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Sample records for all-optical feedback loop

  1. High Power Passive Phase Locking of Four Yb-Doped Fiber Amplifiers by an All-Optical Feedback Loop

    NASA Astrophysics Data System (ADS)

    Xue, Yu-Hao; He, Bing; Zhou, Jun; Li, Zhen; Fan, Yuan-Yuan; Qi, Yun-Feng; Liu, Chi; Yuan, Zhi-Jun; Zhang, Hai-Bo; Lou, Qi-Hong

    2011-05-01

    We report the passive phase locking of four high power Yb-doped fiber amplifiers with ring cavity. The interference patterns at different output power are observed and the Strehl ratios are measured. The maximum coherent output power of the fiber array is up to 1062 W by multi-stage amplification. The stable beam profiles of various phase relationships are observed by controlling the position of the feedback fiber, in good agreement with the calculated results. By using master oscillator power-amplifier (MOPA) architecture and broadband operation of passively phased systems, higher power scaling with high beam quality appears to be feasible.

  2. All-optical clock recovery for 40Gbs using an amplified feedback DFB laser

    NASA Astrophysics Data System (ADS)

    Sun, Yu; Pan, J. Q.; Zhao, L. J.; Chen, W. X.; Wang, W.; Wang, L.; Zhao, X. F.; Lou, C. Y.

    2009-11-01

    All-optical clock recovery is a key technology in all-optical 3R signal regeneration (Re-amplification, Retiming, and Reshaping) process. In this paper, a monolithic integrated three-section amplified feedback semiconductor laser (AFL) is demonstrated as an all optical clock regenerator. We fabricated a three-section AFL using quantum well intermixing process without regrowth instead of butt-joint process. The tunable characteristics of three-section AFL were investigated, and all optical clock recovery for 40Gb/s return to zero (RZ) 231-1 pseudorandom binary sequence (PRBS) is demonstrated experimentally using AFL with time jitter about 689.2fs.

  3. Dual-control nonlinear-optical loop mirrors for all-optical soliton synchronous modulation

    NASA Astrophysics Data System (ADS)

    Bigo, Sébastien; Desurvire, Emmanuel; Audouin, Olivier

    1996-09-01

    A novel dual-control configuration of nonlinear loop mirrors is used for all-optical soliton synchronous regeneration. Simulations show substantial improvement in transmission in this device compared with single-control devices, owing to chirp-free modulation. The absence of chirp is confirmed experimentally through a spectral analysis of the dual-control modulator.

  4. All-optical analog-to-digital conversion scheme based on Sagnac loop and balanced receivers.

    PubMed

    Xu, Kun; Niu, Jian; Dai, Yitang; Sun, Xiaoqiang; Dai, Jian; Wu, Jian; Lin, Jintong

    2011-05-10

    An all-optical analog-to-digital conversion scheme based on a Sagnac loop and balanced receivers is proposed and experimentally demonstrated. Adjustable phase shift about the transfer function of the Sagnac loop is obtained by using the multiwavelength optical pulses to realize the phase-shift optical quantization. Benefit from the complementary outputs at the transmitted and reflected ports of the Sagnac loop and balanced receiver can be used to obtain the quantized output binary signal for the encoding operation. A proof-of-concept experiment is implemented using a wavelength tunable continuous-wave laser diode. Using 16 different wavelengths, the 16 quantization levels are demonstrated and an effective number of bits (ENOB) of 4 bits is obtained. PMID:21556099

  5. All-optical UWB signal generation and multicasting using a nonlinear optical loop mirror.

    PubMed

    Huang, Tianye; Li, Jia; Sun, Junqiang; Chen, Lawrence R

    2011-08-15

    An all-optical scheme for ultra-wideband (UWB) signal generation (positive and negative monocycle and doublet pulses) and multicasting using a nonlinear optical loop mirror (NOLM) is proposed and demonstrated. Five UWB signals (1 monocycle and 4 doublet pulses) are generated simultaneously from a single Gaussian optical pulse. The fractional bandwidths of the monocycle pulses are approximately 100% while those of the doublet pulses range from 100% to 133%. The UWB signals are then modulated using a 2(15)-1 pseudorandom bit sequence (PRBS) and error-free performance for each multicast channel is obtained. PMID:21934951

  6. All-optical UWB signal generation and multicasting using a nonlinear optical loop mirror

    NASA Astrophysics Data System (ADS)

    Huang, Tianye; Li, Jia; Sun, Junqiang; Chen, Lawrence R.

    2011-08-01

    An all-optical scheme for ultra-wideband (UWB) signal generation (positive and negative monocycle and doublet pulses) and multicasting using a nonlinear optical loop mirror (NOLM) is proposed and demonstrated. Five UWB signals (1 monocycle and 4 doublet pulses) are generated simultaneously from a single Gaussian optical pulse. The fractional bandwidths of the monocycle pulses are approximately 100% while those of the doublet pulses range from 100% to 133%. The UWB signals are then modulated using a 215 - 1 pseudorandom bit sequence (PRBS) and error-free performance for each multicast channel is obtained.

  7. Current Developments on Optical Feedback Interferometry as an All-Optical Sensor for Biomedical Applications.

    PubMed

    Perchoux, Julien; Quotb, Adam; Atashkhooei, Reza; Azcona, Francisco J; Ramírez-Miquet, Evelio E; Bernal, Olivier; Jha, Ajit; Luna-Arriaga, Antonio; Yanez, Carlos; Caum, Jesus; Bosch, Thierry; Royo, Santiago

    2016-01-01

    Optical feedback interferometry (OFI) sensors are experiencing a consistent increase in their applications to biosensing due to their contactless nature, low cost and compactness, features that fit very well with current biophotonics research and market trends. The present paper is a review of the work in progress at UPC-CD6 and LAAS-CNRS related to the application of OFI to different aspects of biosensing, both in vivo and ex vivo. This work is intended to present the variety of opportunities and potential applications related to OFI that are available in the field. The activities presented are divided into two main sensing strategies: The measurement of optical path changes and the monitoring of flows, which correspond to sensing strategies linked to the reconstruction of changes of amplitude from the interferometric signal, and to classical Doppler frequency measurements, respectively. For optical path change measurements, measurements of transient pulses, usual in biosensing, together with the measurement of large displacements applied to designing palliative care instrumentation for Parkinson disease are discussed. Regarding the Doppler-based approach, progress in flow-related signal processing and applications in real-time monitoring of non-steady flows, human blood flow monitoring and OFI pressure myograph sensing will be presented. In all cases, experimental setups are discussed and results presented, showing the versatility of the technique. The described applications show the wide capabilities in biosensing of the OFI sensor, showing it as an enabler of low-cost, all-optical, high accuracy biomedical applications. PMID:27187406

  8. Current Developments on Optical Feedback Interferometry as an All-Optical Sensor for Biomedical Applications

    PubMed Central

    Perchoux, Julien; Quotb, Adam; Atashkhooei, Reza; Azcona, Francisco J.; Ramírez-Miquet, Evelio E.; Bernal, Olivier; Jha, Ajit; Luna-Arriaga, Antonio; Yanez, Carlos; Caum, Jesus; Bosch, Thierry; Royo, Santiago

    2016-01-01

    Optical feedback interferometry (OFI) sensors are experiencing a consistent increase in their applications to biosensing due to their contactless nature, low cost and compactness, features that fit very well with current biophotonics research and market trends. The present paper is a review of the work in progress at UPC-CD6 and LAAS-CNRS related to the application of OFI to different aspects of biosensing, both in vivo and ex vivo. This work is intended to present the variety of opportunities and potential applications related to OFI that are available in the field. The activities presented are divided into two main sensing strategies: The measurement of optical path changes and the monitoring of flows, which correspond to sensing strategies linked to the reconstruction of changes of amplitude from the interferometric signal, and to classical Doppler frequency measurements, respectively. For optical path change measurements, measurements of transient pulses, usual in biosensing, together with the measurement of large displacements applied to designing palliative care instrumentation for Parkinson disease are discussed. Regarding the Doppler-based approach, progress in flow-related signal processing and applications in real-time monitoring of non-steady flows, human blood flow monitoring and OFI pressure myograph sensing will be presented. In all cases, experimental setups are discussed and results presented, showing the versatility of the technique. The described applications show the wide capabilities in biosensing of the OFI sensor, showing it as an enabler of low-cost, all-optical, high accuracy biomedical applications. PMID:27187406

  9. Feedback loop compensates for rectifier nonlinearity

    NASA Technical Reports Server (NTRS)

    1966-01-01

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

  10. UWB communication receiver feedback loop

    DOEpatents

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

    2007-12-04

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

  11. Low timing jitter 40 Gb/s all-optical clock recovery based on an amplified feedback laser diode

    NASA Astrophysics Data System (ADS)

    Chen, Cheng; Qiu, Jifang; Zhao, Lingjuan; Wu, Jian; Lou, Caiyun; Wang, Wei

    2012-06-01

    We demonstrate 40 Gb/s all-optical clock recovery by using a monolithic integrated amplified-feedback laser (AFL) with coherent injection-locked method. The AFL consists of a gain-coupled DFB laser and an optical amplified feedback external cavity. With proper design and operation of AFL, the device can work at self-pulsation state that resulted from the beating between two lasing modes. The self-pulsation can be injection-locked to the optical clock embedded in input data streams. Due to different work mechanisms, there are two all-optical clock recovery operation modes: incoherent injection-locked and coherent injection-locked. It's predicted that the coherent injection method has various advantages: 1) requiring low injection power recovery, 2) independent of the bit rate and 3) introducing little timing jitter to the recovered clock. The robustness of coherent clock recovery is confirmed by our experimental results. We set up a return-to- zero (RZ) pseudorandom binary sequence (PRBS) data streams all-optical clock recovery system. This coherent injection-locked based clock recovery method is optical signal noise ratio (OSNR) and chromatic dispersion (CD) degeneration tolerant, and has low timing jitter and high sensitivity.

  12. Polarization Maintaining Fibre Loop Mirror for NRZ-to-PRZ Conversion in All-Optical Clock Recovery

    NASA Astrophysics Data System (ADS)

    Xu, Fan; Zhang, Xin-Liang; Liu, Hai-Rong; Liu, De-Ming; Huang, De-Xiu

    2006-02-01

    We propose a novel configuration for clock extraction by converting the NRZ data into the PRZ data and by employing a polarization-maintaining fibre loop mirror (PMFLM) which is usually used as an optical comb filter. It is found that the PMFLM can simply be constructed by a polarization controller and polarization-maintaining fibre (PMF). We theoretically analyse the principle of PMFLM for the NRZ-to-PRZ conversion. Experimentally we demonstrate 10 Gbit/s all-optical clock recovery through our proposed setup. It is shown that recovered clock signal with an extinction ratio above 10 dB can be achieved.

  13. The ionospheric outflow feedback loop

    NASA Astrophysics Data System (ADS)

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

    2014-08-01

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

  14. All-optical switching in Sagnac loop mirror containing an ytterbium-doped fiber and fiber Bragg grating.

    PubMed

    Zang, Zhigang

    2013-08-10

    A configuration of all-optical switching based on a Signac loop mirror that incorporates an ytterbium-doped fiber and uniform fiber Bragg grating (FBG) is proposed in this paper. It is found that the transmission spectrum of this structure is the narrow splitting of the reflection spectrum of the FBG. The shift of this ultranarrow transmission spectrum is very sensitive to the intensity of the pump power. Thus, the threshold switching power can be greatly reduced by shifting such narrow transmission spectrum. Compared with the single FBG, the threshold switching power of this configuration is reduced by 4 orders of magnitude. In addition, the results indicate that this optical switching has a high extinction ratio of 20 dB and a ultrafast response time of 3 ns. The operation regime and switching performance under the cross-phase modulation cases are also investigated. PMID:23938421

  15. Are feedback loops destructive to synchronization?

    NASA Astrophysics Data System (ADS)

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

    2015-08-01

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

  16. Monitoring Digital Closed-Loop Feedback Systems

    NASA Technical Reports Server (NTRS)

    Katz, Richard; Kleyner, Igor

    2011-01-01

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

  17. Numerical simulation of a novel all-optical flip-flop based on a chirped nonlinear distributed feedback semiconductor laser structure using GPGPU computing

    NASA Astrophysics Data System (ADS)

    Zoweil, H.

    2015-05-01

    A novel all-optical flip-flop based on a chirped nonlinear distributed feedback laser structure is proposed. The flip-flop does not require a holding beam. The optical gain is provided by a current injection into an active layer. The nonlinear wave-guiding layer consists of a chirped phase shifted grating accompanied with a negative nonlinear refractive index coefficient that increases in magnitude along the wave-guide. In the 'OFF' state, the chirped grating does not provide the required optical feedback to start lasing. An optical pulse switches the device 'ON' by reducing the chirp due to the negative nonlinear refractive index coefficient. The reduced chirp grating provides enough feedback to sustain a laser mode. The device is switched 'OFF' by cross gain modulation. GPGPU computing allows for long simulation time of multiple SET-RESET operations. The 'ON/OFF' transitions delays are in nanoseconds time scale.

  18. Adaptive restoration of a partially coherent blurred image using an all-optical feedback interferometer with a liquid-crystal device.

    PubMed

    Shirai, Tomohiro; Barnes, Thomas H

    2002-02-01

    A liquid-crystal adaptive optics system using all-optical feedback interferometry is applied to partially coherent imaging through a phase disturbance. A theoretical analysis based on the propagation of the cross-spectral density shows that the blurred image due to the phase disturbance can be restored, in principle, irrespective of the state of coherence of the light illuminating the object. Experimental verification of the theory has been performed for two cases when the object to be imaged is illuminated by spatially coherent light originating from a He-Ne laser and by spatially incoherent white light from a halogen lamp. We observed in both cases that images blurred by the phase disturbance were successfully restored, in agreement with the theory, immediately after the adaptive optics system was activated. The origin of the deviation of the experimental results from the theory, together with the effect of the feedback misalignment inherent in our optical arrangement, is also discussed. PMID:11822600

  19. All-optical 100-Gbit s word packet time-division-multiplexed access node in a looped-back configuration: enabling technologies for sequential add drop functionality

    NASA Astrophysics Data System (ADS)

    Lou, Janet W.; Liang, Yi; Boyraz, Ozdal; Islam, Mohammed N.

    2000-10-01

    We experimentally demonstrate the adding, dropping, and passing through of 100-Gbit s word packets in a looped-back all-optical time-division-multiplexed (TDM) access node. Packets are routed with a 17-dB contrast ratio and demultiplexed with a 20-dB contrast ratio. This node uses short 100-Gbit s words to demonstrate its potential to process data packets from multiple sources and to perform packet switching in a multinode ring network configuration. The ability to tolerate timing jitter as well as varying input signal characteristics is essential to an all-optical access node in a multinode network. For 2-ps input pulses, the header processor has a timing window of 5 ps, and the demultiplexer has a timing window of 5.5 ps. This allows for tolerance to bit-to-bit timing jitters or to an increase in the pulse width of as much as 3 ps. Packet-to-packet timing jitter is detected and compensated by the technique used to synchronize the local source to each packet. The key enabling technologies of an all-optical TDM packet add drop multiplexer are discussed, including an erbium-doped fiber laser, a nonlinear optical loop mirror logic gate, self-synchronization to incoming packets with a fast-saturation slow-recovery gain element followed by an intensity discriminator, a two-wavelength nonlinear optical loop mirror demultiplexer, and synchronization of new packets to the network packet rate with a phase-locked loop. The local source is automatically synchronized to the incoming packet, because it uses an extracted pulse from the packet, which has a contrast ratio of 20 dB to the rest of the packet. Finally, new packets are added by use of a local laser and a synchronization method, which gives a timing jitter of 1 ps. Using a statistical method of measuring Q value with picosecond resolution, we show that a header processor with two cascaded logic gates has a Q value of 7.1 with a 95% confidence level.

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

    PubMed

    Palu, Rebecca A S; Thummel, Carl S

    2015-11-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-02-01

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

  3. Decision feedback loop for tracking a polyphase modulated carrier

    NASA Technical Reports Server (NTRS)

    Simon, M. K. (Inventor)

    1974-01-01

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

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

    PubMed

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

    2006-03-01

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

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

    NASA Technical Reports Server (NTRS)

    Rippy, R. R. (Inventor)

    1976-01-01

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

  6. Feedback Control Systems Loop Shaping Design with Practical Considerations

    NASA Technical Reports Server (NTRS)

    Kopsakis, George

    2007-01-01

    This paper describes loop shaping control design in feedback control systems, primarily from a practical stand point that considers design specifications. Classical feedback control design theory, for linear systems where the plant transfer function is known, has been around for a long time. But it s still a challenge of how to translate the theory into practical and methodical design techniques that simultaneously satisfy a variety of performance requirements such as transient response, stability, and disturbance attenuation while taking into account the capabilities of the plant and its actuation system. This paper briefly addresses some relevant theory, first in layman s terms, so that it becomes easily understood and then it embarks into a practical and systematic design approach incorporating loop shaping design coupled with lead-lag control compensation design. The emphasis is in generating simple but rather powerful design techniques that will allow even designers with a layman s knowledge in controls to develop effective feedback control designs.

  7. All-optical analog comparator.

    PubMed

    Li, Pu; Yi, Xiaogang; Liu, Xianglian; Zhao, Dongliang; Zhao, Yongpeng; Wang, Yuncai

    2016-01-01

    An analog comparator is one of the core units in all-optical analog-to-digital conversion (AO-ADC) systems, which digitizes different amplitude levels into two levels of logical '1' or '0' by comparing with a defined decision threshold. Although various outstanding photonic ADC approaches have been reported, almost all of them necessitate an electrical comparator to carry out this binarization. The use of an electrical comparator is in contradiction to the aim of developing all-optical devices. In this work, we propose a new concept of an all-optical analog comparator and numerically demonstrate an implementation based on a quarter-wavelength-shifted distributed feedback laser diode (QWS DFB-LD) with multiple quantum well (MQW) structures. Our results show that the all-optical comparator is very well suited for true AO-ADCs, enabling the whole digital conversion from an analog optical signal (continuous-time signal or discrete pulse signal) to a binary representation totally in the optical domain. In particular, this all-optical analog comparator possesses a low threshold power (several mW), high extinction ratio (up to 40 dB), fast operation rate (of the order of tens of Gb/s) and a step-like transfer function. PMID:27550874

  8. All-optical analog comparator

    PubMed Central

    Li, Pu; Yi, Xiaogang; Liu, Xianglian; Zhao, Dongliang; Zhao, Yongpeng; Wang, Yuncai

    2016-01-01

    An analog comparator is one of the core units in all-optical analog-to-digital conversion (AO-ADC) systems, which digitizes different amplitude levels into two levels of logical ‘1’ or ‘0’ by comparing with a defined decision threshold. Although various outstanding photonic ADC approaches have been reported, almost all of them necessitate an electrical comparator to carry out this binarization. The use of an electrical comparator is in contradiction to the aim of developing all-optical devices. In this work, we propose a new concept of an all-optical analog comparator and numerically demonstrate an implementation based on a quarter-wavelength-shifted distributed feedback laser diode (QWS DFB-LD) with multiple quantum well (MQW) structures. Our results show that the all-optical comparator is very well suited for true AO-ADCs, enabling the whole digital conversion from an analog optical signal (continuous-time signal or discrete pulse signal) to a binary representation totally in the optical domain. In particular, this all-optical analog comparator possesses a low threshold power (several mW), high extinction ratio (up to 40 dB), fast operation rate (of the order of tens of Gb/s) and a step-like transfer function. PMID:27550874

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

    PubMed

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

    2014-03-01

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

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

    SciTech Connect

    Li, L. )

    1991-08-01

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

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

    NASA Technical Reports Server (NTRS)

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

    1992-01-01

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

  12. Closed loop kinesthetic feedback for postural control rehabilitation.

    PubMed

    Vérité, Fabien; Bachta, Wael; Morel, Guillaume

    2014-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2002-12-01

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

  14. Practical Loop-Shaping Design of Feedback Control Systems

    NASA Technical Reports Server (NTRS)

    Kopasakis, George

    2010-01-01

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

  15. On the dynamics of delayed neural feedback loops

    NASA Astrophysics Data System (ADS)

    Brandt, Sebastian F.

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

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

    PubMed

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

    2008-01-01

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

  17. Degenerate four-wave mixing based all-optical wavelength conversion in a semiconductor optical amplifier and highly-nonlinear photonic crystal fiber parametric loop mirror

    NASA Astrophysics Data System (ADS)

    Liu, Jianguo; Cheng, Tee Hiang; Yeo, Yong kee; Wang, Yixin; Xue, Lifang; Wang, Dawei; Yu, Xiaojun

    2008-11-01

    The idler is separated from the co-propagating pump in a degenerate four-wave mixing (DFWM) with a symmetrical parametric loop mirror (PALM), which is composed of two identical SOAs and a 70 m highly-nonlinear photonic crystal fiber (HN-PCF). The signal and pump are coupled into the symmetrical PALM from different ports, respectively. After the DFWM based wavelength conversion (WC) in the clockwise and anticlockwise, the idler exits from the signal port, while the pump outputs from its input port. Therefore, the pump is effectively suppressed in the idler channel without a high-speed tunable filter. Contrast to a traditional PALM, the DFWM based conversion efficiency is increased greatly, and the functions of the amplification and the WC are integrated in the smart SOA and HN-PCF PALM.

  18. Single all-optical platform for measurement of twist and transverse stress using polarization modulation in distinct dual-mode fiber placed in a Sagnac loop.

    PubMed

    Khan, Saba N; Chatterjee, Sudip K; Chaudhuri, Partha Roy

    2016-01-01

    We report here the experimental demonstration of measurement of both twist and transverse stress using polarization modulation in a single all-fiber circuit consisting of a single-mode fiber (SMF)/dual-mode fiber (DMF) in a Sagnac interferometer (SI) loop. The SMF-SI prototype setup is seen to be suitable for precise measurement of twist over a broad range of ±50° and transverse stress up to 5 N with a sensitivity as high as 2.85×10(6)  pW/° and 2.08×10(7)  pW/N, respectively. It is envisaged that nearly ideal operation for twist measurement can be achieved by appropriately selecting the operating domain (pretwisted Sagnac loop for practical realization of the device) and required magnitude of applied transverse stress (weight yielding maximum sensitivity). Unlike SMF-SI, a DMF assisted SI exhibits asymmetric transmittance yielding a peak shift (∼45°) in addition to falling/rising peak amplitude of effective power(∼20  μW). This key characteristic is further utilized for tunable measurement of torsion (unidirectional from -70° to 40°) while keeping the sensitivity fixed. This research problem is then analyzed on the avenue of theoretical consideration and using classical polarization optics; we have derived the Jones birefringence matrix that accurately describes the transmission behavior of the configured fiber circuit (SMF-SI and DMF-SI) for each of the three cases, namely, transverse stress, twist, and both twist and transverse stress. Series of experimental measurements for various conditions of induced birefringence (linear/circular) were performed at length, and the results were compared with those determined theoretically towards configuring a twist and stress measuring device. The study provides an understanding of the underlying physics of dual-mode interference in a Sagnac configuration experiencing linear and circular birefringence. PMID:26831594

  19. Regulatory feedback loop between TP73 and TRIM32.

    PubMed

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

    2013-01-01

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

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

    PubMed Central

    Rosenfeld, Daniel; Rudich, Yinon; Lahav, Ronen

    2001-01-01

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

  1. A Moral Experience Feedback Loop: Modeling a System of Moral Self-Cultivation in Everyday Life

    ERIC Educational Resources Information Center

    Sherblom, Stephen A.

    2015-01-01

    This "systems thinking" model illustrates a common feedback loop by which people engage the moral world and continually reshape their moral sensibility. The model highlights seven processes that collectively form this feedback loop: beginning with (1) one's current moral sensibility which shapes processes of (2) perception, (3)…

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

    SciTech Connect

    Huang, G.; Byrd, J. M.

    2006-11-20

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

  3. All-optical clock recovery of 20 Gbit/s NRZ-DPSK signals using polarization-maintaining fiber loop mirror filter and semiconductor optical amplifier fiber ring laser

    NASA Astrophysics Data System (ADS)

    Wang, Fei; Yu, Yu; Huang, Xi; Zhang, Xinliang

    2009-06-01

    All-optical clock recovery (CR) from 20 Gbit/s nonreturn-to-zero differential phase-shift-keying (NRZ-DPSK) signals are demonstrated experimentally by using a polarization-maintaining fiber loop mirror filter (PMF-LMF) and a semiconductor optical amplifier (SOA) fiber ring laser. Only by adjusting polarization controller (PC), NRZ-DPSK signals were conveniently and fast converted to pseudo return-to-zero (PRZ) signal via PMF-LMF. Then the PRZ signals are injected into the SOA fiber laser for CR. The recovered clock signals is with the extinction ratio (ER) of 10 dB and the root-mean-square (RMS) timing jitter of 750 fs in 2 31 - 1 long pseudorandom binary sequence (PRBS) NRZ-DPSK signals measurement. Moreover, the broad wavelength tunability of recovered clock stemmed from the use of SOAs as modulator and the gain medium are shown too.

  4. A Feedback Loop between Inflammation and Zn Uptake

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-01-01

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

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

    NASA Technical Reports Server (NTRS)

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

    1975-01-01

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

  8. Positive And Negative Feedback Loops Coupled By Common Transcription Activator And Repressor

    NASA Astrophysics Data System (ADS)

    Sielewiesiuk, Jan; Łopaciuk, Agata

    2015-03-01

    Dynamical systems consisting of two interlocked loops with negative and positive feedback have been studied using the linear analysis of stability and numerical solutions. Conditions for saddle-node bifurcation were formulated in a general form. Conditions for Hopf bifurcations were found in a few symmetrical cases. Auto-oscillations, when they exist, are generated by the negative feedback repressive loop. This loop determines the frequency and amplitude of oscillations. The positive feedback loop of activation slightly modifies the oscillations. Oscillations are possible when the difference between Hilll's coefficients of the repression and activation is sufficiently high. The highly cooperative activation loop with a fast turnover slows down or even makes the oscillations impossible. The system under consideration can constitute a component of epigenetic or enzymatic regulation network.

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

    PubMed

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

    2015-10-01

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

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

    PubMed Central

    Brainard, Michael S.; Jin, Dezhe Z.

    2015-01-01

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

  11. All-Optical Implementation of the Ant Colony Optimization Algorithm

    NASA Astrophysics Data System (ADS)

    Hu, Wenchao; Wu, Kan; Shum, Perry Ping; Zheludev, Nikolay I.; Soci, Cesare

    2016-05-01

    We report all-optical implementation of the optimization algorithm for the famous “ant colony” problem. Ant colonies progressively optimize pathway to food discovered by one of the ants through identifying the discovered route with volatile chemicals (pheromones) secreted on the way back from the food deposit. Mathematically this is an important example of graph optimization problem with dynamically changing parameters. Using an optical network with nonlinear waveguides to represent the graph and a feedback loop, we experimentally show that photons traveling through the network behave like ants that dynamically modify the environment to find the shortest pathway to any chosen point in the graph. This proof-of-principle demonstration illustrates how transient nonlinearity in the optical system can be exploited to tackle complex optimization problems directly, on the hardware level, which may be used for self-routing of optical signals in transparent communication networks and energy flow in photonic systems.

