Keita; Yasunaga, Shin'ichiro; Kurogi, Toshiaki; Suzuki-Takedachi, Kyoko; Shirai, Manabu; Mihara, Keichiro; Yoshida, Kenichi; Voncken, J. Willem; Ohtsubo, Motoaki; Takihara, Yoshihiro

2014-01-01

136

Messenger RNA fluctuations and regulatory RNAs shape the dynamics of a negative feedback loop  

NASA Astrophysics Data System (ADS)

Single-cell experiments of simple regulatory networks can markedly differ from cell population experiments. Such differences arise from stochastic events in individual cells that are averaged out in cell populations. For instance, while individual cells may show sustained oscillations in the concentrations of some proteins, such oscillations may appear damped in the population average. In this paper we investigate the role of RNA stochastic fluctuations as a leading force to produce a sustained excitatory behavior at the single-cell level. As opposed to some previous models, we build a fully stochastic model of a negative feedback loop that explicitly takes into account the RNA stochastic dynamics. We find that messenger RNA random fluctuations can be amplified during translation and produce sustained pulses of protein expression. Motivated by the recent appreciation of the importance of noncoding regulatory RNAs in post-transcription regulation, we also consider the possibility that a regulatory RNA transcript could bind to the messenger RNA and repress translation. Our findings show that the regulatory transcript helps reducing gene expression variability both at the single-cell level and at the cell population level.

Rodríguez Martínez, María; Soriano, Jordi; Tlusty, Tsvi; Pilpel, Yitzhak; Furman, Itay

2010-03-01

137

ASDTIC: A feedback control innovation  

NASA Technical Reports Server (NTRS)

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.

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

1972-01-01

138

An appropriate bounded invariant region for a bistable reaction-diffusion model of the caspase-3/8 feedback loop.  

PubMed

The apoptotic caspase-3/8 feedback loop describes the core of the extrinsic pro-apoptotic signaling pathway, an essential part of apoptosis. Latter is a prototype of the programmed cell death, which enables organisms to remove damaged or infected cells. The reaction network of the caspase-3/8 feedback loop in a single cell is modeled by a reaction-diffusion system, which shows a bistable behavior. In this work, we present an appropriate bounded invariant region for the bistable reaction-diffusion system in order to theoretically confirm that diffusion rapidly balances the concentrations of the different caspase types. This justifies the decomposition of the dynamics into a diffusion dominated part on a very short time scale and a pure reaction driven dynamics on a large time scale. PMID:24091780

Daub, Markus

2013-11-01

139

Automated Performance Optimisation and Layout Synthesis of MEMS Accelerometer with Sigma-Delta Force-Feedback Control Loop  

Microsoft Academic Search

This contribution presents a novel methodology for automated optimal design of a MEMS accelerometer with Sigma-Delta force-feedback control loop from user defined high-level performance specifications and design constraints. The proposed approach is based on a simulation-based optimization technology using a genetic algorithm. The layout of the mechanical sensing element is generated simultaneously with the optimal design parameters of the Sigma-Delta

Chenxu Zhao; Tom J. Kazmierski

2008-01-01

140

The ZEB\\/miR200 feedback loop—a motor of cellular plasticity in development and cancer?  

Microsoft Academic Search

Epithelial-to-mesenchymal transition (EMT) is a fundamental process in development and disease. Zinc-finger enhancer binding (ZEB) transcription factors (ZEB1 and ZEB2) are crucial EMT activators, whereas members of the miR-200 family induce epithelial differentiation. They are reciprocally linked in a feedback loop, each strictly controlling the expression of the other. Now data show that EMT not only confers cellular motility, but

Simone Brabletz; Thomas Brabletz

2010-01-01

141

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

PubMed Central

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.

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

2012-01-01

142

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

NASA Astrophysics Data System (ADS)

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

Huebert, B. J.

2004-12-01

143

On the design of a low-voltage two-stage OTA using bulk-driven and positive feedback techniques  

Microsoft Academic Search

This article presents the design and simulation of a fully differential two-stage operational transconductance amplifier (OTA) in a 0.18?µm CMOS process with a 0.9?V supply voltage. For this purpose, both the bulk-driven and positive feedback techniques are employed. These techniques increase the DC gain by about 18.5?dB without consuming more power and changing the unity-gain bandwidth and phase margin of

Hassan Khameh; Hossein Shamsi

2012-01-01

144

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

NASA Astrophysics Data System (ADS)

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

Shen, B.-W.

2014-04-01

145

Functional characteristics of a double negative feedback loop mediated by microRNAs.  

PubMed

MicroRNAs (miRNAs) are a class of small, noncoding RNAs that play crucial roles in almost all cellular processes. As key post-transcriptional regulators of gene expression, miRNAs mainly induce mRNA degradation or translational repression. Recently computational and experimental studies have identified an abundance of motifs involving miRNAs and transcriptional factors (TFs). Here, we study the functional characteristics of one such motif, a two-node miRNA-mediated double negative feedback loop (MDNFL) in which a TF suppresses an miRNA and the TF itself is negatively regulated by the miRNA. Several examples of this motif are described from the literature. We propose a general computational model for the MDNFL based on biochemical regulations and explore its dynamics by using bifurcation analysis. Our results show that the MDNFL can behave as a bistable switch. This functional feature is in agreement with experimental observations of the widespread appearance of miRNAs in fate decisions such as differentiation during development. Importantly, it is found that under the interplay of a TF and an miRNA, the MDNFL model can behave as switches for wide ranges of parameters even without cooperative binding of the TF. In addition, we also investigate how extrinsic noise affects dynamic behavior of the MDNFL. Interestingly, it is found that when the MDNFL is in the bistable region, by choosing the appropriate extrinsic noise source, the MDNFL system can switch from one steady state to the other and meanwhile the production of either miRNA or protein is amplified significantly. From an engineering perspective, this noise-based switch and amplifier for gene expression is very easy to control. It is hoped that the results presented here would provide a new insight on how gene expression is regulated by miRNAs and further guidance for experiments. PMID:24427216

Cai, Shuiming; Zhou, Peipei; Liu, Zengrong

2013-10-01

146

Huwe1-mediated ubiquitylation of dishevelled defines a negative feedback loop in the Wnt signaling pathway.  

PubMed

Wnt signaling plays a central role in development, adult tissue homeostasis, and cancer. Several steps in the canonical Wnt/?-catenin signaling cascade are regulated by ubiquitylation, a protein modification that influences the stability, subcellular localization, or interactions of target proteins. To identify regulators of the Wnt/?-catenin pathway, we performed an RNA interference screen in Caenorhabditis elegans and identified the HECT domain-containing ubiquitin ligase EEL-1 as an inhibitor of Wnt signaling. In human embryonic kidney 293T cells, knockdown of the EEL-1 homolog Huwe1 enhanced the activity of a Wnt reporter in cells stimulated with Wnt3a or in cells that overexpressed casein kinase 1 (CK1) or a constitutively active mutant of the Wnt co-receptor low-density lipoprotein receptor-related protein 6 (LRP6). However, knockdown of Huwe1 had no effect on reporter gene expression in cells expressing constitutively active ?-catenin, suggesting that Huwe1 inhibited Wnt signaling upstream of ?-catenin and downstream of CK1 and LRP6. Huwe1 bound to and ubiquitylated the cytoplasmic Wnt pathway component Dishevelled (Dvl) in a Wnt3a- and CK1?-dependent manner. Mass spectrometric analysis showed that Huwe1 promoted K63-linked, but not K48-linked, polyubiquitination of Dvl. Instead of targeting Dvl for degradation, ubiquitylation of the DIX domain of Dvl by Huwe1 inhibited Dvl multimerization, which is necessary for its function. Our findings indicate that Huwe1 is part of an evolutionarily conserved negative feedback loop in the Wnt/?-catenin pathway. PMID:24643799

de Groot, Reinoud E A; Ganji, Ranjani S; Bernatik, Ondrej; Lloyd-Lewis, Bethan; Seipel, Katja; Šedová, Kate?ina; Zdráhal, Zbyn?k; Dhople, Vishnu M; Dale, Trevor C; Korswagen, Hendrik C; Bryja, Vitezslav

2014-03-18

147

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

PubMed Central

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

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

2012-01-01

148

Does not hUTP14a promoter form a regulation feedback loop with P53?  

PubMed Central

Objective We previously found that hUTP14a binds P53 and promotes P53 degradation. However, if hUTP14a is a downstream gene of P53 remains to be determined. This study aimed to identify the promoter of hUTP14a and investigate if hUTP14a is regulated by P53. Methods The hUTP14a promoter region was cloned into pGL3-Basic-luciferase reporter plasmid to get pGL3-hUTP14a-luc. The reporter plasmid was transfected into 293T cells and luciferase activity was evaluated by the Dual-Luciferase Reporter Assay System. Putative transcription factors were identified through searching MatInspector Professional and Algorismica i Genetica databases. Either pGL3-hUTP14a-luc or p21 promoter reporter plasmid was co-transfected with increasing dose of p53 plasmid, and luciferase activity was evaluated. A series of deletion constructs of pGL3-hUTP14a-luc were constructed and minimal promoter region of hUTP14a was determined. Differences of the luciferase activities between different groups were assessed by statistical analysis. Results The hUTP14a gene promoter reporter construct was correctly cloned and was demonstrated to possess promoter activity. The transcription of hUTP14a was not regulated by P53. The minimal promoter region of hUTP14a gene is located between -203 to -100 of the transcription initiation site. Conclusion Unlike other P53-interacting proteins such as MDM2, Pirh2 and Cop I which promote P53 degradation and whose transcriptions are regulated by P53, does not hUTP14a transcription form a regulation feedback loop with P53.

Zhang, Jingyi; Guo, Yafei; Du, Xiaojuan

2014-01-01

149

STAT5 and Prolactin Participate in a Positive Autocrine Feedback Loop That Promotes Angiogenesis*  

PubMed Central

We have shown previously that the murine prolactin/growth hormone family member proliferin plays a pivotal role in angiogenesis induced by the FGF2/STAT5 signaling cascade. To delineate the signaling pathway downstream of STAT5 in the human system, where proliferin does not exist, we expressed constitutively active (CA) or dominant-negative (DN) mutant STAT5A in hCMEC/D3 human brain endothelial cells. We found that conditioned medium from CA-STAT5A- but not from DN-STAT5A-overexpressing endothelial cells (EC) is sufficient to induce EC migration and tube formation but not proliferation, indicating that STAT5A regulates the secretion of autocrine proangiogenic factors. We identified prolactin (PRL) as a candidate autocrine factor. CA-STAT5A expression stimulates PRL production at the RNA and protein level, and STAT5A binds to the PRL promoter region, suggesting direct transcriptional regulation. Medium conditioned by CA-STAT5A-overexpressing EC induces phosphorylation of the PRL receptor and activates MAPK. Knockdown of PRL expression by shRNA or blocking of PRL activity with neutralizing antibodies removed the CA-STAT5A-dependent proangiogenic activity from the conditioned medium of EC. The addition of recombinant PRL restores this activity. STAT5A-induced PRL in the conditioned medium can activate STAT5, STAT1, and to a lesser extent STAT3 in hCMEC/D3 cells, suggesting the existence of a positive feedback loop between STAT5 and PRL that promotes angiogenesis. Furthermore, we find that VEGF, a potent proangiogenic factor, is induced by activation of STAT5A, and VEGF induction depends on PRL expression. These observations demonstrate a STAT5/PRL/VEGF signaling cascade in human brain EC and implicate PRL and VEGF as autocrine regulators of EC migration, invasion, and tube formation.

Yang, Xinhai; Meyer, Kristy; Friedl, Andreas

2013-01-01

150

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

PubMed Central

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

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

2013-01-01

151

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

PubMed

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

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

152

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

PubMed Central

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

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

2013-01-01

153

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

PubMed Central

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.

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

2011-01-01

154

Feedback-induced voltage change of a Vertical-Cavity Surface-Emitting Laser as an active detection system for miniature optical scanning probe microscopes  

Microsoft Academic Search

We propose a novel detection technique for scanning probe microscopy based on the measuring of the feedback-induced voltage change of 780-nm VCSEL operating at constant current in far-field regime when we modulate mechanically the length of a coupled-cavity generating the feedback conditions. The voltage change of the VCSEL is produced by light back reflected from the sample to the laser

Dominique Heinis; Christophe Gorecki; Sylwester Bargiel; Bernard Cretin

2006-01-01

155

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

PubMed Central

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.

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

2014-01-01

156

The functional genomics of an eco-evolutionary feedback loop: linking gene expression, trait evolution, and community dynamics.  

PubMed

Feedbacks between ecological and evolutionary change may play important roles in community and ecosystem functioning, but a complete eco-evolutionary feedback loop has not been demonstrated at the community level, and we know little about molecular mechanisms underlying this kind of eco-evolutionary dynamics. In predator-prey (rotifer-alga) microcosms, cyclical changes in predator abundance generated fluctuating selection for a heritable prey defence trait, cell clumping. Predator population growth was affected more by prey evolution than by changes in prey abundance, and changes in predator abundance drove further prey evolution, completing the feedback loop. Within a predator-prey cycle, genes up-regulated as clumping declined were down-regulated as clumping increased, and vice-versa. Genes changing most in expression tended to be associated with defence or its cost. Expression patterns of individual genes differed greatly between consecutive cycles (often reversing direction), suggesting that a particular phenotype may be produced by several (perhaps many) different gene transcription pathways. PMID:22417636

Becks, Lutz; Ellner, Stephen P; Jones, Laura E; Hairston, Nelson G

2012-05-01

157

An autoregulatory feedback loop involving PAP1 and TAS4 in response to sugars in Arabidopsis  

PubMed Central

miR828 in Arabidopsis triggers the cleavage of Trans-Acting SiRNA Gene 4 (TAS4) transcripts and production of small interfering RNAs (ta-siRNAs). One siRNA, TAS4-siRNA81(?), targets a set of MYB transcription factors including PAP1, PAP2, and MYB113 which regulate the anthocyanin biosynthesis pathway. Interestingly, miR828 also targets MYB113, suggesting a close relationship between these MYBs, miR828, and TAS4, but their evolutionary origins are unknown. We found that PAP1, PAP2, and TAS4 expression is induced specifically by exogenous treatment with sucrose and glucose in seedlings. The induction is attenuated in abscisic acid (ABA) pathway mutants, especially in abi3-1 and abi5-1 for PAP1 or PAP2, while no such effect is observed for TAS4. PAP1 is under regulation by TAS4, demonstrated by the accumulation of PAP1 transcripts and anthocyanin in ta-siRNA biogenesis pathway mutants. TAS4-siR81(?) expression is induced by physiological concentrations of Suc and Glc and in pap1-D, an activation-tagged line, indicating a feedback regulatory loop exists between PAP1 and TAS4. Bioinformatic analysis revealed MIR828 homologues in dicots and gymnosperms, but only in one basal monocot, whereas TAS4 is only found in dicots. Consistent with this observation, PAP1, PAP2, and MYB113 dicot paralogs show peptide and nucleotide footprints for the TAS4-siR81(?) binding site, providing evidence for purifying selection in contrast to monocots. Extended sequence similarities between MIR828, MYBs, and TAS4 support an inverted duplication model for the evolution of MIR828 from an ancestral gymnosperm MYB gene and subsequent formation of TAS4 by duplication of the miR828* arm. We obtained evidence by modified 5?-RACE for a MYB mRNA cleavage product guided by miR828 in Pinus resinosa. Taken together, our results suggest that regulation of anthocyanin biosynthesis by TAS4 and miR828 in higher plants is evolutionarily significant and consistent with the evolution of TAS4 since the dicot—monocot divergence.

Luo, Qing-Jun; Mittal, Amandeep; Jia, Fan

2011-01-01

158

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

PubMed

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

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

2014-03-28

159

Note: Phase-locked loop with a voltage controlled oscillator based on a liquid crystal cell as variable capacitance  

NASA Astrophysics Data System (ADS)

A phase-locked loop is demonstrated using a twisted-nematic liquid crystal cell as a capacitance that can be varied as a function of applied voltage. The system is formed by a phase detector, a low-pass filter, as well as a voltage controlled oscillator including such variable capacitance. A theoretical study is proposed and experimentally validated. Capture and locked ranges of hundreds of kHz have been obtained for the configuration used in this circuit. An application as frequency demodulator using a practical implementation of this circuit has been demonstrated.

Marcos, Carlos; Sánchez-Pena, José M.; Torres, Juan C.; Pérez, Isabel; Urruchi, Virginia

2011-12-01

160

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)

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.

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

1974-01-01

161

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

NASA Astrophysics Data System (ADS)

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.

Small, Ward; 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

162

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

SciTech Connect

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.

Small, W., LLNL

1997-02-28

163

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

PubMed Central

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

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

2011-01-01

164

A NON-INVASIVE TECHNIQUE FOR CONFIGURING LOW LEVEL RF FEEDBACK LOOPS IN PEP-II  

Microsoft Academic Search

The RF system of the PEP-II collider uses two fast feed- back loops around each klystron and set of cavities. These loops reduce the impedance of the fundamental mode of the accelerating cavities seen by the beam, and are nec- essary to reduce the growth rates of longitudinal modes within the RF system bandwidth. Operation of the accel- erator at

D. Teytelmany

165

Regulation of HDAC9 Gene Expression by MEF2 Establishes a Negative-Feedback Loop in the Transcriptional Circuitry of Muscle Differentiation?  

PubMed Central

Skeletal muscle development is controlled by the myocyte enhancer factor (MEF2) and myogenic basic helix-loop-helix (bHLH) families of transcription factors, which associate and synergistically activate muscle gene expression. Muscle differentiation is further reinforced by positive-feedback loops in which myogenic bHLH proteins activate their own expression and the expression of MEF2, while MEF2 stimulates expression of myogenic bHLH genes and the Mef2c gene. Here we describe a myogenic negative-feedback loop that consists of MEF2 proteins and the transcriptional repressor histone deacetylase 9 (HDAC9). We show that the HDAC9 gene is a direct transcriptional target of MEF2 in vitro and in vivo. HDAC9 can associate with MEF2 proteins and suppress their transcriptional activity. The transcriptional repressor HDAC9 thus forms a negative-feedback loop in the transcriptional circuitry of muscle differentiation.

Haberland, Michael; Arnold, Michael A.; McAnally, John; Phan, Dillon; Kim, Yuri; Olson, Eric N.

2007-01-01

166

An integrated low-voltage SLIC\\/codec for short loop applications  

Microsoft Academic Search

A single chip solution for doing analog and digital signal processing for subscriber line telephony is proposed. Conventional line cards use a set of two chips for doing the same job: a low voltage mixed signal chip operating as a voice coder and a high voltage chip to fulfill high voltage requirement (up to 70 V) of the line. The

M. Sharifichani; B. Sheikholeslami; O. Shoaei

2004-01-01

167

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

SciTech Connect

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

Lee, S.; Gildemeister, J.M.; Holmes, W.; Lee, A.T.; Richards, P.L. [Department of Physics and the Materials Sciences Division, Lawrence Berkeley National Laboratory, University of California, Berkeley, California 94720-7300 (United States)

1998-06-01

168

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

PubMed Central

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.

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

2011-01-01

169

An NF-?B pathway-mediated positive feedback loop amplifies Ras activity to pathological levels in mice  

PubMed Central

Genetic mutations that give rise to active mutant forms of Ras are oncogenic and found in several types of tumor. However, such mutations are not clear biomarkers for disease, since they are frequently detected in healthy individuals. Instead, it has become clear that elevated levels of Ras activity are critical for Ras-induced tumorigenesis. However, the mechanisms underlying the production of pathological levels of Ras activity are unclear. Here, we show that in the presence of oncogenic Ras, inflammatory stimuli initiate a positive feedback loop involving NF-?B that further amplifies Ras activity to pathological levels. Stimulation of Ras signaling by typical inflammatory stimuli was transient and had no long-term sequelae in wild-type mice. In contrast, these stimuli generated prolonged Ras signaling and led to chronic inflammation and precancerous pancreatic lesions (PanINs) in mice expressing physiological levels of oncogenic K-Ras. These effects of inflammatory stimuli were disrupted by deletion of inhibitor of NF-?B kinase 2 (IKK2) or inhibition of Cox-2. Likewise, expression of active IKK2 or Cox-2 or treatment with LPS generated chronic inflammation and PanINs only in mice expressing oncogenic K-Ras. The data support the hypothesis that in the presence of oncogenic Ras, inflammatory stimuli trigger an NF-?B–mediated positive feedback mechanism involving Cox-2 that amplifies Ras activity to pathological levels. Because a large proportion of the adult human population possesses Ras mutations in tissues including colon, pancreas, and lung, disruption of this positive feedback loop may be an important strategy for cancer prevention.

Daniluk, Jaroslaw; Liu, Yan; Deng, Defeng; Chu, Jun; Huang, Haojie; Gaiser, Sebastian; Cruz-Monserrate, Zobeida; Wang, Huamin; Ji, Baoan; Logsdon, Craig D.

2012-01-01

170

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

SciTech Connect

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.

Tomilin, V. A., E-mail: 8342tomilin@mail.ru; Il'ichev, L. V. [Russian Academy of Sciences, Institute of Automatics and Electrometry, Siberian Branch (Russian Federation)] [Russian Academy of Sciences, Institute of Automatics and Electrometry, Siberian Branch (Russian Federation)

2013-02-15

171

Cyclostationary Crosstalk Suppression by Decision Feedback Equalization on Digital Subscriber Loops  

Microsoft Academic Search

Interference from digital signals in multipair cables has been shown to be cyclostationary under some conditions. This work evaluates the performance of a decision feedback equalizer (DFE) in the presence of cyclostationary interference (CI), intersymbol interference (ISI), and additive white noise (AWN). A comparison between a DFE with CI and one with stationary interference (SI) shows the ability of the

Majeed Abdulrahman; David D. Falconer

1992-01-01

172

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

PubMed

In case of delayed visual feedback during visuomotor tasks, like in some sluggish computer games, humans can modulate their behavior to compensate for the delay. However, opinions on the nature of this compensation diverge. Some studies suggest that humans adapt to feedback delays with lasting changes in motor behavior (aftereffects) and a recalibration of time perception. Other studies have shown little or no evidence for such semipermanent recalibration in the temporal domain. We hypothesize that predictability of the reference signal (target to be tracked) is necessary for semipermanent delay adaptation. To test this hypothesis, we trained participants with a 200 ms visual feedback delay in a visually guided manual tracking task, varying the predictability of the reference signal between conditions, but keeping reference motion and feedback delay constant. In Experiment 1, we focused on motor behavior. Only training in the predictable condition brings about all of the adaptive changes and aftereffects expected from delay adaptation. In Experiment 2, we used a synchronization task to investigate perceived simultaneity (perceptuomotor learning). Supporting the hypothesis, participants recalibrated subjective visuomotor simultaneity only when trained in the predictable condition. Such a shift in perceived simultaneity was also observed in Experiment 3, using an interval estimation task. These results show that delay adaptation in motor control can modulate the perceived temporal alignment of vision and kinesthetically sensed movement. The coadaptation of motor prediction and target prediction (reference extrapolation) seems necessary for such genuine delay adaptation. This offers an explanation for divergent results in the literature. PMID:24599942

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

2014-01-01

173

Open-Loop Digital Predistortion Using Cartesian Feedback for Adaptive RF Power Amplifier Linearization  

Microsoft Academic Search

We present a new adaptive power amplifier (PA) linearization technique. We leverage analog Cartesian feedback (CFB) to train a Cartesian look-up table, reducing DSP and power amplifier modeling requirements to a minimum and eliminating model convergence as a design issue. Because the CFB system does not continuously operate, we overcome the bandwidth limitation traditionally associated with this technique. In addition,

SungWon Chung; Jack W. Holloway; Joel L. Dawson

2007-01-01

174

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

SciTech Connect

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.

De Doncker, Rik W. A. A. (Schenectady, NY); King, Robert D. (Schenectady, NY); Sanza, Peter C. (Clifton Park, NY); Haefner, Kenneth B. (Schenectady, NY)

1992-01-01

175

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

SciTech Connect

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.

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

1992-11-24

176

A Negative-Feedback Loop between the Detoxification/Antioxidant Response Factor SKN-1 and Its Repressor WDR-23 Matches Organism Needs with Environmental Conditions  

PubMed Central

Negative-feedback loops between transcription factors and repressors in responses to xenobiotics, oxidants, heat, hypoxia, DNA damage, and infection have been described. Although common, the function of feedback is largely unstudied. Here, we define a negative-feedback loop between the Caenorhabditis elegans detoxification/antioxidant response factor SKN-1/Nrf and its repressor wdr-23 and investigate its function in vivo. Although SKN-1 promotes stress resistance and longevity, we find that tight regulation by WDR-23 is essential for growth and reproduction. By disabling SKN-1 transactivation of wdr-23, we reveal that feedback is required to set the balance between growth/reproduction and stress resistance/longevity. We also find that feedback is required to set the sensitivity of a core SKN-1 target gene to an electrophile. Interestingly, the effect of feedback on target gene induction is greatly reduced when the stress response is strongly activated, presumably to ensure maximum activation of cytoprotective genes during potentially fatal conditions. Our work provides a framework for understanding the function of negative feedback in inducible stress responses and demonstrates that manipulation of feedback alone can shift the balance of competing animal processes toward cell protection, health, and longevity.

Leung, Chi K.; Wang, Ying; Deonarine, Andrew; Tang, Lanlan; Prasse, Stephanie

2013-01-01

177

A negative-feedback loop between the detoxification/antioxidant response factor SKN-1 and its repressor WDR-23 matches organism needs with environmental conditions.  

PubMed

Negative-feedback loops between transcription factors and repressors in responses to xenobiotics, oxidants, heat, hypoxia, DNA damage, and infection have been described. Although common, the function of feedback is largely unstudied. Here, we define a negative-feedback loop between the Caenorhabditis elegans detoxification/antioxidant response factor SKN-1/Nrf and its repressor wdr-23 and investigate its function in vivo. Although SKN-1 promotes stress resistance and longevity, we find that tight regulation by WDR-23 is essential for growth and reproduction. By disabling SKN-1 transactivation of wdr-23, we reveal that feedback is required to set the balance between growth/reproduction and stress resistance/longevity. We also find that feedback is required to set the sensitivity of a core SKN-1 target gene to an electrophile. Interestingly, the effect of feedback on target gene induction is greatly reduced when the stress response is strongly activated, presumably to ensure maximum activation of cytoprotective genes during potentially fatal conditions. Our work provides a framework for understanding the function of negative feedback in inducible stress responses and demonstrates that manipulation of feedback alone can shift the balance of competing animal processes toward cell protection, health, and longevity. PMID:23836880

Leung, Chi K; Wang, Ying; Deonarine, Andrew; Tang, Lanlan; Prasse, Stephanie; Choe, Keith P

2013-09-01

178

Acceleration feedback of a CCD-based tracking loop for fast steering mirror  

Microsoft Academic Search

In the control system of a CCD-based tracking loop for a fast steering mirror (FSM), the most effective method often employed to improve pointing performance is to increase high gain of the control system for a high bandwidth, which, however, usually suffers a great deal from a low CCD sampling rate and the mechanics of the FSM. Moreover, the amount

Tao Tang; Yongmei Huang; Chengyu Fu; Shunfa Liu

2009-01-01

179

Power hardware in the loop simulation with feedback current filtering for electric systems  

Microsoft Academic Search

Power Hardware-in-the-Loop (PHIL) simulations are suited for electric component tests and electric tests of hardware interacting with complex systems that are simulated. PHIL simulations combine the advantages of a pure software simulation and a hardware system test. At the present time, PHIL simulations unfortunately are not “plug and play”, some important considerations have to be made before a PHIL experiment

Georg Lauss; Felix Lehfuss; Alexander Viehweider; Thomas Strasser

2011-01-01

180

In vivo glucose monitoring: Towards ‘Sense and Act’ feedback-loop individualized medical systems  

Microsoft Academic Search

Glucose biosensors are key components of closed-loop glycaemic control (insulin delivery) systems for effective management of diabetes. By providing a fast return of the analytical information in a timely fashion, such sensors offer direct and reliable assessment of rapid changes in the glucose level, as desired for making optimal and timely therapeutic interventions in cases of hypo- and hyperglycemia. The

Joseph Wang

2008-01-01

181

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

NASA Astrophysics Data System (ADS)

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.

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

2005-12-01

182

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

SciTech Connect

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

Crisp, J.

1990-10-25

183

The resource regulation hypothesis and positive feedback loops in plant–herbivore interactions  

Microsoft Academic Search

Resource regulation occurs when herbivory maintains or increases plant susceptibility to further herbivory by the same species.\\u000a A review of the literature indicates it is a widespread plant–animal interaction involving a diverse array of herbivores.\\u000a At least three mechanisms can produce this positive feedback cycle. First, phytophagous insect and mammalian herbivore damage\\u000a can stimulate dormant buds to produce vigorous juvenile

Timothy Paul Craig

2010-01-01

184

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

NASA Astrophysics Data System (ADS)

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.

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

2012-06-01

185

Hunger states switch a flip-flop memory circuit via a synaptic AMPK-dependent positive feedback loop  

PubMed Central

SUMMARY Synaptic plasticity in response to changes in physiologic state is coordinated by hormonal signals across multiple neuronal cell types. Here, we combine cell type-specific electrophysiological, pharmacological, and optogenetic techniques to dissect neural circuits and molecular pathways controlling synaptic plasticity onto AGRP neurons, a population that regulates feeding. We find that food deprivation elevates excitatory synaptic input, which is mediated by a presynaptic positive feedback loop involving AMP-activated protein kinase. Potentiation of glutamate release was triggered by the orexigenic hormone ghrelin and exhibited hysteresis, persisting for hours after ghrelin removal. Persistent activity was reversed by the anorexigenic hormone leptin, and optogenetic photostimulation demonstrated involvement of opioid release from POMC neurons. Based on these experiments, we propose a memory storage device for physiological state constructed from bistable synapses that are flipped between two sustained activity states by transient exposure to hormones signaling energy levels.

Yang, Yunlei; Atasoy, Deniz; Su, Helen H.; Sternson, Scott M.

2011-01-01

186

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

PubMed Central

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

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

2013-01-01

187

A Closed-Loop Digitally Controlled MEMS Gyroscope With Unconstrained Sigma-Delta Force-Feedback  

Microsoft Academic Search

In this paper, we describe the system architecture and prototype measurements of a MEMS gyroscope system with a resolution of 0.025deg\\/s\\/ radic(Hz). The architecture makes extensive use of control loops, which are mostly in the digital domain. For the primary mode both the amplitude and the resonance frequency are tracked and controlled. The secondary mode readout is based on unconstrained

J. Raman; E. Cretu; P. Rombouts; L. Weyten

2009-01-01

188

Drosophila Jing is part of the breathless fibroblast growth factor receptor positive feedback loop  

Microsoft Academic Search

In the developing Drosophila trachea, extensive cell migration lays the foundation for an elaborate network of tubules to form. This process is controlled\\u000a by the Drosophila fibroblast growth factor receptor, known as Breathless (Btl), whose expression is activated by the Trachealess (Trh) and\\u000a Tango (Tgo) basic helix-loop-helix (bHLH)-PAS transcription factors. We previously identified the jing zinc finger transcription factor as

Margaret Sonnenfeld; Tatiana Morozova; Joanne Hackett; Xuetao Sun

2010-01-01

189

Analog control loops for the Milan K800 cyclotron RF system.  

National Technical Information Service (NTIS)

In this paper the design criteria and the main features of the two analog feedback loops which are used to control the phase and the amplitude stability of the Milan Superconducting Cyclotron accelerating voltage are described, together with the resonator...

A. Bosotti C. Pagani M. Di Giacomo A. Gallo

1989-01-01

190

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

NASA Astrophysics Data System (ADS)

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.

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

2014-06-01

191

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

NASA Astrophysics Data System (ADS)

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.

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

2010-09-01

192

Analysis of a sleep-dependent neuronal feedback loop: the slow-wave microcontinuity of the EEG.  

PubMed

Increasing depth of sleep corresponds to an increasing gain in the neuronal feedback loops that generate the low-frequency (slow-wave) electroencephalogram (EEG). We derived the maximum-likelihood estimator of the feedback gain and applied it to quantify sleep depth. The estimator computes the fraction (0%-100%) of the current slow wave which continues in the near-future (0.02 s later) EEG. Therefore, this percentage was dubbed slow-wave microcontinuity (SW%). It is not affected by anatomical parameters such as skull thickness, which can considerably bias the commonly used slow-wave power (SWP). In our study, both of the estimators SW% and SWP were monitored throughout two nights in 22 subjects. Each subject took temazepam (a benzodiazepine) on one of the two nights. Both estimators detected the effects of age, temazepam, and time of night on sleep. Females were found to have twice the SWP of males, but no gender effect on SW% was found. This confirms earlier reports that gender affects SWP but not sleep depth. Subjectively assessed differences in sleep quality between the nights were correlated to differences in SW%, not in SWP. These results demonstrate that slow-wave microcontinuity, being based on a physiological model of sleep, reflects sleep depth more closely than SWP does. PMID:11008419

Kemp, B; Zwinderman, A H; Tuk, B; Kamphuisen, H A; Oberyé, J J

2000-09-01

193

Interrogation of Inhibitor of Nuclear Factor ?B ?/Nuclear Factor ?B (I?B?/NF-?B) Negative Feedback Loop Dynamics  

PubMed Central

Full understanding of the biological significance of negative feedback processes requires interrogation at multiple scales as follows: in single cells, cell populations, and live animals in vivo. The transcriptionally coupled I?B?/NF-?B negative feedback loop, a pivotal regulatory node of innate immunity and inflammation, represents a model system for multiscalar reporters. Using a ?B5?I?B?-FLuc bioluminescent reporter, we rigorously evaluated the dynamics of ??B? degradation and subsequent NF-?B transcriptional activity in response to diverse modes of TNF? stimulation. Modulating TNF? concentration or pulse duration yielded complex, reproducible, and differential ??B? dynamics in both cell populations and live single cells. Tremendous heterogeneity in the transcriptional amplitudes of individual responding cells was observed, which was greater than the heterogeneity in the transcriptional kinetics of responsive cells. Furthermore, administration of various TNF? doses in vivo generated ??B? dynamic profiles in the liver resembling those observed in single cells and populations of cells stimulated with TNF? pulses. This suggested that dose modulation of circulating TNF? was perceived by hepatocytes in vivo as pulses of increasing duration. Thus, a robust bioluminescent reporter strategy enabled rigorous quantitation of NF-?B/??B? dynamics in both live single cells and cell populations and furthermore, revealed reproducible behaviors that informed interpretation of in vivo studies.

Moss, Britney L.; Elhammali, Adnan; Fowlkes, Tiffanie; Gross, Shimon; Vinjamoori, Anant; Contag, Christopher H.; Piwnica-Worms, David

2012-01-01

194

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

PubMed

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

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

2000-07-28

195

Tunable stochastic pulsing in the Escherichia coli multiple antibiotic resistance network from interlinked positive and negative feedback loops.  

PubMed

Cells live in uncertain, dynamic environments and have many mechanisms for sensing and responding to changes in their surroundings. However, sudden fluctuations in the environment can be catastrophic to a population if it relies solely on sensory responses, which have a delay associated with them. Cells can reconcile these effects by using a tunable stochastic response, where in the absence of a stressor they create phenotypic diversity within an isogenic population, but use a deterministic response when stressors are sensed. Here, we develop a stochastic model of the multiple antibiotic resistance network of Escherichia coli and show that it can produce tunable stochastic pulses in the activator MarA. In particular, we show that a combination of interlinked positive and negative feedback loops plays an important role in setting the dynamics of the stochastic pulses. Negative feedback produces a pulsatile response that is tunable, while positive feedback serves to amplify the effect. Our simulations show that the uninduced native network is in a parameter regime that is of low cost to the cell (taxing resistance mechanisms are expressed infrequently) and also elevated noise strength (phenotypic variability is high). The stochastic pulsing can be tuned by MarA induction such that variability is decreased once stresses are sensed, avoiding the detrimental effects of noise when an optimal MarA concentration is needed. We further show that variability in the expression of MarA can act as a bet hedging mechanism, allowing for survival in time-varying stress environments, however this effect is tunable to allow for a fully induced, deterministic response in the presence of a stressor. PMID:24086119

Garcia-Bernardo, Javier; Dunlop, Mary J

2013-01-01

196

Tunable Stochastic Pulsing in the Escherichia coli Multiple Antibiotic Resistance Network from Interlinked Positive and Negative Feedback Loops  

PubMed Central

Cells live in uncertain, dynamic environments and have many mechanisms for sensing and responding to changes in their surroundings. However, sudden fluctuations in the environment can be catastrophic to a population if it relies solely on sensory responses, which have a delay associated with them. Cells can reconcile these effects by using a tunable stochastic response, where in the absence of a stressor they create phenotypic diversity within an isogenic population, but use a deterministic response when stressors are sensed. Here, we develop a stochastic model of the multiple antibiotic resistance network of Escherichia coli and show that it can produce tunable stochastic pulses in the activator MarA. In particular, we show that a combination of interlinked positive and negative feedback loops plays an important role in setting the dynamics of the stochastic pulses. Negative feedback produces a pulsatile response that is tunable, while positive feedback serves to amplify the effect. Our simulations show that the uninduced native network is in a parameter regime that is of low cost to the cell (taxing resistance mechanisms are expressed infrequently) and also elevated noise strength (phenotypic variability is high). The stochastic pulsing can be tuned by MarA induction such that variability is decreased once stresses are sensed, avoiding the detrimental effects of noise when an optimal MarA concentration is needed. We further show that variability in the expression of MarA can act as a bet hedging mechanism, allowing for survival in time-varying stress environments, however this effect is tunable to allow for a fully induced, deterministic response in the presence of a stressor.

Garcia-Bernardo, Javier; Dunlop, Mary J.

2013-01-01

197

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

NASA Technical Reports Server (NTRS)

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.

Connolly, Joseph W.; Kopasakis, George

2010-01-01

198

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

PubMed Central

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 ?-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.

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

199

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

PubMed

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

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

2014-07-11

200

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

PubMed

A central unanswered question in stem cell biology, both in plants and in animals, is how the spatial organization of stem cell niches are maintained as cells move through them. We address this question for the shoot apical meristem (SAM) which harbors pluripotent stem cells responsible for growth of above-ground tissues in flowering plants. We find that localized perception of the plant hormone cytokinin establishes a spatial domain in which cell fate is respecified through induction of the master regulator WUSCHEL as cells are displaced during growth. Cytokinin-induced WUSCHEL expression occurs through both CLAVATA-dependent and CLAVATA-independent pathways. Computational analysis shows that feedback between cytokinin response and genetic regulators predicts their relative patterning, which we confirm experimentally. Our results also may explain how increasing cytokinin concentration leads to the first steps in reestablishing the shoot stem cell niche in vitro. PMID:19717465

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

2009-09-22

201

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

PubMed Central

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.

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

2007-01-01

202

p53 inactivation by MDM2 and MDMX negative feedback loops in testicular germ cell tumors  

PubMed Central

Testicular germ cell tumors (TGCT) are unique in their excellent response to DNA-damaging chemotherapy. Mutation of p53 is rare in both untreated and relapsed TGCTs, suggesting that p53 fails to respond effectively against malignant transformation in germ cells. Previous studies implicated the presence of a poorly defined TGCT-specific mechanism of p53 inactivation. Here we show that disruption of p53-mdm2 binding using the MDM2-specific inhibitor Nutlin activates p53 in TGCT cells and is sufficient to induce strong apoptosis. Knockdown of MDMX cooperates with Nutlin to activate p53. Surprisingly, we found that p53 activation induced a two-fold increase in MDMX mRNA and protein expression in TGCT cells. A p53-responsive promoter is identified in MDMX intron 1 that contains a functional p53-binding site, suggesting that MDMX also functions as a negative feedback regulator of p53 in a cell line-dependent fashion. These findings suggest that MDM2 and MDMX are responsible for the functional inactivation of p53 in TGCT. Furthermore, TGCT cells are unique in having a strong apoptosis response to p53. Direct activation of p53 by targeting MDM2 and MDMX may provide a backup approach for the treatment of TGCTs resistant to DNA-damaging drugs.

Li, Baozong; Cheng, Qian; Li, Zhenyu; Chen, Jiandong

2010-01-01

203

Distinct Roles of DBHS Family Members in the Circadian Transcriptional Feedback Loop  

PubMed Central

Factors interacting with core circadian clock components are essential to achieve transcriptional feedback necessary for metazoan clocks. Here, we show that all three members of the Drosophila behavior human splicing (DBHS) family of RNA-binding proteins play a role in the mammalian circadian oscillator, abrogating or altering clock function when overexpressed or depleted in cells. Although these proteins are members of so-called nuclear paraspeckles, depletion of paraspeckles themselves via silencing of the structural noncoding RNA (ncRNA) Neat1 did not affect overall clock function, suggesting that paraspeckles are not required for DBHS-mediated circadian effects. Instead, we show that the proteins bound to circadian promoter DNA in a fashion that required the PERIOD (PER) proteins and potently repressed E-box-mediated transcription but not cytomegalovirus (CMV) promoter-mediated transcription when they were exogenously recruited. Nevertheless, mice with one or both copies of these genes deleted show only small changes in period length or clock gene expression in vivo. Data from transient transfections show that each of these proteins can either repress or activate, depending on the context. Taken together, our data suggest that all of the DBHS family members serve overlapping or redundant roles as transcriptional cofactors at circadian clock-regulated genes.

Kowalska, Elzbieta; Ripperger, Jurgen A.; Muheim, Christine; Maier, Bert; Kurihara, Yasuyuki; Fox, Archa H.; Kramer, Achim

2012-01-01

204

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

PubMed

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

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

2014-02-01

205

10kV\\/30kA unipolar arbitrary voltage source for Hardware-in-the-Loop Simulation Systems for HVDC circuit breakers  

Microsoft Academic Search

In this paper a novel topology for an unipolar arbitrary voltage source for high power Hardware-in-the-Loop Simulation Systems is presented. The maximal output voltage is 10 kV and a maximal output current of 30 kA can be provided for a duration of 20 ms with a maximal current gradient of 200 A\\/µs. The system enables in-depth research and future developments

C. Carstensen; J. Biela

2011-01-01

206

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

SciTech Connect

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.

Komatsu, Yoko; Ito, Ichiaki; Wayama, Mitsutoshi; Fujimura, Akiko; Akaogi, Kensuke; Machida, Hikaru; Nakajima, Yuka; Kuroda, Takao; Ohmori, Kazuji; Murayama, Akiko; Kimura, Keiji [Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba Science City, Ibaraki 305-8572 (Japan); Yanagisawa, Junn [Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba Science City, Ibaraki 305-8572 (Japan)], E-mail: junny@agbi.tsukuba.ac.jp

2008-05-23

207

A positive feedback loop between EBP2 and c-Myc regulates rDNA transcription, cell proliferation, and tumorigenesis  

PubMed Central

The oncoprotein c-Myc is a key transcription factor with essential functions in the nucleolus (NO) to regulate ribosomal RNA (rRNA) synthesis, ribosome biogenesis, and cell proliferation. Yet, the mechanism that regulates the distribution and function of nucleolar c-Myc is still not completely understood. In this study, we identified nucleolar protein ENBA1 binding protein 2 (EBP2) as a novel functional binding partner of c-Myc. We found that coexpression of EBP2 markedly relocalized c-Myc from the nucleus to the NO, whereas depletion of EBP2 reduced the nucleolar distribution of c-Myc. Further study indicated that EBP2 is a direct binding partner of c-Myc and can block the degradation of c-Myc in a FBW7 (F-box and WD repeat domain containing 7)-independent manner. Moreover, EBP2 is a transcriptional target of c-Myc. c-Myc can bind to the promoter of EBP2 and positively regulate the EBP2 expression. Both protein and mRNA levels of EBP2 are upregulated in lung cancer samples and positively correlated with c-Myc expression. Functionally, EBP2 promotes c-Myc-mediated rRNA synthesis and cell proliferation. Collectively, our study indicates that EBP2 is a novel binding partner of c-Myc that regulates the function of nucleolar c-Myc, cell proliferation, and tumorigenesis via a positive feedback loop.