  12. All-Optical Implementation of the Ant Colony Optimization Algorithm.

    PubMed

    Hu, Wenchao; Wu, Kan; Shum, Perry Ping; Zheludev, Nikolay I; Soci, Cesare

    2016-01-01

    We report all-optical implementation of the optimization algorithm for the famous "ant colony" problem. Ant colonies progressively optimize pathway to food discovered by one of the ants through identifying the discovered route with volatile chemicals (pheromones) secreted on the way back from the food deposit. Mathematically this is an important example of graph optimization problem with dynamically changing parameters. Using an optical network with nonlinear waveguides to represent the graph and a feedback loop, we experimentally show that photons traveling through the network behave like ants that dynamically modify the environment to find the shortest pathway to any chosen point in the graph. This proof-of-principle demonstration illustrates how transient nonlinearity in the optical system can be exploited to tackle complex optimization problems directly, on the hardware level, which may be used for self-routing of optical signals in transparent communication networks and energy flow in photonic systems. PMID:27222098

  13. All-Optical Implementation of the Ant Colony Optimization Algorithm

    PubMed Central

    Hu, Wenchao; Wu, Kan; Shum, Perry Ping; Zheludev, Nikolay I.; Soci, Cesare

    2016-01-01

    We report all-optical implementation of the optimization algorithm for the famous “ant colony” problem. Ant colonies progressively optimize pathway to food discovered by one of the ants through identifying the discovered route with volatile chemicals (pheromones) secreted on the way back from the food deposit. Mathematically this is an important example of graph optimization problem with dynamically changing parameters. Using an optical network with nonlinear waveguides to represent the graph and a feedback loop, we experimentally show that photons traveling through the network behave like ants that dynamically modify the environment to find the shortest pathway to any chosen point in the graph. This proof-of-principle demonstration illustrates how transient nonlinearity in the optical system can be exploited to tackle complex optimization problems directly, on the hardware level, which may be used for self-routing of optical signals in transparent communication networks and energy flow in photonic systems. PMID:27222098

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

    ERIC Educational Resources Information Center

    Barker, Martin; Pinard, Michelle

    2014-01-01

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

  15. All optical OFDM transmission systems

    NASA Astrophysics Data System (ADS)

    Rhee, June-Koo K.; Lim, Seong-Jin; Kserawi, Malaz

    2011-12-01

    All-optical OFDM data transmission opens up a new realm of advanced optical transmission at extreme data rates, as subcarriers are multiplexed and demultiplexed by all optical discrete Fourier transforms (DFT). This paper reviews the principles of all optical OFDM transmission and its system application techniques, providing the generic ideas and the practical implementation issues to achieve 100Gbps or higher data rates with a spectral efficiency of 1 bps/Hz or better. This paper also include discussions on all-optical OFDM implementation variants such as an AWG-based OFDM multiplexer and demultiplexer, a receiver design without optical sampling, a transmitter design with frequency-locked cw lasers, an OFDM cyclic prefix designs, and a chromatic dispersion mitigation technique.

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

    ERIC Educational Resources Information Center

    O'Donnell, Kerri

    2011-01-01

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

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

    NASA Technical Reports Server (NTRS)

    Thompson, P. M.

    1979-01-01

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

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

    PubMed

    Sriram, K; Soliman, Sylvain; Fages, François

    2009-05-01

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

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

    NASA Technical Reports Server (NTRS)

    Hoelscher, Brian R.; Vadali, Srinvas R.

    1993-01-01

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

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

    NASA Technical Reports Server (NTRS)

    Stalford, Harold

    1988-01-01

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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  3. All optical binary delta-sigma modulator

    NASA Astrophysics Data System (ADS)

    Sayeh, Mohammad R.; Siahmakoun, Azad

    2005-09-01

    This paper describes a novel A/D converter called "Binary Delta-Sigma Modulator" (BDSM) which operates only with nonnegative signal with positive feedback and binary threshold. This important modification to the conventional delta-sigma modulator makes the high-speed (>100GHz) all-optical implementation possible. It has also the capability to modify its own sampling frequency as well as its input dynamic range. This adaptive feature helps designers to optimize the system performance under highly noisy environment and also manage the power consumption of the A/D converters.

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

    PubMed

    Barnes, Richard; Lehman, Clarence

    2013-06-01

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

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

    PubMed

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

    1988-04-01

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

  6. Fast all-optical switch

    NASA Technical Reports Server (NTRS)

    Shay, Thomas M. (Inventor); Poliakov, Evgeni Y. (Inventor); Hazzard, David A. (Inventor)

    2001-01-01

    An apparatus and method wherein polarization rotation in alkali vapors or other mediums is used for all-optical switching and digital logic and where the rate of operation is proportional to the amplitude of the pump field. High rates of speed are accomplished by Rabi flopping of the atomic states using a continuously operating monochromatic atomic beam as the pump.

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

    PubMed Central

    2011-01-01

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

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

    ERIC Educational Resources Information Center

    Hokayem, Hayat; Ma, Jingjing; Jin, Hui

    2015-01-01

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

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

    PubMed

    Ito, Sosuke; Sagawa, Takahiro

    2015-01-01

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

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

    NASA Astrophysics Data System (ADS)

    Ito, Sosuke; Sagawa, Takahiro

    2015-06-01

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

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

    NASA Technical Reports Server (NTRS)

    Hinedi, Sami; Lindsey, William C.

    1989-01-01

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

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

    PubMed

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

    2016-03-16

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

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

    PubMed Central

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

    2015-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2011-06-01

    The combination of brain-computer interfaces (BCIs) with robot-assisted physical therapy constitutes a promising approach to neurorehabilitation of patients with severe hemiparetic syndromes caused by cerebrovascular brain damage (e.g. stroke) and other neurological conditions. In such a scenario, a key aspect is how to reestablish the disrupted sensorimotor feedback loop. However, to date it is an open question how artificially closing the sensorimotor feedback loop influences the decoding performance of a BCI. In this paper, we answer this issue by studying six healthy subjects and two stroke patients. We present empirical evidence that haptic feedback, provided by a seven degrees of freedom robotic arm, facilitates online decoding of arm movement intention. The results support the feasibility of future rehabilitative treatments based on the combination of robot-assisted physical therapy with BCIs.

  15. All-optical repetition rate multiplication of pseudorandom bit sequences by employing power coupler and equalizer

    NASA Astrophysics Data System (ADS)

    Sun, Zhenchao; Wang, Zhi; Wu, Chongqing; Wang, Fu; Li, Qiang

    2015-10-01

    A scheme for all-optical repetition rate multiplication of pseudorandom bit sequences (PRBS) is demonstrated with a precision delay feedback loop cascaded with a terahertz optical asymmetric demultiplexer (TOAD)-based power equalizer. Its feasibility has been verified by experiments, which show a multiplication for PRBS at cycle 2^7-1 from 2.5 to 10 Gb/s. This scheme can be employed for the rate multiplication of a much longer cycle PRBS at a much higher bit rate over 40 Gb/s if the time-delay, the loss, and the dispersion of an optical delay line are all precisely managed.

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

    NASA Astrophysics Data System (ADS)

    Han, Wang; Maomao, Sun

    2014-04-01

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

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

    NASA Astrophysics Data System (ADS)

    Jones, Lloyd E.; Sandberg, Richard D.

    2011-12-01

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

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

    PubMed

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

    2015-03-01

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

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

    PubMed Central

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

    2010-01-01

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

  20. Closed loop control of dielectric elastomer actuators based on self-sensing displacement feedback

    NASA Astrophysics Data System (ADS)

    Rizzello, G.; Naso, D.; York, A.; Seelecke, S.

    2016-03-01

    This paper describes a sensorless control algorithm for a positioning system based on a dielectric elastomer actuator (DEA). The voltage applied to the membrane and the resulting current can be measured during the actuation and used to estimate its displacement, i.e., to perform self-sensing. The estimated displacement can be then used as a feedback signal for a position control algorithm, which results in a compact device capable of operating in closed loop control without the need for additional electromechanical or optical transducers. In this work, a circular DEA preloaded with a bi-stable spring is used as a case of study to validate the proposed control architecture. A comparison of the closed loop performance achieved using an accurate laser displacement sensor for feedback is also provided to better assess the performance limitations of the overall sensorless scheme.

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

    NASA Astrophysics Data System (ADS)

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

    2015-05-01

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

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

    PubMed

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

    2002-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2010-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  6. All-optical encrypted movie.

    PubMed

    Mosso, Fabian; Barrera, John Fredy; Tebaldi, Myrian; Bolognini, Néstor; Torroba, Roberto

    2011-03-14

    We introduce for the first time the concept of an all-optical encrypted movie. This movie joints several encrypted frames corresponding to a time evolving situation employing the same encoding mask. Thanks to a multiplexing operation we compact the encrypted movie information into a single package. But the decryption of this single package implies the existence of cross-talk if we do not adequately pre-process the encoded information before multiplexing. In this regard, we introduce a grating modulation to each encoded image, and then we proceed to multiplexing. After appropriate filtering and synchronizing procedures applied to the multiplexing, we are able to decrypt and to reproduce the movie. This movie is only properly decoded when in possession of the right decoding key. The concept development is carried-out in virtual optical systems, both for the encrypting and the filtering-decrypting stages. Experimental results are shown to confirm our approach. PMID:21445211

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

    SciTech Connect

    Dunlop, Mary; Keasling, Jay; Mukhopadhyay, Aindrila

    2011-07-14

    Cells use feedback to implement a diverse range of regulatory functions. Building synthetic feedback control systems may yield insight into the roles that feedback can play in regulation since it can be introduced independently of native regulation, and alternative control architectures can be compared. We propose a model for microbial biofuel production where a synthetic control system is used to increase cell viability and biofuel yields. Although microbes can be engineered to produce biofuels, the fuels are often toxic to cell growth, creating a negative feedback loop that limits biofuel production. These toxic effects may be mitigated by expressing efflux pumps that export biofuel from the cell. We developed a model for cell growth and biofuel production and used it to compare several genetic control strategies for their ability to improve biofuel yields. We show that controlling efflux pump expression directly with a biofuel-responsive promoter is a straight forward way of improving biofuel production. In addition, a feed forward loop controller is shown to be versatile at dealing with uncertainty in biofuel production rates.

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

    PubMed

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

    2012-12-01

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

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

    PubMed Central

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

    2012-01-01

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

  10. High speed all optical networks

    NASA Technical Reports Server (NTRS)

    Chlamtac, Imrich; Ganz, Aura

    1990-01-01

    An inherent problem of conventional point-to-point wide area network (WAN) architectures is that they cannot translate optical transmission bandwidth into comparable user available throughput due to the limiting electronic processing speed of the switching nodes. The first solution to wavelength division multiplexing (WDM) based WAN networks that overcomes this limitation is presented. The proposed Lightnet architecture takes into account the idiosyncrasies of WDM switching/transmission leading to an efficient and pragmatic solution. The Lightnet architecture trades the ample WDM bandwidth for a reduction in the number of processing stages and a simplification of each switching stage, leading to drastically increased effective network throughputs. The principle of the Lightnet architecture is the construction and use of virtual topology networks, embedded in the original network in the wavelength domain. For this construction Lightnets utilize the new concept of lightpaths which constitute the links of the virtual topology. Lightpaths are all-optical, multihop, paths in the network that allow data to be switched through intermediate nodes using high throughput passive optical switches. The use of the virtual topologies and the associated switching design introduce a number of new ideas, which are discussed in detail.

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

    PubMed

    Yousaf, Saqib; Qin, Shiyin

    2015-12-01

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

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

    NASA Astrophysics Data System (ADS)

    Gaspari, Massimo

    2015-08-01

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

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

    NASA Astrophysics Data System (ADS)

    Gaspari, Massimo

    2015-08-01

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

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

    NASA Astrophysics Data System (ADS)

    Gaspari, Massimo

    2015-08-01

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

  15. Demonstration and characterisation of a non-inverting all-optical read/write regenerative memory

    NASA Astrophysics Data System (ADS)

    Johnson, N. C.; Harrison, J. A.; Blow, K. J.

    2008-09-01

    An all-optical regenerative memory device using a single loop mirror and a semiconductor optical amplifier is experimentally demonstrated. This configuration has potential for a low power all-optical stable memory device with non-inverting characteristics where packets are stored by continuously injecting the regenerated data back into the loop.

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

    NASA Astrophysics Data System (ADS)

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

    2012-07-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    NASA Astrophysics Data System (ADS)

    Banerjee, Subhasis; Bose, Indrani

    2008-12-01

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

  19. Androgynous, Reconfigurable Closed Loop Feedback Controlled Low Impact Docking System With Load Sensing Electromagnetic Capture Ring

    NASA Technical Reports Server (NTRS)

    Lewis, James L. (Inventor); Carroll, Monty B. (Inventor); Morales, Ray H. (Inventor); Le, Thang D. (Inventor)

    2002-01-01

    The present invention relates to a fully androgynous, reconfigurable closed loop feedback controlled low impact docking system with load sensing electromagnetic capture ring. The docking system of the present invention preferably comprises two Docking- assemblies, each docking assembly comprising a load sensing ring having an outer face, one of more electromagnets, one or more load cells coupled to said load sensing ring. The docking assembly further comprises a plurality of actuator arms coupled to said load sensing ring and capable of dynamically adjusting the orientation of said load sensing ring and a reconfigurable closed loop control system capable of analyzing signals originating from said plurality of load cells and of outputting real time control for each of the actuators. The docking assembly of the present invention incorporates an active load sensing system to automatically dynamically adjust the load sensing ring during capture instead of requiring significant force to push and realign the ring.

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

    PubMed Central

    Harrison, Mary E.; Dunlop, Mary J.

    2012-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2016-08-01

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

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

    NASA Astrophysics Data System (ADS)

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

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

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

    NASA Astrophysics Data System (ADS)

    Ishikawa, Kaoru; Nakamura, Taro; Osumi, Hisashi

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

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

    PubMed

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

    2015-11-12

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

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

    NASA Astrophysics Data System (ADS)

    Narula, Jatin; Igoshin, Oleg

    2011-03-01

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

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

    NASA Technical Reports Server (NTRS)

    Thompson, P. M.

    1980-01-01

    Equations are derived for the angles of general multivariable root loci and linear quadratic optimal root loci, including angles of departure and approach. The generalized eigenvalue problem is used to compute angles of approach. Equations are also derived to find the sensitivity of closed loop eigenvalue and the directional derivatives of closed loop eigenvectors. An equivalence class of quadratic weights that produce the same asymptotic eigenstructure is defined, a canonical element is defined, and an algorithm to find it is given. The behavior of the optimal root locus in the nonasymptotic region is shown to be different for quadratic weights with the same asymptotic properties. An algorithm is presented that can be used to select a feedback gain matrix for the linear state feedback problem which produces a specified asymptotic eigenstructure. Another algorithm is given to compute the asymptotic eigenstructure properties inherent in a given set of quadratic weights. Finally, it is shown that optimal root loci for nongeneric problems can be approximated by generic ones in the nonasymptotic region.

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

    SciTech Connect

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

    1994-04-01

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

  8. High speed all-optical data processing in fast semiconductor and optical fiber based devices

    NASA Astrophysics Data System (ADS)

    Sun, Hongzhi

    Future generations of communication systems demand ultra high speed data processing and switching components. Conventional electrical parts have reached their bottleneck both speed-wise and efficiency-wise. The idea of manipulating high speed data in optical domain is gaining more popularity. In this PhD thesis work, we proposed and demonstrated various schemes of all-optical Boolean logic gate at data rate as high as 80Gb/s by using semiconductor optical amplifier (SOA), SOA Mach-Zehnder interferometer (SOA-MZI), highly nonlinear fiber (HNLF) and optical fiber based components. With the invention of quantum dot (QD) based semiconductor devices, speed limit of all optical data processing has a chance to boost up to 250Gb/s. We proposed and simulated QD-SOA based Boolean functions, and their application such as shift register and pseudorandom bit sequence generation (PRBS). Clock and data recovery of high speed data signals has been simulated and demonstrated by injection lock and phase lock loop techniques in a fiber and SOA ring and an optical-electrical (OE) feedback loop.

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

    PubMed Central

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

    2010-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

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

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

    PubMed

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

    2010-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2008-11-01

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

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

    NASA Astrophysics Data System (ADS)

    Krishna, Sandeep

    2008-03-01

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

  14. Computer program for single input-output, single-loop feedback systems

    NASA Technical Reports Server (NTRS)

    1976-01-01

    Additional work is reported on a completely automatic computer program for the design of single input/output, single loop feedback systems with parameter uncertainly, to satisfy time domain bounds on the system response to step commands and disturbances. The inputs to the program are basically the specified time-domain response bounds, the form of the constrained plant transfer function and the ranges of the uncertain parameters of the plant. The program output consists of the transfer functions of the two free compensation networks, in the form of the coefficients of the numerator and denominator polynomials, and the data on the prescribed bounds and the extremes actually obtained for the system response to commands and disturbances.

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

    PubMed

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

    2013-11-01

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

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed Central

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

    2012-01-01

    We present a system to artificially correlate the spike timing between sets of arbitrary neurons that were interfaced to a complementary metal–oxide–semiconductor (CMOS) high-density microelectrode array (MEA). The system features a novel reprogrammable and flexible event engine unit to detect arbitrary spatio-temporal patterns of recorded action potentials and is capable of delivering sub-millisecond closed-loop feedback of electrical stimulation upon trigger events in real-time. The relative timing between action potentials of individual neurons as well as the temporal pattern among multiple neurons, or neuronal assemblies, is considered an important factor governing memory and learning in the brain. Artificially changing timings between arbitrary sets of spiking neurons with our system could provide a “knob” to tune information processing in the network. PMID:23335887

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

    PubMed Central

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

    2016-01-01

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

  19. Feedback loops and temporal misalignment in component-based hydrologic modeling

    NASA Astrophysics Data System (ADS)

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

    2011-12-01

    In component-based modeling, a complex system is represented as a series of loosely integrated components with defined interfaces and data exchanges that allow the components to be coupled together through shared boundary conditions. Although the component-based paradigm is commonly used in software engineering, it has only recently been applied for modeling hydrologic and earth systems. As a result, research is needed to test and verify the applicability of the approach for modeling hydrologic systems. The objective of this work was therefore to investigate two aspects of using component-based software architecture for hydrologic modeling: (1) simulation of feedback loops between components that share a boundary condition and (2) data transfers between temporally misaligned model components. We investigated these topics using a simple case study where diffusion of mass is modeled across a water-sediment interface. We simulated the multimedia system using two model components, one for the water and one for the sediment, coupled using the Open Modeling Interface (OpenMI) standard. The results were compared with a more conventional numerical approach for solving the system where the domain is represented by a single multidimensional array. Results showed that the component-based approach was able to produce the same results obtained with the more conventional numerical approach. When the two components were temporally misaligned, we explored the use of different interpolation schemes to minimize mass balance error within the coupled system. The outcome of this work provides evidence that component-based modeling can be used to simulate complicated feedback loops between systems and guidance as to how different interpolation schemes minimize mass balance error introduced when components are temporally misaligned.

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

    PubMed

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

    2016-02-01

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

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

    PubMed

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

    2010-11-01

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

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

    NASA Technical Reports Server (NTRS)

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

    1995-01-01

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

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

    PubMed Central

    Servedio, Maria R; Saetre, Glenn-Peter

    2003-01-01

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

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

    PubMed Central

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

    2008-01-01

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

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

    PubMed

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

    2013-03-28

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

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

    PubMed Central

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

    2014-01-01

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

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

    SciTech Connect

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

    2004-03-19

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

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

    PubMed

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

    2016-07-15

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2011-01-01

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

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

    NASA Astrophysics Data System (ADS)

    Soprano, C.

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

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

    SciTech Connect

    Venediktov, Vladimir Yu; Ivanova, Natalya L; Freigang, N N; Laskin, V A

    2009-10-31

    A system for recording a dynamic holographic grating in an optically addressed liquid-crystal spatial light modulator is studied. The system provides the asymmetrisation of the grating profile by using a TV-locked optical feedback loop (nonlinear or adaptive interferometer). (laser applications and other topics in quantum electronics)

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

    PubMed

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

    2015-03-15

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

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

    PubMed

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

    2011-12-15

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2008-05-23

    PPARgamma is a nuclear hormone receptor that plays a key role in the induction of peroxisome proliferation. A number of studies showed that PPARgamma ligands suppress cell cycle progression; however, the mechanism remains to be determined. Here, we showed that PPARgamma ligand troglitazone inhibited G1/S transition in colon cancer cells, LS174T. Troglitazone did not affect on either expression of CDK inhibitor (p18) or Wnt signaling pathway, indicating that these pathways were not involved in the troglitazone-dependent cell cycle arrest. GeneChip and RT-PCR analyses revealed that troglitazone decreased mRNA levels of cell cycle regulatory factors E2F2 and cyclin-E1 whose expression is activated by E2F2. Down-regulation of E2F2 by troglitazone results in decrease of cyclin-E1 transcription, which could inhibit phosphorylation of Rb protein, and consequently evoke the suppression of E2F2 transcriptional activity. Thus, we propose that troglitazone suppresses the feedback loop containing E2F2, cyclin-E1, and Rb protein. PMID:18355447

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

    PubMed

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

    2016-03-01

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

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

    SciTech Connect

    Iizuka, Katsumi; Horikawa, Yukio

    2008-09-12

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

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed

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

    2016-09-01

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

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

    PubMed

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

    2013-03-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2014-04-01

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

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2009-07-10

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

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

    SciTech Connect

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

    2015-12-01

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

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

    DOE PAGESBeta

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

    2015-12-01

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

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

    PubMed Central

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

    2012-01-01

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

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

    NASA Astrophysics Data System (ADS)

    Kravtsov, Andrey

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

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

    PubMed Central

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

    2012-01-01

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

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

    NASA Astrophysics Data System (ADS)

    Huebert, B. J.

    2004-12-01

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

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

    PubMed

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

    2012-10-01

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

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

    PubMed Central

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

    2015-01-01

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

  15. Nonlinear fiber applications for ultrafast all-optical signal processing

    NASA Astrophysics Data System (ADS)

    Kravtsov, Konstantin

    In the present dissertation different aspects of all-optical signal processing, enabled by the use of nonlinear fibers, are studied. In particular, we focus on applications of a novel heavily GeO2-doped (HD) nonlinear fiber, that appears to be superior to many other types of nonlinear fibers because of its high nonlinearity and suitability for the use in nonlinear optical loop mirrors (NOLMs). Different functions, such as all-optical switching, thresholding, and wavelength conversion, are demonstrated with the HD fibers in the NOLM configuration. These basic functions are later used for realization of ultrafast time-domain demultiplexers, clock recovery, detectors of short pulses in stealth communications, and primitive elements for analog computations. Another important technology that benefits from the use of nonlinear fiber-based signal processing is optical code-division multiple access (CDMA). It is shown in both theory and experiment that all-optical thresholding is a unique way of improving existing detection methods for optical CDMA. Also, it is the way of implementation of true asynchronous optical spread-spectrum networks, which allows full realization of optical CDMA potential. Some aspects of quantum signal processing and manipulation of quantum states are also studied in this work. It is shown that propagation and collisions of Thirring solitons lead to a substantial squeezing of quantum states, which may find applications for generation of squeezed light.

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

    NASA Astrophysics Data System (ADS)

    Shen, B.-W.

    2014-04-01

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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

    Lee, Der-Yen; Chang, Geen-Dong

    2014-01-01

    Glyoxalase 1 (GlxI) is the key enzyme that converts the highly reactive α-oxo-aldehydes into the corresponding α-hydroxy acids using l-glutathione as a cofactor. In our preliminary data, GlxI was identified as a substrate of transglutaminase 2 (TG2), a ubiquitous enzyme with multiple functions. According to the catalytic properties of TG2, protein cross-linking, polyamine conjugation, and/or deamidation are potential post-translational modifications. In this article, we have demonstrated that TG2 catalyzes either polyamine conjugation or deamidation to GlxI depending on the presence of polyamines or not. Deamidation leads to activation of GlxI while polyamine conjugation results in activation of GlxI as well as stabilization of GlxI against denaturation treatment. In cultured HeLa cells, methylglyoxal challenge causes increase in intracellular levels of reactive oxygen species (ROS) and calcium leading to TG2 activation and subsequent transamidation and activation of GlxI. The inhibition of TG2 significantly weakens the cell resistance to the methylglyoxal challenge. Thus, GlxI is a novel substrate of TG2 and is activated by TG2 in vitro and in cellulo. Exposure to methylglyoxal elicits a negative feedback loop entailing ROS, calcium, TG2 and GlxI, thus leading to attenuation of the increase in the methylglyoxal level. The results imply that cancer cells highly express TG2 or GlxI can endure the oxidative stress derived from higher glycolytic flux and may gain extra growth advantage from the aerobic glycolysis. PMID:24494193

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed

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

    2016-05-01

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

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

    SciTech Connect

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

    2014-03-28

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

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

    PubMed

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

    2016-06-01

    A control system model was developed to analyze data on in vivo coronary blood flow regulation and to probe how different mechanisms work together to control coronary flow from rest to exercise, and under a variety of experimental conditions, including cardiac pacing and with changes in coronary arterial pressure (autoregulation). In the model coronary flow is determined by the combined action of a feedback pathway signal that is determined by the level of plasma ATP in coronary venous blood, an adrenergic open-loop (feed-forward) signal that increases with exercise, and a contribution of pressure-mediated myogenic control. The model was identified based on data from exercise experiments where myocardial oxygen extraction, coronary flow, cardiac interstitial norepinephrine concentration, and arterial and coronary venous plasma ATP concentrations were measured during control and during adrenergic and purinergic receptor blockade conditions. The identified model was used to quantify the relative contributions of open-loop and feedback pathways and to illustrate the degree of redundancy in the control of coronary flow. The results indicate that the adrenergic open-loop control component is responsible for most of the increase in coronary blood flow that occurs during high levels of exercise. However, the adenine nucleotide-mediated metabolic feedback control component is essential. The model was evaluated by predicting coronary flow in cardiac pacing and autoregulation experiments with reasonable fits to the data. The analysis shows that a model in which coronary venous plasma adenine nucleotides are a signal in local metabolic feedback control of coronary flow is consistent with the available data. PMID:27037372

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

    PubMed

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

    2014-03-28

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

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

    PubMed Central

    2008-01-01

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

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

    PubMed

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

    2015-12-18

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

  7. All-Optical Nanomechanical Heat Engine

    NASA Astrophysics Data System (ADS)

    Dechant, Andreas; Kiesel, Nikolai; Lutz, Eric

    2015-05-01

    We propose and theoretically investigate a nanomechanical heat engine. We show how a levitated nanoparticle in an optical trap inside a cavity can be used to realize a Stirling cycle in the underdamped regime. The all-optical approach enables fast and flexible control of all thermodynamical parameters and the efficient optimization of the performance of the engine. We develop a systematic optimization procedure to determine optimal driving protocols. Further, we perform numerical simulations with realistic parameters and evaluate the maximum power and the corresponding efficiency.

  8. All-optical nanomechanical heat engine.

    PubMed

    Dechant, Andreas; Kiesel, Nikolai; Lutz, Eric

    2015-05-01

    We propose and theoretically investigate a nanomechanical heat engine. We show how a levitated nanoparticle in an optical trap inside a cavity can be used to realize a Stirling cycle in the underdamped regime. The all-optical approach enables fast and flexible control of all thermodynamical parameters and the efficient optimization of the performance of the engine. We develop a systematic optimization procedure to determine optimal driving protocols. Further, we perform numerical simulations with realistic parameters and evaluate the maximum power and the corresponding efficiency. PMID:26001001

  9. Simple novel all-optical wavelength converter

    NASA Astrophysics Data System (ADS)

    Chen, Zhixin

    2009-02-01

    Based on Sagnac interferometric structure, a simple novel ultrafast scheme for an all-optical wavelength converter is proposed. The operations of this scheme with a 80-Gbits/s return to zero (RZ) pseudorandom bit sequence (PRBS) are simulated correctly with an output extinction ratio of more than 17.2 dB. Through numerical analysis, by comparison of the performance at 40- and 80-Gbits/s operation, the operating characteristics of the scheme are illustrated. Furthermore, the carrier recovery time of the semiconductor amplifier (SOA) is no longer a crucial parameter to restrict the operation speed of this scheme.

  10. Ultrafast all-optical switching in bacteriorhodopsin

    NASA Astrophysics Data System (ADS)

    Roy, Sukhdev; Singh, C. P.; Reddy, K. P. J.

    2001-04-01

    All-optical switching has been demonstrated in bacteriorhodopsin based on excited-state nonlinear absorption. A probe laser beam at 640 nm corresponding to the O-state absorption maximum is switched due to a strong pulsed pump laser beam at 570 nm, that corresponds to the maximum ground state absorption. We have studied the effect of variation in pulse width and in small signal absorption coefficient on the switching characteristics. The switching time decreases as the pulse width of the pump beam decreases and the small signal absorption coefficient increases. The switching contrast depends mainly on the peak pumping intensity.

  11. All-optical symmetric ternary logic gate

    NASA Astrophysics Data System (ADS)

    Chattopadhyay, Tanay

    2010-09-01

    Symmetric ternary number (radix=3) has three logical states (1¯, 0, 1). It is very much useful in carry free arithmetical operation. Beside this, the logical operation using this type of number system is also effective in high speed computation and communication in multi-valued logic. In this literature all-optical circuits for three basic symmetrical ternary logical operations (inversion, MIN and MAX) are proposed and described. Numerical simulation verifies the theoretical model. In this present scheme the different ternary logical states are represented by different polarized state of light. Terahertz optical asymmetric demultiplexer (TOAD) based interferometric switch has been used categorically in this manuscript.