Liao, P; Wang, W; Shen, M; Pan, W; Zhang, K; Wang, R; Chen, T; Chen, Y; Chen, H; Wang, P

2014-01-01

208

Actin-regulated feedback loop based on Phactr4, PP1 and cofilin maintains the actin monomer pool.  

PubMed

Phactr proteins bind actin and protein phosphatase 1 (PP1), and are involved in processes ranging from angiogenesis to cell cycle regulation. Phactrs share a highly conserved RPEL domain with the myocardin-related transcription factor (MRTF) family, where actin binding to this domain regulates both the nuclear localization and the activity of these transcription coactivators. We show here that in contrast to MRTF-A, the RPEL domain is dispensable for the subcellular localization of Phactr4. Instead, we find the domain facilitating competitive binding of monomeric actin and PP1 to Phactr4. Binding of actin to Phactr4 influences the activity of PP1 and the phosphorylation status of one of its downstream targets, cofilin. Consequently, at low actin monomer levels, Phactr4 guides PP1 to dephosphorylate cofilin. This active form of cofilin is then able to sever and depolymerize actin filaments and thus restore the actin monomer pool. Accordingly, our data discloses the central role of Phactr4 in a feedback loop, where actin monomers regulate their own number via the activation of a key regulator of actin dynamics. Depending on the protein context, the RPEL domain can thus elicit mechanistically different responses to maintain the cellular actin balance. PMID:23203801

Huet, Guillaume; Rajakylä, Eeva Kaisa; Viita, Tiina; Skarp, Kari-Pekka; Crivaro, Marko; Dopie, Joseph; Vartiainen, Maria K

2013-01-15

209

Role of miR-17 Family in the Negative Feedback Loop of Bone Morphogenetic Protein Signaling in Neuron  

PubMed Central

Bone morphogenetic protein (BMP) signaling is active in many tissues including the central nervous system, in which it regulates cell proliferation, differentiation and maturation. The modulation of BMP pathway is crucial since abnormality of BMP signaling may cause cellular malfunction such as apoptosis. There are evidences indicating that miR-17 family is involved in the BMP signaling. In the present study, we demonstrated that BMP2 stimulation directly increased the transcription of miR-17-92 and miR-106b-25 cluster via Smad activation, which leads to the up-regulation of mature miR-17/20a/93. In addition, we provided evidence that BMP2 activation repressed BMPRII expression through modulating miR-17 family in primary neurons. Furthermore, we proved that such negative regulation protected neurons from apoptosis induced by abnormal BMP signaling. Taken together, these results suggest a regulatory pathway of BMP-miR-17 family-BMPRII, which consist a negative feedback loop that balances BMP signaling and maintains cell homeostasis in neurons.

Li, Hanqin; Zen, Ke; Zhang, Chen-Yu; Li, Liang

2013-01-01

210

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

PubMed Central

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

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

2013-01-01

211

Interaction of Apoptotic Cells with Macrophages Upregulates COX-2/PGE2 and HGF Expression via a Positive Feedback Loop  

PubMed Central

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

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

2014-01-01

212

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

SciTech Connect

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.

Lai, Serene R. [Department of Biology, University of Alabama at Birmingham, AL 35294 (United States); Cunningham, Amanda P. [Department of Biology, University of Alabama at Birmingham, AL 35294 (United States); Huynh, Vu Q.; Andrews, Lucy G. [Department of Biology, University of Alabama at Birmingham, AL 35294 (United States); Tollefsbol, Trygve O. [Department of Biology, University of Alabama at Birmingham, AL 35294 (United States) and Center for Aging, University of Alabama at Birmingham, AL 35294 (United States) and Comprehensive Cancer Center, University of Alabama at Birmingham, AL 25294 (United States)]. E-mail: trygve@uab.edu

2007-01-15

213

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

PubMed

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. PMID:24583132

Kido, Tatsuo; Lau, Yun-Fai Chris

2014-03-28

214

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

PubMed

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

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

2013-04-23

215

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

PubMed

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

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

2013-12-01

216

Blockage of a miR-21/EGFR regulatory feedback loop augments anti-EGFR therapy in glioblastomas.  

PubMed

Epidermal growth factor receptors (EGFR) expression is frequently amplified in human glioblastoma cells. Nimotuzumab, a monoclonal antibody (mAb) against EGFR, has been used globally in clinics as an anti-cancer agent. It is largely unknown whether the blockade of miR-21, a microRNA that is upregulated in glioma cells, could amplify the effects of nimotuzumab. Herein, we have demonstrated that miR-21 directly targets von Hippel-Lindau (VHL) and peroxisome-proliferator-activated receptor ? (PPAR?) and that miR-21 regulates EGFR/AKT signaling through VHL/?-catenin and the PPAR?/AP-1 axis. Further, the expression of miR-21 is regulated by EGFR via the activation of ?-catenin and AP-1. These data indicate that a feedback loop exists between miR-21 and EGFR. We also show that the combination of nimotuzumab and an inhibitor of miR-21 is superior to single-agent therapy. These results clarify a novel association between miR-21 and EGFR in the regulation of cancer cell progression. PMID:24012640

Zhang, Kai-Liang; Han, Lei; Chen, Lu-Yue; Shi, Zhen-Dong; Yang, Ming; Ren, Yu; Chen, Ling-Chao; Zhang, Jun-Xia; Pu, Pei-Yu; Kang, Chun-Sheng

2014-01-01

217

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

NASA Technical Reports Server (NTRS)

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.

Bearden, Douglas B. (Inventor)

2007-01-01

218

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

NASA Technical Reports Server (NTRS)

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.

Bearden, Douglas B. (Inventor)

2007-01-01

219

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

NASA Astrophysics Data System (ADS)

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

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

2014-05-01

220

Phase-shifting interferometry by an open-loop voltage controlled laser diode  

NASA Astrophysics Data System (ADS)

The paper presents a simple and straightforward procedure for determining the phase of an interferogram by exploiting the specific behavior of laser diodes—i.e., the small variation of the operating wavelength attainable by varying the forward current of the diode. The proposed procedure was developed by using a laser diode for feeding a quasi-balanced Michelson interferometer, by which the optimal operating conditions were investigated—i.e., the proper unbalancing and the proper variation of the supply voltage of the diode. The selected operating conditions were then used for evaluating the phase-steps by a simple algorithm developed on purpose for the present application. The phase measurements carried out by the proposed method have shown a very good accordance with those obtained by a conventional temporal phase-shifting procedure performed by a high-end commercial PZT actuator with quasi-nanometric accuracy.

Bruno, Luigi; Poggialini, Andrea

2013-03-01

221

Assessing the impact of thermal feedback and recycling in open-loop groundwater heat pump (GWHP) systems: a complementary design tool  

NASA Astrophysics Data System (ADS)

Thermal feedback and thermal recycling in open-loop groundwater heat pump (GWHP) systems occurs when a fraction of the injected water in a well doublet returns to the production well. They reflect two different mathematical representations of the same physical process. Thermal feedback assumes a constant injection temperature, while thermal recycling couples the injection and production temperatures by a constant temperature difference. It is shown that thermal feedback, commonly used in GWHP design, and recycling reflect two thermal end-members. This work addresses the coupled problem of thermal recycling, which is, so far, the missing link for complete GWHP assessment. An analytical solution is presented to determine the return-flow fraction in a well doublet and is combined with a heat-balance calculation to determine the steady-state well temperatures in response to thermal feedback and recycling. This is then extended to advective-dispersive systems using transfer functions, revealing that the well temperatures in response to thermal feedback and recycling are functions of the capture probability. Conjunctive interpretation of thermal feedback and recycling yields a novel design approach with which major difficulties in the assessment of the sustainability of GWHP systems can be addressed.

Milnes, Ellen; Perrochet, Pierre

2013-03-01

222

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

PubMed Central

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

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

2013-01-01

223

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

PubMed

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

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

2013-06-01

224

Position Control of Electron Energy Loss Spectrum in Case of Accelerating-Voltage Fluctuation  

NASA Astrophysics Data System (ADS)

In the parallel detection EELS, the fluctuation effect of the accelerating voltage is compensated both by the open loop and negative feedback controls. The fundamental frequency components of the AC power line and the excitation of Cockcroft-Walton circuit are canceled by applying the inverse-phase signal to the deflection coil, while the effect from the drift and the higher-order ripples is controlled by the negative feedback. The energy resolution is increased from 9.3 eV to 5.7 eV by the open loop control and can be improved up to 3.8 eV by the negative feedback. As the loop gain increases, the resolution increases at first, but then decreases. This decrease results from the shot noise of electron beam and the phase shift of the feedback loop. It is theoretically shown that the optimum condition to the loop gain and the bandwidth exists for the feedback control.

Yoshida, Kiyokazu; Takaoka, Akio; Ura, Katsumi; Fujita, Hiroshi

1990-11-01

225

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

PubMed Central

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.

Seydel, U; Jans, D A

1996-01-01

226

HGF/c-met/Stat3 signaling during skin tumor cell invasion: indications for a positive feedback loop  

PubMed Central

Background Stat3 is a cytokine- and growth factor-inducible transcription factor that regulates cell motility, migration, and invasion under normal and pathological situations, making it a promising target for cancer therapeutics. The hepatocyte growth factor (HGF)/c-met receptor tyrosine kinase signaling pathway is responsible for stimulation of cell motility and invasion, and Stat3 is responsible for at least part of the c-met signal. Methods We have stably transfected a human squamous cell carcinoma (SCC) cell line (SRB12-p9) to force the expression of a dominant negative form of Stat3 (S3DN), which we have previously shown to suppress Stat3 activity. The in vitro and in vivo malignant behavior of the S3DN cells was compared to parental and vector transfected controls. Results Suppression of Stat3 activity impaired the ability of the S3DN cells to scatter upon stimulation with HGF (c-met ligand), enhanced their adhesion, and diminished their capacity to invade in vitro and in vivo. Surprisingly, S3DN cells also showed suppressed HGF-induced activation of c-met, and had nearly undetectable basal c-met activity, as revealed by a phospho-specific c-met antibody. In addition, we showed that there is a strong membrane specific localization of phospho-Stat3 in the wild type (WT) and vector transfected control (NEO4) SRB12-p9 cells, which is lost in the S3DN cells. Finally, co-immunoprecipitation experiments revealed that S3DN interfered with Stat3/c-met interaction. Conclusion These studies are the first confirm that interference with the HGF/c-met/Stat3 signaling pathway can block tumor cell invasion in an in vivo model. We also provide novel evidence for a possible positive feedback loop whereby Stat3 can activate c-met, and we correlate membrane localization of phospho-Stat3 with invasion in vivo.

2011-01-01

227

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

PubMed Central

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.

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

2014-01-01

228

Activation of a positive feedback loop involving IL-6 and aromatase promotes intratumoral 17?-estradiol biosynthesis in endometrial carcinoma microenvironment.  

PubMed

Tumor-stroma interactions contribute greatly to intratumoral estrogen biosynthesis in endometrial carcinoma, but the mechanisms involved remain largely unknown. Previous study demonstrated that intratumoral aromatase upregulation in stromal cells participated in this process, but the specific aromatase-regulators have not been reported. In the present study, we found that aromatase expression in intratumoral stroma, but not in tumor epithelium, correlated positively with interleukin 6 (IL-6) expression in cancer epithelial cells by immunohistochemistry, which was confirmed using laser capture microdissection/real-time reverse transcription-PCR. With stimulation by exogenous IL-6, aromarase expression was increased in stromal cells not but not in cancer cells. Aromatase mRNA levels in endometrial cancer cells were not influenced by cocultivation with intratumoral stromal cells. When cocultured with 17?-estradiol (E2 )-treated cancer cells, aromatase mRNA in stromal cells was significantly elevated and increased IL-6 protein levels were detected in E2 -treated culture medium. Next, we demonstrated that E2 -induced IL-6 production was through cooperation between estrogen receptor ? and nuclear factor-kappa B. Furthermore, an IL-6 receptor blocking antibody could attenuate the upregulation of aromatase expression in stromal cells and the E2 concentration in coculture systems of cancer and stromal cells. The results were confirmed by an orthotopic nude endometrial carcinoma model in vivo. These studies elucidated the activation of a positive feedback loop, that is, IL-6 stimulated by E2 in endometrial cancer cells induced aromatase expression in stromal cells, promoting enhanced intratumoral E2 synthesis. Blocking of this tumor-stroma interaction may be a therapeutic strategy to overcome in situ estrogen biosynthesis in endometrial carcinoma. PMID:24347287

Che, Qi; Liu, Bin-Ya; Liao, Yun; Zhang, Hui-Juan; Yang, Ting-Ting; He, Yin-Yan; Xia, Yu-Hong; Lu, Wen; He, Xiao-Ying; Chen, Zheng; Wang, Fang-Yuan; Wan, Xiao-Ping

2014-07-15

229

A Study of Dual-loop Control Scheme and Corresponding Neutral-point Voltage Balance Control Method for Three-level PWM Rectifiers  

Microsoft Academic Search

The mathematical model of the three-level PWM rectifiers is set up in this paper. By comparing it with the model of DC motors, some similarities are established. Based on the state feedback decoupling, the dual-loop close control scheme of DC motors is implemented to three-level PWM rectifiers. As a result, the three-level rectifier has favorable dynamic and steady state performance,

Lin Lei; Zhong Heqing; Deng Yu; Zhang Jie; Zou Yunping; She Xu

2009-01-01

230

Acidic Amino Acids in the First Intracellular Loop Contribute to Voltage- and Calcium- Dependent Gating of Anoctamin1/TMEM16A  

PubMed Central

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

Xiao, Qinghuan; Cui, Yuanyuan

2014-01-01

231

A Negative Feedback Loop That Limits the Ectopic Activation of a Cell Type-Specific Sporulation Sigma Factor of Bacillus subtilis  

PubMed Central

Two highly similar RNA polymerase sigma subunits, ?F and ?G, govern the early and late phases of forespore-specific gene expression during spore differentiation in Bacillus subtilis. ?F drives synthesis of ?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 ?G while discriminating between ?F and ?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 ?G (N45E) strongly reduced binding by a previously characterized anti-sigma factor, CsfB (also known as Gin), in vitro, and increased the activity of ?G in vivo. The N45E mutation caused the appearance of a sub-population of pre-divisional cells with strong activity of ?G. CsfB is normally produced in the forespore, under ?F control, but sigGN45E mutant cells also expressed csfB and did so in a ?G-dependent manner, autonomously from ?F. Thus, a negative feedback loop involving CsfB counteracts the positive feedback loop resulting from ectopic ?G activity. N45 is invariant in the homologous position of ?G orthologues, whereas its functional equivalent in ?F proteins, E39, is highly conserved. While CsfB does not bind to wild-type ?F, a E39N substitution in ?F resulted in efficient binding of CsfB to ?F. Moreover, under certain conditions, the E39N alteration strongly restrains the activity of ?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.

Serrano, Monica; Carneiro, Jorge; Moran, Charles P.; Henriques, Adriano O.

2011-01-01

232

PANET: A GPU-Based Tool for Fast Parallel Analysis of Robustness Dynamics and Feed-Forward/Feedback Loop Structures in Large-Scale Biological Networks  

PubMed Central

It has been a challenge in systems biology to unravel relationships between structural properties and dynamic behaviors of biological networks. A Cytoscape plugin named NetDS was recently proposed to analyze the robustness-related dynamics and feed-forward/feedback loop structures of biological networks. Despite such a useful function, limitations on the network size that can be analyzed exist due to high computational costs. In addition, the plugin cannot verify an intrinsic property which can be induced by an observed result because it has no function to simulate the observation on a large number of random networks. To overcome these limitations, we have developed a novel software tool, PANET. First, the time-consuming parts of NetDS were redesigned to be processed in parallel using the OpenCL library. This approach utilizes the full computing power of multi-core central processing units and graphics processing units. Eventually, this made it possible to investigate a large-scale network such as a human signaling network with 1,609 nodes and 5,063 links. We also developed a new function to perform a batch-mode simulation where it generates a lot of random networks and conducts robustness calculations and feed-forward/feedback loop examinations of them. This helps us to determine if the findings in real biological networks are valid in arbitrary random networks or not. We tested our plugin in two case studies based on two large-scale signaling networks and found interesting results regarding relationships between coherently coupled feed-forward/feedback loops and robustness. In addition, we verified whether or not those findings are consistently conserved in random networks through batch-mode simulations. Taken together, our plugin is expected to effectively investigate various relationships between dynamics and structural properties in large-scale networks. Our software tool, user manual and example datasets are freely available at http://panet-csc.sourceforge.net/.

Trinh, Hung-Cuong; Le, Duc-Hau; Kwon, Yung-Keun

2014-01-01

233

Nitric oxide augments voltage-gated P\\/Q-type Ca 2+ channels constituting a putative positive feedback loop  

Microsoft Academic Search

P\\/Q-type Ca2+ channels, which are postulated to play major roles in synaptic transmission, are regulated in a variety of ways. Ca2+ currents through P\\/Q-type Ca2+ channels (Cav2.1\\/?1a\\/?2?) heterologously expressed in mammalian cells were recorded using the whole-cell patch clamp method. The oxidant H2O2 increased the current amplitude and the effect was reversed by the reducing agent dithiothreitol (DTT). The stimulatory

Jianguo Chen; Heather Daggett; Michel De Waard; S. H Heinemann; Toshinori Hoshi

2002-01-01

234

HER2 Phosphorylation Is Maintained by a PKB Negative Feedback Loop in Response to Anti-HER2 Herceptin in Breast Cancer  

PubMed Central

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

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

2010-01-01

235

Feedback Configuration Tools for LHC Low Level RF System.  

National Technical Information Service (NTIS)

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...

A. Butterworth C. Rivetta D. Van Winkle J. Fox J. Molendijk P. Baudrenghien T. Mastorides

2012-01-01

236

Active Voltage control of IGBTs for high power applications  

Microsoft Academic Search

The operation of an insulated gate bipolar transistor (IGBT) in its active region is a well established technique for withstanding short circuits and also for dv\\/dt control. In this paper, we exploit the active behavior of the IGBT, applying a voltage feedback loop to the IGBT to control its switching. It is shown that adding a bias to the demand

Patrick R. Palmer; Haile S. Rajamani

2004-01-01

237

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

NASA Technical Reports Server (NTRS)

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.

Bragg-Sitton, Shannon M.; Forsbacka, Matthew

2004-01-01

238

A Cost-effective Sub-terahertz Continuous Wave Generation Scheme Using a Broadband Optical Source and An Optical Feedback Loop  

NASA Astrophysics Data System (ADS)

We have proposed a cost-effective sub-terahertz (THz) continuous wave (CW) generation scheme based on a usual double sideband-suppressed carrier (DSB-SC) scheme. The usual DSB-SC scheme, which consists of a discrete optical source, an optical intensity modulator (OIM), a local oscillator (LO), an optical notch filter, and an erbium doped fiber amplifier (EDFA), is one of well-known photonic-based sub-THz CW generation schemes. As the discrete optical source of the usual DSB-SC scheme is eliminated and an optical feedback loop is incorporated with the usual DSB-SC scheme, our proposed scheme is constructed to decrease implementation costs. Without an optical input, the output of the pump laser of the DC-biased EDFA is inserted to the optical notch filter. Reflected lightwaves with fiber bragg grating wavelengths of the optical notch filter is fed back to the input of the OIM through the optical feedback loop, which is composed of a circulator and a 90:10-coupler. DSB-SC lightwaves have been made by modulating feedbacked lightwaves on the OIM with the frequency of the LO. A sub-THz CW is generated by photomixing them. To verify feasibility of our proposed scheme, we generated and characterized a 120 GHz CW. The measurement results were also compared to those of the usual DSB-SC scheme. Based on our measurement results, we found that characteristics of the generated 120 GHz CW using our proposed scheme are comparable to those using the usual DSB-SC scheme. Consequently, our proposed scheme can be helpful to make a cost-effective sub-THz CW generator based on photonics.

Kim, Sungil; Ahn, Seung-Ho

2013-02-01

239

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

PubMed Central

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-?B–regulated 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.

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

240

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

NASA Technical Reports Server (NTRS)

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

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

1978-01-01

241

Effects of cascade length, kinetics, and feedback loops on biological signal transduction dynamics in a simplified cascade model  

PubMed Central

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

Qu, Zhilin; Vondriska, Thomas M.

2009-01-01

242

Enhanced continuous-variable entanglement by a self-phase-locked type-II optical parameter oscillator with feedback loops  

NASA Astrophysics Data System (ADS)

We consider a three-level cascade laser with a self-phase-locked type-II nondegenerate optical parameter oscillator via a homodyne-mediate quantum feedback. Applying the pertinent master equation, we investigate the squeezing, entanglement properties and the mean photon number produced by our system. It is found that highly squeezed and macroscopic entangled light with high intensity can be generated.