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed

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

    2013-10-15

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

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

    PubMed Central

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

    2016-01-01

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

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

    SciTech Connect

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

    2009-12-15

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

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

    SciTech Connect

    Small, W., LLNL

    1997-02-28

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

  17. Investigation, development and application of optimal output feedback theory. Volume 2: Development of an optimal, limited state feedback outer-loop digital flight control system for 3-D terminal area operation

    NASA Technical Reports Server (NTRS)

    Broussard, J. R.; Halyo, N.

    1984-01-01

    This report contains the development of a digital outer-loop three dimensional radio navigation (3-D RNAV) flight control system for a small commercial jet transport. The outer-loop control system is designed using optimal stochastic limited state feedback techniques. Options investigated using the optimal limited state feedback approach include integrated versus hierarchical control loop designs, 20 samples per second versus 5 samples per second outer-loop operation and alternative Type 1 integration command errors. Command generator tracking techniques used in the digital control design enable the jet transport to automatically track arbitrary curved flight paths generated by waypoints. The performance of the design is demonstrated using detailed nonlinear aircraft simulations in the terminal area, frequency domain multi-input sigma plots, frequency domain single-input Bode plots and closed-loop poles. The response of the system to a severe wind shear during a landing approach is also presented.

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

    PubMed

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

    2016-05-01

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

  19. All-optical OFDM network coding scheme for all-optical virtual private communication in PON

    NASA Astrophysics Data System (ADS)

    Li, Lijun; Gu, Rentao; Ji, Yuefeng; Bai, Lin; Huang, Zhitong

    2014-03-01

    A novel optical orthogonal frequency division multiplexing (OFDM) network coding scheme is proposed over passive optical network (PON) system. The proposed scheme for all-optical virtual private network (VPN) does not only improve transmission efficiency, but also realize full-duplex communication mode in a single fiber. Compared with the traditional all-optical VPN architectures, the all-optical OFDM network coding scheme can support higher speed, more flexible bandwidth allocation, and higher spectrum efficiency. In order to reduce the difficulty of alignment for encoding operation between inter-communication traffic, the width of OFDM subcarrier pulse is stretched in our proposed scheme. The feasibility of all-optical OFDM network coding scheme for VPN is verified, and the relevant simulation results show that the full-duplex inter-communication traffic stream can be transmitted successfully. Furthermore, the tolerance of misalignment existing in inter-ONUs traffic is investigated and analyzed for all-optical encoding operation, and the difficulty of pulse alignment is proved to be lower.

  20. All-optical phase-preserving multilevel amplitude regeneration.

    PubMed

    Roethlingshoefer, Tobias; Richter, Thomas; Schubert, Colja; Onishchukov, Georgy; Schmauss, Bernhard; Leuchs, Gerd

    2014-11-01

    The possibility of all-optical phase-preserving amplitude regeneration for star-8QAM is demonstrated using a modified nonlinear optical loop mirror. Experiments show a reduction in amplitude noise on both amplitude levels simultaneously, considering two different types of signal distortions: deterministic low-frequency amplitude modulation and broadband amplitude noise. Furthermore, using this amplitude regeneration, the robustness against nonlinear phase noise from fiber nonlinearity in a transmission line is increased. The scheme suppresses the conversion of amplitude noise to nonlinear phase noise. This is shown for simultaneous amplitude regeneration of the two amplitude states as well as for amplitude regeneration of the high-power states only. If the transmission is limited by nonlinear phase noise, single-level operation at the more critical higher-power state will benefit because of the wider plateau region. Numerical simulations confirm the experimental results. PMID:25401858

  1. All-optical time-stretch digitizer

    NASA Astrophysics Data System (ADS)

    Fard, A. M.; Buckley, B.; Zlatanovic, S.; Brès, C.-S.; Radic, S.; Jalali, B.

    2012-07-01

    We propose and demonstrate an all-optical time-stretch digitizer for real-time capture of ultrafast optical signals, beyond the bandwidths achievable by electronics. This approach uniquely combines four-wave mixing and photonic time-stretch technique to slow down and record high-speed optical signals. As a proof-of-concept, real-time recording of 40-Gb/s non-return-to-zero on-off-keying optical data stream is experimentally demonstrated using a stretch factor of 54 and 1.5-GHz back-end electronic bandwidth. We also report on the observation of dispersion penalty and its mitigation via single-sideband conversion enabled by an optical bandpass filter. Our technique may provide a path to real-time capture of ultrahigh-speed optical data streams.

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2016-09-01

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

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

    PubMed

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

    2015-12-01

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

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

    SciTech Connect

    Kido, Tatsuo; Lau, Yun-Fai Chris

    2014-03-28

    Highlights: • Y-encoded proto-oncoprotein TSPY amplifies its expression level via a positive feedback loop. • TSPY binds to the chromatin/DNA at exon 1 of TSPY gene. • TSPY enhances the gene expression in a TSPY exon 1 sequence dependent manner. • The conserved SET/NAP-domain is essential for TSPY transactivation. • Insights on probable mechanisms on TSPY exacerbation on cancer development in men. - Abstract: The testis-specific protein Y-encoded (TSPY) is a repetitive gene located on the gonadoblastoma region of the Y chromosome, and has been considered to be the putative gene for this oncogenic locus on the male-only chromosome. It is expressed in spermatogonial cells and spermatocytes in normal human testis, but abundantly in gonadoblastoma, testicular germ cell tumors and a variety of somatic cancers, including melanoma, hepatocellular carcinoma and prostate cancer. Various studies suggest that TSPY accelerates cell proliferation and growth, and promotes tumorigenesis. In this report, we show that TSPY could bind directly to the chromatin/DNA at exon 1 of its own gene, and greatly enhance the transcriptional activities of the endogenous gene in the LNCaP prostate cancer cells. Domain mapping analyses of TSPY have localized the critical and sufficient domain to the SET/NAP-domain. These results suggest that TSPY could efficiently amplify its expression and oncogenic functions through a positive feedback loop, and contribute to the overall tumorigenic processes when it is expressed in various human cancers.

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed

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

    1983-10-01

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

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

    SciTech Connect

    Tomilin, V. A. Il'ichev, L. V.

    2013-02-15

    The statistics of photoemission events of a pair of closely spaced two-level atoms is calculated in a classical light field whose phase is changed by {pi} after the detection of each spontaneous photon. This statistics is compared with the statistics in the case when the feedback is missing. In both cases, one can observe noticeable antibunching of photons in the range of parameters where no antibunching is observed in a single-atom system. The feedback substantially increases the antibunching. This effect manifests itself more strongly in relatively weak fields and for considerable frequency detunings.

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

    SciTech Connect

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

    2015-01-13

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

  13. High speed all-optical encryption and decryption using quantum dot semiconductor optical amplifiers

    NASA Astrophysics Data System (ADS)

    Li, Wenbo; Hu, Hongyu; Dutta, Niloy K.

    2013-11-01

    A scheme to realize high speed all-optical encryption and decryption using key-stream generators and an XOR gate based on quantum dot semiconductor optical amplifiers (QD-SOAs) was studied. The key used for encryption and decryption is a high speed all-optical pseudorandom bit sequence (PRBS) which is generated by a linear feedback shift register (LFSR) composed of QD-SOA-based logic XOR and AND gates. Two other kinds of more secure key-stream generators, i.e. cascaded design and parallel design, were also designed and investigated. Nonlinear dynamics including carrier heating and spectral hole-burning in the QD-SOA are taken into account together with the rate equations in order to realize all-optical logic operations. Results show that this scheme can realize all-optical encryption and decryption by using key-stream generators at high speed (~250 Gb/s).

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

    PubMed

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

    2015-03-15

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

  15. All-Optical Interrogation of Neural Circuits

    PubMed Central

    2015-01-01

    There have been two recent revolutionary advances in neuroscience: First, genetically encoded activity sensors have brought the goal of optical detection of single action potentials in vivo within reach. Second, optogenetic actuators now allow the activity of neurons to be controlled with millisecond precision. These revolutions have now been combined, together with advanced microscopies, to allow “all-optical” readout and manipulation of activity in neural circuits with single-spike and single-neuron precision. This is a transformational advance that will open new frontiers in neuroscience research. Harnessing the power of light in the all-optical approach requires coexpression of genetically encoded activity sensors and optogenetic probes in the same neurons, as well as the ability to simultaneously target and record the light from the selected neurons. It has recently become possible to combine sensors and optical strategies that are sufficiently sensitive and cross talk free to enable single-action-potential sensitivity and precision for both readout and manipulation in the intact brain. The combination of simultaneous readout and manipulation from the same genetically defined cells will enable a wide range of new experiments as well as inspire new technologies for interacting with the brain. The advances described in this review herald a future where the traditional tools used for generations by physiologists to study and interact with the brain—stimulation and recording electrodes—can largely be replaced by light. We outline potential future developments in this field and discuss how the all-optical strategy can be applied to solve fundamental problems in neuroscience. SIGNIFICANCE STATEMENT This review describes the nexus of dramatic recent developments in optogenetic probes, genetically encoded activity sensors, and novel microscopies, which together allow the activity of neural circuits to be recorded and manipulated entirely using light. The

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

    PubMed

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

    2015-08-01

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

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

    DOEpatents

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

    1992-11-24

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

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

    SciTech Connect

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

    1992-01-01

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

  19. Chaotic Feedback Loops within Decision Making Groups: Towards an Integration of Chaos Theory and Cybernetics.

    ERIC Educational Resources Information Center

    Keaten, James A.

    This paper offers a model that integrates chaos theory and cybernetics, which can be used to describe the structure of decision making within small groups. The paper begins with an overview of cybernetics and chaos. Definitional characteristics of cybernetics are reviewed along with salient constructs, such as goal-seeking, feedback, feedback…

  20. The GALAXIE all-optical FEL project

    SciTech Connect

    Rosenzweig, J. B.; Arab, E.; Andonian, G.; Cahill, A.; Fitzmorris, K.; Fukusawa, A.; Hoang, P.; Jovanovic, I.; Marcus, G.; Marinelli, A.; Murokh, A.; Musumeci, P.; Naranjo, B.; O'Shea, B.; O'Shea, F.; Ovodenko, A.; Pogorelsky, I.; Putterman, S.; Roberts, K.; Shumail, M.; and others

    2012-12-21

    We describe a comprehensive project, funded under the DARPA AXiS program, to develop an all-optical table-top X-ray FEL based on dielectric acceleration and electromagnetic undulators, yielding a compact source of coherent X-rays for medical and related applications. The compactness of this source demands that high field (>GV/m) acceleration and undulation-inducing fields be employed, thus giving rise to the project's acronym: GV/m AcceLerator And X-ray Integrated Experiment (GALAXIE). There are numerous physics and technical hurdles to surmount in this ambitious scenario, and the integrated solutions include: a biharmonic photonic TW structure, 200 micron wavelength electromagnetic undulators, 5 {mu}m laser development, ultra-high brightness magnetized/asymmetric emittance electron beam generation, and SASE FEL operation. We describe the overall design philosophy of the project, the innovative approaches to addressing the challenges presented by the design, and the significant progress towards realization of these approaches in the nine months since project initialization.

  1. All-optical beamlet train generation

    SciTech Connect

    Cary, John; Giacone, Rodolfo; Nieter, Chet; Bruhwiler, David; Esarey, Eric; Fubiani, Gwenael; Leemans, Wim

    2003-05-12

    One of the critical issues for the development of Laser Wake Field Acceleration (LWFA), which has the promise of creating table-top, GeV accelerators, is the loading of beamlets into the accelerating buckets. All optical injection schemes, which include LILAC, beat-wave colliding pulse injection, wave breaking injection, and phase-kick injection, provide a technique for doing so. Although a single bunch can have desirable properties such as energy spread of the order of a few percent, femtosecond duration k and low emittance (<1 mm-mrad), recent simulations show that such methods lead to efficiencies of transfer of plasma wave energy to beam energy that are low compared with conventional RF accelerators when only a single pulse is generated. Our latest simulations show that one can improve on this situation through the generation of a beamlet train. This can occur naturally through phase-kick injection at the front of the train and transverse wave breaking for the trailing pulses. The result is an efficiency improvement of the order of the number of beamlets in the train.

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

    PubMed Central

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

    2016-01-01

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

  3. Model-based rational feedback controller design for closed-loop deep brain stimulation of Parkinson's disease

    NASA Astrophysics Data System (ADS)

    Gorzelic, P.; Schiff, S. J.; Sinha, A.

    2013-04-01

    Objective. To explore the use of classical feedback control methods to achieve an improved deep brain stimulation (DBS) algorithm for application to Parkinson's disease (PD). Approach. A computational model of PD dynamics was employed to develop model-based rational feedback controller design. The restoration of thalamocortical relay capabilities to patients suffering from PD is formulated as a feedback control problem with the DBS waveform serving as the control input. Two high-level control strategies are tested: one that is driven by an online estimate of thalamic reliability, and another that acts to eliminate substantial decreases in the inhibition from the globus pallidus interna (GPi) to the thalamus. Control laws inspired by traditional proportional-integral-derivative (PID) methodology are prescribed for each strategy and simulated on this computational model of the basal ganglia network. Main Results. For control based upon thalamic reliability, a strategy of frequency proportional control with proportional bias delivered the optimal control achieved for a given energy expenditure. In comparison, control based upon synaptic inhibitory output from the GPi performed very well in comparison with those of reliability-based control, with considerable further reduction in energy expenditure relative to that of open-loop DBS. The best controller performance was amplitude proportional with derivative control and integral bias, which is full PID control. We demonstrated how optimizing the three components of PID control is feasible in this setting, although the complexity of these optimization functions argues for adaptive methods in implementation. Significance. Our findings point to the potential value of model-based rational design of feedback controllers for Parkinson's disease.

  4. Nanofiber-based all-optical switches

    NASA Astrophysics Data System (ADS)

    Le Kien, Fam; Rauschenbeutel, A.

    2016-01-01

    We study all-optical switches operating on a single four-level atom with the N -type transition configuration in a two-mode nanofiber cavity with a significant length (on the order of 20 mm) and a moderate finesse (on the order of 300) under the electromagnetically induced transparency (EIT) conditions. In our model, the gate and probe fields are the quantum nanofiber-cavity fields excited by weak classical light pulses, and the parameters of the D2 line of atomic cesium are used. We examine two different switching schemes. The first scheme is based on the effect of the presence of a photon in the gate mode on the EIT of the probe mode. The second scheme is based on the use of EIT to store a photon of the gate mode in the population of an appropriate atomic level, which leads to the reduction of the transmission of the field in the probe mode. We investigate the dependencies of the switching contrast on various parameters, such as the cavity length, the mirror reflectivity, and the detunings and powers of the cavity driving field pulses. For a nanofiber cavity with fiber radius of 250 nm, cavity length of 20 mm, and cavity finesse of 313 and a cesium atom at a distance of 200 nm from the fiber surface, we numerically obtain a switching contrast on the order of about 67% for the first scheme and of about 95% for the second scheme. These switching operations require small mean numbers of photons in the nanofiber cavity gate and probe modes.

  5. All optical modulator based on silicon resonator

    NASA Astrophysics Data System (ADS)

    Pinhas, Hadar; Bidani, Liron; Baharav, Oded; Sinvani, Moshe; Danino, Meir; Zalevsky, Zeev

    2015-08-01

    In this paper we present an all-optical silicon modulator, where a silicon slab (450 μm) thick is coated on both sides to get a Fabry-Perot resonator for laser beam at wavelength of 1550nm. Most of the modulators discussed in literature, are driven by electrical field rather than by light. We investigate new approaches regarding the dependence of the absorption of the optical signal on the control laser pulse at 532 nm having 5nm pulse width. Our silicon based Fabry-Perot resonator increases the intrinsic c-Si finesse to >10, instead of the uncoated silicon with natural finesse of 2.5. The improved finesse is shown to have significant effect on the modulation depth using a pulsed laser. A modulation of 12dB was attained. The modulation is ascribed to two different effects - The Plasma Dispersion Effect (PDE) and the Thermo- Optic Effect (TOE). The PDE causes increase in the signal absorption in silicon via the absorption of the control laser light. On top of that, the transmission of the signal can decrease dramatically in high finesse resonators due to change in the refractive index due to TOE. The changes in the signal's absorption coefficient and in the refractive index are the result of incremental change in the concentration of free carriers. The TOE gives rise to higher refractive index as opposed to the PDE which triggers a decrease in the refractive index. Finally, tradeoff considerations are presented on how to modify one effect to counter the other one, leading to an optimal device having reduced temperature dependence.

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

    PubMed

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

    2016-05-01

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

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

    PubMed Central

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

    2013-01-01

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

  8. All-optical switching and all-optical logic gates based on bacteriorhodopsin

    NASA Astrophysics Data System (ADS)

    Huang, Yuhua; Wu, Shin-Tson; Zhao, Youyuan

    2004-06-01

    We demonstrate an all-optical switching using a bacteriorhodopsin (bR) film. The transmission of the bR film is investigated using the pump-probe method. A diode-pumped second harmonic YAG laser (λ = 532nm which is around the maximum initial B state absorption) was used as a pumping beam and a cw He-Ne laser (λ = 632 nm which is around the peaks of K and O states) was used as a probe. Due to the nonlinear intensity induced excited state absorption of the K, L, M, N, and O states in the bR photocycle, the switching characteristics are sensitive to the intensity of the probe and pump beams. Based on this property, we design an all-optical operating device functioning as 11 kinds of variable binary all-optical logic gates. The incident 532nm beam acts as an input to the logic gate and the transmission of the 632nm bears the output of the gate.

  9. Fault tolerant all-optical router with photorefractive all-optical switch

    NASA Astrophysics Data System (ADS)

    Kaino, Toshiya; Okamoto, Atsushi; Honma, Satoshi

    2003-08-01

    We propose a new type of the fault tolerant all-optical router (FTAR) by using an all-optical switch with photorefractive two-wave mixing. FTAR can detect a cutoff of a main transmitting line and automatically reroute a signal beam from the main line to a backup line. These functions can increase communication reliability of optical wireless. FTAR is composed of ony all-optical devices without any electronic devices or any mechanical operations. In the new type of FTAR, the routing of the signal beam is controlled by a control beam transmitting on the main line from a different light source at a receiver in the opposite direction with the signal beam. Compared with the previous type of FTAR composed of two photorefractinve crystals, the new configuration offers the simplification of the construction and high transmission efficiency of the signal beam. In this report, we experiment on the FTAR by usign a BaTiO3 and Ar+ laser whose wavelength is 514.5nm, and confirm the fundamental fucntin of FTAR. We give comparison of the result with the numerical analysis. We also analyze the dependence of the switching time on the input beam intensity of the crystal by a numerical analysis and an experiment.

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

    PubMed

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

    2011-04-01

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

  11. New numerical methods for open-loop and feedback solutions to dynamic optimization problems

    NASA Astrophysics Data System (ADS)

    Ghosh, Pradipto

    The topic of the first part of this research is trajectory optimization of dynamical systems via computational swarm intelligence. Particle swarm optimization is a nature-inspired heuristic search method that relies on a group of potential solutions to explore the fitness landscape. Conceptually, each particle in the swarm uses its own memory as well as the knowledge accumulated by the entire swarm to iteratively converge on an optimal or near-optimal solution. It is relatively straightforward to implement and unlike gradient-based solvers, does not require an initial guess or continuity in the problem definition. Although particle swarm optimization has been successfully employed in solving static optimization problems, its application in dynamic optimization, as posed in optimal control theory, is still relatively new. In the first half of this thesis particle swarm optimization is used to generate near-optimal solutions to several nontrivial trajectory optimization problems including thrust programming for minimum fuel, multi-burn spacecraft orbit transfer, and computing minimum-time rest-to-rest trajectories for a robotic manipulator. A distinct feature of the particle swarm optimization implementation in this work is the runtime selection of the optimal solution structure. Optimal trajectories are generated by solving instances of constrained nonlinear mixed-integer programming problems with the swarming technique. For each solved optimal programming problem, the particle swarm optimization result is compared with a nearly exact solution found via a direct method using nonlinear programming. Numerical experiments indicate that swarm search can locate solutions to very great accuracy. The second half of this research develops a new extremal-field approach for synthesizing nearly optimal feedback controllers for optimal control and two-player pursuit-evasion games described by general nonlinear differential equations. A notable revelation from this development

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

    PubMed

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

    2000-07-28

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

  13. Photonic encryption using all optical logic.

    SciTech Connect

    Blansett, Ethan L.; Schroeppel, Richard Crabtree; Tang, Jason D.; Robertson, Perry J.; Vawter, Gregory Allen; Tarman, Thomas David; Pierson, Lyndon George

    2003-12-01

    With the build-out of large transport networks utilizing optical technologies, more and more capacity is being made available. Innovations in Dense Wave Division Multiplexing (DWDM) and the elimination of optical-electrical-optical conversions have brought on advances in communication speeds as we move into 10 Gigabit Ethernet and above. Of course, there is a need to encrypt data on these optical links as the data traverses public and private network backbones. Unfortunately, as the communications infrastructure becomes increasingly optical, advances in encryption (done electronically) have failed to keep up. This project examines the use of optical logic for implementing encryption in the photonic domain to achieve the requisite encryption rates. In order to realize photonic encryption designs, technology developed for electrical logic circuits must be translated to the photonic regime. This paper examines two classes of all optical logic (SEED, gain competition) and how each discrete logic element can be interconnected and cascaded to form an optical circuit. Because there is no known software that can model these devices at a circuit level, the functionality of the SEED and gain competition devices in an optical circuit were modeled in PSpice. PSpice allows modeling of the macro characteristics of the devices in context of a logic element as opposed to device level computational modeling. By representing light intensity as voltage, 'black box' models are generated that accurately represent the intensity response and logic levels in both technologies. By modeling the behavior at the systems level, one can incorporate systems design tools and a simulation environment to aid in the overall functional design. Each black box model of the SEED or gain competition device takes certain parameters (reflectance, intensity, input response), and models the optical ripple and time delay characteristics. These 'black box' models are interconnected and cascaded in an

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

    NASA Astrophysics Data System (ADS)

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

    2014-06-01

    It is increasingly acknowledged that, in order to sustainably manage global freshwater resources, it is critical that we better understand the nature of human-hydrology interactions at the broader catchment system scale. Yet to date, a generic conceptual framework for building models of catchment systems that include adequate representation of socioeconomic systems - and the dynamic feedbacks between human and natural systems - has remained elusive. In an attempt to work towards such a model, this paper outlines a generic framework for models of socio-hydrology applicable to agricultural catchments, made up of six key components that combine to form the coupled system dynamics: namely, catchment hydrology, population, economics, environment, socioeconomic sensitivity and collective response. The conceptual framework posits two novel constructs: (i) a composite socioeconomic driving variable, termed the Community Sensitivity state variable, which seeks to capture the perceived level of threat to a community's quality of life, and acts as a key link tying together one of the fundamental feedback loops of the coupled system, and (ii) a Behavioural Response variable as the observable feedback mechanism, which reflects land and water management decisions relevant to the hydrological context. The framework makes a further contribution through the introduction of three macro-scale parameters that enable it to normalise for differences in climate, socioeconomic and political gradients across study sites. In this way, the framework provides for both macro-scale contextual parameters, which allow for comparative studies to be undertaken, and catchment-specific conditions, by way of tailored "closure relationships", in order to ensure that site-specific and application-specific contexts of socio-hydrologic problems can be accommodated. To demonstrate how such a framework would be applied, two socio-hydrological case studies, taken from the Australian experience, are presented

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

    PubMed

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

    2015-12-01

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

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

    NASA Technical Reports Server (NTRS)

    Connolly, Joseph W.; Kopasakis, George

    2010-01-01

    This paper covers the propulsion system component modeling and controls development of an integrated mixed compression inlet and turbojet engine that will be used for an overall vehicle Aero-Propulso-Servo-Elastic (APSE) model. Using previously created nonlinear component-level propulsion system models, a linear integrated propulsion system model and loop shaping control design have been developed. The design includes both inlet normal shock position control and jet engine rotor speed control for a potential supersonic commercial transport. A preliminary investigation of the impacts of the aero-elastic effects on the incoming flow field to the propulsion system are discussed, however, the focus here is on developing a methodology for the propulsion controls design that prevents unstart in the inlet and minimizes the thrust oscillation experienced by the vehicle. Quantitative Feedback Theory (QFT) specifications and bounds, and aspects of classical loop shaping are used in the control design process. Model uncertainty is incorporated in the design to address possible error in the system identification mapping of the nonlinear component models into the integrated linear model.

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

    PubMed Central

    Selitrennik, Michael; Lev, Sima

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-11-16

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

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

    PubMed

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

    2015-08-12

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

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

    PubMed Central

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

    2014-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2015-09-01

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

  3. Autonomous Closed-Loop Tasking, Acquisition, Processing, and Evaluation for Situational Awareness Feedback

    NASA Technical Reports Server (NTRS)

    Frye, Stuart; Mandl, Dan; Cappelaere, Pat

    2016-01-01

    This presentation describes the closed loop satellite autonomy methods used to connect users and the assets on Earth Orbiter- 1 (EO-1) and similar satellites. The base layer is a distributed architecture based on Goddard Mission Services Evolution Concept (GMSEC) thus each asset still under independent control. Situational awareness is provided by a middleware layer through common Application Programmer Interface (API) to GMSEC components developed at GSFC. Users setup their own tasking requests, receive views into immediate past acquisitions in their area of interest, and into future feasibilities for acquisition across all assets. Automated notifications via pubsub feeds are returned to users containing published links to image footprints, algorithm results, and full data sets. Theme-based algorithms are available on-demand for processing.

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

    PubMed

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

    2016-02-22

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

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

    NASA Astrophysics Data System (ADS)

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

    2011-12-01

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

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

    PubMed Central

    Bleris, Leonidas; Ma, Lan

    2015-01-01

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

  7. All-optical devices based on carrier nonlinearities for optical filtering and spectral equalization

    NASA Astrophysics Data System (ADS)

    Burger, Johan Petrus

    InGaAsP-based quantum wells can display nonlinear refractive index changes of ~0.1 near the band-edge for intrawell carrier density changes of 1 × 1018cm-3, due to effects like bandfilling and the plasma effect, which make these materials promising for the realization of all-optical signal processing devices, as demonstrated here. A novel single passband filter with sub-gigahertz bandwidth and greater than 40nm of tunability was experimentally demonstrated. The filter uses the detuning characteristics of nearly degenerate four-wave mixing in a broad area semiconductor optical amplifier to obtain frequency selectivity. The key to this demonstration was the spatial separation of the filtered signal from the input signal, based on their different propagation directions. An analysis of an analogous integrated optic dual-order mode nonlinear mode-converter, with integrated mode sorters which separate the signal from the interacting modes, was also undertaken. This device is promising as a filter, a wavelength converter, notch filter, and a wavelength recognizing switch. Novel ways to prevent carrier diffusion, which washes out the nonlinear grating, were suggested. It is important to have a large mutual overlap to modal overlap ratio of the two interacting modes on the nonlinear medium, because the mixing efficiency scales as the fourth power of this number. Three types of integrated optic limiters (based on Kerr- like nonlinearities) namely an all-optical cutoff modulator, a nonlinear Y-branch and an interferometer with an internal Kerr element, were theoretically investigated. A beam propagation program, which can solve the propagation of an optical field in a semiconductor in the presence of carrier diffusion, was developed for the numerical analysis of these structures. A negative feedback mechanism was identified in the Y-branch devices and a new limiting configuration was discovered in a Y- branch with a selectively placed defocusing nonlinearity. Dichroic

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

    PubMed

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

    2016-01-15

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

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

    PubMed Central

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

    2016-01-01

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

  10. Tunable optoelectronic oscillator incorporating an all-optical microwave photonic filter

    NASA Astrophysics Data System (ADS)

    Li, Cheng-Xin; Chen, Fu-Shen; Zhang, Jia-Hong

    2015-01-01

    A tunable optoelectronic oscillator (OEO), which employs an all-optical microwave photonic filter (MPF) consisting of two laser sources (LD1 and LD2), an optical coupler (OC, 50:50), a Mach-Zehnder modulator (MZM), and a chirped fiber Bragg grating, is proposed. Because the central frequency of the all-optical MPF can be shifted by changing the wavelength spacing between the two laser sources, the frequency tunability of the OEO can be realized by incorporating such an all-optical MPF into an optical domain dual-loop OEO without any electronic microwave filters. A detailed theoretical analysis is presented and the results are confirmed by an experiment. A microwave signal with a frequency-tuning range from 4.057 to 8.595 GHz is generated. The phase noise, the long-term stability, and the side-mode suppression performance of the generated microwave signal are also investigated.

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

    PubMed Central

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

    2012-01-01

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

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

    NASA Astrophysics Data System (ADS)

    Shen, Bo-Wen

    2016-07-01

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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-09-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2016-01-01

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

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

    PubMed

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

    2013-04-23

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

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

    PubMed

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

    2016-08-01

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

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

    SciTech Connect

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

    2007-01-15

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-12-01

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

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

    PubMed

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

    2011-05-01

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

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

    PubMed

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

    2015-11-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2013-08-01

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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2015-05-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-01-28

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  15. All-optical signal processing using dynamic Brillouin gratings

    NASA Astrophysics Data System (ADS)

    Santagiustina, Marco; Chin, Sanghoon; Primerov, Nicolay; Ursini, Leonora; Thévenaz, Luc

    2013-04-01

    The manipulation of dynamic Brillouin gratings in optical fibers is demonstrated to be an extremely flexible technique to achieve, with a single experimental setup, several all-optical signal processing functions. In particular, all-optical time differentiation, time integration and true time reversal are theoretically predicted, and then numerically and experimentally demonstrated. The technique can be exploited to process both photonic and ultra-wide band microwave signals, so enabling many applications in photonics and in radio science.

  16. All-optical signal processing using dynamic Brillouin gratings

    PubMed Central

    Santagiustina, Marco; Chin, Sanghoon; Primerov, Nicolay; Ursini, Leonora; Thévenaz, Luc

    2013-01-01

    The manipulation of dynamic Brillouin gratings in optical fibers is demonstrated to be an extremely flexible technique to achieve, with a single experimental setup, several all-optical signal processing functions. In particular, all-optical time differentiation, time integration and true time reversal are theoretically predicted, and then numerically and experimentally demonstrated. The technique can be exploited to process both photonic and ultra-wide band microwave signals, so enabling many applications in photonics and in radio science. PMID:23549159

  17. An approach toward the holy grail in all-optical circuit switching: the monster all-optical crossconnect

    NASA Astrophysics Data System (ADS)

    Riza, Nabeel A.; Mughal, M. J.

    2003-12-01

    A new robust approach is presented for achieving very large fiber port count all-optical crossconnect switches. This three dimensional optics-based switch has built-in alignment capabilities with fault-tolerance, allowing graceful port count scaling.

  18. All-optical code routing in interconnected optical CDMA and WDM ring networks.

    PubMed

    Deng, Yanhua; Fok, Mable P; Prucnal, Paul R; Wang, Ting

    2010-11-01

    We propose an all-optical hybrid network composed of optical code division multiple access (CDMA) rings interconnecting through a reconfigurable wavelength division multiplexing (WDM) metro area ring. This network retains the advantages of both the optical CDMA and WDM techniques, including asynchronous access and differentiated quality of service, while removing the hard limit on the number of subscribers and increasing network flexibility. The all-optical network is enabled by using nonlinear optical loop mirrors in an add/drop router (ADR) that performs code conversion, dropping, and switching asynchronously. We experimentally demonstrate the functionalities of the ADR in the proposed scheme asynchronously and obtain error-free performance. The bit-error rate measurements show acceptable power penalties for different code routes. PMID:21042372

  19. Passive all-optical polarization switch, binary logic gates, and digital processor.

    PubMed

    Zaghloul, Y A; Zaghloul, A R M; Adibi, A

    2011-10-10

    We introduce the passive all-optical polarization switch, which modulates light with light. That switch is used to construct all the binary logic gates of two or more inputs. We discuss the design concepts and the operation of the AND, OR, NAND, and NOR gates as examples. The rest of the 16 logic gates are similarly designed. Cascading of such gates is straightforward as we show and discuss. Cascading in itself does not require a power source, but feedback at this stage of development does. The design and operation of an SR Latch is presented as one of the popular basic sequential devices used for memory cells. That completes the essential components of an all-optical polarization digital processor. The speed of such devices is well above 10 GHz for bulk implementations and is much higher for chip-size implementations. In addition, the presented devices do have the four essential characteristics previously thought unique to the microelectronic ones. PMID:21997044

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

    PubMed

    Hou, Yubin; Zhang, Qian; Wang, Pu

    2016-06-13

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

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

    PubMed Central

    Morgans, Aimee S.

    2016-01-01

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

  2. All-optical signal processing technique for secure optical communication

    NASA Astrophysics Data System (ADS)

    Qian, Feng-chen; Su, Bing; Ye, Ya-lin; Zhang, Qian; Lin, Shao-feng; Duan, Tao; Duan, Jie

    2015-10-01

    Secure optical communication technologies are important means to solve the physical layer security for optical network. We present a scheme of secure optical communication system by all-optical signal processing technique. The scheme consists of three parts, as all-optical signal processing unit, optical key sequence generator, and synchronous control unit. In the paper, all-optical signal processing method is key technology using all-optical exclusive disjunction (XOR) gate based on optical cross-gain modulation effect, has advantages of wide dynamic range of input optical signal, simple structure and so on. All-optical XOR gate composed of two semiconductor optical amplifiers (SOA) is a symmetrical structure. By controlling injection current, input signal power, delay and filter bandwidth, the extinction ratio of XOR can be greater than 8dB. Finally, some performance parameters are calculated and the results are analyzed. The simulation and experimental results show that the proposed method can be achieved over 10Gbps optical signal encryption and decryption, which is simple, easy to implement, and error-free diffusion.

  3. Simple novel all-optical half-adder

    NASA Astrophysics Data System (ADS)

    Chen, Zhixin

    2010-04-01

    On the basis of Sagnac interferometric structure, a simple novel ultrafast scheme of all-optical half-adder is proposed. The structure comprises two of the same balanced terahertz optical asymmetric demultiplexers (TOADs). One TOAD is utilized to achieve an all-optical XOR gate, which is logic SUM. The other is utilized to obtain an all-optical AND gate, which is logic CARRY. Logical SUM and CARRY are simultaneously realized at 80 Gbit/s. Through numerical analysis, the operating characteristics of the scheme are illustrated at 80 Gbit/s. Furthermore, the carrier recovery time of the semiconductor optical amplifier is no longer a crucial parameter to restrict the operation speed of this scheme.

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

    PubMed

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

    2016-01-01

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

  5. All-optical pseudorandom bit sequences generator based on TOADs

    NASA Astrophysics Data System (ADS)

    Sun, Zhenchao; Wang, Zhi; Wu, Chongqing; Wang, Fu; Li, Qiang

    2016-03-01

    A scheme for all-optical pseudorandom bit sequences (PRBS) generator is demonstrated with optical logic gate 'XNOR' and all-optical wavelength converter based on cascaded Tera-Hertz Optical Asymmetric Demultiplexer (TOADs). Its feasibility is verified by generation of return-to-zero on-off keying (RZ-OOK) 263-1 PRBS at the speed of 1 Gb/s with 10% duty radio. The high randomness of ultra-long cycle PRBS is validated by successfully passing the standard benchmark test.

  6. Photonic temporal integrator for all-optical computing.

    PubMed

    Slavík, Radan; Park, Yongwoo; Ayotte, Nicolas; Doucet, Serge; Ahn, Tae-Jung; LaRochelle, Sophie; Azaña, José

    2008-10-27

    We report the first experimental realization of an all-optical temporal integrator. The integrator is implemented using an all-fiber active (gain-assisted) filter based on superimposed fiber Bragg gratings made in an Er-Yb co-doped optical fiber that behaves like an 'optical capacitor'. Functionality of this device was tested by integrating different optical pulses, with time duration down to 60 ps, and by integration of two consecutive pulses that had different relative phases, separated by up to 1 ns. The potential of the developed device for implementing all-optical computing systems for solving ordinary differential equations was also experimentally tested. PMID:18958098

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

    PubMed

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

    2014-12-01

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

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

    PubMed Central

    Grimm, Florian; Naros, Georgios; Gharabaghi, Alireza

    2016-01-01

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

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

    PubMed

    Grimm, Florian; Naros, Georgios; Gharabaghi, Alireza

    2016-01-01

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

  10. Analysis of all-optical temporal integrator employing phased-shifted DFB-SOA.

    PubMed

    Jia, Xin-Hong; Ji, Xiao-Ling; Xu, Cong; Wang, Zi-Nan; Zhang, Wei-Li

    2014-11-17

    All-optical temporal integrator using phase-shifted distributed-feedback semiconductor optical amplifier (DFB-SOA) is investigated. The influences of system parameters on its energy transmittance and integration error are explored in detail. The numerical analysis shows that, enhanced energy transmittance and integration time window can be simultaneously achieved by increased injected current in the vicinity of lasing threshold. We find that the range of input pulse-width with lower integration error is highly sensitive to the injected optical power, due to gain saturation and induced detuning deviation mechanism. The initial frequency detuning should also be carefully chosen to suppress the integration deviation with ideal waveform output. PMID:25402095

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

    PubMed

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

    2015-02-01

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

  12. Coherent controllers for optical-feedback cooling of quantum oscillators

    NASA Astrophysics Data System (ADS)

    Hamerly, Ryan; Mabuchi, Hideo

    2013-01-01

    We study the cooling performance of optical-feedback controllers for open optical and mechanical resonators in the linear quadratic Gaussian setting of stochastic control theory. We utilize analysis and numerical optimization of closed-loop models based on quantum stochastic differential equations to show that coherent control schemes, where we embed the resonator in an interferometer to achieve all-optical feedback, can outperform optimal measurement-based feedback control schemes in the quantum regime of low steady-state excitation number. These performance gains are attributed to the coherent controller's ability to simultaneously process both quadratures of an optical probe field without measurement or loss of fidelity, and may guide the design of coherent feedback schemes for more general problems of robust nonlinear and robust control.

  13. All-optical tunable microwave interference suppression filter based on SOA

    NASA Astrophysics Data System (ADS)

    Xu, Enming; Zhang, Xinliang; Zhou, Lina; Huang, Dexiu

    2008-12-01

    An all-optical filter structure for interference suppression of microwave signals is presented. The filter is based on a recirculating delay line (RDL) loop consisting of a semiconductor optical amplifier (SOA) followed by a tunable narrowband optical filter, and a fiber Bragg grating connected after the RDL loop. Negative tap is generated in wavelength conversion process based on cross-gain modulation of amplified spontaneous emission spectrum of the SOA. A narrow passband filter with negative coefficients and a broadband all-pass filter are synthesized to achieve a narrow notch filter with flat passband which can excise interference with minimal impact on the wanted signal over a wide microwave range. Experimental results show that measured and theoretical frequency responses agree well and the filter is tunable.

  14. Simple nonlinear interferometer-based all-optical thresholder and its applications for optical CDMA.

    PubMed

    Kravtsov, Konstantin; Prucnal, Paul R; Bubnov, Mikhail M

    2007-10-01

    We present an experimental demonstration of an ultrafast all-optical thresholder based on a nonlinear Sagnac interferometer. The proposed design is intended for operation at very small nonlinear phase shifts. Therefore, it requires an in-loop nonlinearity lower than for the classical nonlinear loop mirror scheme. Only 15 meters of conventional (non-holey) silica-based fiber is used as a nonlinear element. The proposed thresholder is polarization insensitive and is good for multi-wavelength operation, meeting all the requirements for autocorrelation detection in various optical CDMA communication systems. The observed cubic transfer function is superior to the quadratic transfer function of second harmonic generation-based thresholders. PMID:19550579

  15. All optical mode controllable Er-doped random fiber laser with distributed Bragg gratings.

    PubMed

    Zhang, W L; Ma, R; Tang, C H; Rao, Y J; Zeng, X P; Yang, Z J; Wang, Z N; Gong, Y; Wang, Y S

    2015-07-01

    An all-optical method to control the lasing modes of Er-doped random fiber lasers (RFLs) is proposed and demonstrated. In the RFL, an Er-doped fiber (EDF) recoded with randomly separated fiber Bragg gratings (FBG) is used as the gain medium and randomly distributed reflectors, as well as the controllable element. By combining random feedback of the FBG array and Fresnel feedback of a cleaved fiber end, multi-mode coherent random lasing is obtained with a threshold of 14 mW and power efficiency of 14.4%. Moreover, a laterally-injected control light is used to induce local gain perturbation, providing additional gain for certain random resonance modes. As a result, active mode selection of the RFL is realized by changing locations of the laser cavity that is exposed to the control light. PMID:26125397

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

    PubMed

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

    2014-09-30

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

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

    NASA Technical Reports Server (NTRS)

    Bragg-Sitton, Shannon M.; Forsbacka, Matthew

    2004-01-01

    For a compact, fast-spectrum reactor, reactivity feedback is dominated by core deformation at elevated temperature. Given the use of accurate deformation measurement techniques, it is possible to simulate nuclear feedback in non-nuclear electrically heated reactor tests. Implementation of simulated reactivity feedback in response to measured deflection is being tested at the NASA Marshall Space Flight Center Early Flight Fission Test Facility (EFF-TF). During tests of the SAFE-100 reactor prototype, core deflection was monitored using a high resolution camera. "virtual" reactivity feedback was accomplished by applying the results of Monte Carlo calculations (MCNPX) to core deflection measurements; the computational analysis was used to establish the reactivity worth of van'ous core deformations. The power delivered to the SAFE-100 prototype was then dusted accordingly via kinetics calculations, The work presented in this paper will demonstrate virtual reactivity feedback as core power was increased from 1 kilowatt(sub t), to 10 kilowatts(sub t), held approximately constant at 10 kilowatts (sub t), and then allowed to decrease based on the negative thermal reactivity coefficient.

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

    PubMed

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

    2016-03-01

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

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

    PubMed Central

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

    2014-01-01

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

  20. High speed all-optical PRBS generation using binary phase shift keyed signal based on QD-SOA

    NASA Astrophysics Data System (ADS)

    Li, Wenbo; Hu, Hongyu; Dutta, Niloy K.

    2014-09-01

    A scheme to generate return-to-zero on-off keying (RZ-OOK) high speed all-optical pseudo random bit sequence (PRBS) using binary phase shift keyed (BPSK) signal based on quantum-dot semiconductor optical amplifiers (QD-SOA) has been designed and studied. The PRBS is generated by a linear feedback shift register (LFSR) composed of all-optical logic XOR and AND gates. The XOR gate is composed of a pair of QD SOA Mach-Zehnder interferometers, which can generate BSPK signal to realize all-optical logic XOR gate. Results show that this scheme can mitigate the patterning effects and increase the operation speed to ~250Gb/s.

  1. Bufferless Ultra-High Speed All-Optical Packet Routing

    NASA Astrophysics Data System (ADS)

    Muttagi, Shrihari; Prince, Shanthi

    2011-10-01

    All-Optical network is still in adolescence to cope up with steep rise in data traffic at the backbone network. Routing of packets in optical network depends on the processing speed of the All-Optical routers, thus there is a need to enhance optical processing to curb the delay in packet forwarding unit. In the proposed scheme, the header processing takes place on fly, therefore processing delay is at its lower limit. The objective is to propose a framework which establishes high data rate transmission with least latency in data routing from source to destination. The Routing table and optical header pulses are converted into Pulse Position (PP) format, thus reducing the complexity and in turn the processing delay. Optical pulse matching is exercised which results in multi-output transmission. This results in ultra-high speed packet forwarding unit. In addition, this proposed scheme includes dispersion compensation unit, which makes the data reliable.

  2. All-optical SOA latch fail-safe alarm system

    NASA Astrophysics Data System (ADS)

    McAulay, Alastair D.

    2004-11-01

    Emergency alarm systems, for example, that switch off critical processes in process plant, are vulnerable to deliberate or accidental sabotage through coupling of electromagnetic pulses (EMP) to wires and/or from sparks due to broken wires. A proposed system significantly reduces vulnerability by using a fast all-optical latch in conjunction with an optical sensor and optical fibers. Sparks cannot be created on breaking an optical beam and electromagnetic field transients have negligible effect on optical signals. The optical latch uses optical semiconductor amplifiers (SOAs) configured to form a flip-flop. The flip-flop latches after the occurrence of an intrusion that may be as short as a few nanoseconds, much faster than most environmental changes occur. Detection of an emergency or any break in connections causes the light to drop, triggering the alarm. Computer simulation shows that the all-optical latch is fast and effective.

  3. All-optical switching in optically induced nonlinear waveguide couplers

    SciTech Connect

    Diebel, Falko Boguslawski, Martin; Rose, Patrick; Denz, Cornelia; Leykam, Daniel; Desyatnikov, Anton S.

    2014-06-30

    We experimentally demonstrate all-optical vortex switching in nonlinear coupled waveguide arrays optically induced in photorefractive media. Our technique is based on multiplexing of nondiffracting Bessel beams to induce various types of waveguide configurations. Using double- and quadruple-well potentials, we demonstrate precise control over the coupling strength between waveguides, the linear and nonlinear dynamics and symmetry-breaking bifurcations of guided light, and a power-controlled optical vortex switch.

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

    PubMed

    Hao, Lijie; Yang, Zhuoqin; Bi, Yuanhong

    2016-04-01

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

  5. Integrated all-optical logic and arithmetic operations with the help of a TOAD-based interferometer device--alternative approach

    NASA Astrophysics Data System (ADS)

    Nath Roy, Jitendra; Gayen, Dilip Kumar

    2007-08-01

    Interferometric devices have drawn a great interest in all-optical signal processing for their high-speed photonic activity. The nonlinear optical loop mirror provides a major support to optical switching based all-optical logic and algebraic operations. The gate based on the terahertz optical asymmetric demultiplexer (TOAD) has added new momentum in this field. Optical tree architecture (OTA) plays a significant role in the optical interconnecting network. We have tried to exploit the advantages of both OTA- and TOAD-based switches. We have proposed a TOAD-based tree architecture, a new and alternative scheme, for integrated all-optical logic and arithmetic operations.

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

    NASA Technical Reports Server (NTRS)

    Birchenough, A. G.

    1975-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    NASA Astrophysics Data System (ADS)

    Donovan, Diane; Loch, Birgit

    2013-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2016-05-01

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

  10. Ultrafast all-optical technologies for bidirectional optical wireless communications.

    PubMed

    Jin, Xian; Hristovski, Blago A; Collier, Christopher M; Geoffroy-Gagnon, Simon; Born, Brandon; Holzman, Jonathan F

    2015-04-01

    In this Letter, a spherical retro-modulator architecture is introduced for operation as a bidirectional transceiver in passive optical wireless communication links. The architecture uses spherical retroreflection to enable retroreflection with broad directionality (2π steradians), and it uses all-optical beam interaction to enable modulation on ultrafast timescales (120 fs duration). The spherical retro-modulator is investigated from a theoretical standpoint and is fabricated for testing with three glasses, N-BK7, N-LASF9, and S-LAH79. It is found that the S-LAH79 structure provides the optimal refraction and nonlinearity for the desired retroreflection and modulation capabilities. PMID:25831390

  11. In-fiber all-optical fractional differentiator.

    PubMed

    Cuadrado-Laborde, C; Andrés, M V

    2009-03-15

    We demonstrate that an asymmetrical pi phase-shifted fiber Bragg grating operated in reflection can provide the required spectral response for implementing an all-optical fractional differentiator. There are different (but equivalent) ways to design it, e.g., by using different gratings lengths and keeping the same index modulation depth at both sides of the pi phase shift, or vice versa. Analytical expressions were found relating the fractional differentiator order with the grating parameters. The device shows a good accuracy calculating the fractional time derivatives of the complex field of an arbitrary input optical waveform. The introduced concept is supported by numerical simulations. PMID:19282948

  12. Realization of an all optical exciton-polariton router

    NASA Astrophysics Data System (ADS)

    Marsault, Félix; Nguyen, Hai Son; Tanese, Dimitrii; Lemaître, Aristide; Galopin, Elisabeth; Sagnes, Isabelle; Amo, Alberto; Bloch, Jacqueline

    2015-11-01

    We report on the experimental realization of an all optical router for exciton-polaritons. This device is based on the design proposed by Flayac and Savenko [Appl. Phys. Lett. 103, 201105 (2013)], in which a zero-dimensional island is connected through tunnel barriers to two periodically modulated wires of different periods. Selective transmission of polaritons injected in the island, into either of the two wires, is achieved by tuning the energy of the island state across the band structure of the modulated wires. We demonstrate routing of ps polariton pulses using an optical control beam which controls the energy of the island quantum states, thanks to polariton-exciton interactions.

  13. All-optical processing in coherent nonlinear spectroscopy

    SciTech Connect

    Oron, Dan; Dudovich, Nirit; Silberberg, Yaron

    2004-08-01

    In spectroscopy, the fingerprint of a substance is usually comprised of a sequence of spectral lines with characteristic frequencies and strengths. Identification of substances often involves postprocessing, where the measured spectrum is compared with tabulated fingerprint spectra. Here we suggest a scheme for nonlinear spectroscopy, where, through coherent control of the nonlinear process, the information from the entire spectrum can be practically collected into a single coherent entity. We apply this for all-optical analysis of coherent Raman spectra and demonstrate enhanced detection and effective background suppression using coherent processing.

  14. Realization of an all optical exciton-polariton router

    SciTech Connect

    Marsault, Félix; Nguyen, Hai Son; Tanese, Dimitrii; Lemaître, Aristide; Galopin, Elisabeth; Sagnes, Isabelle; Amo, Alberto

    2015-11-16

    We report on the experimental realization of an all optical router for exciton-polaritons. This device is based on the design proposed by Flayac and Savenko [Appl. Phys. Lett. 103, 201105 (2013)], in which a zero-dimensional island is connected through tunnel barriers to two periodically modulated wires of different periods. Selective transmission of polaritons injected in the island, into either of the two wires, is achieved by tuning the energy of the island state across the band structure of the modulated wires. We demonstrate routing of ps polariton pulses using an optical control beam which controls the energy of the island quantum states, thanks to polariton-exciton interactions.

  15. All-optical flip-flop and control methods thereof

    DOEpatents

    Maywar, Drew; Agrawal, Govind P.

    2010-03-23

    Embodiments of the invention pertain to remote optical control of holding beam-type, optical flip-flop devices, as well as to the devices themselves. All-optical SET and RE-SET control signals operate on a cw holding beam in a remote manner to vary the power of the holding beam between threshold switching values to enable flip-flop operation. Cross-gain modulation and cross-polarization modulation processes can be used to change the power of the holding beam.

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

    NASA Astrophysics Data System (ADS)

    Ahmed, Tarek; Noro, Osamu; Nakaoka, Mutsuo

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

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

    PubMed

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

    2015-06-28

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

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

    PubMed

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

    2014-08-15

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

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

    PubMed

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

    2015-12-01

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

  20. Pilot-in-the-Loop Evaluation of a Yaw Rate to Throttle Feedback Control with Enhanced Engine Response

    NASA Technical Reports Server (NTRS)

    Litt, Jonathan S.; Guo, Ten-Huei; Sowers, T. Shane; Chicatelli, Amy K.; Fulton, Christopher E.; May, Ryan D.; Owen, A. Karl

    2012-01-01

    This paper describes the implementation and evaluation of a yaw rate to throttle feedback system designed to replace a damaged rudder. It can act as a Dutch roll damper and as a means to facilitate pilot input for crosswind landings. Enhanced propulsion control modes were implemented to increase responsiveness and thrust level of the engine, which impact flight dynamics and performance. Piloted evaluations were performed to determine the capability of the engines to substitute for the rudder function under emergency conditions. The results showed that this type of implementation is beneficial, but the engines' capability to replace the rudder is limited.

  1. Derivation of three closed loop kinematic velocity models using normalized quaternion feedback for an autonomous redundant manipulator with application to inverse kinematics

    SciTech Connect

    Unseren, M.A.

    1993-04-01

    The report discusses the orientation tracking control problem for a kinematically redundant, autonomous manipulator moving in a three dimensional workspace. The orientation error is derived using the normalized quaternion error method of Ickes, the Luh, Walker, and Paul error method, and a method suggested here utilizing the Rodrigues parameters, all of which are expressed in terms of normalized quaternions. The analytical time derivatives of the orientation errors are determined. The latter, along with the translational velocity error, form a dosed loop kinematic velocity model of the manipulator using normalized quaternion and translational position feedback. An analysis of the singularities associated with expressing the models in a form suitable for solving the inverse kinematics problem is given. Two redundancy resolution algorithms originally developed using an open loop kinematic velocity model of the manipulator are extended to properly take into account the orientation tracking control problem. This report furnishes the necessary mathematical framework required prior to experimental implementation of the orientation tracking control schemes on the seven axis CESARm research manipulator or on the seven-axis Robotics Research K1207i dexterous manipulator, the latter of which is to be delivered to the Oak Ridge National Laboratory in 1993.

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

    PubMed

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

    2015-05-10

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

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

    PubMed

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

    2016-02-10

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

  4. All-optical biomolecular parallel logic gates with bacteriorhodopsin.

    PubMed

    Sharma, Parag; Roy, Sukhdev

    2004-06-01

    All-optical two input parallel logic gates with bacteriorhodopsin (BR) protein have been designed based on nonlinear intensity-induced excited-state absorption. Amplitude modulation of a continuous wave (CW) probe laser beam transmission at 640 nm corresponding to the peak absorption of O intermediate state through BR, by a modulating CW pump laser beam at 570 nm corresponding to the peak absorption of initial BR state has been analyzed considering all six intermediate states in its photocycle using the rate equation approach. The transmission characteristics have been shown to exhibit a dip, which is sensitive to normalized small-signal absorption coefficient (beta), rate constants of O and N intermediate states and absorption of the O state at 570 nm. There is an optimum value of beta for a given pump intensity range for which maximum modulation can be achieved. It is shown that 100% modulation can be achieved if the initial state of BR does not absorb the probe beam. The results have been used to design low-power all-optical parallel NOT, AND, OR, XNOR, and the universal NAND and NOR logic gates for two cases: 1) only changing the output threshold and 2) considering a common threshold with different beta values. PMID:15382746

  5. Vibration modal analysis using all-optical photorefractive processing

    SciTech Connect

    Hale, T.; Telschow, K.

    1996-12-31

    A new experimental method for vibration modal analysis based on all- optical photorefractive processing is presented. The method utilizes an optical lock-in approach to measure phase variations in light scattered from optically rough, continuously vibrating surfaces. In this four-wave mixing technique, all-optical processing refers to mixing the object beam containing the frequency modulation due to vibration with a single frequency modulated pump beam in the photorefractive medium that processes the modulated signals. This allows for simple detection of the conjugate wavefront image at a CCD. The conjugate intensity is shown to be a function of the first-order ordinary Bessel function and linearly dependent on the vibration displacement induced phase. Furthermore, the results demonstrate the unique capabilities of the optical lock-in vibration detection technique to measure vibration signals with very narrow bandwidth (< 1 Hz) and high displacement sensitivity (sub-Angstrom). This narrow bandwidth detection can be achieved over a wide frequency range from the photorefractive response limit to the reciprocal of the photoinduced carrier recombination time. The technique is applied to determine the modal characteristics of a rigidly clamped circular disc from 10 kHz to 100 kHz.

  6. All-optical nonlinear plasmonic ring resonator switches

    NASA Astrophysics Data System (ADS)

    Nozhat, N.; Granpayeh, N.

    2014-11-01

    In this paper, all-optical nonlinear plasmonic ring resonator (PRR) switches containing 90o sharp and smooth bends have been proposed and numerically analyzed by the finite-difference time-domain method. Kerr nonlinear self-phase modulation (SPM) and cross-phase modulation (XPM) effects on the switching performance of the device have been studied. By applying a high-power lightwave, the signal can switch from one port to the other port due to the ON/OFF resonant states of the ring. We have shown that by utilizing the XPM effect, the output power ratio is improved by a factor of 2.5 and the required switching power is 31% of that of the case with only the SPM effect. Moreover, by utilizing sharp bend square-shaped ring resonators, the switching power is 10.4% lower than that of the smooth ones. The nonlinear PRR switches are suitable for application in photonic-integrated circuits as all-optical switches because of their nanoscale size and low required switching power.

  7. Rapidly reconfigurable all-optical universal logic gate

    DOEpatents

    Goddard, Lynford L.; Bond, Tiziana C.; Kallman, Jeffrey S.

    2010-09-07

    A new reconfigurable cascadable all-optical on-chip device is presented. The gate operates by combining the Vernier effect with a novel effect, the gain-index lever, to help shift the dominant lasing mode from a mode where the laser light is output at one facet to a mode where it is output at the other facet. Since the laser remains above threshold, the speed of the gate for logic operations as well as for reprogramming the function of the gate is primarily limited to the small signal optical modulation speed of the laser, which can be on the order of up to about tens of GHz. The gate can be rapidly and repeatedly reprogrammed to perform any of the basic digital logic operations by using an appropriate analog optical or electrical signal at the gate selection port. Other all-optical functionality includes wavelength conversion, signal duplication, threshold switching, analog to digital conversion, digital to analog conversion, signal routing, and environment sensing. Since each gate can perform different operations, the functionality of such a cascaded circuit grows exponentially.