Ma, Yong-Hong; Mu, Qing-Xia; Yang, Guo-Hui; Zhou, Ling

2008-11-01

243

Microgyroscope with closed loop output  

NASA Technical Reports Server (NTRS)

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

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

2002-01-01

244

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

PubMed Central

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

Kolesnikova, Olga; Back, Regis; Graille, Marc; Seraphin, Bertrand

2013-01-01

245

Effects of voltage unbalance and harmonics on three-phase SPWM AC-to-DC converters with instantaneous power feedback  

Microsoft Academic Search

A PWM three-phase AC-to-DC converter with unity input power factor can be approached by setting the required active power and setting reactive power to zero in the instantaneous reactive power theory. The instantaneous reactive power theory, proposed by Akagi, is usually used to design reactive power and harmonic compensators, and it is based on a balanced three-phase voltage source. But,

Wen-Inne Tsai; Ming-Tsung Tsai; York-Yih Sun

1993-01-01

246

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

NASA Technical Reports Server (NTRS)

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

Birchenough, A. G.

1975-01-01

247

Disruption of negative feedback loop between vasohibin-1 and vascular endothelial growth factor decreases portal pressure, angiogenesis, and fibrosis in cirrhotic rats.  

PubMed

Pathological angiogenesis represents a critical hallmark for chronic liver diseases. Understanding the mechanisms regulating angiogenesis is essential to develop new therapeutic strategies that specifically target pathological angiogenesis without affecting physiological angiogenesis. Here we investigated the contribution and therapeutic impact of the endogenous angioinhibitor vasohibin-1 in portal hypertension and cirrhosis. The spatiotemporal expression profiling of vasohibin-1 and its relationship with vascular endothelial growth factor (VEGF), angiogenesis, and fibrogenesis was determined through the analysis of human cirrhotic liver specimens, widely accepted in vivo animal models of portal hypertension and cirrhosis, and in vitro angiogenesis assays. Effects of vasohibin-1 overexpression by adenoviral-mediated gene transfer on angiogenesis, fibrogenesis, and portal hypertension-associated hemodynamic alterations were also studied in rats. We found that vasohibin-1 and VEGF are up-regulated, in mesentery and liver, in cirrhotic and precirrhotic portal hypertensive rats and cirrhosis patients. Our results are consistent with vasohibin-1/VEGF cascades being spatially and temporally coordinated through a negative-feedback loop driving pathological angiogenesis. Paradoxically, further overexpression of vasohibin-1 by adenoviral gene transfer exerts multifold beneficial effects in portal hypertension and cirrhosis: reduction of pathologic angiogenesis, attenuation of liver fibrogenesis partly mediated through inhibition of hepatic stellate cell activation, and significant decreases in portocollateralization, splanchnic blood flow, portohepatic resistance, and portal pressure. The explanation for this apparent contradiction is that, unlike endogenous vasohibin-1, the ectopic overexpression is not regulated by VEGF and therefore disrupts the negative-feedback loop, thus generating constant, but lower levels of VEGF synthesis sufficient to maintain vascular homeostasis but not pathological angiogenesis. Conclusion: Our study provides evidence that vasohibin-1 regulates portal hypertension-associated pathological angiogenesis and highlights that increasing vasohibin-1 might be a promising novel therapeutic strategy for portal hypertension and cirrhosis. (Hepatology 2014;60:633-647). PMID:24390792

Coch, Laura; Mejias, Marc; Berzigotti, Annalisa; Garcia-Pras, Ester; Gallego, Javier; Bosch, Jaime; Mendez, Raul; Fernandez, Mercedes

2014-08-01

248

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

PubMed Central

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.

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

2011-01-01

249

A novel bidirectional positive-feedback loop between Wnt-?-catenin and EGFR-ERK plays a role in context-specific modulation of epithelial tissue regeneration  

PubMed Central

ABSTRACT By operating as both a subunit of the cadherin complex and a key component of Wnt signalling, ?-catenin acts as the lynchpin between cell–cell contact and transcriptional regulation of proliferation, coordinating epithelial tissue homeostasis and regeneration. The integration of multiple growth-regulatory inputs with ?-catenin signalling has been observed in cancer-derived cells, yet the existence of pathway crosstalk in normal cells is unknown. Using a highly regenerative normal human epithelial culture system that displays contact inhibition, we demonstrate that the receptor tyrosine kinase (RTK)-driven MAPK and Wnt–?-catenin signalling axes form a bidirectional positive-feedback loop to drive cellular proliferation. We show that ?-catenin both drives and is regulated by proliferative signalling cues, and its downregulation coincides with the switch from proliferation to contact-inhibited quiescence. We reveal a novel contextual interrelationship whereby positive and negative feedback between three major signalling pathways – EGFR–ERK, PI3K–AKT and Wnt–?-catenin – enable autocrine-regulated tissue homeostasis as an emergent property of physical interactions between cells. Our work has direct implications for normal epithelial tissue homeostasis and provides insight as to how dysregulation of these pathways could drive excessive and sustained cellular growth in disease.

Georgopoulos, Nikolaos T.; Kirkwood, Lisa A.; Southgate, Jennifer

2014-01-01

250

Altering Expression of Cinnamic Acid 4-Hydroxylase in Transgenic Plants Provides Evidence for a Feedback Loop at the Entry Point into the Phenylpropanoid Pathway1  

PubMed Central

Pharmacological evidence implicates trans-cinnamic acid as a feedback modulator of the expression and enzymatic activity of the first enzyme in the phenylpropanoid pathway, l-phenylalanine ammonia-lyase (PAL). To test this hypothesis independently of methods that utilize potentially non-specific inhibitors, we generated transgenic tobacco lines with altered activity levels of the second enzyme of the pathway, cinnamic acid 4-hydroxylase (C4H), by sense or antisense expression of an alfalfa C4H cDNA. PAL activity and levels of phenylpropanoid compounds were reduced in leaves and stems of plants in which C4H activity had been genetically down-regulated. However, C4H activity was not reduced in plants in which PAL activity had been down-regulated by gene silencing. In crosses between a tobacco line over-expressing PAL from a bean PAL transgene and a C4H antisense line, progeny populations harboring both the bean PAL sense and C4H antisense transgenes had significantly lower extractable PAL activity than progeny populations harboring the PAL transgene alone. Our data provide genetic evidence for a feedback loop at the entry point into the phenylpropanoid pathway that had previously been inferred from potentially artifactual pharmacological experiments.

Blount, Jack W.; Korth, Kenneth L.; Masoud, Sameer A.; Rasmussen, Susanne; Lamb, Chris; Dixon, Richard A.

2000-01-01

251

A CD40/CD40L feedback loop drives the breakdown of CD8(+) T-cell tolerance following depletion of suppressive CD4(+) T cells.  

PubMed

Dendritic cells (DCs) are the key APCs not only for the priming of naïve T cells, but also for the induction and maintenance of peripheral T-cell tolerance. We have recently shown that cognate interactions between Foxp3(+) Tregs and steady-state DCs are crucial to maintain the tolerogenic potential of DCs. Using DIETER mice, which allow the induction of antigen presentation selectively on DCs without altering their maturation status, we show here that breakdown of CD8(+) T-cell tolerance, which ensues after depletion of suppressive CD4(+) T cells, is driven by a positive feedback loop in which autoreactive CD8(+) T cells activate DCs via CD40. These data identify ligation of CD40 on DCs as a stimulus that promotes autoreactive T-cell priming when regulatory T-cell suppression fails and suggest that feedback from autoreactive T cells to DCs may contribute to the well-documented involvement of CD40 in many autoimmune diseases. PMID:24420080

Muth, Sabine; Schütze, Kristian; Hain, Tobias; Yagita, Hideo; Schild, Hansjörg; Probst, Hans Christian

2014-04-01

252

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

SciTech Connect

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.

Vuckovic, V.; Vukosavic, S. (Electrical Engineering Inst. Nikola Tesla, Viktora Igoa 3, Belgrade, 11000 (Yugoslavia))

1992-01-01

253

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

NASA Astrophysics Data System (ADS)

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.

Vachirasricirikul, Sitthidet; Ngamroo, Issarachai; Kaitwanidvilai, Somyot

254

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

PubMed Central

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

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

2003-01-01

255

Robust Model-Following Control for the Current Loop of a Medium Voltage Neutral Point Clamped Active Filter  

Microsoft Academic Search

This work presents a robust model-following control technique applied to the current loop of a three phase shunt active filter based on an NPC inverter. A modelling procedure for implementing the proposed control is also shown. The transfer functions for the control of the currents injected by the active filter in the synchronous dq frame have been derived. The proposed

Alejandro Munduate; Ifiigo Garin; Gabriel Garcera; Emilio Figueres

2007-01-01

256

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

SciTech Connect

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.

Horan, D.

1999-04-13

257

Activation of Extracellular Signal-Regulated Kinase 5 Reduces Cardiac Apoptosis and Dysfunction via Inhibition of a Phosphodiesterase 3A/Inducible cAMP Early Repressor Feedback Loop  

PubMed Central

Substantial evidence suggests that the progressive loss of cardiomyocytes caused by apoptosis significantly contributes to the development of heart failure. ?-Adrenergic receptor activation and subsequent persistent phosphodiesterase 3A (PDE3A) downregulation and concomitant inducible cAMP early repressor (ICER) upregulation (PDE3A/ICER feedback loop) has been proposed to play a key role in the pathogenesis of cardiomyocyte apoptosis. In contrast, insulin-like growth factor-1 can activate cell survival pathways, providing protection against cell death and restoring muscle function. In this study, we found that insulin-like growth factor-1 activates extracellular signal-regulated kinase 5 (ERK5) and inhibits PDE3A/ICER feedback loop. Insulin-like growth factor-1 normalized isoproterenol-mediated PDE3A downregulation and ICER upregulation via ERK5/MEF2 activation, and also inhibited isoproterenol-induced myocyte apoptosis. To determine the physiological relevance of ERK5 activation in regulating PDE3A/ICER feedback loop, we investigated the PDE3A/ICER expression and cardiomyocyte apoptosis in transgenic mice with cardiac specific expression of a constitutively active form of mitogen-activated protein (MAP)/extracellular signal-regulated protein kinase (ERK) kinase 5? (MEK5?) (CA-MEK5?-Tg). In wild-type mice, pressure overload– or doxorubicin-induced significant reduction of PDE3A expression and subsequent ICER induction. Cardiac specific expression of CA-MEK5? rescued pressure overload– or doxorubicin-mediated PDE3A downregulation and ICER upregulation and inhibited myocyte apoptosis as well as subsequent cardiac dysfunction in vivo. These data suggest that preventing the feedback loop of PDE3A/ICER by ERK5 activation could inhibit progression of myocyte apoptosis as well as cardiac dysfunction. These data suggest a new therapeutic paradigm for end stage of heart failure by inhibiting the PDE3A/ICER feedback loop via activating ERK5.

Yan, Chen; Ding, Bo; Shishido, Tetsuro; Woo, Chang-Hoon; Itoh, Seigo; Jeon, Kye-Im; Liu, Weimin; Xu, Haodong; McClain, Carolyn; Molina, Carlos A.; Blaxall, Burns C.; Abe, Jun-ichi

2014-01-01

258

Feedback control of chlorine inductively coupled plasma etch processing  

SciTech Connect

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

Lin Chaung; Leou, K.-C.; Shiao, K.-M. [Department of Engineering and System Science, National Tsing Hua University, 100, section 2, Kuang Fu Road, Hsinchu, Taiwan 30043 (China)

2005-03-01

259

DSP-based closed-loop control of bi-directional voltage mode high frequency link inverter with active clamp  

Microsoft Academic Search

This paper presents a novel modulation and digital controller based on a bi-directional voltage mode high frequency link inverter with active clamp to achieve fast dynamic response and high static performance. The inverter consists of a full-bridge converter, a bi-directional active rectifier, an active clamp branch and a pulse width modulation (SPWM) inverter bridge. A novel modulation strategy is applied

Zhao Qinglin; Xu Yunhua; Jin Xiaoyi; Wu Weiyang; Cao Lingling

2005-01-01

260

Pax-2 and N-myc regulate epithelial cell proliferation and apoptosis in a positive autocrine feedback loop.  

PubMed

Both paired homeo box-2 (Pax-2) and N-myc genes play pivotal roles in renal morphogenesis via their effects on cell proliferation and differentiation, but whether and how they interact have not been addressed. In the present study, we investigated such a potential interaction using embryonic renal cells in vitro. Mouse embryonic mesenchymal (MK4) cells stably transfected with Pax-2 cDNA in sense (+) or antisense (-) orientation were used for experiments. Pax-2 promoter activity was monitored by luciferase assay. Reactive oxygen species (ROS) generation, cell proliferation, and cell apoptosis were evaluated. We found that Pax-2 and N-myc gene expression were upregulated and downregulated in Pax-2 (+) and Pax-2 (-) stable transformants, respectively. ROS generation and apoptosis were significantly reduced both in Pax-2 (+) transformants compared with Pax-2 (-) transformants and in naïve MK4 cells cultured in either normal- (5 mM) or high-glucose (25 mM) medium. Transient transfection of N-myc cDNA into Pax-2 (-) stable transformants restored Pax-2 gene expression and prevented ROS generation induced by high glucose. Our data demonstrate that Pax-2 gene overexpression prevents hyperglycemia-induced apoptosis, and N-myc appears to provide a positive autocrine feedback on Pax-2 gene expression in embryonic mesenchymal cells. PMID:17357786

Zhang, Shao-Ling; Chen, Yun-Wen; Tran, Stella; Liu, Fang; Nestoridi, Eirini; Hébert, Marie-Josée; Ingelfinger, Julie R

2007-06-01

261

New soft-switching inverter with auxiliary resonant snubbers using pulse current feedback transformer  

Microsoft Academic Search

In this paper, a practical design procedure for prototype of the auxiliary resonant commutated snubber circuit (ARCS) incorporating a current feedback frequency transformer with power regeneration loop is described. For three phase voltage fed soft-switching inverter, soft-switching active power filter and reactive power compensator. This topology has significant merit of effective current rating reduction for auxiliary active switching devices in

H. Yamamoto; H. Iwamoto; H. Hattori; M. Nakaoka

1999-01-01

262

Fast flux locked loop  

DOEpatents

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.

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

2002-09-10

263

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

PubMed

Platelet-derived growth factor BB and its receptor (PDGFR?) 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

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

264

Multiple high voltage output DC-to-DC power converter  

NASA Technical Reports Server (NTRS)

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

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

1977-01-01

265

A three-component signalling system fine-tunes expression kinetics of HPPK responsible for folate synthesis by positive feedback loop during stress response of Xanthomonas campestris.  

PubMed

During adaptation to environments, bacteria employ two-component signal transduction systems, which contain histidine kinases and response regulators, to sense and respond to exogenous and cellular stimuli in an accurate spatio-temporal manner. Although the protein phosphorylation process between histidine kinase and response regulator has been well documented, the molecular mechanism fine-tuning phosphorylation levels of response regulators is comparatively less studied. Here we combined genetic and biochemical approaches to reveal that a hybrid histidine kinase, SreS, is involved in the SreK-SreR phosphotransfer process to control salt stress response in the bacterium Xanthomonas campestris. The N-terminal receiver domain of SreS acts as a phosphate sink by competing with the response regulator SreR to accept the phosphoryl group from the latter's cognate histidine kinase SreK. This regulatory process is critical for bacterial survival because the dephosphorylated SreR protein participates in activating one of the tandem promoters (P2) at the 5' end of the sreK-sreR-sreS-hppK operon, and then modulates a transcriptional surge of the stress-responsive gene hppK, which is required for folic acid synthesis. Therefore, our study dissects the biochemical process of a positive feedback loop in which a 'three-component' signalling system fine-tunes expression kinetics of downstream genes. PMID:24119200

Wang, Fang-Fang; Deng, Chao-Ying; Cai, Zhen; Wang, Ting; Wang, Li; Wang, Xiao-Zheng; Chen, Xiao-Ying; Fang, Rong-Xiang; Qian, Wei

2014-07-01

266

Cytokinin Regulation of Auxin Synthesis in Arabidopsis Involves a Homeostatic Feedback Loop Regulated via Auxin and Cytokinin Signal Transduction[W][OA  

PubMed Central

Together, auxin and cytokinin regulate many of the processes that are critical to plant growth, development, and environmental responsiveness. We have previously shown that exogenous auxin regulates cytokinin biosynthesis in Arabidopsis thaliana. In this work, we show that, conversely, the application or induced ectopic biosynthesis of cytokinin leads to a rapid increase in auxin biosynthesis in young, developing root and shoot tissues. We also show that reducing endogenous cytokinin levels, either through the induction of CYTOKININ OXIDASE expression or the mutation of one or more of the cytokinin biosynthetic ISOPENTENYLTRANSFERASE genes leads to a reduction in auxin biosynthesis. Cytokinin modifies the abundance of transcripts for several putative auxin biosynthetic genes, suggesting a direct induction of auxin biosynthesis by cytokinin. Our data indicate that cytokinin is essential, not only to maintain basal levels of auxin biosynthesis in developing root and shoot tissues but also for the dynamic regulation of auxin biosynthesis in response to changing developmental or environmental conditions. In combination with our previous work, the data suggest that a homeostatic feedback regulatory loop involving both auxin and cytokinin signaling acts to maintain appropriate auxin and cytokinin concentrations in developing root and shoot tissues.

Jones, Brian; Gunneras, Sara Andersson; Petersson, Sara V.; Tarkowski, Petr; Graham, Neil; May, Sean; Dolezal, Karel; Sandberg, Goran; Ljung, Karin

2010-01-01

267

A feedback regulatory loop between G3P and lipid transfer proteins DIR1 and AZI1 mediates azelaic-acid-induced systemic immunity.  

PubMed

Systemic acquired resistance (SAR), a highly desirable form of plant defense, provides broad-spectrum immunity against diverse pathogens. The recent identification of seemingly unrelated chemical inducers of SAR warrants an investigation of their mutual interrelationships. We show that SAR induced by the dicarboxylic acid azelaic acid (AA) requires the phosphorylated sugar derivative glycerol-3-phosphate (G3P). Pathogen inoculation induced the release of free unsaturated fatty acids (FAs) and thereby triggered AA accumulation, because these FAs serve as precursors for AA. AA accumulation in turn increased the levels of G3P, which is required for AA-conferred SAR. The lipid transfer proteins DIR1 and AZI1, both of which are required for G3P- and AA-induced SAR, were essential for G3P accumulation. Conversely, reduced G3P resulted in decreased AZI1 and DIR1 transcription. Our results demonstrate that an intricate feedback regulatory loop among G3P, DIR1, and AZI1 regulates SAR and that AA functions upstream of G3P in this pathway. PMID:23602565

Yu, Keshun; Soares, Juliana Moreira; Mandal, Mihir Kumar; Wang, Caixia; Chanda, Bidisha; Gifford, Andrew N; Fowler, Joanna S; Navarre, Duroy; Kachroo, Aardra; Kachroo, Pradeep

2013-04-25

268

SIRT1 Promotes N-Myc Oncogenesis through a Positive Feedback Loop Involving the Effects of MKP3 and ERK on N-Myc Protein Stability  

PubMed Central

The N-Myc oncoprotein is a critical factor in neuroblastoma tumorigenesis which requires additional mechanisms converting a low-level to a high-level N-Myc expression. N-Myc protein is stabilized when phosphorylated at Serine 62 by phosphorylated ERK protein. Here we describe a novel positive feedback loop whereby N-Myc directly induced the transcription of the class III histone deacetylase SIRT1, which in turn increased N-Myc protein stability. SIRT1 binds to Myc Box I domain of N-Myc protein to form a novel transcriptional repressor complex at gene promoter of mitogen-activated protein kinase phosphatase 3 (MKP3), leading to transcriptional repression of MKP3, ERK protein phosphorylation, N-Myc protein phosphorylation at Serine 62, and N-Myc protein stabilization. Importantly, SIRT1 was up-regulated, MKP3 down-regulated, in pre-cancerous cells, and preventative treatment with the SIRT1 inhibitor Cambinol reduced tumorigenesis in TH-MYCN transgenic mice. Our data demonstrate the important roles of SIRT1 in N-Myc oncogenesis and SIRT1 inhibitors in the prevention and therapy of N-Myc–induced neuroblastoma.

Gherardi, Samuele; Scarlett, Christopher J.; Bedalov, Antonio; Xu, Ning; Iraci, Nuncio; Valli, Emanuele; Ling, Dora; Thomas, Wayne; van Bekkum, Margo; Sekyere, Eric; Jankowski, Kacper; Trahair, Toby; MacKenzie, Karen L.; Haber, Michelle; Norris, Murray D.; Biankin, Andrew V.; Perini, Giovanni; Liu, Tao

2011-01-01

269

SIRT1 promotes N-Myc oncogenesis through a positive feedback loop involving the effects of MKP3 and ERK on N-Myc protein stability.  