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

    PubMed Central

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

    2003-01-01

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

  9. Thermally induced all-optical inverter and dynamic hysteresis loops in graphene oxide dispersions.

    PubMed

    Melle, Sonia; Calderón, Oscar G; Egatz-Gómez, Ana; Cabrera-Granado, E; Carreño, F; Antón, M A

    2015-11-01

    We experimentally study the temporal dynamics of amplitude-modulated laser beams propagating through a water dispersion of graphene oxide sheets in a fiber-to-fiber U-bench. Nonlinear refraction induced in the sample by thermal effects leads to both phase reversing of the transmitted signals and dynamic hysteresis in the input-output power curves. A theoretical model including beam propagation and thermal lensing dynamics reproduces the experimental findings. PMID:26560566

  10. Fast flux locked loop

    DOEpatents

    Ganther, Jr., Kenneth R.; Snapp, Lowell D.

    2002-09-10

    A flux locked loop for providing an electrical feedback signal, the flux locked loop employing radio-frequency components and technology to extend the flux modulation frequency and tracking loop bandwidth. The flux locked loop of the present invention has particularly useful application in read-out electronics for DC SQUID magnetic measurement systems, in which case the electrical signal output by the flux locked loop represents an unknown magnetic flux applied to the DC SQUID.

  11. Experimental validation of optical layer performance monitoring using an all-optical network testbed

    NASA Astrophysics Data System (ADS)

    Vukovic, Alex; Savoie, Michel J.; Hua, Heng

    2004-11-01

    Communication transmission systems continue to evolve towards higher data rates, increased wavelength densities, longer transmission distances and more intelligence. Further development of dense wavelength division multiplexing (DWDM) and all-optical networks (AONs) will demand ever-tighter monitoring to assure a specified quality of service (QoS). Traditional monitoring methods have been proven to be insufficient. Higher degree of self-control, intelligence and optimization for functions within next generation networks require new monitoring schemes to be developed and deployed. Both perspective and challenges of performance monitoring, its techniques, requirements and drivers are discussed. It is pointed out that optical layer monitoring is a key enabler for self-control of next generation optical networks. Aside from its real-time feedback and the safeguarding of neighbouring channels, optical performance monitoring ensures the ability to build and control complex network topologies while maintaining an efficiently high QoS. Within an all-optical network testbed environment, key performance monitoring parameters are identified, assessed through real-time proof-of-concept, and proposed for network applications for the safeguarding of neighbouring channels in WDM systems.

  12. All-optical 20 Gbit/s NRZ-DPSK demodulation and clock recovery

    NASA Astrophysics Data System (ADS)

    Wang, Fei; Zhang, Xinliang; Dong, Jianji; Yu, Yu; Huang, Xi

    2008-11-01

    All-optical clock recovery (CR) from 20-Gbit/s nonreturn-to-zero differential phase-shift-keying (NRZ-DPSK) signal is demonstrated experimentally by using Polarization-Maintaining Fiber Loop Mirror Filter and semiconductor optical amplifier (SOA) fiber ring laser. Only by adjusting polarization controller (PC), NRZ-DPSK signal were conveniently and fast converted to pseudo return-to-zero (PRZ) signal via PMF-LMF. Then the PRZ signal is injected into the SOA fiber laser for CR. The recovered clock signals with the extinction ratio of 10 dB and the root-mean-square timing jitter of 850 fs is achieved under 231-1 pseudorandom binary sequence NRZ-DPSK signals measurement.

  13. New approach to fault-tolerant routing in all-optical networks

    NASA Astrophysics Data System (ADS)

    Sengupta, Abhijit; Alluri, Shailesh; Bandyopadhyay, Subir; Jaekel, Arunita

    1999-08-01

    Fault management in WDM routed all-optical networks has mostly been addressed either by automatic protection switching or through loop-back recovery. These schemes are designed for managing single fault occurrence and generalization method to handle multiple faults are not known. Conventional routing schemes are static in nature (where the routers are programmed to realize the lightpaths between the end-nodes) and hence a fault management scheme needs to find a fault-free path between end-nodes using the settings of the routers. This paper considers the principle of survival route graphs to construct fault-free paths between end-nodes. As a result, the fault avoiding route between two end-nodes might be a multihop route in which the number of hops are limited to reduce the communication delay. The performance degradations of the network because of fault occurrence are studied through simulations and measured in terms of blocking probability and communication delay.

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

    PubMed Central

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

    2015-01-01

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

  15. Graphene based All-Optical Spatial Terahertz Modulator

    PubMed Central

    Wen, Qi-Ye; Tian, Wei; Mao, Qi; Chen, Zhi; Liu, Wei-Wei; Yang, Qing-Hui; Sanderson, Matthew; Zhang, Huai-Wu

    2014-01-01

    We demonstrate an all-optical terahertz modulator based on single-layer graphene on germanium (GOG), which can be driven by a 1.55 μm CW laser with a low-level photodoping power. Both the static and dynamic THz transmission modulation experiments were carried out. A spectrally wide-band modulation of the THz transmission is obtained in a frequency range from 0.25 to 1 THz, and a modulation depth of 94% can be achieved if proper pump power is applied. The modulation speed of the modulator was measured to be ~200 KHz using a 340 GHz carrier. A theoretical model is proposed for the modulator and the calculation results indicate that the enhanced THz modulation is mainly due to the third order nonlinear effect in the optical conductivity of the graphene monolayer. PMID:25491194

  16. All-optical generation of surface plasmons in graphene

    NASA Astrophysics Data System (ADS)

    Constant, T. J.; Hornett, S. M.; Chang, D. E.; Hendry, E.

    2016-02-01

    Surface plasmons in graphene offer a compelling route to many useful photonic technologies. As a plasmonic material, graphene offers several intriguing properties, such as excellent electro-optic tunability, crystalline stability, large optical nonlinearities and extremely high electromagnetic field concentration. As such, recent demonstrations of surface plasmon excitation in graphene using near-field scattering of infrared light have received intense interest. Here we present an all-optical plasmon coupling scheme which takes advantage of the intrinsic nonlinear optical response of graphene. Free-space, visible light pulses are used to generate surface plasmons in a planar graphene sheet using difference frequency wave mixing to match both the wavevector and energy of the surface wave. By carefully controlling the phase matching conditions, we show that one can excite surface plasmons with a defined wavevector and direction across a large frequency range, with an estimated photon efficiency in our experiments approaching 10-5.

  17. All-optical reservoir computer based on saturation of absorption.

    PubMed

    Dejonckheere, Antoine; Duport, François; Smerieri, Anteo; Fang, Li; Oudar, Jean-Louis; Haelterman, Marc; Massar, Serge

    2014-05-01

    Reservoir computing is a new bio-inspired computation paradigm. It exploits a dynamical system driven by a time-dependent input to carry out computation. For efficient information processing, only a few parameters of the reservoir needs to be tuned, which makes it a promising framework for hardware implementation. Recently, electronic, opto-electronic and all-optical experimental reservoir computers were reported. In those implementations, the nonlinear response of the reservoir is provided by active devices such as optoelectronic modulators or optical amplifiers. By contrast, we propose here the first reservoir computer based on a fully passive nonlinearity, namely the saturable absorption of a semiconductor mirror. Our experimental setup constitutes an important step towards the development of ultrafast low-consumption analog computers. PMID:24921786

  18. All-optical optoacoustic microscope based on wideband pulse interferometry.

    PubMed

    Wissmeyer, Georg; Soliman, Dominik; Shnaiderman, Rami; Rosenthal, Amir; Ntziachristos, Vasilis

    2016-05-01

    Optical and optoacoustic (photoacoustic) microscopy have been recently joined in hybrid implementations that resolve extended tissue contrast compared to each modality alone. Nevertheless, the application of the hybrid technique is limited by the requirement to combine an optical objective with ultrasound detection collecting signal from the same micro-volume. We present an all-optical optoacoustic microscope based on a pi-phase-shifted fiber Bragg grating (π-FBG) with coherence-restored pulsed interferometry (CRPI) used as the interrogation method. The sensor offers an ultra-small footprint and achieved higher sensitivity over piezoelectric transducers of similar size. We characterize the spectral bandwidth of the ultrasound detector and interrogate the imaging performance on phantoms and tissues. We show the first optoacoustic images of biological specimen recorded with π-FBG sensors. We discuss the potential uses of π-FBG sensors based on CRPI. PMID:27128047

  19. High-contrast, all-optical switching in bacteriorhodopsin films

    NASA Astrophysics Data System (ADS)

    Banyal, Ravinder Kumar; Raghavendra Prasad, B.

    2005-09-01

    We report experiments with nonlinear-absorption-based, high-contrast, all-optical switching in photochromic bacteriorhodopsin (BR) films. The switching action is accomplished by control of the transmission of a weak probe beam through a BR sample with the help of strong pump beam illumination at 532 nm wavelength. We found that the switching properties of BR films depend on several experimentally controllable parameters such as probe wavelength, pump beam intensity, and excitation rate. A comparative study of the switching behavior and other parameters of practical use was carried out at three probe wavelengths (543, 594, and 633 nm) and various beam powers and pump excitation rates. The results are presented for commercially available wild-type and D96N variant BR films.

  20. High-contrast, all-optical switching in bacteriorhodopsin films.

    PubMed

    Banyal, Ravinder Kumar; Prasad, B Raghavendra

    2005-09-10

    We report experiments with nonlinear-absorption-based, high-contrast, all-optical switching in photochromic bacteriorhodopsin (BR) films. The switching action is accomplished by control of the transmission of a weak probe beam through a BR sample with the help of strong pump beam illumination at 532 nm wavelength. We found that the switching properties of BR films depend on several experimentally controllable parameters such as probe wavelength, pump beam intensity, and excitation rate. A comparative study of the switching behavior and other parameters of practical use was carried out at three probe wavelengths (543, 594, and 633 nm) and various beam powers and pump excitation rates. The results are presented for commercially available wild-type and D96N variant BR films. PMID:16161665

  1. Generalized model for all-optical light modulation in bacteriorhodopsin

    NASA Astrophysics Data System (ADS)

    Roy, Sukhdev; Singh, C. P.; Reddy, K. P. J.

    2001-10-01

    We present a generalized model for the photochemical cycle of bacteriorhodopsin (bR) protein molecule. Rate equations have been solved for the detailed light-induced processes in bR for its nine states: B→K↔L↔MI→MII↔N↔O↔P→Q→B. The complete steady-state intensity-induced population densities in various states of the molecule have been computed to obtain a general, exact, and analytical expression for the nonlinear absorption coefficient for multiple modulation pump laser beams. All-optical light modulation of different probe laser beam transmissions by intensity induced population changes due to one and two modulation laser beams has been analyzed. The proposed model has been shown to accurately model experimental results.

  2. Production and all-optical deceleration of molecular beams

    NASA Astrophysics Data System (ADS)

    Chen, Gary; Jayich, Andrew; Long, Xueping; Ransford, Anthony; Campbell, Wesley

    2015-05-01

    Ultracold molecules open up new opportunities in many areas of study, including many-body physics, quantum chemistry, quantum information, and precision measurements. Current methods cannot easily address the spontaneous decay of molecules into dark states without an amalgam of repump lasers. We present an alternative method to produce cold molecules. A cryogenic buffer gas beam (CBGB) is used to create an intense, slow, cold source of molecules. By using a CBGB for the production, we can quench vibrational modes that cannot be addressed with optical methods. This is then followed by an all-optical scheme using a single ultra-fast laser to decelerate the molecules and a continuous wave laser to cool the species. We have started experiments with strontium monohydride (SrH), but the proposed method should be applicable to a wide range of molecular species.

  3. Self-organized plasmonic metasurfaces for all-optical modulation

    NASA Astrophysics Data System (ADS)

    Della Valle, G.; Polli, D.; Biagioni, P.; Martella, C.; Giordano, M. C.; Finazzi, M.; Longhi, S.; Duò, L.; Cerullo, G.; Buatier de Mongeot, F.

    2015-06-01

    We experimentally demonstrate a self-organized metasurface with a polarization dependent transmittance that can be dynamically controlled by optical means. The configuration consists of tightly packed plasmonic nanowires with a large dispersion of width and height produced by the defocused ion-beam sputtering of a thin gold film supported on a silica glass. Our results are quantitatively interpreted according to a theoretical model based on the thermomodulational nonlinearity of gold and a finite-element numerical analysis of the absorption and scattering cross-sections of the nanowires. We found that the polarization sensitivity of the metasurface can be strongly enhanced by pumping with ultrashort laser pulses, leading to potential applications in ultrafast all-optical modulation and switching of light.

  4. Bandwidth analysis of all-optical turbo-switch

    NASA Astrophysics Data System (ADS)

    Zhou, Peng; Yang, Xuelin; Hu, Xiaonan; Hu, Weisheng

    2015-01-01

    We propose and develop a frequency-domain model to analyze the bandwidth of all-optical turbo-switch. The model has taken the spatial inhomogeneity of semiconductor optical amplifier (SOA) into consideration for the first time. The simulations based on the model show that the 3-dB bandwidth of turbo-switch could reach up to ~270 GHz when the second SOA is oversaturated. However, the overshoot will be higher, which may result in the distortion of the output signal. There is a trade-off between the bandwidth and the flatness of frequency response characteristics for turbo-switch operation. In addition, the optimum position of the delay-interferometer (DI) is investigated, showing that the level of the overshoot is relatively lower if the DI is placed between the two SOAs.

  5. Microscopic model for all optical switching in ferromagnets

    NASA Astrophysics Data System (ADS)

    Cornelissen, T. D.; Córdoba, R.; Koopmans, B.

    2016-04-01

    The microscopic mechanism behind the all optical switching (AOS) in ferromagnets has triggered intense scientific debate. Here, the microscopic three-temperature model is utilized to describe AOS in a perpendicularly magnetized ferromagnetic Co/Pt system. We demonstrate that AOS in such a ferromagnet can be explained with the Inverse Faraday Effect (IFE). The influence of the strength and lifetime of the IFE induced field pulse on the switching process are investigated. We found that because of strong spin-orbit coupling, the minimal lifetime of the IFE needed to obtain switching is of the order of 0.1 ps, which is shorter than previously assumed. Moreover, spatial images of the domain pattern after AOS in Co/Pt, as well as their dependence on applying an opposite magnetic field, are qualitatively reproduced.

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2014-06-01

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

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

    PubMed

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

    2014-01-01

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

  9. All-optical wavelength conversion for mode division multiplexed superchannels.

    PubMed

    Gong, Jiaxin; Xu, Jing; Luo, Ming; Li, Xiang; Qiu, Ying; Yang, Qi; Zhang, Xinliang; Yu, Shaohua

    2016-04-18

    We report in this work the first all-optical wavelength conversion (AOWC) of a mode division multiplexed (MDM) superchannel consisting of 2N modes by dividing the superchannel into N single-mode (SM) tributaries, wavelength converting N SM signals using well developed SM-AOWC techniques, and finally combining the N SM tributaries back to an MDM superchannel at the converted wavelength, inspired by the idea of using SM filtering techniques to filter multimode signals in astronomy. The conversions between multimode and SM are realized by 3D laser-writing photonic lanterns and SM-AOWCs are realized based on polarization insensitive four wave mixing (FWM) configuration in N semiconductor optical amplifiers (SOAs). As a proof of concept demonstration, the conversion of a 6-mode MDM superchannel with each mode modulated with orthogonal frequency division multiplexed (OFDM) quadrature phase-shift keying (QPSK)/16 quadrature amplitude modulation (QAM) signals is demonstrated in this work, indicating that the scheme is transparent to data format, polarization and compatible with multi-carrier signals. Data integrity of the converted superchannel has been verified by using coherent detection and digital signal processing (DSP). Bit error rates (BERs) below the forward error correction (FEC) hard limit (3.8 × 10-3) have been obtained for QPSK modulation at a net bitrate of 104.2 Gbit/s and BERs below the soft decision FEC threshold (1.98 × 10-2) have been achieved for 16-QAM format, giving a total aggregate bit rate of 185.8 Gbit/s when taking 20% coding overhead into account. Add and drop functionalities that usually come along with wavelength conversion in flexible network nodes have also been demonstrated. The working conditions of the SOAs, especially the pump and signal power levels, are critical for the quality of the converted signal and have been thoroughly discussed. The impact of imbalanced FWM conversion efficiency among different SM

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

    PubMed Central

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

    2015-01-01

    Purpose Hepatocyte growth factor (HGF)/Met signaling plays critical roles in pancreatic ductal adenocarcinoma (PDA) development and progression and is considered a potential therapeutic target for this disease. However, the mechanism of aberrant activation of HGF/Met signaling and resistance to Met inhibition in PDA remains unclear. Experimental Design The mechanistic role of cross-talk between Forkhead box M1 (FOXM1) and HGF/Met signaling in promotion of PDA growth and resistance to Met inhibition was examined using cell culture, molecular biology and mouse models; and the relevance of our experimental and mechanistic findings were validated using human PDA tissues. Results Met was markedly overexpressed in both PDA cell lines and pancreatic tumor specimens, and the expression of Met correlated directly with that of FOXM1 in human tumor specimens. Mechanistically, FOXM1 bound to the promoter region of the Met gene and transcriptionally increased the expression of Met. Increased expression of FOXM1 enhanced the activation of HGF/Met signaling and its downstream pathways, including RAS/extracellular signal-regulated kinase 1/2, phosphoinositide 3-kinase/AKT, and signal transducer and activator of transcription 3. Furthermore, activation of HGF/Met signaling increased the expression and transcriptional activity of FOXM1, and the cross-talk between FOXM1 and HGF/Met signaling promoted PDA growth and resistance to Met inhibition. Conclusions Collectively, our findings identified a positive feedback loop formed by FOXM1 and HGF/Met and revealed that this loop is a potentially effective therapeutic target for PDA. PMID:26876216

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

    MicroRNA array analysis revealed that miR-217 expression was decreased in anti-cancer drug-resistant Malme3MR cancer cells. CAGE, a cancer/testis antigen, was predicted as a target of miR-217. Luciferase activity and ChIP assays revealed a negative feedback relationship between CAGE and miR-217. miR-217 and CAGE oppositely regulated the response to anti-cancer drugs such as taxol, gefitinib and trastuzumab, an inhibitor of HER2. miR-217 negatively regulated the tumorigenic, metastatic, angiogenic, migration and invasion potential of cancer cells. The xenograft of Malme3MR cells showed an increased expression of pEGFRY845. CAGE and miR-217 inhibitor regulated the expression of pEGFRY845. CAGE showed interactions with EGFR and HER2 and regulated the in vivo sensitivity to trastuzumab. The down-regulation of EGFR or HER2 enhanced the sensitivity to anti-cancer drugs. CAGE showed direct regulation of HER2 and was necessary for the interaction between EGFR and HER2 in Malme3MR cells. miR-217 inhibitor induced interactions of CAGE with EGFR and HER2 in Malme3M cells. The inhibition of EGFR by CAGE-binding GTGKT peptide enhanced the sensitivity to gefitinib and trastuzumab and prevented interactions of EGFR with CAGE and HER2. Our results show that miR-217-CAGE feedback loop serves as a target for overcoming resistance to various anti-cancer drugs, including EGFR and HER2 inhibitors. PMID:26863629

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

    NASA Astrophysics Data System (ADS)

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

    2015-10-01

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

  14. All-optical nonlinear holographic correlation using bacteriorhodopsin films

    NASA Astrophysics Data System (ADS)

    Thoma, Ralph; Dratz, Michael; Hampp, Norbert

    1995-05-01

    Films made of the halobacterial photochrome bacteriorhodopsin (BR) can be used in a number of holographic real-time applications. Their application as active material in a dual-axis joint- Fourier-transform (DAJFT) real-time correlator was shown recently. The BR films have a strong nonlinear intensity dependence on the light-induced absorption and refractive-index changes. Therefore the holographic diffraction efficiency also shows a nonlinear dependence on the writing intensity. We investigate the effect of this nonlinearity on the result of the correlation process in a bacteriorhodopsin-based DAJFT correlator. Numerical models supporting the experimental observations are presented. It was found that the BR film combines the holographic function for most objects with that of a spatial bandpass filter, whose center frequency is tuned by the writing intensity. This results in smaller peak widths and a suppression of the sidelobes. BR films allow the application of this nonlinear behavior in real time to the all-optical correlation process.

  15. All-optical broadband ultrasonography of single cells

    PubMed Central

    Dehoux, T.; Ghanem, M. Abi; Zouani, O. F.; Rampnoux, J.-M.; Guillet, Y.; Dilhaire, S.; Durrieu, M.-C.; Audoin, B.

    2015-01-01

    Cell mechanics play a key role in several fundamental biological processes, such as migration, proliferation, differentiation and tissue morphogenesis. In addition, many diseased conditions of the cell are correlated with altered cell mechanics, as in the case of cancer progression. For this there is much interest in methods that can map mechanical properties with a sub-cell resolution. Here, we demonstrate an inverted pulsed opto-acoustic microscope (iPOM) that operates in the 10 to 100 GHz range. These frequencies allow mapping quantitatively cell structures as thin as 10 nm and resolving the fibrillar details of cells. Using this non-invasive all-optical system, we produce high-resolution images based on mechanical properties as the contrast mechanisms, and we can observe the stiffness and adhesion of single migrating stem cells. The technique should allow transferring the diagnostic and imaging abilities of ultrasonic imaging to the single-cell scale, thus opening new avenues for cell biology and biomaterial sciences. PMID:25731090

  16. All-optical active switching in individual semiconductor nanowires

    NASA Astrophysics Data System (ADS)

    Piccione, Brian; Cho, Chang-Hee; van Vugt, Lambert K.; Agarwal, Ritesh

    2012-10-01

    The imminent limitations of electronic integrated circuits are stimulating intense activity in the area of nanophotonics for the development of on-chip optical components, and solutions incorporating direct-bandgap semiconductors are important in achieving this end. Optical processing of data at the nanometre scale is promising for circumventing these limitations, but requires the development of a toolbox of components including emitters, detectors, modulators, waveguides and switches. In comparison to components fabricated using top-down methods, semiconductor nanowires offer superior surface properties and stronger optical confinement. They are therefore ideal candidates for nanoscale optical network components, as well as model systems for understanding optical confinement. Here, we demonstrate all-optical switching in individual CdS nanowire cavities with subwavelength dimensions through stimulated polariton scattering, as well as a functional NAND gate built from multiple switches. The device design exploits the strong light-matter coupling present in these nanowires, leading to footprints that are a fraction of those of comparable silicon-based dielectric contrast and photonic crystal devices.

  17. All-optical broadband ultrasonography of single cells

    NASA Astrophysics Data System (ADS)

    Dehoux, T.; Ghanem, M. Abi; Zouani, O. F.; Rampnoux, J.-M.; Guillet, Y.; Dilhaire, S.; Durrieu, M.-C.; Audoin, B.

    2015-03-01

    Cell mechanics play a key role in several fundamental biological processes, such as migration, proliferation, differentiation and tissue morphogenesis. In addition, many diseased conditions of the cell are correlated with altered cell mechanics, as in the case of cancer progression. For this there is much interest in methods that can map mechanical properties with a sub-cell resolution. Here, we demonstrate an inverted pulsed opto-acoustic microscope (iPOM) that operates in the 10 to 100 GHz range. These frequencies allow mapping quantitatively cell structures as thin as 10 nm and resolving the fibrillar details of cells. Using this non-invasive all-optical system, we produce high-resolution images based on mechanical properties as the contrast mechanisms, and we can observe the stiffness and adhesion of single migrating stem cells. The technique should allow transferring the diagnostic and imaging abilities of ultrasonic imaging to the single-cell scale, thus opening new avenues for cell biology and biomaterial sciences.

  18. All-optical photoacoustic microscopy using a MEMS scanning mirror

    NASA Astrophysics Data System (ADS)

    Chen, Sung-Liang; Xie, Zhixing; Ling, Tao; Wei, Xunbin; Guo, L. Jay; Wang, Xueding

    2013-03-01

    It has been studied that a potential marker to obtain prognostic information about bladder cancer is tumor neoangiogenesis, which can be quantified by morphometric characteristics such as microvascular density. Photoacoustic microscopy (PAM) can render sensitive three-dimensional (3D) mapping of microvasculature, providing promise to evaluate the neoangiogenesis that is closely related to the diagnosis of bladder cancer. To ensure good image quality, it is desired to acquire bladder PAM images from its inside via the urethra, like conventional cystoscope. Previously, we demonstrated all-optical PAM systems using polymer microring resonators to detect photoacoustic signals and galvanometer mirrors for laser scanning. In this work, we build a miniature PAM system using a microelectromechanical systems (MEMS) scanning mirror, demonstrating a prototype of an endoscopic PAM head capable of high imaging quality of the bladder. The system has high resolutions of 17.5 μm in lateral direction and 19 μm in the axial direction at a distance of 5.4 mm. Images of printed grids and the 3D structure of microvasculature in animal bladders ex vivo by the system are demonstrated.

  19. All-optical control of ultrafast photocurrents in unbiased graphene

    PubMed Central

    Obraztsov, Petr A.; Kaplas, Tommi; Garnov, Sergey V.; Kuwata-Gonokami, Makoto; Obraztsov, Alexander N.; Svirko, Yuri P.

    2014-01-01

    Graphene has recently become a unique playground for studying light-matter interaction effects in low-dimensional electronic systems. Being of strong fundamental importance, these effects also open a wide range of opportunities in photonics and optoelectronics. In particular, strong and broadband light absorption in graphene allows one to achieve high carrier densities essential for observation of nonlinear optical phenomena. Here, we make use of strong photon-drag effect to generate and optically manipulate ultrafast photocurrents in graphene at room temperature. In contrast to the recent reports on injection of photocurrents in graphene due to external or built-in electric field effects and by quantum interference, we force the massless charge carriers to move via direct transfer of linear momentum from photons of incident laser beam to excited electrons in unbiased sample. Direction and amplitude of the drag-current induced in graphene are determined by polarization, incidence angle and intensity of the obliquely incident laser beam. We also demonstrate that the irradiation of graphene with two laser beams of the same wavelength offers an opportunity to manipulate the photocurrents in time domain. The obtained all-optical control of the photocurrents opens new routes towards graphene based high-speed and broadband optoelectronic devices. PMID:24500084

  20. Quasi-all-optical network extension for submarine cabled observatories

    NASA Astrophysics Data System (ADS)

    Audo, Frederic; Guegan, Mikael; Quintard, Véronique; Perennou, Andre; Le Bihan, Jean; Auffret, Yves

    2011-04-01

    Submarine cabled networks are designed to collect valuable data in geophysics, geochemistry, biology, or oceanography. Unfortunately, the development of such a network is expensive and needs complex subsea infrastructures. Once in place, a cabled network cannot be easily relocated. The current cost of cables and their installation are one of the major obstacles to these networks deployment. On the one hand, these cables are necessary to provide power supply and communication data, and on the other hand they drastically reduce the possibilities to extend the cabled observatory network in order to reach a closed area of significant interest. This is why, to address this issue, we propose a quasi-all-optical architecture to easily extend multidisciplinary cabled networks or to create a dedicated submarine hydrophone or seismometer network. This solution consists of using only a single fiber optic to transmit both the energy, required to supply the instrument, and the data, exchanged between the shore station or equivalent. In this paper, we present our proposed architecture, and we discuss its feasibility thanks to experimental results.

  1. Rapidly Reconfigurable All-Optical Universal Logic Gates

    SciTech Connect

    Goddard, L L; Kallman, J S; Bond, T C

    2006-06-21

    We present designs and simulations for a highly cascadable, rapidly reconfigurable, all-optical, universal logic gate. We will discuss the gate's expected performance, e.g. speed, fanout, and contrast ratio, as a function of the device layout and biasing conditions. The gate is a three terminal on-chip device that consists of: (1) the input optical port, (2) the gate selection port, and (3) the output optical port. The device can be built monolithically using a standard multiple quantum well graded index separate confinement heterostructure laser configuration. The gate can be rapidly and repeatedly reprogrammed to perform any of the basic digital logic operations by using an appropriate analog electrical or optical signal at the gate selection port. Specifically, the same gate can be selected to execute one of the 2 basic unary operations (NOT or COPY), or one of the 6 binary operations (OR, XOR, AND, NOR, XNOR, or NAND), or one of the many logic operations involving more than two inputs. The speed of the gate for logic operations as well as for reprogramming the function of the gate is primarily limited to the small signal modulation speed of a laser, which can be on the order of tens of GHz. The reprogrammable nature of the universal gate offers maximum flexibility and interchangeability for the end user since the entire application of a photonic integrated circuit built from cascaded universal logic gates can be changed simply by adjusting the gate selection port signals.

  2. All-optical regulation of gene expression in targeted cells

    NASA Astrophysics Data System (ADS)

    Wang, Yisen; He, Hao; Li, Shiyang; Liu, Dayong; Lan, Bei; Hu, Minglie; Cao, Youjia; Wang, Chingyue

    2014-06-01

    Controllable gene expression is always a challenge and of great significance to biomedical research and clinical applications. Recently, various approaches based on extra-engineered light-sensitive proteins have been developed to provide optogenetic actuators for gene expression. Complicated biomedical techniques including exogenous genes engineering, transfection, and material delivery are needed. Here we present an all-optical method to regulate gene expression in targeted cells. Intrinsic or exogenous genes can be activated by a Ca2+-sensitive transcription factor nuclear factor of activated T cells (NFAT) driven by a short flash of femtosecond-laser irradiation. When applied to mesenchymal stem cells, expression of a differentiation regulator Osterix can be activated by this method to potentially induce differentiation of them. A laser-induced ``Ca2+-comb'' (LiCCo) by multi-time laser exposure is further developed to enhance gene expression efficiency. This noninvasive method hence provides an encouraging advance of gene expression regulation, with promising potential of applying in cell biology and stem-cell science.

  3. Flexible all-optical frequency allocation of OFDM subcarriers.

    PubMed

    Lowery, Arthur James; Schröder, Jochen; Du, Liang B

    2014-01-13

    We investigate the underlying mechanism that allows OFDM subcarriers in an all-optical OFDM system to be assigned to any optical frequency using an optical filter, even if that frequency is not generated by the comb-line source feeding the filters. We confirm our analysis using simulations, and present experimental results from a 252-subcarrier system that uses a mode-locked laser (MLL) as the comb source and a wavelength selective switch. The experimental results show that there is no correlation between the programmed frequency offset between a subcarrier and nearest comb line, and the received signal quality. Thus, subcarriers could be inserted into unused portions of an optical transmission system's spectrum without restriction on their particular center frequencies. Any percentage of cyclic prefix can be added to the OFDM symbol simply by reprogramming the optical filter to give wider subcarrier frequency spacing than the comb line spacing, which is useful for tailoring the CP to the dispersion of various optical transmission paths, to maximize the spectral efficiency. Finally, the MLL's center frequency need not be locked to a system reference. PMID:24515064

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2012-07-01

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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    SciTech Connect

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

    2010-05-28

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2015-05-01

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

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-01-01

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

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

    PubMed

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

    2014-11-30

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

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

    NASA Astrophysics Data System (ADS)

    Lin, Chun-Ju; Lin, Gong-Ru

    2013-04-01

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

  20. All-Optical Ultrasound Transducers for High Resolution Imaging

    NASA Astrophysics Data System (ADS)

    Sheaff, Clay Smith

    High frequency ultrasound (HFUS) has increasingly been used within the past few decades to provide high resolution (< 200 mum) imaging in medical applications such as endoluminal imaging, intravascular imaging, ophthalmology, and dermatology. The optical detection and generation of HFUS using thin films offers numerous advantages over traditional piezoelectric technology. Circumvention of an electronic interface with the device head is one of the most significant given the RF noise, crosstalk, and reduced capacitance that encumbers small-scale electronic transducers. Thin film Fabry-Perot interferometers - also known as etalons - are well suited for HFUS receivers on account of their high sensitivity, wide bandwidth, and ease of fabrication. In addition, thin films can be used to generate HFUS when irradiated with optical pulses - a method referred to as Thermoelastic Ultrasound Generation (TUG). By integrating a polyimide (PI) film for TUG into an etalon receiver, we have created for the first time an all-optical ultrasound transducer that is both thermally stable and capable of forming fully sampled 2-D imaging arrays of arbitrary configuration. Here we report (1) the design and fabrication of PI-etalon transducers; (2) an evaluation of their optical and acoustic performance parameters; (3) the ability to conduct high-resolution imaging with synthetic 2-D arrays of PI-etalon elements; and (4) work towards a fiber optic PI-etalon for in vivo use. Successful development of a fiber optic imager would provide a unique field-of-view thereby exposing an abundance of prospects for minimally-invasive analysis, diagnosis, and treatment of disease.

  1. Amorphous silicon thin film for all-optical micromodulator

    NASA Astrophysics Data System (ADS)

    Nigro, Maria Arcangela M.; Cantore, Francesca; Della Corte, Francesco Giuseppe; Summonte, Caterina

    2003-04-01

    Photoinduced absorption by VIS radiation in a-Si:H has been studied in-guide, in order to realise a novel all-optical waveguide micromodulator for application at 1.3 and 1.55 μm fiber communication wavelengths. In a-Si:H the photoinduced effects and the NIR absorption both involve dangling bonds states. The density of these states, deep in the gap, can be varied with doping. Therefore three waveguide prototypes have been fabricated by Plasma Enhanced Chemical Vapour Deposition on a silicon wafer. Their structure consist of a a-Si:H/SiO2 stack where the a-Si:H cores have different doping. The upper cladding is air. Optical measures on the core materials and signal transmission analysis in-guide at bit rates up to 200 kBit/s have been carried out. The excitation source of the VIS pump system for in-guide analysis consisted of simple, low cost AlInGaP LED"s controlled by a pulse generator. The pump and probe measures have been performed with different pump wavelengths and by varying the illumination intensity. LED"s with wavelengths of 644, 612, 590 and 571 nm have been alternatively used. For each pump wavelength, the light intensity was varied between 0,15 and 0,85 mW/mm2. The results confirms that the optical modulation of the NIR signal enhances at high doping levels and for longer wavelengths. The modulation speed is probably limited by recombination phenomena.

  2. Phase-coherent all-optical frequency division by three

    SciTech Connect

    Lee, Dong-Hoon; Klein, Marvin E.; Meyn, Jan-Peter; Wallenstein, Richard; Gross, Petra; Boller, Klaus-Jochen

    2003-01-01

    The properties of all-optical phase-coherent frequency division by 3, based on a self-phase-locked continuous-wave (cw) optical parametric oscillator (OPO), are investigated theoretically and experimentally. The frequency to be divided is provided by a diode laser master-oscillator power-amplifier system operated at a wavelength of 812 nm and used as the pump source of the OPO. Optical self-phase-locking of the OPO signal and idler waves is achieved by mutual injection locking of the signal wave and the intracavity frequency-doubled idler wave. The OPO process and the second-harmonic generation of the idler wave are simultaneously phase matched through quasi-phase-matching using two periodically poled sections of different period manufactured within the same LiNbO{sub 3} crystal. An optical self-phase-locking range of up to 1 MHz is experimentally observed. The phase coherence of frequency division by three is measured via the phase stability of an interference pattern formed by the input and output waves of the OPO. The fractional frequency instability of the divider is measured to be smaller than 7.6x10{sup -14} for a measurement time of 10 s (resolution limited). The self-phase-locking characteristics of the cw OPO are theoretically investigated by analytically solving the coupled field equations in the steady-state regime. For the experimental parameters of the OPO, the calculations predict a locking range of 1.3 MHz and a fractional frequency instability of 1.6x10{sup -15}, in good agreement with the experimental results.

  3. Description of all-optical network test bed and applications

    NASA Astrophysics Data System (ADS)

    Marquis, Douglas; Castagnozzi, Daniel M.; Hemenway, B. R.; Parikh, Salil A.; Stevens, Mark L.; Swanson, Eric A.; Thomas, Robert E.; Ozveren, C.; Kaminow, Ivan P.

    1995-12-01

    We describe an all-optical network testbed deployed in the Boston metropolitan area, and some of the experimental applications running over the network. The network was developed by a consortium of AT&T Bell Laboratories, Digital Equipment Corporation, and Massachusetts Institute of Technology under a grant from ARPA. The network is an optical WDM system organized as a hierarchy consisting of local, metropolitan, and wide area nodes that support optical broadcast and routing modes. Frequencies are shared and reused to enhance network scalability. Electronic access is provided through optical terminals that support multiple services having data rates between 10 Mbps/user and 10 Gbps/user. Novel components used to implement the network include fast-tuning 1.5 micrometers distributed Bragg reflector lasers, passive wavelength routers, and broadband optical frequency converters. An overlay control network implemented at 1.3 micrometers allows reliable out-of-band control and standardized network management of all network nodes. We have created interfaces between the AON and commercially available electronic circuit-switched and packet-switched networks. We will report on network applications that can dynamically allocate optical bandwidth between electronic packet-switches based on the offered load presented by users, without requiring interfaces between users and the AON control system. We will also describe video and telemedicine applications running over the network. We have demonstrated an audio/video codec that is directly interfaced to the optical network, and is capable of transmitting high-rate digitized video signals for broadcast or videoconferencing applications. We have also demonstrated a state-of-the-art radiological workstation that uses the AON to transport 2000 X 2000 X 16 bit images from a remote image server.

  4. All-optical controllable channel-drop filters in two-dimensional square-lattice photonic crystals

    NASA Astrophysics Data System (ADS)

    Fasihi, K.

    2016-05-01

    A novel all-optical controllable channel-drop filter in photonic crystals (PC) of square lattice is presented. We show that using a resonant-cavity-based add-drop filter with a wavelength-selective reflection feedback and a single-control switching module which is based on nonlinear PC microcavities, the dropped channel can be routed to the drop port or returned to the bus waveguide. Using the temporal coupled-mode theory and two-dimensional nonlinear finite-difference time-domain method, the performance of the proposed device is investigated and the simulation results show the validity of the proposed design.

  5. All-optical metamaterial modulators: Fabrication, simulation and characterization

    NASA Astrophysics Data System (ADS)

    Ku, Zahyun

    Artificially structured composite metamaterials consist of sub-wavelength sized structures that exhibit unusual electromagnetic properties not found in nature. Since the first experimental verification in 2000, metamaterials have drawn considerable attention because of their broad range of potential applications. One of the most attractive features of metamaterials is to obtain negative refraction, termed left-handed materials or negative-index metamaterials, over a limited frequency band. Negative-index metamaterials at near infrared wavelength are fabricated with circular, elliptical and rectangular holes penetrating through metal/dielectric/metal films. All three negative-index metamaterial structures exhibit similar figure of merit; however, the transmission is higher for the negative-index metamaterial with rectangular holes as a result of an improved impedance match with the substrate-superstrate (air-glass) combination. In general, the processing procedure to fabricate the fishnet structured negative-index metamaterials is to define the hole-size using a polymetric material, usually by lithographically defining polymer posts, followed by deposition of the constitutive materials and dissolution of the polymer (liftoff processing). This processing (fabrication of posts: multi-layer deposition: liftoff) often gives rise to significant sidewall-angle because materials accumulate on the tops of the posts that define the structure, each successive film deposition has a somewhat larger aperture on the bottom metamaterial film, giving rise to a nonzero sidewall-angle and to optical bianisotropy. Finally, we demonstrate a nanometer-scale, sub-picosecond metamaterial device capable of over terabit/second all-optical communication in the near infrared spectrum. We achieve a 600 fs device response by utilizing a regime of sub-picosecond carrier dynamics in amorphous silicon and ˜70% modulation in a path length of only 124 nm by exploiting the strong nonlinearities in

  6. Photonic encryption : modeling and functional analysis of all optical logic.

    SciTech Connect

    Tang, Jason D.; Schroeppel, Richard Crabtree; Robertson, Perry J.

    2004-10-01

    With the build-out of large transport networks utilizing optical technologies, more and more capacity is being made available. Innovations in Dense Wave Division Multiplexing (DWDM) and the elimination of optical-electrical-optical conversions have brought on advances in communication speeds as we move into 10 Gigabit Ethernet and above. Of course, there is a need to encrypt data on these optical links as the data traverses public and private network backbones. Unfortunately, as the communications infrastructure becomes increasingly optical, advances in encryption (done electronically) have failed to keep up. This project examines the use of optical logic for implementing encryption in the photonic domain to achieve the requisite encryption rates. This paper documents the innovations and advances of work first detailed in 'Photonic Encryption using All Optical Logic,' [1]. A discussion of underlying concepts can be found in SAND2003-4474. In order to realize photonic encryption designs, technology developed for electrical logic circuits must be translated to the photonic regime. This paper examines S-SEED devices and how discrete logic elements can be interconnected and cascaded to form an optical circuit. Because there is no known software that can model these devices at a circuit level, the functionality of S-SEED devices in an optical circuit was modeled in PSpice. PSpice allows modeling of the macro characteristics of the devices in context of a logic element as opposed to device level computational modeling. By representing light intensity as voltage, 'black box' models are generated that accurately represent the intensity response and logic levels in both technologies. By modeling the behavior at the systems level, one can incorporate systems design tools and a simulation environment to aid in the overall functional design. Each black box model takes certain parameters (reflectance, intensity, input response), and models the optical ripple and time delay

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

    PubMed

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

    2016-01-01

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

  8. Interrupted E2F1-miR-34c-SCF negative feedback loop by hyper-methylation promotes colorectal cancer cell proliferation

    PubMed Central

    Yang, Shu; Wu, Bo; Sun, Haimei; Ji, Fengqing; Sun, Tingyi; Zhao, Yan; Zhou, Deshan

    2015-01-01

    Tumour suppressor miR-34c deficiency resulted from hyper-methylation in its promoter is believed to be one of the main causes of colorectal cancer (CRC). Till date, miR-34c has been validated as a direct target of p53; but previous evidence suggested other transcription factor(s) must be involved in miR-34c transcription. In the present study, we in the first place identified a core promoter region (−1118 to −883 bp) of pre-miR-34c which was embedded within a hyper-methylated CpG island. Secondly, E2F1 promoted miR-34c transcription by physical interaction with the miR-34c promoter at site −897 to −889 bp. The transcriptional activating effect of E2F1 on miR-34c was in a p53 independent manner but profoundly promoted in the presence of p53 with exposure to 5-aza-2′-deoxycytidine (DAC). Thirdly, stem cell factor (SCF), a miR-34c target, was specifically reduced upon an introduction of E2F1 which lead to suppression of CRC cell proliferation. The E2F1-suppressed cell proliferation was partially abrogated by additional miR-34c inhibitor, indicating that the anti-proliferation effect of E2F1 was probably through activating miR-34c-SCF axis. Finally, SCF/KIT signalling increased E2F1 production by reducing its proteosomal degradation dependent on PI3K/Akt-GSK3β pathway. In conclusion, our results suggested the existence of E2F1-miR-34c-SCF negative feedback loop which was interrupted by the hyper-methylation of miR-34c promoter in CRC cells and increased cell proliferation. PMID:26704889

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

    PubMed Central

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

    2016-01-01

    Accumulating evidence indicates that plant MYB transcription factors participate in defense against pathogen attack, but their regulatory targets and related signaling processes remain largely unknown. Here, we identified a defense-related MYB gene (GhMYB108) from upland cotton (Gossypium hirsutum) and characterized its functional mechanism. Expression of GhMYB108 in cotton plants was induced by Verticillium dahliae infection and responded to the application of defense signaling molecules, including salicylic acid, jasmonic acid, and ethylene. Knockdown of GhMYB108 expression led to increased susceptibility of cotton plants to V. dahliae, while ecotopic overexpression of GhMYB108 in Arabidopsis thaliana conferred enhanced tolerance to the pathogen. Further analysis demonstrated that GhMYB108 interacted with the calmodulin-like protein GhCML11, and the two proteins form a positive feedback loop to enhance the transcription of GhCML11 in a calcium-dependent manner. Verticillium dahliae infection stimulated Ca2+ influx into the cytosol in cotton root cells, but this response was disrupted in both GhCML11-silenced plants and GhMYB108-silenced plants in which expression of several calcium signaling-related genes was down-regulated. Taken together, these results indicate that GhMYB108 acts as a positive regulator in defense against V. dahliae infection by interacting with GhCML11. Furthermore, the data also revealed the important roles and synergetic regulation of MYB transcription factor, Ca2+, and calmodulin in plant immune responses. PMID:26873979

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

    NASA Astrophysics Data System (ADS)

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

    2013-12-01

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

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

    PubMed

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

    2016-04-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2015-01-01

    Human chorionic gonadotropin (hCG) is composed of a common α subunit and a placenta-specific β subunit. Importantly, hCG is highly expressed in the differentiated and multinucleated syncytiotrophoblast, which is formed via trophoblast cell fusion and stimulated by cyclic AMP (cAMP). Although the ubiquitous activating protein 2 (AP2) transcription factors TFAP2A and TFAP2C may regulate hCGβ expression, it remains unclear how cAMP stimulates placenta-specific hCGβ gene expression and trophoblastic differentiation. Here we demonstrated that the placental transcription factor glial cells missing 1 (GCM1) binds to a highly conserved promoter region in all six hCGβ paralogues by chromatin immunoprecipitation-on-chip (ChIP-chip) analyses. We further showed that cAMP stimulates GCM1 and the CBP coactivator to activate the hCGβ promoter through a GCM1-binding site (GBS1), which also constitutes a previously identified AP2 site. Given that TFAP2C may compete with GCM1 for GBS1, cAMP enhances the association between the hCGβ promoter and GCM1 but not TFAP2C. Indeed, the hCG-cAMP-protein kinase A (PKA) signaling pathway also stimulates Ser269 and Ser275 phosphorylation of GCM1, which recruits CBP to mediate GCM1 acetylation and stabilization. Consequently, hCG stimulates the expression of GCM1 target genes, including the fusogenic protein syncytin-1, to promote placental cell fusion. Our study reveals a positive feedback loop between GCM1 and hCG regulating placental hCGβ expression and cell differentiation. PMID:26503785

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

    PubMed

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

    2016-01-01

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

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

    PubMed

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

    2015-03-01

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

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed

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

    2012-07-13

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2016-05-01

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

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

    PubMed Central

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

    2010-01-01

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

  5. All-optical flip-flop based on coupled SOA-PSW

    NASA Astrophysics Data System (ADS)

    Wang, Lina; Wang, Yongjun; Wu, Chen; Wang, Fu

    2016-07-01

    The semiconductor optical amplifier (SOA) has obvious advantages in all-optical signal processing, because of the simple structure, strong non-linearity, and easy integration. A variety of all-optical signal processing functions, such as all-optical wavelength conversion, all-optical logic gates and all-optical sampling, can be completed by SOA. So the SOA has been widespread concerned in the field of all-optical signal processing. Recently, the polarization rotation effect of SOA is receiving considerable interest, and many researchers have launched numerous research work utilizing this effect. In this paper, a new all-optical flip-flop structure using polarization switch (PSW) based on polarization rotation effect of SOA is presented.

  6. Carrier transport in an InGaAs(P)/InP all-optical switching structure

    SciTech Connect

    Knorr, C.; Wilhelm, U.; Ottenwaelder, D.; Scholz, F.; Hangleiter, A.

    1996-12-31

    All-optical switches play a central role in optical computing and optical data processing. SEEDs (self electro-optic effect devices) are one class of devices, which work at low optical power, but need an external electrical feedback. The authors presented a specially designed SCMQW structure, where hole transport is controlled by an additional large heterobarrier. This barrier gives access to steady state escape times by measuring the charge carrier induced field change in the MWQ region. The authors get a minimum value for the hole extraction time over the barrier of several {micro}s at 77 K. At a temperature of 200 K the measured time constants lie below the values, which their rate equation model and the semi-classical model predict, and show a stronger field dependence. This could be accounted for thermally assisted tunneling and contribution of light hole transport, which both reduce the effective barrier height and show a stronger field dependence. Further investigations of the transport times are currently in progress by changing the thickness of the InP barrier and the barrier height of the quaternary material.

  7. An all-optical locking of a semiconductor laser to the atomic resonance line with 1 MHz accuracy.

    PubMed

    Zhang, Xiaogang; Tao, Zhiming; Zhu, Chuanwen; Hong, Yelong; Zhuang, Wei; Chen, Jingbiao

    2013-11-18

    An all-optical locking technique without extra electrical feedback control system for a semiconductor laser has been used in stabilizing the laser frequency to a hyperfine crossover transition of 87Rb 5(2)S(1/2), F = 2 → 5(2)P(3/2), F' = 2, 3 with 1 MHz level accuracy. The optical feedback signal is generated from the narrow-band Faraday anomalous dispersion optical filter (FADOF) with nonlinear saturation effect. The peak transmission of the narrow-band FADOF corresponding to 5(2)S(1/2), F = 2 → 5(2)P(3/2), F' = 2, 3 crossover transition is 18.6 %. The bandwidth is as wide as 38.9 MHz as the laser frequency changes. After locking, the laser frequency fluctuation is reduced to 1.7 MHz. The all-optical laser locking technique can be improved to much higher accuracy with increased external cavity length. The laser we have realized can provide light exactly resonant with atomic transitions used for other atom-light interaction experiments. PMID:24514314

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

    PubMed

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

    2016-06-30

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-05-01

    Several miRNAs have recently been identified to regulate adipocyte or osteoblast differentiation or both. In this study, miR-223 was found to be involved in the reciprocal regulation of adipocyte and osteoblast differentiation. miR-223 was induced in primary cultured mouse marrow stromal cell, mesenchymal line C3H10T1/2 and stromal line ST2 after adipogenic treatment. Conversely, it was reduced in preosteoblast MC3T3-E1 after osteogenic treatment. Supplementing miR-223 levels using synthetic miR-223 mimics significantly suppressed the growth of the C3H10T1/2 and ST2 cells and induced the progenitor cells to fully differentiate into adipocytes, along with induction of adipocyte-specific transcription factors peroxisome proliferator-activated receptor γ, CCAAT/enhancer binding protein-α (C/EBPα), and marker genes aP2 and adipsin. By contrast, depletion of the endogenous miR-223 using synthetic miR-223 inhibitor repressed the progenitor cells to differentiate. The effects of miR-223 on adipocyte formation from ST2 cells were also demonstrated by using lentivirus that overexpresses miR-223. Conversely, supplementing miR-223 blocked ST2 to differentiate into osteoblasts. Fibroblast growth factor receptor 2 (Fgfr2), a critical regulator of osteoblast, was shown to be a direct target of miR-223 by using dual luciferase reporter assay. Knockdown of Fgfr2 in C3H10T1/2 downregulated phosphorylation of ERK1/2 and upregulated expression of C/EBPα and dramatically enhanced the differentiation of the cells into adipocytes. Further investigation of mechanisms that control miR-223 expression demonstrated that C/EBPs induced miR-223 expression through binding to the promoter regions of the miR-223. Taken together, our study provides evidences that miR-223 regulates adipocyte and osteoblast differentiation through a novel C/EBPs/miR-223/FGFR2 regulatory feedback loop. PMID:25641499

  11. All-optical switching of magnetoresistive devices using telecom-band femtosecond laser

    SciTech Connect

    He, Li; Chen, Jun-Yang; Wang, Jian-Ping E-mail: moli@umn.edu; Li, Mo E-mail: moli@umn.edu

    2015-09-07

    Ultrafast all-optical switching of the magnetization of various magnetic systems is an intriguing phenomenon that can have tremendous impact on information storage and processing. Here, we demonstrate all-optical switching of GdFeCo alloy films using a telecom-band femtosecond fiber laser. We further fabricate Hall cross devices and electrically readout all-optical switching by measuring anomalous Hall voltage changes. The use of a telecom laser and the demonstrated all-optical switching of magnetoresistive devices represent the first step toward integration of opto-magnetic devices with mainstream photonic devices to enable novel optical and spintronic functionalities.

  12. All-optical signal processing at 10 GHz using a photonic crystal molecule

    SciTech Connect

    Combrié, Sylvain; Lehoucq, Gaëlle; Junay, Alexandra; De Rossi, Alfredo; Malaguti, Stefania; Bellanca, Gaetano; Trillo, Stefano; Ménager, Loic; Peter Reithmaier, Johann

    2013-11-04

    We report on 10 GHz operation of an all-optical gate based on an Indium Phosphide Photonic Crystal Molecule. Wavelength conversion and all-optical mixing of microwave signals are demonstrated using the 2 mW output of a mode locked diode laser. The spectral separation of the optical pump and signal is crucial in suppressing optical cross-talk.

  13. Global Feedback Simulator

    SciTech Connect

    Carlos Serrano, Lawrence Doolittle

    2015-10-29

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

  14. Global Feedback Simulator

    2015-10-29

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

  15. All-optical control of cardiac excitation: combined high-resolution optogenetic actuation and optical mapping.

    PubMed

    Entcheva, Emilia; Bub, Gil

    2016-05-01

    Cardiac tissue is an excitable system that can support complex spatiotemporal dynamics, including instabilities (arrhythmias) with lethal consequences. While over the last two decades optical mapping of excitation (voltage and calcium dynamics) has facilitated the detailed characterization of such arrhythmia events, until recently, no precise tools existed to actively interrogate cardiac dynamics in space and time. In this work, we discuss the combined use of new methods for space- and time-resolved optogenetic actuation and simultaneous fast, high resolution optical imaging of cardiac excitation waves. First, the mechanisms, limitations and unique features of optically induced responses in cardiomyocytes are outlined. These include the ability to bidirectionally control the membrane potential using depolarizing and hyperpolarizing opsins; the ability to induce prolonged sustained voltage changes; and the ability to control refractoriness and the shape of the cardiac action potential. At the syncytial tissue level, we discuss optogenetically enabled experimentation on cell-cell coupling, alteration of conduction properties and termination of propagating waves by light. Specific attention is given to space- and time-resolved application of optical stimulation using dynamic light patterns to perturb ongoing activation and to probe electrophysiological properties at desired tissue locations. The combined use of optical methods to perturb and to observe the system can offer new tools for precise feedback control of cardiac electrical activity, not available previously with pharmacological and electrical stimulation. These new experimental tools for all-optical electrophysiology allow for a level of precise manipulation and quantification of cardiac dynamics comparable in robustness to the computational setting, and can provide new insights into pacemaking, arrhythmogenesis and suppression or cardioversion. PMID:26857427

  16. Feedback control of waiting times

    NASA Astrophysics Data System (ADS)

    Brandes, Tobias; Emary, Clive

    2016-04-01

    Feedback loops are known as a versatile tool for controlling transport in small systems, which usually have large intrinsic fluctuations. Here we investigate the control of a temporal correlation function, the waiting-time distribution, under active and passive feedback conditions. We develop a general formalism and then specify to the simple unidirectional transport model, where we compare costs of open-loop and feedback control and use methods from optimal control theory to optimize waiting-time distributions.

  17. Feedback control of waiting times.

    PubMed

    Brandes, Tobias; Emary, Clive

    2016-04-01

    Feedback loops are known as a versatile tool for controlling transport in small systems, which usually have large intrinsic fluctuations. Here we investigate the control of a temporal correlation function, the waiting-time distribution, under active and passive feedback conditions. We develop a general formalism and then specify to the simple unidirectional transport model, where we compare costs of open-loop and feedback control and use methods from optimal control theory to optimize waiting-time distributions. PMID:27176250

  18. All-optical logic gates and wavelength conversion via the injection locking of a Fabry-Perot semiconductor laser

    NASA Astrophysics Data System (ADS)

    Harvey, E.; Pochet, M.; Schmidt, J.; Locke, T.; Naderi, N.; Usechak, N. G.

    2013-03-01

    This work investigates the implementation of all-optical logic gates based on optical injection locking (OIL). All-optical inverting, NOR, and NAND gates are experimentally demonstrated using two distributed feedback (DFB) lasers, a multi-mode Fabry-Perot laser diode, and an optical band-pass filter. The DFB lasers are externally modulated to represent logic inputs into the cavity of the multi-mode Fabry-Perot slave laser. The input DFB (master) lasers' wavelengths are aligned with the longitudinal modes of the Fabry-Perot slave laser and their optical power is used to modulate the injection conditions in the Fabry-Perot slave laser. The optical band-pass filter is used to select a Fabry- Perot mode that is either suppressed or transmitted given the logic state of the injecting master laser signals. When the input signal(s) is (are) in the on state, injection locking, and thus the suppression of the non-injected Fabry-Perot modes, is induced, yielding a dynamic system that can be used to implement photonic logic functions. Additionally, all-optical photonic processing is achieved using the cavity-mode shift produced in the injected slave laser under external optical injection. The inverting logic case can also be used as a wavelength converter — a key component in advanced wavelength-division multiplexing networks. As a result of this experimental investigation, a more comprehensive understanding of the locking parameters involved in injecting multiple lasers into a multi-mode cavity and the logic transition time is achieved. The performance of optical logic computations and wavelength conversion has the potential for ultrafast operation, limited primarily by the photon decay rate in the slave laser.