PubMed

The N-Myc oncoprotein is a critical factor in neuroblastoma tumorigenesis which requires additional mechanisms converting a low-level to a high-level N-Myc expression. N-Myc protein is stabilized when phosphorylated at Serine 62 by phosphorylated ERK protein. Here we describe a novel positive feedback loop whereby N-Myc directly induced the transcription of the class III histone deacetylase SIRT1, which in turn increased N-Myc protein stability. SIRT1 binds to Myc Box I domain of N-Myc protein to form a novel transcriptional repressor complex at gene promoter of mitogen-activated protein kinase phosphatase 3 (MKP3), leading to transcriptional repression of MKP3, ERK protein phosphorylation, N-Myc protein phosphorylation at Serine 62, and N-Myc protein stabilization. Importantly, SIRT1 was up-regulated, MKP3 down-regulated, in pre-cancerous cells, and preventative treatment with the SIRT1 inhibitor Cambinol reduced tumorigenesis in TH-MYCN transgenic mice. Our data demonstrate the important roles of SIRT1 in N-Myc oncogenesis and SIRT1 inhibitors in the prevention and therapy of N-Myc-induced neuroblastoma. PMID:21698133

Marshall, Glenn M; Liu, Pei Y; Gherardi, Samuele; Scarlett, Christopher J; Bedalov, Antonio; Xu, Ning; Iraci, Nuncio; Valli, Emanuele; Ling, Dora; Thomas, Wayne; van Bekkum, Margo; Sekyere, Eric; Jankowski, Kacper; Trahair, Toby; Mackenzie, Karen L; Haber, Michelle; Norris, Murray D; Biankin, Andrew V; Perini, Giovanni; Liu, Tao

2011-06-01

270

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

PubMed Central

Blood coagulation is triggered not only by surface tissue factor (TF) density but also by surface TF distribution. We investigated recognition of surface TF distribution patterns during blood coagulation and identified the underlying molecular mechanisms. For these investigations, we employed 1), an in vitro reaction-diffusion experimental model of coagulation; and 2), numerical simulations using a mathematical model of coagulation in a three-dimensional space. When TF was uniformly immobilized over the activating surface, the clotting initiation time in normal plasma increased from 4 min to >120 min, with a decrease in TF density from 100 to 0.7 pmol/m2. In contrast, surface-immobilized fibroblasts initiated clotting within 3–7 min, independently of fibroblast quantity and despite a change in average surface TF density from 0.5 to 130 pmol/m2. Experiments using factor V-, VII-, and VIII-deficient plasma and computer simulations demonstrated that different responses to these two TF distributions are caused by two positive feedback loops in the blood coagulation network: activation of the TF–VII complex by factor Xa, and activation of factor V by thrombin. This finding suggests a new role for these reactions: to supply sensitivity to local TF density during blood coagulation.

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

2011-01-01

271

Fas-associated factor (Faf1) is a novel CD40 interactor that regulates CD40-induced NF-?B activation via a negative feedback loop  

PubMed Central

CD40-induced signalling through ligation with its natural ligand (CD40L/CD154) is dependent on recruitment of TRAF molecules to the cytoplasmic domain of the receptor. Here, we applied the yeast two-hybrid system to examine whether other proteins can interact with CD40. Fas-Associated Factor 1(FAF1) was isolated from a HeLa cDNA library using the CD40 cytoplasmic tail (216–278 aa) as a bait construct. FAF1 was able to interact with CD40 both in vitro and in vivo. The FAF1 N-terminal domain was sufficient to bind CD40 and required the TRAF6-binding domain within the cytoplasmic tail of CD40 for binding. CD40 ligation induced FAF1 expression in an NF?B-dependent manner. Knockdown of FAF1 prolonged CD40-induced NF?B, whereas overexpression of FAF1 suppressed CD40-induced NF?B activity and this required interaction of FAF1 with the CD40 receptor via its FID domain. Thus, we report a novel role for FAF1in regulating CD40-induced NF?B activation via a negative feedback loop. Loss of FAF1 function in certain human malignancies may contribute to oncogenesis through unchecked NF?B activation, and further understanding of this process may provide a biomarker of NF?B-targeted therapies for such malignancies.

Elmetwali, T; Young, L S; Palmer, D H

2014-01-01

272

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

PubMed Central

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

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

2011-01-01

273

The Caenorhabditis elegans rhy-1 Gene Inhibits HIF-1 Hypoxia-Inducible Factor Activity in a Negative Feedback Loop That Does Not Include vhl-1  

PubMed Central

Hypoxia-inducible factor (HIF) transcription factors implement essential changes in gene expression that enable animals to adapt to low oxygen (hypoxia). The stability of the C. elegans HIF-1 protein is controlled by the evolutionarily conserved EGL-9/VHL-1 pathway for oxygen-dependent degradation. Here, we describe vhl-1-independent pathways that attenuate HIF-1 transcriptional activity in C. elegans. First, the expression of HIF-1 target genes is markedly higher in egl-9 mutants than in vhl-1 mutants. We show that HIF-1 protein levels are similar in animals carrying strong loss-of-function mutations in either egl-9 or vhl-1. We conclude that EGL-9 inhibits HIF-1 activity, as well as HIF-1 stability. Second, we identify the rhy-1 gene and show that it acts in a novel negative feedback loop to inhibit expression of HIF-1 target genes. rhy-1 encodes a multi-pass transmembrane protein. Although loss-of-function mutations in rhy-1 cause relatively modest increases in hif-1 mRNA and HIF-1 protein expression, some HIF-1 target genes are expressed at higher levels in rhy-1 mutants than in vhl-1 mutants. Animals lacking both vhl-1 and rhy-1 function have a more severe phenotype than either single mutant. Collectively, these data support models in which RHY-1 and EGL-9 function in VHL-1-independent pathway(s) to repress HIF-1 transcriptional activity.

Shen, Chuan; Shao, Zhiyong; Powell-Coffman, Jo Anne

2006-01-01

274

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

PubMed

The transcription factor p63, member of the p53 gene family, encodes for two main isoforms, TAp63 and ?Np63 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

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

2014-01-01

275

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

PubMed Central

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 Fbw7?, thereby directly bearing on the process of lateral inhibition. Fbw7?/+ 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/FBW7? positive feedback loop underlies Fbw7 haploinsufficiency. Thus repression of Fbw7? 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.

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

2013-01-01

276

E2F1 promotes angiogenesis through the VEGF-C/VEGFR-3 axis in a feedback loop for cooperative induction of PDGF-B.  

PubMed

Angiogenesis is essential for primary tumor growth and metastatic dissemination. E2F1, frequently upregulated in advanced cancers, was recently shown to drive malignant progression. In an attempt to decipher the molecular events underlying this behavior, we demonstrate that the tumor cell-associated vascular endothelial growth factor-C/receptor-3 (VEGF-C/VEGFR-3) axis is controlled by E2F1. Activation or forced expression of E2F1 in cancer cells leads to the upregulation of VEGFR-3 and its ligand VEGF-C, whereas E2F1 depletion prevents their expression. E2F1-dependent receptor induction is crucial for tumor cells to enhance formation of capillary tubes and neovascularization in mice. We further provide evidence for a positive feedback loop between E2F1 and VEGFR-3 signaling to stimulate pro-angiogenic platelet-derived growth factor B (PDGF-B). E2F1 or VEGFR-3 knockdown results in reduced PDGF-B levels, while the coexpression synergistically upregulates promoter activity and endogenous protein expression of PDGF-B. Our findings delineate an as yet unrecognized function of E2F1 as enhancer of angiogenesis via regulation of VEGF-C/VEGFR-3 signaling in tumors to cooperatively activate PDGF-B expression. Targeting this pathway might be reasonable to complement standard anti-angiogenic treatment of cancers with deregulated E2F1. PMID:24014887

Engelmann, David; Mayoli-Nüssle, Deborah; Mayrhofer, Christian; Fürst, Katharina; Alla, Vijay; Stoll, Anja; Spitschak, Alf; Abshagen, Kerstin; Vollmar, Brigitte; Ran, Sophia; Pützer, Brigitte M

2013-12-01

277

A Feedback Loop Consisting of MicroRNA 23a/27a and the ?-Like Globin Suppressors KLF3 and SP1 Regulates Globin Gene Expression  

PubMed Central

The developmental stage-specific expression of the human ?-like globin genes has been studied for decades, and many transcriptional factors as well as other important cis elements have been identified. However, little is known about the microRNAs that potentially regulate ?-like globin gene expression directly or indirectly during erythropoiesis. In this study, we show that microRNA 23a (miR-23a) and miR-27a promote ?-like globin gene expression in K562 cells and primary erythroid cells through targeting of the transcription factors KLF3 and SP1. Intriguingly, miR-23a and miR-27a further enhance the transcription of ?-like globin genes through repression of KLF3 and SP1 binding to the ?-like globin gene locus during erythroid differentiation. Moreover, KLF3 can bind to the promoter of the miR-23a?27a?24-2 cluster and suppress this microRNA cluster expression. Hence, a positive feedback loop comprised of KLF3 and miR-23a promotes the expression of ?-like globin genes and the miR-23a?27a?24-2 cluster during erythropoiesis.

Ma, Yanni; Wang, Bin; Jiang, Fengbing; Wang, Dongsheng; Liu, Huiwen; Yan, Yunmeng; Dong, He; Wang, Fang; Gong, Bei; Zhu, Yong; Dong, Lei; Yin, Haixin; Zhang, Zhongzu; Zhao, Hualu; Wu, Zhikui; Zhang, Junwu

2013-01-01

278

Distinct stages of cytochrome c release from mitochondria: evidence for a feedback amplification loop linking caspase activation to mitochondrial dysfunction in genotoxic stress induced apoptosis.  

PubMed

Cytochrome c (cyto c) release from mitochondria is a critical event in apoptosis. By investigating the ordering of molecular events during genotoxic stress-induced apoptosis, we found that ionizing radiation (IR) and etoposide induced the release of cyto c from mitochondria in two distinct stages. The early release of low levels of cyto c into the cytosol preceded the activation of caspase 9 and 3, but had no effect on ATP levels or mitochrondrial transmembrane potential (Deltapsim). In contrast, the late stage cyto c release resulted in a drastic loss of mitochondrial cyto c and was associated with reduction of ATP levels and Deltapsim. Moreover, caspases contributed to the late cyto c release since the caspase inhibitor zVAD prevented only the late but not the early-stage cyto c release. Recombinant caspase 3 induced cyto c release from isolated mitochondria in the absence of cytosolic factors. Bcl-2 but not Bid was cleaved during apoptosis after caspase activation. This suggests that Bcl-2 cleavage might contribute to the late cyto c release, which results in mitochondrial dysfunction manifested by the decrease of ATP and Deltapsim. zVAD prevented the reduction of ATP, Deltapsim, and nuclear condensation when added up to 8 h after IR, at the time the caspases were highly activated but when the majority of cyto c was still maintained in the mitochondria. These findings link the feedback loop control of caspase-induced cyto c release with mitochondrial dysfunction manifested by ATP and Deltapsim decline. PMID:10713737

Chen, Q; Gong, B; Almasan, A

2000-02-01

279

Fas-associated factor (Faf1) is a novel CD40 interactor that regulates CD40-induced NF-?B activation via a negative feedback loop.  

PubMed

CD40-induced signalling through ligation with its natural ligand (CD40L/CD154) is dependent on recruitment of TRAF molecules to the cytoplasmic domain of the receptor. Here, we applied the yeast two-hybrid system to examine whether other proteins can interact with CD40. Fas-Associated Factor 1(FAF1) was isolated from a HeLa cDNA library using the CD40 cytoplasmic tail (216-278 aa) as a bait construct. FAF1 was able to interact with CD40 both in vitro and in vivo. The FAF1 N-terminal domain was sufficient to bind CD40 and required the TRAF6-binding domain within the cytoplasmic tail of CD40 for binding. CD40 ligation induced FAF1 expression in an NF?B-dependent manner. Knockdown of FAF1 prolonged CD40-induced NF?B, whereas overexpression of FAF1 suppressed CD40-induced NF?B activity and this required interaction of FAF1 with the CD40 receptor via its FID domain. Thus, we report a novel role for FAF1in regulating CD40-induced NF?B activation via a negative feedback loop. Loss of FAF1 function in certain human malignancies may contribute to oncogenesis through unchecked NF?B activation, and further understanding of this process may provide a biomarker of NF?B-targeted therapies for such malignancies. PMID:24810049

Elmetwali, T; Young, L S; Palmer, D H

2014-01-01

280

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

SciTech Connect

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

Silverman, .F.

1985-01-01

281

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

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.

Yu, Hong-Wei; Liu, Qi-Feng [Department of Cardiology, The First Affiliated Hospital of China Medical University, 155th North of Nanjing Street, Heping Block, Shenyang, 110001 Liaoning Province (China)] [Department of Cardiology, The First Affiliated Hospital of China Medical University, 155th North of Nanjing Street, Heping Block, Shenyang, 110001 Liaoning Province (China); Liu, Gui-Nan, E-mail: guinanliu@hotmail.com [Department of Cardiology, The First Affiliated Hospital of China Medical University, 155th North of Nanjing Street, Heping Block, Shenyang, 110001 Liaoning Province (China)] [Department of Cardiology, The First Affiliated Hospital of China Medical University, 155th North of Nanjing Street, Heping Block, Shenyang, 110001 Liaoning Province (China)

2010-05-28

282

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

PubMed

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

Pasillas-Lépine, William

2013-06-01

283

A multistage amplifier topology with nested GmC compensation for low-voltage application  

Microsoft Academic Search

To design an operational amplifier for low-voltage applications, cascoding is no longer a suitable technique for achieving high DC gain. Instead, multiple cascaded stages must he used, with each stage a simple (noncascode) inverting or noninverting amplifier. In designing a multistage opamp with multiple feedback loops, special care must be taken to ensure stability. A well-known compensation technique is nested

Fan You; S. H. K. Embabi; Edgar Sanchez-Sinencio

1997-01-01

284

Load-Line Regulation With Estimated Load-Current Feedforward: Application to Microprocessor Voltage Regulators  

Microsoft Academic Search

A consistent framework for load-line regulation design is presented, applicable to microprocessor voltage regulators (VRs) using either electrolytic or ceramic output capacitors. With conventional feedback control, the loop bandwidth is limited by stability constraints linked to the switching frequency. The output capacitor has to be chosen sufficiently large to meet the stability requirement. Load-current feedforward can extend the useful bandwidth

Angel V. Peterchev; Seth R. Sanders

2006-01-01

285

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

PubMed

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

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

2014-07-01

286

TakeCare: A home-based sensor system for the management of cardiovascular risk factors Primary prevention by monitoring vital body signs, analysing the data and closing the loop by feedback, coaching, and motivation  

Microsoft Academic Search

Unobtrusive and easy-to-use sensor devices are used for monitoring the health condition of people interested in adopting a healthier lifestyle. The collected data from body sensors and input from questionnaires are analyzed allowing to derive improvement plans and recommendations. With the help of feedback, coaching and motivation a closed-loop system approach is realized optimally supporting people to reach their goals

Harald Reiter; Elke Naujokat; Robert Pinter; Sandrine Devot

2008-01-01

287

Differential regulation of p21waf-1/cip-1 and Mdm2 by etoposide: etoposide inhibits the p53-Mdm2 autoregulatory feedback loop.  

PubMed

The Mdm2 protein is frequently overexpressed in human non-seminomatous germ cell tumours and transitional carcinoma of the bladder where it may contribute to tolerance of wtp53. Mdm2 forms an autoregulatory feedback loop with p53; the Mdm2 gene is responsive to transactivation by p53 and once synthesized the Mdm2 protein terminates the p53 response. We show here that the topoisomerase poison etoposide, like ultra violet irradiation, inhibits Mdm2 synthesis. Cytotoxic concentrations of etoposide (IC90 for > 3 h) result in inhibition of Mdm2 induction at both the RNA and protein level. Rapid apoptosis ensues. Global transcription is not inhibited: p21waf-1/cip1 and GADD45 expression increase in a dose dependent manner. Inhibition of Mdm2 synthesis depends on the continuous presence of etoposide, suggesting the DNA damage may prevent transcription. Downregulation of Mdm2 transcript occurs in cells expressing HPV16-E6 suggesting that inhibition of Mdm2 transcription is p53-independent. When cells are -treated with a pulse (1 h) of etoposide and reincubated in drug free medium, Mdm2 synthesis commences immediately after damage is repaired (3 h) and the p53 response is attenuated. Induction of apoptosis and loss of clonogenicity are 3-5-fold lower under pulse treatment conditions. This is the first observation of inhibition of Mdm2 transcription following treatment with topoisomerase (topo II) poisons, a feature that may be useful in tumour types where p53 is tolerated by overexpression of Mdm2. PMID:10023685

Arriola, E L; Lopez, A R; Chresta, C M

1999-01-28

288

The c-myb proto-oncogene and microRNA-15a comprise an active autoregulatory feedback loop in human hematopoietic cells  

PubMed Central

The c-myb proto-oncogene encodes an obligate hematopoietic cell transcription factor important for lineage commitment, proliferation, and differentiation. Given its critical functions, c-Myb regulatory factors are of great interest but remain incompletely defined. Herein we show that c-Myb expression is subject to posttranscriptional regulation by microRNA (miRNA)–15a. Using a luciferase reporter assay, we found that miR-15a directly binds the 3?-UTR of c-myb mRNA. By transfecting K562 myeloid leukemia cells with a miR-15a mimic, functionality of binding was shown. The mimic decreased c-Myb expression, and blocked the cells in the G1 phase of cell cycle. Exogenous expression of c-myb mRNA lacking the 3?-UTR partially rescued the miR-15a induced cell-cycle block. Of interest, the miR-15a promoter contained several potential c-Myb protein binding sites. Occupancy of one canonical c-Myb binding site was demonstrated by chromatin immunoprecipitation analysis and shown to be required for miR-15a expression in K562 cells. Finally, in studies using normal human CD34+ cells, we showed that c-Myb and miR-15a expression were inversely correlated in cells undergoing erythroid differentiation, and that overexpression of miR-15a blocked both erythroid and myeloid colony formation in vitro. In aggregate, these findings suggest the presence of a c-Myb–miR-15a autoregulatory feedback loop of potential importance in human hematopoiesis.

Zhao, Huiwu; Kalota, Anna; Jin, Shenghao

2009-01-01

289

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)

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.

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

2013-12-01

290

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

PubMed Central

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

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

2012-01-01

291

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

PubMed

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

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

2012-07-13

292

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

PubMed Central

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

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

2002-01-01

293

Frequency-Offset Cartesian Feedback Based on Polyphase Difference Amplifiers  

PubMed Central

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.

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

2010-01-01

294

The autoregulatory feedback loop of microRNA-21/programmed cell death protein 4/activation protein-1 (MiR-21/PDCD4/AP-1) as a driving force for hepatic fibrosis development.  

PubMed

Sustained activation of hepatic stellate cells (HSCs) leads to hepatic fibrosis, which is characterized by excessive collagen production, and for which there is no available drug clinically. Despite tremendous progress, the cellular activities underlying HSC activation, especially the driving force in the perpetuation stage, are only partially understood. Recently, microRNA-21 (miR-21) has been found to be prevalently up-regulated during fibrogenesis in different tissues, although its detailed role needs to be further elucidated. In the present study, miR-21 expression was examined in human cirrhotic liver samples and in murine fibrotic livers induced by thioacetamide or carbon tetrachloride. A dramatic miR-21 increase was noted in activated HSCs. We further found that miR-21 maintained itself at constant high levels by using a microRNA-21/programmed cell death protein 4/activation protein-1 (miR-21/PDCD4/AP-1) feedback loop. Disrupting this loop with miR-21 antagomir or AP-1 inhibitors significantly suppressed fibrogenic activities in HSCs and ameliorated liver fibrosis. In contrast, reinforcing this loop with small interfering RNA (siRNA) against PDCD4 promoted fibrogenesis in HSCs. Further analysis indicated that the up-regulated miR-21 promoted the central transforming growth factor-? (TGF-?) signaling pathway underlying HSC activation. In summary, we suggest that the miR-21/PDCD4/AP-1 autoregulatory loop is one of the main driving forces for hepatic fibrosis progression. Targeting this aberrantly activated feedback loop may provide a new therapeutic strategy and facilitate drug discovery against hepatic fibrosis. PMID:24196965

Zhang, Zhengping; Zha, Yinhe; Hu, Wei; Huang, Zhen; Gao, Zhongfei; Zang, Yuhui; Chen, Jiangning; Dong, Lei; Zhang, Junfeng

2013-12-27

295

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

PubMed Central

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.

2014-01-01

296

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

PubMed Central

Purpose This study investigated possible mechanisms of autoregulation of Ca2+ signalling pathways in adipocytes responsible for Ca2+ and NO oscillations and switching phenomena promoted by acetylcholine (ACh), norepinephrine (NE) and atrial natriuretic peptide (ANP). Methods Fluorescent microscopy was used to detect changes in Ca2+ and NO in cultures of rodent white adipocytes. Agonists and inhibitors were applied to characterize the involvement of various enzymes and Ca2+-channels in Ca2+ signalling pathways. Results ACh activating M3-muscarinic receptors and G?? protein dependent phosphatidylinositol 3 kinase induces Ca2+ and NO oscillations in adipocytes. At low concentrations of ACh which are insufficient to induce oscillations, NE or ?1, ?2-adrenergic agonists act by amplifying the effect of ACh to promote Ca2+ oscillations or switching phenomena. SNAP, 8-Br-cAMP, NAD and ANP may also produce similar set of dynamic regimes. These regimes arise from activation of the ryanodine receptor (RyR) with the implication of a long positive feedback loop (PFL): Ca2+? NO?cGMP?cADPR?Ca2+, which determines periodic or steady operation of a short PFL based on Ca2+-induced Ca2+ release via RyR by generating cADPR, a coagonist of Ca2+ at the RyR. Interplay between these two loops may be responsible for the observed effects. Several other PFLs, based on activation of endothelial nitric oxide synthase or of protein kinase B by Ca2+-dependent kinases, may reinforce functioning of main PFL and enhance reliability. All observed regimes are independent of operation of the phospholipase C/Ca2+-signalling axis, which may be switched off due to negative feedback arising from phosphorylation of the inositol-3-phosphate receptor by protein kinase G. Conclusions This study presents a kinetic model of Ca2+-signalling system operating in adipocytes and integrating signals from various agonists, which describes it as multivariable multi feedback network with a family of nested positive feedback.

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

2013-01-01

297

Positive feedback from hilar mossy cells to granule cells in the dentate gyrus revealed by voltage-sensitive dye and microelectrode recording.  