  19. PAPR Reduction in All-optical OFDM Systems Based on Phase Pre-emphasis

    NASA Astrophysics Data System (ADS)

    He, Zhou; Li, Wei; Tao, Zhiyong; Shao, Ji ng; Liang, Xiaojun; Deng, Zhuanhua; Huang, Dexiu

    2011-02-01

    This paper investigates the peak-to-average power ratio (PAPR) theory in all-optical orthogonal frequency division multiplexing (OFDM) optical fibre communication systems. We find out that phase pre-emphasis could effectively reduce PAPR in all-optical OFDM communication systems which employ intensity modulation-direct detection (IM-DD) method. An equation is developed and proposed to calculate suitable phasing values for pre-emphasis. Furthermore, we find out that phase pre-emphasis cannot reduce PAPR effectively in all-optical OFDM systems that employ Phase Shift Keying (PSK) or Quadracture Amplitude Modulation (QAM) method.

  20. A reconfigurable all-optical VPN based on XGM effect of SOA in WDM PON

    NASA Astrophysics Data System (ADS)

    Hu, Xiaofeng; Zhang, Liang; Cao, Pan; Wang, Tao; Su, Yikai

    2010-12-01

    We propose and experimentally demonstrate a reconfigurable all-optical VPN scheme enabling intercommunications among different ONUs in a WDM PON. Reconfiguration is realized by dynamically setting wavelength conversion of optical VPN signal using a SOA in the OLT.

  1. Polarization-based all-optical logic operations in volume holographic photopolymer

    NASA Astrophysics Data System (ADS)

    Li, Chengmingyue; Cao, Liangcai; Li, Jingming; Wang, Zheng; Jin, Guofan

    2014-11-01

    Polarization-based all-optical logic operations were realized with dual-channel polarization holographic recording system. The polarization property of 9, 10-phenanthrenequinone-doped poly-methyl methacrylate (PQ/PMMA) photopolymer is investigated experimentally. To accurately represent the optical operations, the diffraction efficiency of parallel and orthogonal polarization recording in PQ/PMMA with the thickness of 1 mm are characterized for holographic recording and reconstruction process. A dual-channel polarization holographic recording system is set up for simultaneously recording two input pages. By changing the polarization state of the diffraction beam, all-optical logic OR and NAND operations are realized in the volume holograms. The polarization-based all-optical logic operations in the volume holographic photopolymer may pave a way for practical all-optical logic devices with high speed and large information capacity.

  2. Integrated all-optical logic discriminators based on plasmonic bandgap engineering

    PubMed Central

    Lu, Cuicui; Hu, Xiaoyong; Yang, Hong; Gong, Qihuang

    2013-01-01

    Optical computing uses photons as information carriers, opening up the possibility for ultrahigh-speed and ultrawide-band information processing. Integrated all-optical logic devices are indispensible core components of optical computing systems. However, up to now, little experimental progress has been made in nanoscale all-optical logic discriminators, which have the function of discriminating and encoding incident light signals according to wavelength. Here, we report a strategy to realize a nanoscale all-optical logic discriminator based on plasmonic bandgap engineering in a planar plasmonic microstructure. Light signals falling within different operating wavelength ranges are differentiated and endowed with different logic state encodings. Compared with values previously reported, the operating bandwidth is enlarged by one order of magnitude. Also the SPP light source is integrated with the logic device while retaining its ultracompact size. This opens up a way to construct on-chip all-optical information processors and artificial intelligence systems. PMID:24071647

  3. All-Optical Terahertz Optical Asymmetric Demultiplexer (toad) Based Binary Comparator:. a Proposal

    NASA Astrophysics Data System (ADS)

    Chattopadhyay, Tanay

    Comparator determines whether a number is greater than, equals to or less than another number. It plays a significant role in fast central processing unit in all-optical scheme. In all-optical scheme here 1-bit binary comparator is proposed and described by Terahertz Optical Asymmetric Demultiplexer (TOAD) based interferometric switch. Simulation result by Mathcad-7 is also given. Cascading technique of building up the n-bit binary comparator with this 1-bit comparator block is also proposed here.

  4. Balanced bridge feedback control system

    NASA Technical Reports Server (NTRS)

    Lurie, Boris J. (Inventor)

    1990-01-01

    In a system having a driver, a motor, and a mechanical plant, a multiloop feedback control apparatus for controlling the movement and/or positioning of a mechanical plant, the control apparatus has a first local bridge feedback loop for feeding back a signal representative of a selected ratio of voltage and current at the output driver, and a second bridge feedback loop for feeding back a signal representative of a selected ratio of force and velocity at the output of the motor. The control apparatus may further include an outer loop for feeding back a signal representing the angular velocity and/or position of the mechanical plant.

  5. Feedback: Theory and Accelerator Applications

    NASA Astrophysics Data System (ADS)

    Himel, T.

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

  6. Analytical Investigation of an All-Optical T-Type Flip-Flop Using a Semiconductor Optical Amplifier Mach-Zehnder Interferometer with Push-Pull Configuration

    NASA Astrophysics Data System (ADS)

    Shimizu, Satoshi; Uenohara, Hiroyuki

    2011-06-01

    To achieve an optical regenerator for a differential phase-shift keying signal based on a semiconductor optical amplifier Mach-Zehnder interferometer (SOA-MZI), we need an all-optical T-type flip-flop (T-FF) for encoding. We propose an all-optical T-FF consisting of an SOA-MZI with push-pull configuration and a feedback mirror to overcome the speed limitation of the previously proposed counter-faced configuration. Numerical simulation reveals its possibility of stable operation in 10 Gbps with a 27 - 1 pseudo random binary sequence (PRBS) signal even by using a conventional SOA with a slow carrier recovery of 100 ps, and the possibility of 40 Gbps operation is also investigated.

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

    PubMed

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

    2014-06-01

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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed

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

    2012-01-01

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

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

    PubMed

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

    2016-02-01

    The ErbB signaling network instructs the execution of key cellular programs, such as cell survival, proliferation and motility, through the generation of robust signals of defined strength and duration. In contrast, unabated ErbB signaling disrupts tissue homeostasis and leads to cell transformation. Cells oppose the threat inherent in excessive ErbB activity through several mechanisms of negative feedback regulation. Inducible feedback inhibitors (IFIs) are expressed in the context of transcriptional responses triggered by ErbB signaling, thus being uniquely suited to regulate ErbB activity during the execution of complex cellular programs. This review focuses on MIG6, an IFI that restrains ErbB signaling by mediating ErbB kinase suppression and receptor down-regulation. We will review key issues in MIG6 function, regulation and tumor suppressor activity. Subsequently, the role for MIG6 loss in the pathogenesis of tumors driven by ErbB oncogenes as well as in the generation of cellular addiction to ErbB signaling will be discussed. We will conclude by analyzing feedback inhibition by MIG6 in the context of therapies directed against ErbB and non-ErbB oncogenes. PMID:26456277

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

    PubMed

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

    2016-04-18

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

  13. Study on all-optical switching characteristics of ethyl orange-doped polymer film

    NASA Astrophysics Data System (ADS)

    Xu, Tang; Zhang, Chunping; Lin, Yu; Qi, Shengwen

    2008-10-01

    The all-optical switching polymer thin films with azobenzene dye ethyl orange as the guest material and polyvinyl alcohol (PVA) as the host material were prepared by adulteration and spin-coating methods. The all-optical switching characteristics of the samples were measured at different intensities and modulation frequencies of the pump beam (532 nm, CW); the influence of doping concentration on the all-optical switching effect of the films was studied. It is shown that, under room temperature conditions and with a low pump power of 6 mW, the all-optical switch has a response time of about 2 ms and a modulation depth of 45%, and the maximal modulation depth reaches 90%. In addition, it is found that samples with higher doping concentration show a stronger all-optical switching effect but a larger background signal, and good switching performance is obtained by choosing the doping concentrations from 0.8% to 2% of the sample.

  14. All-optical universal logic gates on nonlinear multimode interference coupler using tunable input intensity

    NASA Astrophysics Data System (ADS)

    Tajaldini, Mehdi; Jafri, Mohd Zubir Mat

    2015-04-01

    The theory of Nonlinear Modal Propagation Analysis Method (NMPA) have shown significant features of nonlinear multimode interference (MMI) coupler with compact dimension and when launched near the threshold of nonlinearity. Moreover, NMPA have the potential to allow studying the nonlinear MMI based the modal interference to explorer the phenomenon that what happen due to the natural of multimode region. Proposal of all-optical switch based NMPA has approved its capability to achieving the all-optical gates. All-optical gates have attracted increasing attention due to their practical utility in all-optical signal processing networks and systems. Nonlinear multimode interference devices could apply as universal all-optical gates due to significant features that NMPA introduce them. In this Paper, we present a novel Ultra-compact MMI coupler based on NMPA method in low intensity compared to last reports either as a novel design method and potential application for optical NAND, NOR as universal gates on single structure for Boolean logic signal processing devices and optimize their application via studding the contrast ratio between ON and OFF as a function of output width. We have applied NMPA for several applications so that the miniaturization in low nonlinear intensities is their main purpose.

  15. Regenerative feedback resonant circuit

    DOEpatents

    Jones, A. Mark; Kelly, James F.; McCloy, John S.; McMakin, Douglas L.

    2014-09-02

    A regenerative feedback resonant circuit for measuring a transient response in a loop is disclosed. The circuit includes an amplifier for generating a signal in the loop. The circuit further includes a resonator having a resonant cavity and a material located within the cavity. The signal sent into the resonator produces a resonant frequency. A variation of the resonant frequency due to perturbations in electromagnetic properties of the material is measured.

  16. All-optical virtual private network and ONUs communication in optical OFDM-based PON system.

    PubMed

    Zhang, Chongfu; Huang, Jian; Chen, Chen; Qiu, Kun

    2011-11-21

    We propose and demonstrate a novel scheme, which enables all-optical virtual private network (VPN) and all-optical optical network units (ONUs) inter-communications in optical orthogonal frequency-division multiplexing-based passive optical network (OFDM-PON) system using the subcarrier bands allocation for the first time (to our knowledge). We consider the intra-VPN and inter-VPN communications which correspond to two different cases: VPN communication among ONUs in one group and in different groups. The proposed scheme can provide the enhanced security and a more flexible configuration for VPN users compared to the VPN in WDM-PON or TDM-PON systems. The all-optical VPN and inter-ONU communications at 10-Gbit/s with 16 quadrature amplitude modulation (16 QAM) for the proposed optical OFDM-PON system are demonstrated. These results verify that the proposed scheme is feasible. PMID:22109510

  17. Two types of all-optical magnetization switching mechanisms using femtosecond laser pulses

    NASA Astrophysics Data System (ADS)

    El Hadri, M. S.; Pirro, P.; Lambert, C.-H.; Petit-Watelot, S.; Quessab, Y.; Hehn, M.; Montaigne, F.; Malinowski, G.; Mangin, S.

    2016-08-01

    Using a time-dependent electrical investigation of the all-optical switching in ferrimagnetic and ferromagnetic Hall crosses via the anomalous Hall effect, intriguing insights into the rich physics underlying the all-optical switching are provided. We demonstrate that two different all-optical magnetization switching mechanisms can be distinguished; a "single pulse" switching for ferrimagnetic GdFeCo alloys, and a "two regimes" switching process for both ferrimagnetic TbCo alloys and ferromagnetic Pt/Co multilayers. We show that the latter takes place at two different time scales, and consists of a steplike helicity-independent multiple-domain formation within the first 1 ms followed by a helicity-dependent remagnetization on several tens of milliseconds.

  18. Numerical investigation of an all-optical switch in a graded nonlinear plasmonic grating.

    PubMed

    Wang, Guoxi; Lu, Hua; Liu, Xueming; Gong, Yongkang

    2012-11-01

    We have proposed and numerically investigated an all-optical switch based on a metal-insulator-metal waveguide with graded nonlinear plasmonic gratings. The influences of grating depth and refractive index of a Kerr nonlinear medium on the transmission of the switch are exactly analyzed by utilizing transmission line theory. The finite-difference time-domain simulation results show that the highly compact structure possesses excellent switch function by tuning the incident electric field intensity. In addition, the simulation results show that this all-optical switch has an ultrawide operating frequency regime and femtosecond-scale response time (~130 fs). Such a switch can find potential applications for all-optical signal processing and optical communication. PMID:23080383

  19. All-Optical Helicity Dependent Spin Switching in a Many-Spin System

    NASA Astrophysics Data System (ADS)

    Latta, Tanner; Zhang, G. P.

    All-optical helicity dependent magnetic switching (AOS) is achieved through using an ultrafast laser pulse to manipulate and switch the spin of an electron from one direction to another. This process happens in a short amount of femtoseconds after the laser pulse is introduced. All-optical helicity dependent magnetic switching (AOS) does not fall to the assistance of any external magnetic field. Linearly polarized light, as well as right and left circularly polarized light are used to manipulate the spin of the electrons. Ferrimagnetic, rather than ferromagnetic, materials are more suitable to create conditions in which AOS are viable due to the orientation of the spins within this material. In the following study we show and conclude that AOS is possible with the use of left and right circularly polarized laser pulses. All-optical helicity dependent magnetic switching has many applications in magnetic recording technology or magnetic memory devices. DE-FG02-06ER46304.

  20. Novel real-time monitoring technique of the all-optical poling process

    NASA Astrophysics Data System (ADS)

    Apostoluk, Aleksandra; Chapron, David; Sahraoui, Bouchta; Gadret, Gregory; Fiorini-Debuisschert, Celine; Raimond, Paul; Nunzi, Jean-Michel

    2002-03-01

    All-optical poling technique permits purely optical orientation of molecules. The experiment consists of two steps: the writing (so-called seeding) period and the readout one. In the seeding phase two beams, the fundamental one ((omega) ) and its second harmonic (SH, 2(omega) ) illuminate the sample and print in the medium the second order (chi) (2) susceptibility grating with a periodicity satisfying the condition of phase matching for SH generation. In the readout period only the fundamental beam irradiates the sample, and the second harmonic generation is observed at the sample output. Efficient all-optical poling requires optimisation of the seeding beam intensities and their relative phase difference. We propose a novel technique for non-perturbative monitoring of the all-optical poling process and the easy method of orienting molecules without any necessity of taking into account the phase difference between seeding beams.

  1. Audio Feedback -- Better Feedback?

    ERIC Educational Resources Information Center

    Voelkel, Susanne; Mello, Luciane V.

    2014-01-01

    National Student Survey (NSS) results show that many students are dissatisfied with the amount and quality of feedback they get for their work. This study reports on two case studies in which we tried to address these issues by introducing audio feedback to one undergraduate (UG) and one postgraduate (PG) class, respectively. In case study one…

  2. All-Optical Switching in Bacteriorhodopsin Based on Excited-State Absorption

    NASA Astrophysics Data System (ADS)

    Roy, Sukhdev

    2008-03-01

    Switching light with light is of tremendous importance for both fundamental and applied science. The advent of nano-bio-photonics has led to the design, synthesis and characterization of novel biomolecules that exhibit an efficient nonlinear optical response, which can be utilized for designing all-optical biomolecular switches. Bacteriorhodopsin (bR) protein found in the purple membrane of Halobacterium halobium has been the focus of intense research due to its unique properties that can also be tailored by physical, chemical and genetic engineering techniques to suit desired applications. The talk would focus on our recent results on all-optical switching in bR and its mutants, based on excited-state absorption, using the pump-probe technique. We would discuss the all-optical control of various features of the switching characteristics such as switching contrast, switching time, switching pump intensity, switched probe profile and phase, and relative phase-shift. Optimized conditions for all-optical switching that include optimized values of the small-signal absorption coefficient (for cw case), the pump pulse width and concentration for maximum switching contrast (for pulsed case), would be presented. We would discuss the desired optimal spectral and kinetic properties for device applications. We would also discuss the application of all-optical switching to design low power all-optical computing devices, such as, spatial light modulators, logic gates and multiplexers and compare their performance with other natural photoreceptors such as pharaonis phoborhodopsin, proteorhodopsin, photoactive yellow protein and the blue light plant photoreceptor phototropin.

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

    PubMed Central

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

    2014-01-01

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

  4. Polarization-encoded all-optical quaternary universal inverter and design of multivalued flip-flop

    NASA Astrophysics Data System (ADS)

    Chattopadhyay, Tanay; Roy, Jitendra Nath

    2010-03-01

    Quaternary inverters are the fundamental building blocks of multivalued flip-flops (MVFFs). A novel all-optical quaternary universal inverter circuit with the help of a semiconductor optical amplifier-assisted Sagnac switch is proposed and described. This circuit exploits the polarization properties of light. Different logical states are represented by different polarization states of light. A terahertz optical asymmetric multiplexer-based gate plays an important role here. Numerical simulation results confirming the described method are given. An all-optical circuit for a MVFF (quaternary) with the help of our proposed quaternary universal inverter is also designed, and simulation results are presented.

  5. Low-power and ultrafast all-optical tunable plasmon-induced transparency in plasmonic nanostructures

    NASA Astrophysics Data System (ADS)

    Chai, Zhen; Hu, Xiaoyong; Zhu, Yu; Zhang, Fan; Yang, Hong; Gong, Qihuang

    2013-05-01

    We report an ultrafast and low-power all-optical tunable plasmon-induced transparency in a plasmonic nanostructure consisting of a gold nanowire grating embedded in a polycrystalline lithium niobate layer, realized based on strong quantum confinement enhancing nonlinearity. The all-optical tunability is realized based on the third-order nonlinear Kerr effect. A shift of 30 nm in the central wavelength of the transparency window is achieved under excitation of a pump light with an intensity as low as 7 MW/cm2. An ultrafast response time of 69 ps is reached because of ultrafast relaxation dynamics of bound electrons in polycrystalline lithium niobate.

  6. High-order all-optical differential equation solver based on microring resonators.

    PubMed

    Tan, Sisi; Xiang, Lei; Zou, Jinghui; Zhang, Qiang; Wu, Zhao; Yu, Yu; Dong, Jianji; Zhang, Xinliang

    2013-10-01

    We propose and experimentally demonstrate a feasible integrated scheme to solve all-optical differential equations using microring resonators (MRRs) that is capable of solving first- and second-order linear ordinary differential equations with different constant coefficients. Employing two cascaded MRRs with different radii, an excellent agreement between the numerical simulation and the experimental results is obtained. Due to the inherent merits of silicon-based devices for all-optical computing, such as low power consumption, small size, and high speed, this finding may motivate the development of integrated optical signal processors and further extend optical computing technologies. PMID:24081039

  7. All-optical steering of the interactions between multiple spatial solitons in isotropic polymers

    NASA Astrophysics Data System (ADS)

    Yan, Li-fen; Zhang, Dong; Jin, Qing-li; Wang, Hong-cheng; Zhang, Yao-ju

    2010-11-01

    All-optical steering of the nonlinear interactions between multiple spatial solitons can be performed in an isotropic photoisomerization polymer, by propagating an external control beam in perpendicular direction. Fusing, giving birth to another new soliton, and transferring energy can take place in the interactions of signal beams, which can be achieved by changing the incident position of the control beam, the initial relative phase and the power ratio between the signal beams and the control beam. These phenomena are physically explained, and they have significantly potential applications in optical signal readdressing, logic gating, and all-optical switching, etc.

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

    PubMed Central

    Singh, Raghvendra

    2016-01-01

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

  9. Regulative Loops, Step Loops and Task Loops

    ERIC Educational Resources Information Center

    VanLehn, Kurt

    2016-01-01

    This commentary suggests a generalization of the conception of the behavior of tutoring systems, which the target article characterized as having an outer loop that was executed once per task and an inner loop that was executed once per step of the task. A more general conception sees these two loops as instances of regulative loops, which…

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

    NASA Astrophysics Data System (ADS)

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

    2014-01-01

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

  11. All-optical microwave signal processing based on optical phase modulation

    NASA Astrophysics Data System (ADS)

    Zeng, Fei

    This thesis presents a theoretical and experimental study of optical phase modulation and its applications in all-optical microwave signal processing, which include all-optical microwave filtering, all-optical microwave mixing, optical code-division multiple-access (CDMA) coding, and ultrawideband (UWB) signal generation. All-optical microwave signal processing can be considered as the use of opto-electronic devices and systems to process microwave signals in the optical domain, which provides several significant advantages such as low loss, low dispersion, light weight, high time bandwidth products, and immunity to electromagnetic interference. In conventional approaches, the intensity of an optical carrier is modulated by a microwave signal based on direct modulation or external modulation. The intensity-modulated optical signal is then fed to a photonic circuit or system to achieve specific signal processing functionalities. The microwave signal being processed is usually obtained based on direct detection, i.e., an opto-electronic conversion by use of a photodiode. In this thesis, the research efforts are focused on the optical phase modulation and its applications in all-optical microwave signal processing. To avoid using coherent detection which is complicated and costly, simple and effective phase modulation to intensity modulation (PM-IM) conversion schemes are pursued. Based on a theoretical study of optical phase modulation, two approaches to achieving PM-IM conversions are proposed. In the first approach, the use of chromatic dispersion induced by a dispersive device to alter the phase relationships among the sidebands and the optical carrier of a phase-modulated optical signal to realize PM-IM conversion is investigated. In the second approach, instead of using a dispersive device, the PM-IM conversion is realized based on optical frequency discrimination implemented using an optical filter. We show that the proposed PM-IM conversion schemes can be

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2016-06-01

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

  14. Enhancement of photoinduced anisotropy and all-optical switching in Bacteriorhodopsin films

    NASA Astrophysics Data System (ADS)

    Wu, Pengfei; Rao, D. V. G. L. N.; Kimball, B. R.; Nakashima, M.; DeCristofano, B. S.

    2002-11-01

    Large enhancement of photoanisotropic effects is demonstrated in thin films of the biomaterial Bacteriorhodopsin by using two exciting beams of orthogonal polarization. The mechanism of the enhancement originates from optimization of direction-selected photoisomerization of the biomaterial controlled by the polarized exciting beams. The technique is applied for achieving an all-optical switch with the additional feature of output sign control.

  15. Polarization encoded all-optical quaternary R-S flip-flop using binary latch

    NASA Astrophysics Data System (ADS)

    Chattopadhyay, Tanay; Roy, Jitendra Nath; Chakraborty, Ajoy Kumar

    2009-04-01

    The developments of different multi-valued logic (MVL) systems have received considerable interests in recent years all over the world. In electronics, efforts have already been made to incorporate multi-valued system in logic and arithmetic data processing. But, very little efforts have been given in realization of MVL with optics. In this paper we present novel designs of certain all-optical circuits that can be used for realizing multi-valued logic functions. Polarization encoded all-optical quaternary (4-valued) R-S flip-flop is proposed and described. Two key circuits (all-optical encoder/decoder and a binary latch) are designed first. They are used to realize quaternary flip-flop in all-optical domain. Here the different quaternary logical states are represented by different polarized state of light. Terahertz Optical Asymmetric Demultiplexer (TOAD) based interferometric switch can take an important role. Computer simulation result confirming described methods and conclusion are given in this paper.

  16. Integration of photonic nanojets and semiconductor nanoparticles for enhanced all-optical switching

    PubMed Central

    Born, Brandon; Krupa, Jeffrey D. A.; Geoffroy-Gagnon, Simon; Holzman, Jonathan F.

    2015-01-01

    All-optical switching is the foundation of emerging all-optical (terabit-per-second) networks and processors. All-optical switching has attracted considerable attention, but it must ultimately support operation with femtojoule switching energies and femtosecond switching times to be effective. Here we introduce an all-optical switch architecture in the form of a dielectric sphere that focuses a high-intensity photonic nanojet into a peripheral coating of semiconductor nanoparticles. Milli-scale spheres coated with Si and SiC nanoparticles yield switching energies of 200 and 100 fJ with switching times of 10 ps and 350 fs, respectively. Micro-scale spheres coated with Si and SiC nanoparticles yield switching energies of 1 pJ and 20 fJ with switching times of 2 ps and 270 fs, respectively. We show that femtojoule switching energies are enabled by localized photoinjection from the photonic nanojets and that femtosecond switching times are enabled by localized recombination within the semiconductor nanoparticles. PMID:26314911

  17. Magnetic induction measurements using an all-optical {sup 87}Rb atomic magnetometer

    SciTech Connect

    Wickenbrock, Arne; Tricot, François; Renzoni, Ferruccio

    2013-12-09

    In this work we propose, and experimentally demonstrate, the use of a self-oscillating all-optical atomic magnetometer for magnetic induction measurements. Given the potential for miniaturization of atomic magnetometers, and their extreme sensitivity, the present work shows that atomic magnetometers may play a key role in the development of instrumentation for magnetic induction tomography.

  18. Numerical investigation of all-optical add-drop multiplexing for spectrally overlapping OFDM signals.

    PubMed

    Sygletos, S; Fabbri, S; Giacoumidis, E; Sorokina, M; Marom, D M; Stephens, M F C; Klonidis, D; Tomkos, I; Ellis, A D

    2015-03-01

    We propose a novel architecture for all-optical add-drop multiplexing of OFDM signals. Sub-channel extraction is achieved by means of waveform replication and coherent subtraction from the OFDM super-channel. Numerical simulations have been carried out to benchmark the performance of the architecture against critical design parameters. PMID:25836815

  19. Analysis of all-optically tunable functionalities in subwavelength periodic structures by the Fourier modal method

    NASA Astrophysics Data System (ADS)

    Bej, Subhajit; Tervo, Jani; Francés, Jorge; Svirko, Yuri P.; Turunen, Jari

    2016-05-01

    We propose the nonlinear Fourier Modal Method (FMM) [J. Opt. Soc. Am. B 31, 2371 (2014)] as a convenient and versatile numerical tool for the design and analysis of grating based next generation all-optical devices. Here, we include several numerical examples where the FMM is used to simulate all-optically tunable functionalities in sub-wavelength periodic structures. At first, we numerically investigate a 1-D periodic nonlinear binary grating with amorphous TiO2. We plot the diffraction efficiency in the transmitted orders against the structure depth for normally incident plane wave. Change in diffraction efficiencies for different incident field amplitudes are evident from the plots. We verify the accuracy of our implementation by comparing our results with the results obtained with the nonlinear Split Field-Finite Difference Time Domain (SF-FDTD) method. Next we repeat the same experiment with vertically standing amorphous Titanium dioxide (TiO2) nanowire arrays grown on top of quartz which are periodic in two mutually perpendicular directions and examine the efficiencies in the direct transmitted light for different incident field amplitudes. Our third example includes analysis of a form birefringent linear grating with Kerr medium. With FMM we demonstrate that the birefringence of such a structure can be tuned by all-optical means. As a final example, we design a narrow band Guided Mode Resonance Filter (GMRF). Numerical experiments based on the nonlinear FMM reveal that the spectral tunability of such a filter can be obtained by all-optical means.

  20. All-optical event horizon in an optical analog of a Laval nozzle

    NASA Astrophysics Data System (ADS)

    Elazar, M.; Fleurov, V.; Bar-Ad, S.

    2012-12-01

    Exploiting the fact that light propagation in defocusing nonlinear media can mimic the transonic flow of an equivalent fluid, we demonstrate experimentally the formation of an all-optical event horizon in a waveguide structure akin to a hydrodynamic Laval nozzle. The analog event horizon which forms at the nozzle throat is suggested as a platform for analogous gravity experiments.

  1. Micro-ring resonator based all-optical reconfigurable logic operations

    NASA Astrophysics Data System (ADS)

    Rakshit, Jayanta Kumar; Roy, Jitendra Nath

    2014-06-01

    An all-optical reconfigurable logic operation essentially constitutes a key technology for performing various processing tasks with ultrafast signal-processing technologies. We present designs and simulations for highly cascadable all-optical reconfigurable logic operations using GaAs-AlGaAs micro-ring resonator based optical switches and multiplexers. The switching action of the ring resonator is achieved through variation in the refractive index of the ring resonator produced by the two-photon absorption (TPA) effect through the application of optical pump pulse. The proposed circuit can perform any of the four digital logic operations (NOT, NOR, XOR, AND) by using the appropriate optical pump signal at the selection port of the multiplexer. We have tried to exploit the advantages of micro-ring resonator based all optical switch to design an all-optical circuit. The reconfigurable nature of the circuit offers maximum flexibility for the end user since the entire application can be changed simply by adjusting the multiplexer select line signals. Numerical simulation confirming described methods is given in this paper.