PubMed

1. Microelectrode recording and fluorescence measurement with voltage-sensitive dyes were employed in horizontal hippocampal slices from rat to investigate responses in the dentate gyrus to molecular layer and hilar stimulation. 2. Both field potential and dye fluorescence measurement revealed that electrical stimulation of the molecular layer produced strong excitation throughout large regions of the dentate gyrus at considerable distances from the site of stimulation. 3. Treatment of slices with the excitatory amino acid receptor antagonists 6,7-dinitroquinoxaline-2,3-dione (DNQX) and (+/-)-2-amino-5-phosphonovaleric acid (APV) unmasked dye fluorescence signals in the outer and middle molecular layers corresponding to action potentials in axons, presumably belonging to the perforant path. The spread of these axonal signals away from the site of stimulation was far less extensive than the spread of control signals through the same regions before blockade of excitatory synapses. Large control responses could be seen in regions distant from the stimulation site where the axonal signals were not detectable. A lack of correlation between control signals and axonal signals revealed by DNQX and APV supports the hypothesis that responses in distal regions of the molecular layer were not dependent on perforant path axons. 4. The perforant path was cut by producing a lesion in the outer two-thirds of the molecular layer. Both dye fluorescence and microelectrode recording showed that stimulation on one side of the lesion could produce signals on the same side as well as across the lesion. The lesion did not block the spread of excitation through the molecular layer. Across the lesion from the site of stimulation, negative-going field potentials were observed to peak in the inner molecular layer, which is the major field of projection of hilar mossy cells. 5. Electrical stimulation in the hilus adjacent to the granule cell layer evoked dye fluorescence responses in the molecular layer. Stimulation at this site evoked negative-going field potentials that peaked in the inner molecular layer. These signals were sensitive to excitatory amino acid receptor antagonists but not to gamma-aminobutyric acid-A (GABAA) receptor antagonists. 6. Activation of excitatory amino acid receptors in the hilus by focal application of (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) and N-methyl-D-aspartic acid (NMDA) elicited negative-going field potentials in the granule cell layer and depolarization of granule cells. Field potentials were blocked by tetrodotoxin (TTX), indicating that they were not caused by direct activation of receptors on granule cells, but rather by synapses from hilar neurons on granule cells. 7. These results taken together with previous studies of hilar mossy cells suggest a fundamental circuit consisting of granule cells exciting hilar mossy cells, which then excite more granule cells. This circuit provides positive feedback and can be considered a form of "recurrent excitation" unique to the dentate gyrus. The robustness of this circuit in hippocampal slices under control conditions suggest that mossy cell excitation of granule cells could play an important role in the normal activity of the hippocampus, and, when inhibition is compromised, this circuit could contribute to the generation and spread of seizures. PMID:8836247

Jackson, M B; Scharfman, H E

1996-07-01

298

A 0.5V fully differential OTA with local common feedback  

Microsoft Academic Search

This paper presents a fully differential OTA with a supply of 0.5V in a 0.18mum CMOS process that has threshold voltages of 0.5V under zero body-source biasing. Unlike a recent two-stage 0.5V OTA architecture, this OTA employs two common mode feedback loops for obtaining a stable operating condition and thus a robust performance against process variations. Body terminals of the

Xiao-yong He; Kong-pang Pun; Oliver Chiu-sing Choy; Cheong-fat Chan

2006-01-01

299

Sensitivity Improvement of Feedback Systems.  

National Technical Information Service (NTIS)

Nominally equivalent control realizations consisting of linear combinations of open-loop and state feedback control for a linear time-invariant completely controllable plant are considered. Two controls are said to be nominally equivalent if they are equa...

J. B. Cruz N. Sundararajan

1971-01-01

300

FORCE FEEDBACK VERSUS ACCELERATION FEEDBACK IN ACTIVE VIBRATION ISOLATION  

Microsoft Academic Search

This paper compares the force feedback and acceleration feedback implementation of the sky-hook damper when it is used to isolate a flexible structure from a disturbance source. It is shown that the use of a force sensor produces always alternating poles and zeros in the open-loop transfer function between the force actuator and the force sensor, which guarantees the stability

A. Preumont; A. François; F. Bossens; A. Abu-Hanieh

2002-01-01

301

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

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

Barak, Moshe

2010-01-01

302

A novel non-fragile single-loop voltage and frequency controller for induction generator based isolated renewable energy conversion system  

Microsoft Academic Search

Poor voltage and frequency regulation under source and load perturbations limit the use of self excited induction generator (SEIG) in isolated and dispersed generation, which can exploit wind\\/microhydro type renewable energy sources. In the present work, a Generalized Impedance Controller (GIC), which is a pulse-width-modulated voltage-source-inverter with a dc-link battery, is used to regulate both, amplitude and frequency of the

J. K. Chatterjee; Priyesh J. Chauhan

2010-01-01

303

On the selection of control-law coefficients for multi-loop PWM switching regulators  

NASA Astrophysics Data System (ADS)

The relationship between the control-law coefficients and the closed-loop transfer functions for second-order, multiloop, pulsewidth-modulated (PWM) switching regulators is examined. Detailed results are presented for input impedance, output-current susceptibility, input-voltage susceptibility, and output impedance of the basic buck, boost, and buck-boost regulators. The relationship is used as a basis for selecting the feedback and feed-forward coefficients for maximum performance of the regulators.

Mitchell, Daniel M.; Schoneman, George K.

304

On the selection of control-law coefficients for multi-loop PWM switching regulators  

Microsoft Academic Search

The relationship between the control-law coefficients and the closed-loop transfer functions for second-order, multiloop, pulsewidth-modulated (PWM) switching regulators is examined. Detailed results are presented for input impedance, output-current susceptibility, input-voltage susceptibility, and output impedance of the basic buck, boost, and buck-boost regulators. The relationship is used as a basis for selecting the feedback and feed-forward coefficients for maximum performance of

Daniel M. Mitchell; George K. Schoneman

1988-01-01

305

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

PubMed Central

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.

Amodio, N; Di Martino, M T; Foresta, U; Leone, E; Lionetti, M; Leotta, M; Gulla, 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

306

Grid connected voltage source inverter control during voltage dips  

Microsoft Academic Search

This paper proposes a combined synchronization method for full scale converter of wind turbine (WT) aiming to ride trough balanced and unbalanced voltage dips due grid faults. A Kalman filter synchronization (KFS), capable extract the positive and negative sequence grid voltages, is designed to have a fast response to voltage disturbances. Then, a synchronous reference frame phase locked loop (SRF-PLL)

I. J. Gabe; F. F. K. Palha; H. Pinheiro

2009-01-01

307

Static VAR Compensator-Based Voltage Regulation for Variable-Speed Prime Mover Coupled Single-Phase Self-Excited Induction Generator  

NASA Astrophysics Data System (ADS)

In this paper, the single-phase static VAR compensator (SVC) is applied to regulate and stabilize smoothly the generated output voltage of the single-phase self-excited induction generator (single-phase SEIG) driven by a variable-speed prime mover (VSPM) under the conditions of inductive load variations and prime mover speed changes. The conventional fixed gain PI controller-based feedback control scheme is employed to adjust the equivalent capacitance of the single-phase SVC composed of the fixed excitation capacitor (FC) in parallel with the thyristor switched capacitor (TSC) and the thyristor controlled reactor TCR. A PI closed-loop feedback voltage control scheme based on the SVC for the single-phase SEIG coupled by a VSPM prototype set-up is established. The closed-loop feedback output voltage responses in the single-phase SEIG coupled by a VSPM with different inductive load variations using the single-phase SVC with the PI controller are considered and discussed herein. Based on the SVC with the PI controller closed-loop feedback voltage regulation scheme, the experimental results for the single-phase SEIG driven by a VSPM are illustrated and proved its practical effectiveness in terms of the fast response and the high performances.

Ahmed, Tarek; Noro, Osamu; Hiraki, Eiji; Nakaoka, Mutsuo

308

Transverse mode control by a self-imaging process in a multimode fibre laser using a single-mode feedback loop  

NASA Astrophysics Data System (ADS)

We propose new laser architecture to improve the spatial emission of a multimode fibre amplifier (MMFA) by using a self-imaging process. Interference between the different modes of the MMFA is filtered by a single-mode fibre section which serves as feedback in a unidirectional ring cavity. The laser self-adjusts its frequency to ensure self-imaging between opposite faces of the multimode fibre. The laser output pattern and longitudinal modes depend on the single-mode fibres' end face position with respect to the MMFA centre axis. As a proof of principle we report experimental results which are in good agreement with numerical simulations.

Shalaby, B. M.; Kermene, V.; Pagnoux, D.; Barthelemy, A.

2008-11-01

309

Model-based feedback control of a microfluidic electroporation system  

NASA Astrophysics Data System (ADS)

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.

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

2013-12-01

310

Destabilizing Effects of Rate Feedback on Strain Actuated Beams  

NASA Astrophysics Data System (ADS)

The stabilizing and destabilizing effects of rate feedback control on all modes of a strain actuated beam are demonstrated here to support earlier theoretical findings by Balakrishnan [1] (1999Journal of Computational and Applied Mathematics18). The destabilizing effects being due to the actual implementation of the rate feedback controller which is unavoidably non-ideal. The main contribution here is the inclusion of the controller circuit model in the closed loop system equations to obtain correct stability estimates for all modes. Closed loop stability estimates computed from thiscircuitry enhanced modelwere corroborated by experiments. The strain actuated beam constructed for this work was made with a fiber glass lay-up and piezo ceramic wafers embedded throughout the length of the lay-up. A charge-to-voltage amplifier, a differentiator, a gain stage, and a power amplifier were also constructed. The most crucial of these components was the differentiator and its tank frequency. The first four modes and transmission zero frequencies, and the corresponding structural damping were obtained through open loop experiments. Mode estimates were within 5% of the computed values. Zero estimates were less accurate due to electric feedthrough, but modelling of this effect helped to improve zero frequency estimates. Closed loop experiments were run to demonstrate the destabilization of beam modes with frequencies higher than the differentiator's tank frequency.

Alvarez-Salazar, O. S.; Iliff, K.

1999-03-01

311

Simple Optoelectronic Feedback in Microwave Oscillators  

NASA Technical Reports Server (NTRS)

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.

Maleki, Lute; Iltchenko, Vladimir

2009-01-01

312

Feedback systems in the SLC  

SciTech Connect

Two classes of computer-controlled feedback have been implemented to stabilize parameters in subsystems of the SLC: (1) ''slow'' (time scales approx. minutes) feedback, and (2) ''fast'', i.e., pulse-to-pulse, feedback. The slow loops run in a single FEEDBACK process in the SLC host VAX, which acquires signals and sets control parameters via communication with the database and the network of normal SLC microprocessors. Slow loops exist to stabilize beam energy and energy spread, beam position and angle, and timing of kicker magnets, and to compensate for changes in the phase length of the rf drive line. The fast loops run in dedicated microprocessors, and may sample and/or feedback on particular parameters as often as every pulse of the SLC beam. The first implementations of fast feedback are to control transverse beam blow-up and to stabilize the energy and energy spread of bunches going into the SLC arcs. The overall architecture of the feedback software and the operator interface for controlling loops are discussed.

Thompson, K.A.; Jobe, R.K.; Johnson, R.; Phinney, N.

1987-02-01

313

Isoform-specific effects of sialic acid on voltage-dependent Na+ channel gating: functional sialic acids are localized to the S5-S6 loop of domain I  

PubMed Central

The isoform specific role of sialic acid in human voltage-gated sodium channel gating was investigated through expression and chimeric analysis of two human isoforms, Nav1.4 (hSkM1), and Nav1.5 (hH1) in Chinese hamster ovary (CHO) cell lines. Immunoblot analyses indicate that both hSkM1 and hH1 are glycosylated and that hSkM1 is more glycosylated than hH1. Four sets of voltage-dependent parameters, the voltage of half-activation (Va), the voltage of half-inactivation (Vi), the time constants for fast inactivation (?h), and the time constants for recovery from inactivation (?rec), were measured for hSkM1 and hH1 expressed in two CHO cell lines, Pro5 and Lec2, to determine the effect of changing sialylation on channel gating under conditions of full (Pro5) or reduced (Lec2) sialylation. For all parameters measured, hSkM1 gating showed a consistent 11–15 mV depolarizing shift under conditions of reduced sialylation, while hH1 showed no significant change in any gating parameter. Shifts in channel Va with changing external [Ca2+] indicated that sialylation of hSkM1, but not hH1, directly contributes to a negative surface potential. Functional analysis of two chimeras, hSkM1P1 and hH1P1, indicated that the responsible sialic acids are localized to the hSkM1 S5-S6 loop of domain I. When hSkM1 IS5-S6 was replaced by the analogous hH1 loop (hSkM1P1), changing sialylation had no significant effect on any voltage-dependent parameter. Conversely, when hSkM1 IS5-S6 was added to hH1 (hH1P1), all four parameters shifted by 6–7 mV in the depolarized direction under conditions of reduced sialylation. In summary, the gating of two human sodium channel isoforms show very different dependencies on sialic acid, with hSkM1 gating uniformly altered by sialic acid levels through an apparent electrostatic mechanism, while hH1 gating is unaffected by changing sialylation. Sialic acid-dependent gating can be removed or created by replacing or inserting hSkM1 IS5-S6, respectively, indicating that the functionally relevant sialic acid residues are localized to the first domain of the channel.

Bennett, Eric S

2002-01-01

314

118dB dynamic range, continuous-time, opened-loop capactance to voltage converter readout for capacitive MEMS accelerometer  

Microsoft Academic Search

A high performance analog front-end (AFE) interface circuit for capacitive MEMS accelerometer is presented in this paper. The AFE was implemented in a continuous-time (CT), chopper stabilized, capacitance to voltage converter (CVC) topology with a variable gain amplifier (VGA) for greater flexibility and a low pass filter (LPF) which limited the signal bandwidth to 300 Hz. Noise analysis of each

T. C. C. Kevin; Dong Han; P. S. Ravinder; D. P. Duy; Y. P. Chin; W. L. Jian; David Nuttman; Minkyu Je

2010-01-01

315

Supervisor Feedback.  

ERIC Educational Resources Information Center

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

Hayman, Marilyn J.

1981-01-01

316

Power amplifier linearization using IF feedback  

Microsoft Academic Search

A narrowband feedback technique for linearizing power amplifiers is presented. The technique uses frequency conversions, thus allowing loop compensation and added loop gain to be implemented at the intermediate frequency (IF). An analysis is presented which allows assessment of the applicability of the technique and which shows the performance advantages of using a two-pole loop compensation filter. When applied to

K. G. Voyce; J. H. McCandless

1989-01-01

317

Open-loop Band excitation Kelvin Probe Force Microscopy  

SciTech Connect

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

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

2012-01-01

318

p53/mdm2 feedback loop sustains miR-221 expression and dictates the response to anticancer treatments in hepatocellular carcinoma.  

PubMed

The overexpression of microRNA-221 (miR-221) is reported in several human cancers including hepatocellular carcinoma, and its targeting by tailored treatments has been proposed. The evidence supporting the role of miR-221 in cancer is growing and has been mainly focused on the discovery of miR-221 targets as well as on its possible therapeutic exploitations. However, the mechanism sustaining miR-221 aberrant expression remains to be elucidated. In this study, MDM2 (E3 ubiquitin-protein ligase homolog), a known p53 (TP53) modulator, is identified as a direct target of miR-221, and a feed-forward loop is described that sustains miR-221 aberrant expression. Interestingly, miR-221 can activate the p53/mdm2 axis by inhibiting MDM2 and, in turn, p53 activation contributes to miR-221 enhanced expression. Moreover, by modulating the p53 axis, miR-221 impacts cell-cycle progression and apoptotic response to doxorubicin in hepatocellular carcinoma-derived cell lines. Finally, CpG island methylation status was assessed as a causative event associated with miR-221 upregulation in hepatocellular carcinoma cells and primary tumor specimens. In hepatocellular carcinoma-derived cell lines, pharmacologically induced DNA hypomethylation potentiated a significant increase in miR-221 expression. These data were confirmed in clinical specimens of hepatocellular carcinoma in which elevated miR-221 expression was associated with the simultaneous presence of wild-type p53 and DNA hypomethylation. Implications: These findings reveal a novel miR-221-sustained regulatory loop that determines a p53-context-specific response to doxorubicin treatment in hepatocellular carcinoma. PMID:24324033

Fornari, Francesca; Milazzo, Maddalena; Galassi, Marzia; Callegari, Elisa; Veronese, Angelo; Miyaaki, Hisamitsu; Sabbioni, Silvia; Mantovani, Vilma; Marasco, Elena; Chieco, Pasquale; Negrini, Massimo; Bolondi, Luigi; Gramantieri, Laura

2014-02-01

319

Effects of antidiuretic hormone, parathyroid hormone and glucagon on transepithelial voltage and resistance of the cortical and medullary thick ascending limb of Henle's loop of the mouse nephron  

Microsoft Academic Search

The effect of antidiuretic hormone (arginine vasopressin, AVP, 10?10mol.l?1), parathyroid hormone (PTH, 10?8 mol.l?8) and glucagon (10?8 mol.l?1) on the transepithelial potential difference (PDte) and the transepithelial resistance (Rte) were tested in in vitro perfused cortical (cTAL) and medullary (mTAL) thick ascending limbs of Henle's loop of the mouse\\u000a nephron. When compared with mTAL segments (PDte: 8.5±0.4 mV,n=16), cTAL segments

M. Wittner; A. Di Stefano

1990-01-01

320

Transcription Factors ER71/ETV2 and SOX9 Participate in a Positive Feedback Loop in Fetal and Adult Mouse Testis*  

PubMed Central

ER71, also known as ETV2, is an ETS transcription factor that is expressed during embryogenesis and in adult testes. We show that Er71 transcription can be up-regulated by SRY, the key determinant of male differentiation. Accordingly, SRY bound to and activated the Er71 promoter, and mutation of a putative SRY binding site abolished this promoter activation. In turn, ER71 was able to bind to the promoter of Sox9, the primary target of SRY and a critical transcription factor for maintenance of the Sertoli cell phenotype. Mutation of the ER71 binding site in the Sox9 promoter suppressed ER71-dependent up-regulation of Sox9 transcription, and a dominant-negative ER71 molecule severely reduced Sox9 transcription in a Sertoli cell line. Conversely, SOX9 bound the Er71 promoter in vivo and Sox9 down-regulation reduced Er71 transcript levels. Together, these data suggest a mechanism by which SRY induces Sox9 and Er71 transcription early in testis differentiation, whereas ER71 and SOX9 participate in an autoregulatory loop to sustain each other's expression after Sry expression has subsided in mice. Thereby, ER71 and SOX9 may affect late testis development as well as the function of the adult male gonad.

DiTacchio, Luciano; Bowles, Josephine; Shin, Sook; Lim, Dae-Sik; Koopman, Peter; Janknecht, Ralf

2012-01-01

321

RIP1 activates PI3K-Akt via a dual mechanism involving NF-kappaB-mediated inhibition of the mTOR-S6K-IRS1 negative feedback loop and down-regulation of PTEN.  

PubMed

Therapeutic inhibition of mammalian target of rapamycin (mTOR) in cancer is complicated by the existence of a negative feedback loop linking mTOR to the phosphatidylinositol 3-kinase (PI3K)-Akt pathway. Thus, mTOR inhibition by rapamycin or TSC1/2 results in increased PI3K-Akt activation. The death domain kinase receptor interacting protein 1 (RIP1) plays a key role in nuclear factor-kappaB (NF-kappaB) activation and also activates the PI3K-Akt pathway through unknown mechanisms. RIP1 has recently been found to be overexpressed in glioblastoma multiforme, the most common adult primary malignant brain tumor, but not in grade II to III glioma. Our data suggest that RIP1 activates PI3K-Akt using dual mechanisms by removing the two major brakes on PI3K-Akt activity. First, increased expression of RIP1 activates PI3K-Akt by interrupting the mTOR negative feedback loop. However, unlike other signals that regulate mTOR activity without affecting its level, RIP1 negatively regulates mTOR transcription via a NF-kappaB-dependent mechanism. The second mechanism used by RIP1 to activate PI3K-Akt is down-regulation of cellular PTEN levels, which appears to be independent of NF-kappaB activation. The clinical relevance of these findings is highlighted by the demonstration that RIP1 levels correlate with activation of Akt in glioblastoma multiforme. Thus, our study shows that RIP1 regulates key components of the PTEN-PI3K-Akt-mTOR pathway and elucidates a novel negative regulation of mTOR signaling at the transcriptional level by the NF-kappaB pathway. Our data suggest that the RIP1-NF-kappaB status of tumors may influence response to treatments targeting the PTEN-PI3K-mTOR signaling axis. PMID:19435890

Park, Seongmi; Zhao, Dawen; Hatanpaa, Kimmo J; Mickey, Bruce E; Saha, Debabrata; Boothman, David A; Story, Michael D; Wong, Eric T; Burma, Sandeep; Georgescu, Maria-Magdalena; Rangnekar, Vivek M; Chauncey, Sandili S; Habib, Amyn A

2009-05-15

322

A double-negative feedback loop between Wnt-?-catenin signaling and HNF4? regulates epithelial-mesenchymal transition in hepatocellular carcinoma.  

PubMed

Wnt-?-catenin signaling participates in the epithelial-mesenchymal transition (EMT) in a variety of cancers; however, its involvement in hepatocellular carcinoma (HCC) and downstream molecular events is largely undefined. HNF4? is the most prominent and specific factor maintaining the differentiation of hepatic lineage cells and a potential EMT regulator in HCC cells. However, the molecular mechanisms by which HNF4? maintains the differentiated liver epithelium and inhibits EMT have not been completely defined. In this study, we systematically explored the relationship between Wnt-?-catenin signaling and HNF4? in the EMT process of HCC cells. Our results indicated that HNF4? expression was negatively regulated during Wnt-?-catenin signaling-induced EMT through Snail and Slug in HCC cells. In contrast, HNF4? was found to directly associate with TCF4 to compete with ?-catenin but facilitate transcription co-repressor activities, thus inhibiting expression of EMT-related Wnt-?-catenin targets. Moreover, HNF4? may control the switch between the transcriptional and adhesion functions of ?-catenin. Overexpression of HNF4? was found to completely compromise the Wnt-?-catenin-signaling-induced EMT phenotype. Finally, we determined the regulation pattern between Wnt-?-catenin signaling and HNF4? in rat tumor models. Our studies have identified a double-negative feedback mechanism controlling Wnt-?-catenin signaling and HNF4? expression in vitro and in vivo, which sheds new light on the regulation of EMT in HCC. The modulation of these molecular processes may be a method of inhibiting HCC invasion by blocking Wnt-?-catenin signaling or restoring HNF4? expression to prevent EMT. PMID:24101726

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

2013-12-15

323

Feedback Analysis and Design of RF Power Links for Low-Power Bionic Systems  

Microsoft Academic Search

This paper presents a feedback-loop technique for analyzing and designing RF power links for transcutaneous bionic systems, i.e., between an external RF coil and an internal RF coil implanted inside the body. The feedback techniques shed geometric insight into link design and minimize algebraic manipulations. We demonstrate that when the loop transmission of the link's feedback loop is -1, the

Michael W. Baker; Rahul Sarpeshkar

2007-01-01

324

Interactive Information Seeking and Retrieving: A Third Feedback Framework.  

ERIC Educational Resources Information Center

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

Spink, Amanda

1996-01-01

325

Amplifier linearization using RF feedback and feedforward techniques  

Microsoft Academic Search

The performance of feedback as a distortion reduction technique is highly dependent on the integrity of the feedback path. Any error or noise generated in this path is directly reflected into the output of the amplifier. Linearized RF power amplifiers (PAs) using Cartesian feedback require a demodulator in the feedback loop, and this is a potential source of linear errors,

Michael Faulkner

1998-01-01

326

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

SciTech Connect

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

Kung, P.J. [Biophysics Group P-6, MS M715, Los Alamos National Laboratory, Los Alamos, New Mexico 87545 (United States)] [Biophysics Group P-6, MS M715, Los Alamos National Laboratory, Los Alamos, New Mexico 87545 (United States); Bracht, R.R. [Systems and Robotics Group ESA-6, MS J580, Los Alamos National Laboratory, Los Alamos, New Mexico 87545 (United States)] [Systems and Robotics Group ESA-6, MS J580, Los Alamos National Laboratory, Los Alamos, New Mexico 87545 (United States); Flynn, E.R. [Biophysics Group P-6, MS M715, Los Alamos National Laboratory, Los Alamos, New Mexico 87545 (United States)] [Biophysics Group P-6, MS M715, Los Alamos National Laboratory, Los Alamos, New Mexico 87545 (United States); Lewis, P.S. [Systems and Robotics Group ESA-6, MS J580, Los Alamos National Laboratory, Los Alamos, New Mexico 87545 (United States)] [Systems and Robotics Group ESA-6, MS J580, Los Alamos National Laboratory, Los Alamos, New Mexico 87545 (United States)

1996-01-01

327

IRE1a constitutes a negative feedback loop with BMP2 and acts as a novel mediator in modulating osteogenic differentiation  

PubMed Central

Bone morphogenetic protein 2 (BMP2) is known to activate unfolded protein response (UPR) signaling molecules, such as BiP (IgH chain-binding protein), PERK (PKR-like ER-resistant kinase), and IRE1?. Inositol-requiring enzyme-1a (IRE1a), as one of three unfolded protein sensors in UPR signaling pathways, can be activated during ER stress. Granulin-epithelin precursor (GEP) is an autocrine growth factor that has been implicated in embryonic development, tissue repair, tumorigenesis, and inflammation. However, the influence on IRE1a in BMP2-induced osteoblast differentiation has not yet been elucidated. Herein we demonstrate that overexpression of IRE1a inhibits osteoblast differentiation, as revealed by reduced activity of alkaline phosphatase (ALP) and osteocalcin; however, knockdown of IRE1a via the RNAi approach stimulates osteoblastogenesis. Mechanistic studies revealed that the expression of IRE1a during osteoblast was a consequence of JunB transcription factor binding to several AP1 sequence (TGAG/CTCA) in the 5?-flanking regulatory region of the IRE1a gene, followed by transcription. In addition, GEP induces IRE1a expressions and this induction of IRE1a by GEP depends on JunB. Furthermore, IRE1a inhibition of GEP-induced osteoblastogenesis relies on JunB. Besides, GEP is required for IRE1a inhibition of BMP2-induced bone formation. Collectively, these findings demonstrate that IRE1a negatively regulates BMP2-induced osteoblast differentiation and this IRE1a inhibition effect depends on GEP growth factor. Thus, IRE1a, BMP2, GEP growth factor, and JunB transcription factor form a regulatory loop and act in concert in the course of osteoblastogenesis.

Guo, F-J; Jiang, R; Xiong, Z; Xia, F; Li, M; Chen, L; Liu, C-J

2014-01-01

328

Voltage shifts and defect-dipoles in ferroelectric capacitors.  

National Technical Information Service (NTIS)

We review the processes and mechanisms by which voltage offsets occur in the hysteresis loop of ferroelectric materials. Simply stated, voltage shifts arise from near-interfacial charge trapping in the ferroelectric. We show that the impetus behind voltag...

W. L. Warren G. E. Pike D. Dimos

1996-01-01

329

Klystron equalization for RF feedback  

SciTech Connect

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

Corredoura, P.

1993-01-01

330

Klystron equalization for RF feedback  

SciTech Connect

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

Corredoura, P.

1993-01-01

331

A Unilateral Negative Feedback Loop Between miR-200 microRNAs and Sox2/E2F3 Controls Neural Progenitor Cell-Cycle Exit and Differentiation  

PubMed Central

MicroRNAs have emerged as key posttranscriptional regulators of gene expression during vertebrate development. We show that the miR-200 family plays a crucial role for the proper generation and survival of ventral neuronal populations in the murine midbrain/hindbrain region, including midbrain dopaminergic neurons, by directly targeting the pluripotency factor Sox2 and the cell-cycle regulator E2F3 in neural stem/progenitor cells. The lack of a negative regulation of Sox2 and E2F3 by miR-200 in conditional Dicer1 mutants (En1+/Cre; Dicer1flox/flox mice) and after miR-200 knockdown in vitro leads to a strongly reduced cell-cycle exit and neuronal differentiation of ventral midbrain/hindbrain (vMH) neural progenitors, whereas the opposite effect is seen after miR-200 overexpression in primary vMH cells. Expression of miR-200 is in turn directly regulated by Sox2 and E2F3, thereby establishing a unilateral negative feedback loop required for the cell-cycle exit and neuronal differentiation of neural stem/progenitor cells. Our findings suggest that the posttranscriptional regulation of Sox2 and E2F3 by miR-200 family members might be a general mechanism to control the transition from a pluripotent/multipotent stem/progenitor cell to a postmitotic and more differentiated cell.

Peng, Changgeng; Li, Na; Ng, Yen-Kar; Zhang, Jingzhong; Meier, Florian; Theis, Fabian J.; Merkenschlager, Matthias; Chen, Wei

2012-01-01

332

The Peroxisome Proliferator-Activated Receptor ?/Retinoid X Receptor ? Heterodimer Targets the Histone Modification Enzyme PR-Set7/Setd8 Gene and Regulates Adipogenesis through a Positive Feedback Loop? †  

PubMed Central

Control of cell differentiation occurs through transcriptional mechanisms and through epigenetic modification. Using a chromatin immunoprecipitation-on-chip approach, we performed a genome-wide search for target genes of peroxisome proliferator-activated receptor ? (PPAR?) and its partner protein retinoid X receptor ? during adipogenesis. We show that these two receptors target several genes that encode histone lysine methyltransferase SET domain proteins. The histone H4 Lys 20 (H4K20) monomethyltransferase PR-Set7/Setd8 gene is upregulated by PPAR? during adipogenesis, and the knockdown of PR-Set7/Setd8 suppressed adipogenesis. Intriguingly, monomethylated H4K20 (H4K20me1) levels are robustly increased toward the end of differentiation. PR-Set7/Setd8 positively regulates the expression of PPAR? and its targets through H4K20 monomethylation. Furthermore, the activation of PPAR? transcriptional activity leads to the induction of H4K20me1 modification of PPAR? and its targets and thereby promotes adipogenesis. We also show that PPAR? targets PPAR?2 and promotes its gene expression through H4K20 monomethylation. Our results connect transcriptional regulation and epigenetic chromatin modulation through H4K20 monomethylation during adipogenesis through a feedback loop.

Wakabayashi, Ken-ichi; Okamura, Masashi; Tsutsumi, Shuichi; Nishikawa, Naoko S.; Tanaka, Toshiya; Sakakibara, Iori; Kitakami, Jun-ichi; Ihara, Sigeo; Hashimoto, Yuichi; Hamakubo, Takao; Kodama, Tatsuhiko; Aburatani, Hiroyuki; Sakai, Juro

2009-01-01

333

TUNE FEEDBACK AT RHIC  

SciTech Connect

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.

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

334

Integrated optical phase locked loop.  

SciTech Connect

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.

Lentine, Anthony L.; Kim, Jungwon (Massachusetts Institute of Technology, Cambridge, MA); Trotter, Douglas Chandler; DeRose, Christopher T.; Kartner, Franz X. (Massachusetts Institute of Technology, Cambridge, MA); Byun, Hyunil (Massachusetts Institute of Technology, Cambridge, MA); Nejadmalayeri, Amir H. (Massachusetts Institute of Technology, Cambridge, MA); Watts, Michael R.; Zortman, William A.

2010-12-01

335

Voltage-Controlled Oscillator  

NASA Technical Reports Server (NTRS)

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.

1995-01-01

336

Fast repetitive controller based low-voltage dynamic voltage restorer for voltage-quality issues in distribution system  

Microsoft Academic Search

Dynamic voltage restorer (DVR) has been demonstrated to be a very effective mechanism to deal with key voltage-quality disturbances. Although the dynamic response requirement for voltage sag could be satisfied with a feedforward control strategy, the steady-state requirement and zero-error tracking need an advanced feedback control strategy. This paper proposes a fast repetitive controller based feedback control strategy for DVR

Suxuan Guo

2010-01-01

337

Large capacitance-voltage hysteresis loops in SiO{sub 2} films containing Ge nanocrystals produced by ion implantation and annealing  

SciTech Connect

Metal-oxide-semiconductor structures containing Ge nanocrystals (NCs) of 3-4 nm diameter and 2x10{sup 12} cm{sup -2} density are shown to exhibit capacitance-voltage hysteresis of 20.9 V, one of the largest observed in Ge-NC based nonvolatile memories. The Ge NCs were fabricated in an oxide of 30 nm thickness by ion implantation with 30 keV Ge{sub 2}{sup -} ions to an equivalent fluence of 1x10{sup 16} Ge cm{sup -2} followed by annealing at 950 deg. C for 10 min. Secondary ion mass spectroscopy and transmission electron microscopy demonstrate the existence of Ge NCs whose average distance from the SiO{sub 2}/Si interface is about 6.7 nm. It is shown that the memory effect is a likely consequence of charge trapping at Ge NCs and that it is enhanced by accurately controlling the distribution of Ge NCs with respect to the Si/SiO{sub 2} interface.

Park, C.J.; Cho, K.H.; Yang, W.-C.; Cho, H.Y.; Choi, Suk-Ho; Elliman, R.G.; Han, J.H.; Kim, Chungwoo [Department of Physics and Quantum-Functional Semiconductor Research Center, Dongguk University, Seoul 100-715 (Korea, Republic of); Department of Physics and Applied Physics, College of Electronics and Informations, Kyung Hee University, Suwon 449-701 (Korea, Republic of); Electronic Materials Engineering Department, Research School of Physical Sciences and Engineering, Australian National University, Canberra ACT0200 (Australia); Semiconductor R and D Center Memory Division, Samsung Electronics Co. LTD., Kyunggi-do, 449-711 (Korea, Republic of)

2006-02-13

338

Control of the reactive line current provided by a Dual-Bridge Matrix Converter using the input-output feedback linearization approach  

Microsoft Academic Search

A new time-invariant reduced-order model expressed in the d-q rotating reference frame of a three-phase dual-bridge matrix converter is presented. Then, a closed-loop control of the reactive component of the line current is developed. The proposed control-law uses the input-output feedback linearization approach. It allows a unity input power factor operation independently of the voltage transfer ratio variation as well

M. hamouda; F. Fnaiech; K. Al-Haddad

2006-01-01

339

Computer automation for feedback system design  

NASA Technical Reports Server (NTRS)

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.

1975-01-01

340

Pulsed feedback defers cellular differentiation.  

PubMed

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

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

2012-01-01

341

STABILITY OF HIGH VOLTAGE MODULATORS FOR NONLINEAR LOADS  

SciTech Connect

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

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

2003-10-01

342

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

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.

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

2014-01-01

343

Feedback control of TET system with variable coupling coefficients for a novel artificial anal sphincter.  

PubMed

For treating severe faecal incontinence, the authors developed an intelligent artificial anal sphincter system (AASS) equipped with a feedback sensor that utilized a transcutaneous energy transfer system (TETS). To deliver the correct amount of power (i.e. to match the load demand under variable coupling conditions caused by changes in positioning between the coils due to fitting and changes in posture), a regulating method to stabilize output voltage with a closed loop variable-frequency controller was developed in this paper. The method via which the voltage gain characteristics of a voltage-fed series-tuned TETS were derived is also described. The theoretical analysis was verified by the results of the experiment. A numerical analysis method was used as a control rule with respect to the relationship between operating frequency and output voltage. To validate the feedback control rules, a prototype of the TET charging system was constructed, and its performance was validated with the coupling variation between 0.12-0.42. The results show that the output voltage of the secondary side can be maintained at a constant 7?V across the whole coupling coefficient range, with a switching frequency regulation range of 271.4-320.5 kHz, and the proposed controller has reached a maximal end-to-end power efficiency of 67.5% at 1 W. PMID:24400997

Ke, L; Yan, G; Yan, S; Wang, Z; Liu, Z

2014-03-01

344

Realistic feedback control of turbogenerators  

SciTech Connect

In this paper, the optimal control of a turboalternator connected to an infinite bus is considered. The alternator is controlled through a linear feedback of the state variables. The feedback parameters are obtained by solving a two-point nonlinear boundary-value problem. The values obtained for these parameters depend on the strength and duration of the disturbance, since the model is nonlinear, contrary to the usual feedback control of a linear model. In contrast to the model used in Ref. 1, the model used here include the transfer functions of the governor, the turbine, and the voltage regulator.

Shamaly, A.; Christensen, G.S.; El-Hawary, M.E.

1981-10-01

345

Pendulum Micromechanical Angular Accelerometer with Force Feedback  

Microsoft Academic Search

This paper bring forward a kind of pendulum micromechanical angular accelerometer with force feedback, which might be proposed by us, first. The sensor adopts a pendulum with mass joined to the anchors by a pair torsion-spring beams as sensing device, differential-capacitor device for detecting the angular acceleration about the X axis, an electrostatic force device for feedback loop. The sensor's

Li Jianli; Fang Jiancheng; Sheng Wei

2007-01-01

346

Digital phase-lock loop  

NASA Technical Reports Server (NTRS)

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.

Thomas, Jr., Jess B. (Inventor)

1991-01-01

347

Phase-locked loops: a control centric tutorial  

Microsoft Academic Search

Presents a tutorial on phase-locked loops from a control systems perspective. It starts with an introduction of the loop as a feedback control problem, with both the similarities and differences to traditional control problems. Chief among the differences is the necessary inclusion of two nonlinearities in the loop that are not parasitic, but essential to the loop's operation. Analysis methods,

Daniel Abramovitch

2002-01-01

348

Loop simulations.  

PubMed

Loop modeling is crucial for high-quality homology model construction outside conserved secondary structure elements. Dozens of loop modeling protocols involving a range of database and ab initio search algorithms and a variety of scoring functions have been proposed. Knowledge-based loop modeling methods are very fast and some can successfully and reliably predict loops up to about eight residues long. Several recent ab initio loop simulation methods can be used to construct accurate models of loops up to 12-13 residues long, albeit at a substantial computational cost. Major current challenges are the simulations of loops longer than 12-13 residues, the modeling of multiple interacting flexible loops, and the sensitivity of the loop predictions to the accuracy of the loop environment. PMID:22323223

Totrov, Maxim

2012-01-01

349

Global Warming, Clouds, and Albedo: Feedback Loops  

NSDL National Science Digital Library

This site, from the University Corporation for Atmospheric Research (UCAR), offers a detailed explanation, with diagrams, of both Earth's water cycle and the global heat flow, including the processes that produce the greenhouse effect. Greenhouse gases are listed, and their relative contributions to the greenhouse effect are enumerated. Special attention is paid to the role of clouds.

2009-05-27

350

An optical-feedback transimpedance receiver for high sensitivity and wide dynamic range at low bit rates  

Microsoft Academic Search

A novel transimpedance optical receiver using optically coupled feedback rather than a conventional feedback resistor is described. The optically coupled feedback has a number of advantages, including: (1) elimination of feedback-resistor Johnson noise for higher sensitivity; (2) elimination of feedback capacitance for higher bandwidth; and (3) the capability of large feedback current with low output voltage for wide dynamic range.

B. L. Kasper; ALFRED R. McCORMICK; J. R. Talman

1988-01-01

351

Balanced-Bridge Feedback Control Of Motor  

NASA Technical Reports Server (NTRS)

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.

Lurie, Boris J.

1990-01-01

352

Predictive feedback control.  

PubMed

In this work a new method for designing predictive controllers for linear single-input/single-output systems is presented. It uses only one prediction of the process output J time intervals ahead to compute the correspondent future error. Then, the predictive feedback controller is defined by introducing a filter which weights the last w predicted errors. In this way, the resulting control action is computed by observing the system future behavior and also by weighting present and past errors. This last feature improves the closed-loop performance to disturbance rejection as shown through simulations of two linear systems and a nonlinear continuous stirred tank reactor. PMID:12708540

Giovanini, Leonardo L

2003-04-01

353

The Anderson Current Loop  

NASA Technical Reports Server (NTRS)

Four-wire-probe concept applied to electrical-resistance transducers. Anderson current loop is excitation-and-signal-conditioning circuit suitable for use with strain gauges, resistance thermometers, and other electrical-resistance transducers mounted in harsh environments. Used as alternative to Wheatstone bridge. Simplifies signal-conditioning problem, enabling precise measurement of small changes in resistance of transducer. Eliminates some uncertainties in Wheatstone-bridge resistance-change measurements in flight research. Current loop configuration makes effects of lead-wire and contact resistances insignificantly small. Also provides output voltage that varies linearly with change in gauge resistance, and does so at double sensitivity of Wheatstone bridge.

Anderson, Karl F.

1994-01-01

354

Self-perpetuating states in signal transduction: positive feedback, double-negative feedback and bistability  

Microsoft Academic Search

Cell signaling systems that contain positive-feedback loops or double-negative feedback loops can, in principle, convert graded inputs into switch-like, irreversible responses. Systems of this sort are termed ‘bistable’. Recently, several groups have engineered artificial bistable systems into Escherichia coli and Saccharomyces cerevisiae, and have shown that the systems exhibit interesting and potentially useful properties. In addition, two naturally occurring signaling

James E Ferrell Jr

2002-01-01

355

Understanding Pound-Drever-Hall locking using voltage controlled radio-frequency oscillators: An undergraduate experiment  

NASA Astrophysics Data System (ADS)

We have developed a senior undergraduate experiment that illustrates frequency stabilization techniques using radio-frequency electronics. The primary objective is to frequency stabilize a voltage controlled oscillator to a cavity resonance at 800 MHz using the Pound-Drever-Hall method. This technique is commonly applied to stabilize lasers at optical frequencies. By using only radio-frequency equipment, it is possible to systematically study aspects of the technique more thoroughly, inexpensively, and free from eye hazards. Students also learn about modular radio-frequency electronics and basic feedback control loops. By varying the temperature of the resonator, students can determine the thermal expansion coefficients of copper, aluminum, and super invar.

Liekhus-Schmaltz, C. E.; Martin, J. D. D.

2012-03-01

356

Control of bistability in a directly modulated semiconductor laser using delayed optoelectronic feedback  

Microsoft Academic Search

We show numerically that direct delayed optoelectronic feedback can suppress hysteresis and bistability in a directly modulated semiconductor laser. The simulation of a laser with feedback is performed for a considerable range of feedback strengths and delays and the corresponding values for the areas of the hysteresis loops are calculated. It is shown that the hysteresis loop completely vanishes for

S. Rajesh; V. M. Nandakumaran

2006-01-01

357

On the functional diversity of dynamical behaviour in genetic and metabolic feedback systems  

Microsoft Academic Search

BACKGROUND: Feedback regulation plays crucial roles in the robust control and maintenance of many cellular systems. Negative feedbacks are found to underline both stable and unstable, often oscillatory, behaviours. We explore the dynamical characteristics of systems with single as well as coupled negative feedback loops using a combined approach of analytical and numerical techniques. Particularly, we emphasise how the loop's

Lan K Nguyen; Don Kulasiri

2009-01-01

358

An improved DSP-based control strategy with predictive current control and fuzzy voltage control for grid-connected voltage source inverters  

Microsoft Academic Search

This paper presents an improved DSP-based control strategy with combined voltage and current for gird-connected voltage source inverters (VSIs). A predictive current control strategy in the inner loop and a fuzzy voltage control strategy in the outer loop are respectively discussed in detail. A new predictive current control expression is obtained, which calculates the inverter voltages required to force the

Bo Yang; Jiande Wu; Xiaodong Lu; Xiangning He

2008-01-01

359

Low-Voltage Room Thermostat Performance.  

National Technical Information Service (NTIS)

To predict performance of low voltage electric thermostats in a dynamic building system, a computer model representing two types of thermal feedback was developed. Unlike the information obtained from existing test standards, this model allows thermostat ...

J. Y. Kao G. Sushinsky D. A. Didion E. J. Mastascusa J. Chi

1983-01-01

360

Laser Doppler vibrometer employing active frequency feedback  

Microsoft Academic Search

We present a heterodyne Michelson interferometer for vibration measurement in which feedback is used to obviate the need to unwrap phase data. The Doppler shift of a vibrating target mirror is sensed interferometrically and compensated by means of a voltage-controlled oscillator driving an acousto-optic modulator. For frequencies within the servo bandwidth, the oscillator control voltage provides a direct measurement of

Akobuije Chijioke; John Lawall

2008-01-01

361

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

SciTech Connect

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.

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

1997-08-01

362

Coress feedback  

PubMed Central

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

2012-01-01

363

A closed loop musculoskeletal model of postural coordination dynamics  

Microsoft Academic Search

A closed-loop model with actuator dynamics and sensory feedback has been developed to capture the complex postural behaviors observed in a human head tracking task. In motor-control litterature, spindle feedback gains are scaled by the central nervous system to adapt muscle stiffness depending on the postural task. We propose to identify spindle reflex equivalent feedback gains for several target's frequency

Vincent Bonnet; Philippe Fraisse; Nacim Ramdani; Julien Lagarde; Sofiane Ramdani; Benoît G. Bardy

2009-01-01

364

Power-MOSFET Voltage Regulator  

NASA Technical Reports Server (NTRS)

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.

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

1982-01-01

365

Linearizing Intra-Train Beam-Beam Deflection Feedback  

SciTech Connect

Beam-beam deflection feedback acting within the crossing time of a single bunch train may be needed to keep linear collider beams colliding at high luminosity. In a short-pulse machine such as the Next Linear Collider (NLC) this feedback must converge quickly to be useful. The non-linear nature of beam-beam deflection vs. beam-beam offset in these machines precludes obtaining both rapid convergence and a stable steady-state lock to beam offsets with a linear feedback algorithm. We show that a simply realizable programmable non-linear amplifier in the feedback loop can linearize the feedback loop, approximately compensating the beam-beam deflection non-linearity. Performance of a prototype non-linear amplifier is shown. Improvement of convergence and stability of the beam-beam feedback loop is simulated.

Smith, S.R.; /SLAC

2006-02-22

366

A phase detection method for harmonics and unbalanced voltage  

Microsoft Academic Search

This paper proposes a phase detection method for harmonics and unbalanced voltage conditions. The proposed method uses harmonics and unbalanced voltage compensation circuit in addition to basic PLL (Phase Locked Loop) circuit. In the harmonic compensation circuit, the harmonic voltage components are eliminated from the input voltages using specific harmonic detection method. Besides, frequency information of power system used in

Tomonobu Senjyu; Yuri Yonaha; Norihiro Nakasone; Atsushi Yona; Chul-Hwan Kim

2008-01-01

367

A linearization voltage control strategy of three-phase PWM rectifier  

Microsoft Academic Search

In the double closed loops control strategy of three-phase voltage source PWM rectifier in the synchronous reference frame, the linear PI control is usually adopted in the voltage control loop, which cannot reflect the nonlinear nature of the PWM rectifier, and restricts the systempsilas control performance. According to the analyses on the voltage equation of the PWM rectifier, a voltage

Yanping Zhong; Yaojun Chen; Dan Chen

2008-01-01

368

Sinusoidal voltage controller for uninterruptible power supply by robust control  

Microsoft Academic Search

The output voltage of an uninterruptible power supply (UPS) is distorted by nonlinear loads. To obtain sinusoidal output voltage of a UPS, a new control method of a pulse width modulated (PWM) inverter is proposed applying sliding mode control. The feedback gains of conventional sliding mode control are determined by offline calculation; however this proposed control method calculates the feedback

Tomonobu Senjyu; Katsumi Uezato

1993-01-01

369

Real-Time Induction Motor Speed Control with a Feedback Utilizing Power Line Communications and a Motor Feeder Cable in Data Transmission  

Microsoft Academic Search

In a motor speed control, a feedback loop is used to transfer the measured motor rotational speed information to the controller. The implementation of the feedback loop requires cabling between the motor and the frequency converter both for signalling and powering. However, the motor feeder cable could be used as a medium for data transmission. A feedback loop that utilizes

Antti Kosonen; Markku Jokinen; Jero Ahola; Markku Niemelä

2006-01-01

370

Voltage Sensor  

NASA Technical Reports Server (NTRS)

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.

1996-01-01

371

A STATE VARIABLE DESCRIPTION OF THE RHIC RF CONTROL LOOPS  

Microsoft Academic Search

The beam transfer function changes during the RHIC ramp. The response of the RF control loops changes as a result. A state-variable description of the beam and the RF control loops was developed. This description was used to generate a set of feedback matrices that keeps the response of the RF control loops constant during the ramp. This paper describes

C. SCHULTHEISS; J. M. BRENNAN

2002-01-01

372

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

NASA Technical Reports Server (NTRS)

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.)

Vorpenian, Vatche

2008-01-01

373

CORESS feedback  

PubMed Central

Three of the cases in this issue of CORESS Feedback relate to failure of either giving or taking of information. A good clinical history underpins management decisions and emphasis on providing the general practitioner (and patient) with a comprehensive written discharge summary, describing treatment, is paramount. The final case illustrates once again that the role of the World Health Organization checklist and the ‘time-out’ cannot be overestimated in facilitating safe surgery. We are grateful to the clinicians who have provided the material for these reports. The online reporting form is on our website (www.coress.org.uk), which also includes all previous Feedback Reports. Published contributions will be acknowledged by a ‘Certificate of Contribution’, which may be included in the contributor’s record of continuing professional development.

Smith, Frank CT

2013-01-01

374

Calibrator for alternating voltage, current, and power  

Microsoft Academic Search

A computer-controlled calibrator capable of delivering ac sinusoidal and distorted waveform voltage, current, and power with an accuracy of several parts per million is described. The reference ac voltage is obtained using digital-to-analog conversion and the reference ac current by applying the reference voltage to a reference ac resistor. The phase relation is obtained digitally. A combination of feedback and

P. N. Miljanic

1989-01-01

375

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

NASA Astrophysics Data System (ADS)

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.

Firlej, M.; Fiutowski, T.; Idzik, M.; Moro?, J.; ?wientek, K.

2014-02-01

376

Research on control strategy for Three-Phase PWM Voltage Source Rectifier  

Microsoft Academic Search

This paper first introduces the topology of three-phase PWM voltage source rectifier (VSR). Then the mathematical models in three-phase static and two-phase rotary coordinate system are built. Based on that theory and the voltage-oriented vector control's idea, the paper introduces a dual-channel closed-loop control strategy with current-inner-loop and voltage-outer-loop. Active power channel is aim to make DC side voltage remain

Yu Wang; Yanbo Che; K. W. E. Cheng

2009-01-01

377

High holding voltage cascoded LVTSCR structures for 5.5-V tolerant ESD protection clamps  

Microsoft Academic Search

This paper presents a new design concept for the control of the holding voltage of LVTSCR ESD protection structures by realizing a negative feedback in the p emitter. The negative feedback is implemented by the creation of a voltage drop using embedded circuit elements. The final clamp voltage is tuned to exceed the power supply level, thus eliminating the potential

Vladislav A. Vashchenko; A. Concannon; M. ter Beek; P. Hopper

2004-01-01

378

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

PubMed

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

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

2012-01-01

379

Neural network based feedback error controller for helicopter  

Microsoft Academic Search

Purpose – This paper seeks to present a feedback error learning neuro-controller for an unstable research helicopter. Design\\/methodology\\/approach – Three neural-aided flight controllers are designed to satisfy the ADS-33 handling qualities specifications in pitch, roll and yaw axes. The proposed controller scheme is based on feedback error learning strategy in which the outer loop neural controller enhances the inner loop

M. Vijaya Kumar; P. Sampath; S. Suresh; S. N. Omkar; Ranjan Ganguli

2011-01-01

380

Inverter output voltage synthesis using novel dead time compensation  

Microsoft Academic Search

In this paper, a novel dead time compensation method is presented that produces inverter output voltages equal to reference voltages. An experimental result is also presented to demonstrate the validity of the proposed method. It shows that the compensation of the dead time is possible up to a sub-microsecond range. Also, the reference voltage can be used as a feedback

Jong-Woo Choi; Seung-Ki Sul

1996-01-01

381

Feedback linearization application for LLRF control system  

SciTech Connect

The Low Energy Demonstration Accelerator (LEDA) being constructed at Los Alamos National Laboratory will serve as the prototype for the low energy section of Acceleration Production of Tritium (APT) accelerator. This paper addresses the problem of the LLRF control system for LEDA. The authors propose a control law which is based on exact feedback linearization coupled with gain scheduling which reduces the effect of the deterministic klystron cathode voltage ripple that is due to harmonics of the high voltage power supply and achieves tracking of desired set points. Also, they propose an estimator of the ripple and its time derivative and the estimates based feedback linearization controller.

Kwon, S.; Regan, A.; Wang, Y.M.; Rohlev, T.

1998-12-31

382

Feedback linearization application for LLRF control system  

SciTech Connect

The Low Energy Demonstration Accelerator (LEDA) being constructed at Los Alamos National Laboratory will serve as the prototype for the low energy section of Acceleration Production of Tritium (APT) accelerator. This paper addresses the problem of the LLRF control system for LEDA. The authors propose a control law which is based on exact feedback linearization coupled with gain scheduling which reduces the effect of the deterministic klystron cathode voltage ripple that is due to harmonics of the high voltage power supply and achieves tracking of desired set points. Also, they propose an estimator of the ripple and its time derivative and the estimates based feedback linearization controller.

Kwon, S.; Regan, A.; Wang, Y.M.; Rohlev, T.

1999-06-01

383

Loop space  

NASA Astrophysics Data System (ADS)

Several topics in the loop-space formulation of non-Abelian gauge theories are considered. The basic objects dealt with are the unrenormalized dimensionally regularized gauge-invariant loop functions W(Cig, ?), where Ci is a set of loops, g is the unrenormalized coupling constant, and ? is the deviation from four space-time dimensions. The renormalization-group equations satisfied by the corresponding renormalized loop functions are derived and, using asymptotic freedom, used to determine the exact behavior of the functions when the length L of the loops approaches zero. The result is (-lnL?)a(?), where ? is the subtraction mass and ? represents the cusp and cross-point angles of the loops. The function a(?) is exactly computable and several examples are given. The equivalent result may be stated as the exact behavior of the renormalization-constant matrix Zij(?, gR, ?) for ?-->0 with fixed renormalized coupling constant gR, or as the exact behavior of the unrenormalized loop function for ?-->0 and gR fixed. It is shown next that the W(Cig, ?) satisfy dimensionally regularized Makeenko-Migdal equations in all orders of perturbation theory. The proof makes detailed use of dimensional regularization, Becchi-Rouet-Stora symmetry, gauge-field combinatorics, and properties of the area functional derivative of path-ordered multiple line integrals. Doubt is cast on the existence of such useful equations when other regularizations are used or when renormalization is performed. The Mandelstam constraints are considered next. Among other things, it is shown that the loop-function renormalization may be performed such that the renormalized functions satisfy a constraint which has the same form as the unrenormalized constraint i=1(N+1)?aiW(Ci)=0, for the U(N) gauge group. The paper concludes with illustrations of how observable matrix elements of physical (color singlet, quark bilinear) flavor currents may be expressed in terms of loop functions. Among other topics discussed in the paper are the N-->? limit, two-dimensional QCD, and normalization conditions on the renormalized loop functions.

Brandt, R. A.; Gocksch, A.; Sato, M.-A.; Neri, F.

1982-12-01

384

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

NASA Technical Reports Server (NTRS)

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.

Bearden, Douglas

2007-01-01

385

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)

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.

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

1973-01-01

386

Robust Output Feedback Control for Dynamic Network Systems  

Microsoft Academic Search

On the basis of robust H? control, the output feedback controller is presented for a class of dynamic time-varying delay network systems. The objective of designing robust H? controller is to achieve the desired queue size and to guarantee the asymptotic stability of the close-loop. The sufficient condition for the existence of a dynamic output feedback controller is presented via

Ping Sun; Deming Li; Shujiang Li

2010-01-01

387

Performance-Rate Functions for Dynamically Quantized Feedback Systems  

Microsoft Academic Search

This paper studies the performance of dynamically quantized feedback systems. In particular, we examine the relationship between the minimum summed squared quantization error and the rate at which feedback measurements are quantized. The closed loop system's performance can vary greatly for a given bit rate, depending on how the quantization bits are allocated. This paper derives the bit assignment policy

Michael D. Lemmon; Rong Sun

2006-01-01

388

Quantum feedback control for deterministic entangled photon generation.  

PubMed

We present quantum feedback control for deterministic entanglement generation at the single-photon level. The protocol of controlling both total photon number and phase difference is based on the cascade structure of cavities placed in an optical closed loop, quantum nondemolition measurement with cross-Kerr interactions, and Lyapunov stability for feedback design. PMID:17155595

Yanagisawa, Masahiro

2006-11-10

389

Quantum Feedback Control for Deterministic Entangled Photon Generation  

NASA Astrophysics Data System (ADS)

We present quantum feedback control for deterministic entanglement generation at the single-photon level. The protocol of controlling both total photon number and phase difference is based on the cascade structure of cavities placed in an optical closed loop, quantum nondemolition measurement with cross-Kerr interactions, and Lyapunov stability for feedback design.

Yanagisawa, Masahiro

2006-11-01

390

Synchronization and communication using semiconductor lasers with optoelectronic feedback  

Microsoft Academic Search

Semiconductor lasers provide an excellent oppor- tunity for communication using chaotic waveforms. We discuss the characteristics and the synchronization of two semiconductor lasers with optoelectronic feedback. The systems exhibit broad- band chaotic intensity oscillations whose dynamical dimension generally increases with the time delay in the feedback loop. We explore the robustness of this synchronization with parameter mismatch in the lasers,

Henry D. I. Abarbanel; Matthew B. Kennel; Lucas Illing; S. Tang; H. F. Chen; J. M. Liu

2001-01-01

391

Beam dynamics in synchrotrons with digital wideband transverse feedback systems  

NASA Astrophysics Data System (ADS)

Current researches on beam dynamics in synchrotrons with digital wideband transverse feedback systems are reviewed. Particular attention is given to quantitative and qualitative regularities in frequency shifts and decrements of coherent betatron oscillation damping when feedback loop signals are digitally processed. Theoretical predictions are compared with the experimental data obtained at the Large Hadron Collider.

Zhabitsky, V. M.

2014-03-01

392

Direct laser additive fabrication system with image feedback control  

DOEpatents

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.

Griffith, Michelle L. (Albuquerque, NM) [Albuquerque, NM; Hofmeister, William H. (Nashville, TN) [Nashville, TN; Knorovsky, Gerald A. (Albuquerque, NM) [Albuquerque, NM; MacCallum, Danny O. (Edgewood, NM) [Edgewood, NM; Schlienger, M. Eric (Albuquerque, NM) [Albuquerque, NM; Smugeresky, John E. (Pleasanton, CA) [Pleasanton, CA

2002-01-01

393

Preamplifier with multi-stage feedback  

Microsoft Academic Search

A circuit for amplifying an input signal comprises an operational amplifier, a dual operational amplifier, and a buffering operational amplifier all cascaded in the afore-mentioned order. The first operational amplifier amplifies the input signal with minimum noise degradation, is set up as a non-inverting amplifier stage, and has a local negative feedback loop comprising a resistor and capacitor in parallel.

James D. Hagerty

1994-01-01

394

FEEDBACK DESIGN METHOD REVIEW AND COMPARISON.  

SciTech Connect

Different methods for feedback designs are compared. These includes classical Proportional Integral Derivative (P. I. D.), state variable based methods like pole placement, Linear Quadratic Regulator (L. Q. R.), H-infinity and p-analysis. These methods are then applied for the design and analysis of the RHIC phase and radial loop, yielding a performance, stability and robustness comparison.

ONILLON,E.

1999-03-29

395

Robust regional pole assignment with output feedback  

Microsoft Academic Search

Considers output feedback control design for regional pole placement for continuous time systems. The techniques presented are based on covariance control theory and yield parametrizations of controllers that assign closed loop poles into regions of specified shape like vertical strip, circle, and parabola. Robustification of pole placement to accommodate plant perturbations and derivation of covariance upper bounds are included

Engin Yaz; Robert E. Skelton; Karolos Grigoriadis

1993-01-01

396

Pole assignment by gain output feedback  

Microsoft Academic Search

This short paper deals with the problem of pole assignment with incomplete state observation. It is shown that if the system is controllable and observable, and ifn leq r + m - 1, an almost arbitrary set of distinct closed-loop poles is assignable by gain output feedback, wheren, r, andmare the numbers of state variables, inputs and outputs, respectively. This

H. Kimura

1975-01-01

397

Feedback linearization for control of air breathing engines  

NASA Technical Reports Server (NTRS)

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.

Phillips, Stephen; Mattern, Duane

1991-01-01

398

RF feedback simulation results for PEP-II  

SciTech Connect

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.

Tighe, R.; Corredoura, P.

1995-06-01

399

Injection-locked semiconductor lasers with delayed optoelectronic feedback  

Microsoft Academic Search

Optical injection and optoelectronic feedback are efficient techniques to externally control the spectral characteristics of a semiconductor laser. This paper presents theoretical and experimental results about the effects of a delayed optoelectronic feedback loop on the stability of an optically injected diode laser. In particular, negative feedback configurations (out-of-phase carrier reinjection) are shown to widen the injection-locking domain of the

Philippe Saboureau; Jean-Paul Foing; Pierre Schanne

1997-01-01

400

Task-Dependent Changes in Visual Feedback Control: A Frequency Analysis of Human Manual Tracking  

Microsoft Academic Search

Prominent components in the frequency spectrum of human manual tracking responses are thought to reflect the visual feedback control loop and have been used in estimations of the visual feedback loop delay. The frequency structure of human tracking was therefore examined here in two tasks: visually guided tracking of slow and fast pseudorandom targets. Visually related frequency components were identified

R. C. Miall

1996-01-01

401

Motor feedback speed control by utilizing the motor feeder cable as a communication channel  

Microsoft Academic Search

A feedback loop is used in the motor speed control in order to transmit the measured motor rotational speed information to the controller. The implementation of the feedback loop requires cabling between the motor and the frequency converter both for signalling and powering. However, the motor power cables could be also used for data transmission. The possibility of using the

A. Kosonen; M. Jokinen; V. Sarkimaki; J. Ahola; M. Niemela

2006-01-01

402

A capacitor-free CMOS LDO regulator with AC-boosting and active-feedback frequency compensation  

NASA Astrophysics Data System (ADS)

A capacitor-free CMOS low-dropout (LDO) regulator for system-on-chip (SoC) applications is presented. By adopting AC-boosting and active-feedback frequency compensation (ACB-AFFC), the proposed LDO regulator, which is independent of an off-chip capacitor, provides high closed-loop stability. Moreover, a slew rate enhancement circuit is adopted to increase the slew rate and decrease the output voltage dips when the load current is suddenly switched from low to high. The LDO regulator is designed and fabricated in a 0.6 ?m CMOS process. The active silicon area is only 770 × 472 ?m2. Experimental results show that the total error of the output voltage due to line variation is less than ±0.197%. The load regulation is only 0.35 mV/mA when the load current changes from 0 to 100 mA.

Qianneng, Zhou; Yongsheng, Wang; Fengchang, Lai

2009-04-01

403

Rogowski Loop design for NSTX  

SciTech Connect

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.

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

2000-01-06

404

Closed Loop RZ-DPSK Alignment for Optical Communications.  

National Technical Information Service (NTIS)

A method and system are provided for using a power spectral density of an output of a modulator to facilitate closed loop feedback for controlling alignment of a pulse with respect to information formed upon the pulse.

G. Yu J. R. Dupont L. C. Wah P. Y. Cheung

2004-01-01

405

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

NASA Technical Reports Server (NTRS)

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.

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

1974-01-01

406

Optical multistability using optoelectronic feedback  

NASA Astrophysics Data System (ADS)

An optical multistable device with good tuning capability was experimentally realized by using a semiconductor light-emitting device, a photodiode, and transistors with positive optoelectronic feedback. By tuning the cutoff current of each stage, optical multiple bistable and multistable loop characteristics are realized. In this device, the number of stable states is determined by the number of transistor pairs. It is noted that this device is easy to integrate and may be used in optical digital computers. A graphical solution method, as well as stability analysis of solutions, is presented to explain the operational principle of this device.

Lee, Chang-Hee; Shin, Sang-Yung; Lee, Soo-Young; Cho, Kun-Ho

1988-10-01

407

Low noise charge sensitive preamplifier using drain current feedback  

Microsoft Academic Search

A method of charge-sensitive amplifier feedback is described, in which the input FET drain current is controlled by the preamplifier output voltage producing stable operation. The circuit design has the benefit of eliminating the feedback resistor, thereby eliminating its parallel white and 1\\/f noise components. The circuit is simple, requiring no specialized FET designs. The FETs may remain in their

F. Olschner; J. C. Lund

1992-01-01

408

Pole-Zero Decision Feedback Equalization with a Rapidly Converging Adaptive IIR Algorithm  

Microsoft Academic Search

A decision feedback equalizer (DFE) containing a feedback filter with both poles and zeroes is proposed for high- speed digital communications over the subscriber loop. The feedback filter is composed of two sections: a relatively short finite impulse response (FIR) filter that cancels the initial part of the channel impulse response, which may contain rapid vari