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

    SciTech Connect

    Vuckovic, V.; Vukosavic, S. )

    1992-01-01

    This paper brings out a control algorithm for VSI fed induction motor drives based on the converter DC link current feedback. It is shown that the speed and flux can be controlled over the wide speed and load range quite satisfactorily for simpler drives. The base commands of both the inverter voltage and frequency are proportional to the reference speed, but each of them is further modified by the signals derived from the DC current sensor. The algorithm is based on the equations well known from the vector control theory, and is aimed to obtain the constant rotor flux and proportionality between the electrical torque, the slip frequency and the active component of the stator current. In this way, the problems of slip compensation, Ri compensation and correction of U/f characteristics are solved in the same time. Analytical considerations and computer simulations of the proposed control structure are in close agreement with the experimental results measured on a prototype drive.

  3. Routing and wavelength assignment based on normalized resource and constraints for all-optical network

    NASA Astrophysics Data System (ADS)

    Joo, Seong-Soon; Nam, Hyun-Soon; Lim, Chang-Kyu

    2003-08-01

    With the rapid growth of the Optical Internet, high capacity pipes is finally destined to support end-to-end IP on the WDM optical network. Newly launched 2D MEMS optical switching module in the market supports that expectations of upcoming a transparent optical cross-connect in the network have encouraged the field applicable research on establishing real all-optical transparent network. To open up a customer-driven bandwidth services, design of the optical transport network becomes more challenging task in terms of optimal network resource usage. This paper presents a practical approach to finding a route and wavelength assignment for wavelength routed all-optical network, which has λ-plane OXC switches and wavelength converters, and supports that optical paths are randomly set up and released by dynamic wavelength provisioning to create bandwidth between end users with timescales on the order of seconds or milliseconds. We suggest three constraints to make the RWA problem become more practical one on deployment for wavelength routed all-optical network in network view: limitation on maximum hop of a route within bearable optical network impairments, limitation on minimum hops to travel before converting a wavelength, and limitation on calculation time to find all routes for connections requested at once. We design the NRCD (Normalized Resource and Constraints for All-Optical Network RWA Design) algorithm for the Tera OXC: network resource for a route is calculated by the number of internal switching paths established in each OXC nodes on the route, and is normalized by ratio of number of paths established and number of paths equipped in a node. We show that it fits for the RWA algorithm of the wavelength routed all-optical network through real experiments on the distributed objects platform.

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

    PubMed Central

    Atkinson, Joanna R.

    2006-01-01

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

  5. All-optical signal amplifier and distributor using cavity-atom coupling systems

    NASA Astrophysics Data System (ADS)

    Duan, Yafan; Lin, Gongwei; Niu, Yueping; Gong, Shangqing

    2016-05-01

    We report an all-optical signal amplifier and a signal distributor using cavity-atom coupling systems. In this system we couple atoms with an optical cavity and realize the great enhancement of a control laser by the cavity with the help of two high coupling lasers. By this effect, we can use one weak control field to control another strong target field and the intensity changes are linear with our experimental conditions. This can be used as an all-optical signal amplifier, also known as a ‘transphasor’. In our experiment, the gain of the weak field to strong field can be as high as 60. Furthermore, we can realize the distribution of optical signals, if we coordinate multiple cavity-atom coupling systems.

  6. All-optical binary phase-coded UWB signal generation for multi-user UWB communications.

    PubMed

    Dong, Jianji; Yu, Yuan; Zhang, Yin; Li, Xiang; Huang, Dexiu; Zhang, Xinliang

    2011-05-23

    An all-optical incoherent scheme for generation of binary phase-coded ultra-wideband (UWB) signals is proposed and experimentally demonstrated. The binary phase coding is performed based on all-optical phase modulation in a semiconductor optical amplifier (SOA) and phase modulation to intensity modulation (PM-IM) conversion in a fiber delay interferometer (DI) that serves as a multichannel frequency discriminator. By locating the phase-modulated light waves at the positive and negative slopes of the DI transmission spectra, binary phase encoded UWB codes (0 and π) are generated. We also experimentally demonstrate a bipolar UWB coding system with a code length of 4, operating at 1.25 Gb/s. And the decoding is analyzed as well. Our proposed system has potential application in future high-speed UWB impulse radio over optical fiber access networks. PMID:21643312

  7. All-optical switching characteristics in bacteriorhodopsin and its applications in integrated optics.

    PubMed

    Huang, Yuhua; Wu, Shin-Tson; Zhao, Youyuan

    2004-03-01

    We experimentally and theoretically investigated the optical switching characteristics of bacteriorhodopsin (bR) at lambda=633 nm using the pump-probe method. A diode-pumped second harmonic YAG laser (lambda=532 nm which is located around the maximum initial Br state absorption) was used as a pumping beam and a cw He-Ne laser (lambda=633 nm which is around the peaks of K and O states) was used as a probe. Due to the nonlinear intensity induced excited state absorption of the K, L, M, N, and O states in the bR photocycle, the switching characteristics are sensitive to the intensity of the probe and pump beams. Based on this property, we have demonstrated an all-optical device functioning as 11 kinds of variable binary all-optical logic gates. PMID:19474900

  8. All-optical switching characteristics in bacteriorhodopsin and its applications in integrated optics

    NASA Astrophysics Data System (ADS)

    Huang, Yuhua; Wu, Shin-Tson; Zhao, Youyuan

    2004-03-01

    We experimentally and theoretically investigated the optical switching characteristics of bacteriorhodopsin (bR) at l=633 nm using the pump-probe method. A diode-pumped second harmonic YAG laser (l=532 nm which is located around the maximum initial Br state absorption) was used as a pumping beam and a cw He-Ne laser (l=633 nm which is around the peaks of K and O states) was used as a probe. Due to the nonlinear intensity induced excited state absorption of the K, L, M, N, and O states in the bR photocycle, the switching characteristics are sensitive to the intensity of the probe and pump beams. Based on this property, we have demonstrated an all-optical device functioning as 11 kinds of variable binary all-optical logic gates.

  9. All-optical repetition rate multiplication of pseudorandom bit sequences based on cascaded TOADs

    NASA Astrophysics Data System (ADS)

    Sun, Zhenchao; Wang, Zhi; Wu, Chongqing; Wang, Fu; Li, Qiang

    2016-03-01

    A scheme for all-optical repetition rate multiplication of pseudorandom bit sequences (PRBS) is demonstrated with all-optical wavelength conversion and optical logic gate 'OR' based on cascaded Tera-Hertz Optical Asymmetric Demultiplexers (TOADs). Its feasibility is verified by multiplication experiments from 500 Mb/s to 4 Gb/s for 23-1 PRBS and from 1 Gb/s to 4 Gb/s for 27-1 PRBS. This scheme can be employed for rate multiplication for much longer cycle PRBS at much higher bit rate over 40 Gb/s when the time-delay, the loss and the dispersion of the optical delay line are all precisely managed. The upper limit of bit rate will be restricted by the recovery time of semiconductor optical amplifier (SOA) finally.

  10. All-optical pseudorandom binary sequence generator with TOAD-based D flip-flops

    NASA Astrophysics Data System (ADS)

    Zoiros, K. E.; Das, M. K.; Gayen, D. K.; Maity, H. K.; Chattopadhyay, T.; Roy, J. N.

    2011-09-01

    An all-optical pseudo random binary sequence (PRBS) generator is designed using serially interconnected discrete Terahertz Optical Asymmetric Demultiplexer (TOAD)-based D flip-flops in a configuration exactly like the standard electronic setup. The performance of the circuit is evaluated through numerical simulation, which confirms its feasibility in terms of the choice of the critical parameters. The proposed scheme has been theoretically demonstrated for a 3-bit and 7-bit degree PRBS but can be extended to higher order by means of additional TOAD-based D flip-flops. Thus it can constitute an efficient solution for implementing all-optically a PRBS in an affordable, controllable and realistic manner.

  11. 20Gbit/s all-optical logic OR in terahertz optical asymmetric demultiplexer (TOAD)

    NASA Astrophysics Data System (ADS)

    Yan, Yumei; Wu, Jian; Lin, Jintong

    2005-01-01

    A scheme for all-optical logic OR based on transparent teraherz optical asymmetric demultiplexer (transparent-TOAD) is proposed in this paper. In the transparent-TOAD, the SOA is biased at transparency and the gain recovery time determined by the intraband effect has the value of only a few picoseconds. Numerical analysis shows that the switching window of the transparent-TOAD is only about 0.54ps and the potential for ultrahigh speed all-optical logic processing is shown. Numerical demonstration is performed for 4-bit and 16-bit logic OR at 20Gbit/s. The results coincide with the OR truth table, showing high extinction ratio and no pattern dependency. Detailed analysis is carried out on the performance of the logic OR scheme.

  12. Ultrafast All-Optical Switching with Magnetic Resonances in Nonlinear Dielectric Nanostructures.

    PubMed

    Shcherbakov, Maxim R; Vabishchevich, Polina P; Shorokhov, Alexander S; Chong, Katie E; Choi, Duk-Yong; Staude, Isabelle; Miroshnichenko, Andrey E; Neshev, Dragomir N; Fedyanin, Andrey A; Kivshar, Yuri S

    2015-10-14

    We demonstrate experimentally ultrafast all-optical switching in subwavelength nonlinear dielectric nanostructures exhibiting localized magnetic Mie resonances. We employ amorphous silicon nanodisks to achieve strong self-modulation of femtosecond pulses with a depth of 60% at picojoule-per-disk pump energies. In the pump-probe measurements, we reveal that switching in the nanodisks can be governed by pulse-limited 65 fs-long two-photon absorption being enhanced by a factor of 80 with respect to the unstructured silicon film. We also show that undesirable free-carrier effects can be suppressed by a proper spectral positioning of the magnetic resonance, making such a structure the fastest all-optical switch operating at the nanoscale. PMID:26393983

  13. Tunable all-optical plasmonic diode based on Fano resonance in nonlinear waveguide coupled with cavities.

    PubMed

    Fan, Cairong; Shi, Fenghua; Wu, Hongxing; Chen, Yihang

    2015-06-01

    Tunable all-optical plasmonic diode is proposed based on the Fano resonance in an asymmetric and nonlinear system, comprising metal-insulator-metal waveguides coupled with nanocavities. The spatial asymmetry of the system gives rise to the nonreciprocity of the field localizations at the nonlinear gap between the coupled cavities and to the nonreciprocal nonlinear response. Nonlinear Fano resonance, originating from the interference between the discrete cavity mode and the continuum traveling mode, is observed and effectively tuned by changing the input power. By combining the unidirectional nonlinear response with the steep dispersion of the Fano asymmetric line shape, a transmission contrast ratio up to 41.46 dB can be achieved between forward and backward transmission. Our all-optical plasmonic diode with compact structure can find important applications in integrated optical nanocircuits. PMID:26030529

  14. All-optical photoacoustic microscopy based on plasmonic detection of broadband ultrasound

    NASA Astrophysics Data System (ADS)

    Wang, Tianxiong; Cao, Rui; Ning, Bo; Dixon, Adam J.; Hossack, John A.; Klibanov, Alexander L.; Zhou, Qifa; Wang, Anbo; Hu, Song

    2015-10-01

    We report on an implementation of all-optical photoacoustic microscopy (PAM), which capitalizes on the effect of surface plasmon resonance (SPR) for optical detection of ultrasound. The SPR sensor in our all-optical PAM shows, experimentally, a linear response to the acoustic pressure from 5.2 kPa to 2.1 MPa, an ultra-flat frequency response (±0.7 dB) from 680 kHz to 126 MHz, and a noise-equivalent pressure sensitivity of 3.3 kPa. With the broadband ultrasonic detection, our SPR-PAM has achieved high spatial resolution with relatively low anisotropy (i.e., 2.0 μm laterally and 8.4 μm axially). Three-dimensional high-resolution imaging of a single melanoma cell is demonstrated.

  15. All-optical background subtraction readout method for bimaterial cantilever array sensing.

    PubMed

    Gong, Cheng; Zhao, Yuejin; Dong, Liquan; Yu, Xiaomei; Chen, Ping; Liu, Weiwei

    2015-08-10

    Optical readout method plays a critical role in bimaterial cantilever array sensing system. The common optical readout methods are based on spectral plane filtering. In the paper an all-optical background subtraction readout approach inspired by total reflection and optical lever principle is presented for the bimaterial cantilever array sensing. Comparing with the spectral plane filtering methods the proposed approach eliminates digital subtraction operation by using optical total reflection instead of digital subtraction and avoids spectral filtering operation. An all-optical background subtraction directly-view infrared sensing system was developed to evaluate the approach. The infrared target can be directly acquired by the visible light CCD. The experimental results and analysis show its unique advantages. PMID:26367910

  16. All-optical scanhead for ultrasound and photoacoustic imaging-Imaging mode switching by dichroic filtering.

    PubMed

    Hsieh, Bao-Yu; Chen, Sung-Liang; Ling, Tao; Guo, L Jay; Li, Pai-Chi

    2014-03-01

    Ultrasound (US) and photoacoustic (PA) multimodality imaging has the advantage of combining good acoustic resolution with high optical contrast. The use of an all-optical scanhead for both imaging modalities can simplify integration of the two systems and miniaturize the imaging scanhead. Herein we propose and demonstrate an all-optical US/PA scanhead using a thin plate for optoacoustic generation in US imaging, a polymer microring resonator for acoustic detection, and a dichroic filter to switch between the two imaging modes by changing the laser wavelength. A synthetic-aperture focusing technique is used to improve the resolution and contrast. Phantom images demonstrate the feasibility of this design, and show that axial and lateral resolutions of 125 μm and 2.52°, respectively, are possible. PMID:25302154

  17. All-optical wavelength conversion of a 100-Gb/s polarization-multiplexed signal.

    PubMed

    Martelli, P; Boffi, P; Ferrario, M; Marazzi, L; Parolari, P; Siano, R; Pusino, V; Minzioni, P; Cristiani, I; Langrock, C; Fejer, M M; Martinelli, M; Degiorgio, V

    2009-09-28

    We present the results of an in-depth experimental investigation about all-optical wavelength conversion of a 100-Gb/s polarization-multiplexed (POLMUX) signal. Each polarization channel is modulated at 25 Gbaud by differential quadrature phase-shift keying (DQPSK). The conversion is realized exploiting the high nonlinear chi((2)) coefficient of a periodically poled lithium niobate waveguide, in a polarization-independent configuration. We find that slight non-idealities in the polarization independent setup of the wavelength converter can significantly impair the performance of POLMUX systems. We show that high-quality wavelength conversion can be nevertheless achieved for both the polarization channels, provided that an accurate optimization of the setup is performed. This is the first demonstration, to the best of our knowledge, of the possibility to obtain penalty-free all-optical wavelength conversion in a 100-Gb/s POLMUX transmission system using direct-detection. PMID:19907562

  18. An all-optical modulation method in sub-micron scale.

    PubMed

    Yang, Longzhi; Pei, Chongyang; Shen, Ao; Zhao, Changyun; Li, Yan; Li, Xia; Yu, Hui; Li, Yubo; Jiang, Xiaoqing; Yang, Jianyi

    2015-01-01

    We report a theoretical study showing that by utilizing the illumination of an external laser, the Surface Plasmon Polaritons (SPP) signals on the graphene sheet can be modulated in the sub-micron scale. The SPP wave can propagate along the graphene in the middle infrared range when the graphene is properly doped. Graphene's carrier density can be modified by a visible laser when the graphene sheet is exfoliated on the hydrophilic SiO2/Si substrate, which yields an all-optical way to control the graphene's doping level. Consequently, the external laser beam can control the propagation of the graphene SPP between the ON and OFF status. This all-optical modulation effect is still obvious when the spot size of the external laser is reduced to 400 nm while the modulation depth is as high as 114.7 dB/μm. PMID:25777581

  19. All-optical quantum random bit generation from intrinsically binary phase of parametric oscillators.

    PubMed

    Marandi, Alireza; Leindecker, Nick C; Vodopyanov, Konstantin L; Byer, Robert L

    2012-08-13

    We demonstrate a novel all-optical quantum random number generator (RNG) based on above-threshold binary phase state selection in a degenerate optical parametric oscillator (OPO). Photodetection is not a part of the random process, and no post processing is required for the generated bit sequence. We show that the outcome is statistically random with 99% confidence, and verify that the randomness is due to the phase of initiating photons generated through spontaneous parametric down conversion of the pump, with negligible contribution of classical noise sources. With the use of micro- and nanoscale OPO resonators, this technique offers a promise for simple, robust, and high-speed on-chip all-optical quantum RNGs. PMID:23038574

  20. Ultrafast, broadband, and configurable midinfrared all-optical switching in nonlinear graphene plasmonic waveguides

    NASA Astrophysics Data System (ADS)

    Ooi, Kelvin J. A.; Cheng, J. L.; Sipe, J. E.; Ang, L. K.; Tan, Dawn T. H.

    2016-07-01

    Graphene plasmonics provides a unique and excellent platform for nonlinear all-optical switching, owing to its high nonlinear conductivity and tight optical confinement. In this paper, we show that impressive switching performance on graphene plasmonic waveguides could be obtained for both phase and extinction modulations at sub-MW/cm2 optical pump intensities. Additionally, we find that the large surface-induced nonlinearity enhancement that comes from the tight confinement effect can potentially drive the propagating plasmon pump power down to the pW range. The graphene plasmonic waveguides have highly configurable Fermi-levels through electrostatic-gating, allowing for versatility in device design and a broadband optical response. The high capabilities of nonlinear graphene plasmonics would eventually pave the way for the adoption of the graphene plasmonics platform in future all-optical nanocircuitry.

  1. All-optical electromagnetically induced transparency using one-dimensional coupled microcavities.

    PubMed

    Naweed, Ahmer; Goldberg, David; Menon, Vinod M

    2014-07-28

    We report the first experimental realization of all-optical electromagnetically induced transparency (EIT) via a pair of coherently interacting SiO2 microcavities in a one-dimensional SiO2/Si3N4 photonic crystal consisting of a distributed Bragg reflector (DBR). The electromagnetic interactions between the coupled microcavities (CMCs), which possess distinct Q-factors, are controlled by varying the number of embedded SiO2/Si3N4 bilayers in the coupling DBR. In case of weak microcavity interactions, the reflectivity spectrum reveals an all-optical EIT resonance which splits into an Autler-Townes-like resonance under condition of strong microcavity coupling. Our results open up the way for implementing optical analogs of quantum coherence in much simpler one-dimensional structures. We also discuss potential applications of CMCs. PMID:25089499

  2. Ultralow-light-level all-optical transistor in rubidium vapor

    SciTech Connect

    Jing, Jietai Zhou, Zhifan; Liu, Cunjin; Qin, Zhongzhong; Fang, Yami; Zhou, Jun; Zhang, Weiping

    2014-04-14

    An all-optical transistor (AOT) is a device in which one light beam can efficiently manipulate another. It is the foundational component of an all-optical communication network. An AOT that can operate at ultralow light levels is especially attractive for its potential application in the quantum information field. Here, we demonstrate an AOT driven by a weak light beam with an energy density of 2.5 × 10{sup −5} photons/(λ{sup 2}/2π) (corresponding to 6  yJ/(λ{sup 2}/2π) and about 800 total photons) using the double-Λ four-wave mixing process in hot rubidium vapor. This makes it a promising candidate for ultralow-light-level optical communication and quantum information science.

  3. An all-optical vector atomic magnetometer for fundamental physics applications

    NASA Astrophysics Data System (ADS)

    Wurm, David; Mateos, Ignacio; Zhivun, Elena; Patton, Brian; Fierlinger, Peter; Beck, Douglas; Budker, Dmitry

    2014-05-01

    We have developed a laboratory prototype of a compact all-optical vector magnetometer. Due to their high precision and absolute accuracy, atomic magnetometers are crucial sensors in fundamental physics experiments which require extremely stable magnetic fields (e.g., neutron EDM searches). This all-optical sensor will allow high-resolution measurements of the magnitude and direction of a magnetic field without perturbing the magnetic environment. Moreover, its absolute accuracy makes it calibration-free, an advantage in space applications (e.g., space-based gravitational-wave detection). Magnetometry in precision experiments or space applications also demands long-term stability and well-understood noise characteristics at frequencies below 10-4 Hz. We have characterized the low-frequency noise floor of this sensor and will discuss methods to improve its long-time performance.

  4. Model for multishot all-thermal all-optical switching in ferromagnets

    NASA Astrophysics Data System (ADS)

    Gorchon, J.; Yang, Y.; Bokor, J.

    2016-07-01

    All-optical magnetic switching (AOS) is a recently observed rich and puzzling phenomenon that offers promising technological applications. However, a fundamental understanding of the underlying mechanisms remains elusive. Here we present a model for multishot helicity-dependent AOS in ferromagnetic materials based on a purely heat-driven mechanism in the presence of magnetic circular dichroism (MCD). We predict that AOS should be possible with as little as 0.5% of MCD, after a minimum number of laser shots heat the sample close to the Curie temperature. Finally, we qualitatively reproduce the all-optically switched domain patterns observed experimentally by numerically simulating the result of multiple laser shots on an FePtC granular ferromagnetic film.

  5. An all-optical modulation method in sub-micron scale

    PubMed Central

    Yang, Longzhi; Pei, Chongyang; Shen, Ao; Zhao, Changyun; Li, Yan; Li, Xia; Yu, Hui; Li, Yubo; Jiang, Xiaoqing; Yang, Jianyi

    2015-01-01

    We report a theoretical study showing that by utilizing the illumination of an external laser, the Surface Plasmon Polaritons (SPP) signals on the graphene sheet can be modulated in the sub-micron scale. The SPP wave can propagate along the graphene in the middle infrared range when the graphene is properly doped. Graphene's carrier density can be modified by a visible laser when the graphene sheet is exfoliated on the hydrophilic SiO2/Si substrate, which yields an all-optical way to control the graphene's doping level. Consequently, the external laser beam can control the propagation of the graphene SPP between the ON and OFF status. This all-optical modulation effect is still obvious when the spot size of the external laser is reduced to 400 nm while the modulation depth is as high as 114.7 dB/μm. PMID:25777581

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

    SciTech Connect

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

    1996-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  8. All-optical switching of diffraction gratings infiltrated with dye-doped liquid crystals

    NASA Astrophysics Data System (ADS)

    Lucchetta, D. E.; Vita, F.; Simoni, F.

    2010-12-01

    We report the realization and the characterization of an all-optical switching device based on a transmission grating recorded in a polymeric substrate infiltrated with a methyl red-doped liquid crystal. The properties of this highly nonlinear mixture are exploited to modulate the diffraction of the grating by a pump beam when a static electric field is applied. The behavior of the device is in agreement with the existing model for methyl red-doped liquid crystals.

  9. All-optical multibit address recognition at 20 Gb/s based on TOAD

    NASA Astrophysics Data System (ADS)

    Yan, Yumei; Wu, Jian; Lin, Jintong

    2005-04-01

    All-optical multibit address recognition at 20 Gb/s is demonstrated based on a special AND logic of terahertz optical asymmetric demultiplexer (TOAD). The semiconductor optical amplifier (SOA) used in the TOAD is biased at transparency status to accelerate the gain recovery. This is the highest bit rate that multibit address recognition is demonstrated with SOA-based interferometer. The experimental results show low pattern dependency. With this method, address recognition can be performed without separating address and payload beforehand.

  10. An integrable high resolution all-optical analog-to-digital conversion scheme

    NASA Astrophysics Data System (ADS)

    Wei, Shile; Jian, Wu; Zhao, Lingjuan; Lu, Dan; Qiu, Jifang

    2014-05-01

    A novel 4 × 4 multimode interference couplers based phase-shifted photonic quantization scheme using multiwavelength mode locked pulse lasers as sampling source for all-optical analog-to-digital converter is proposed. Numerical analysis indicates that 8-bit quantization resolution operating at 40 GHz bandwidth could be achieved with an incident average optical power of 1.932 mW to each photodiode. The whole scheme can be integrated on a InP-based chip.

  11. An All-Optical Microwave Mixer with 8db RF Gain

    NASA Technical Reports Server (NTRS)

    Shieh, W.; Yao, S. X.; Lutes, G.; Maleki, L.

    1997-01-01

    An all-optical microwave mixer with an 8dB RF gain is demonstrated by using a semiconductor optical amplifier (SOA). 6GHz RF signal on a 1312 nm optical carrier is up-converted and down-converted to 1GHZ and 11 GHz by a 5GHz local oscillation (LO) signal on a 1320 nm optical carrier. Such a carrier could readily extend to millimeter wave range.

  12. Realization of all-optical switch and diode via Raman gain process using a Kerr field

    NASA Astrophysics Data System (ADS)

    Abbas, Muqaddar; Qamar, Sajid; Qamar, Shahid

    2016-08-01

    The idea of optical photonic crystal, which is generated using two counter-propagating fields, is revisited to study gain-assisted all-optical switch and diode using Kerr field. Two counter-propagating fields with relative detuning Δ ν generate standing-wave field pattern which interacts with a four-level atomic system. The standing-wave field pattern acts like a static photonic crystal for Δ ν =0 , however, it behaves as a moving photonic crystal for Δ ν \

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

    PubMed Central

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

    2016-01-01

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

  14. Chip-integrated ultrawide-band all-optical logic comparator in plasmonic circuits

    PubMed Central

    Lu, Cuicui; Hu, Xiaoyong; Yang, Hong; Gong, Qihuang

    2014-01-01

    Optical computing opens up the possibility for the realization of ultrahigh-speed and ultrawide-band information processing. Integrated all-optical logic comparator is one of the indispensable core components of optical computing systems. Unfortunately, up to now, no any nanoscale all-optical logic comparator suitable for on-chip integration applications has been realized experimentally. Here, we report a subtle and effective technical solution to circumvent the obstacles of inherent Ohmic losses of metal and limited propagation length of SPPs. A nanoscale all-optical logic comparator suitable for on-chip integration applications is realized in plasmonic circuits directly. The incident single-bit (or dual-bit) logic signals can be compared and the comparison results are endowed with different logic encodings. An ultrabroad operating wavelength range from 700 to 1000 nm, and an ultrahigh output logic-state contrast-ratio of more than 25 dB are realized experimentally. No high power requirement is needed. Though nanoscale SPP light source and the logic comparator device are integrated into the same plasmonic chip, an ultrasmall feature size is maintained. This work not only paves a way for the realization of complex logic device such as adders and multiplier, but also opens up the possibility for realizing quantum solid chips based on plasmonic circuits. PMID:24463956

  15. All-optical tuning of a nonlinear silicon microring assisted microwave photonic filter: theory and experiment.

    PubMed

    Long, Yun; Wang, Jian

    2015-07-13

    We propose and demonstrate an all-optical tuning mechanism to tune the response of a microwave photonic filter (MPF) based on a nonlinear silicon microring resonator (MRR). The tuning mechanism relies on the optical nonlinearities induced resonant wavelength shift in the silicon MRR, leading to the change of frequency difference between the optical carrier frequency and resonant frequency of the silicon MRR. A detailed theoretical model is established to describe the operation of the proposed all-optical tunable MPF. Two cases are studied in the experiment, i.e. the optical carrier frequency is located at the left or right side of the MRR resonant frequency. Both forward and backward pumping configurations in each case are demonstrated. Using the fabricated silicon MRR and exploiting light to control light, the central frequency of the notch MPF can be flexibly tuned by adjusting the pump light power. Moreover, the presented all-optical tuning mechanism might also facilitate interesting applications such as microwave switching and microwave modulation. PMID:26191838

  16. 10Gbit/s all-optical NRZ to RZ conversion based on TOAD

    NASA Astrophysics Data System (ADS)

    Yan, Yumei; Yin, Lina; Zhou, Yunfeng; Liu, Guoming; Wu, Jian; Lin, Jintong

    2006-01-01

    Future network will include wavelength division multiplexing (WDM) and optical time division multiplexing (OTDM) technologies. All-optical format conversion between their respective preferable data formats, non-return-to-zero (NRZ) and return-to-zero (RZ), may become an important technology. In this paper, 10Gbit/s all-optical NRZ-to-RZ conversion is demonstrated based on terahertz optical asymmetric demultiplexer (TOAD) using clock all-optically recovered from the NRZ signal for the first time. The clock component is enhanced in an SOA and the pseudo-return-to-zero (PRZ) signal is filtered. The PRZ signal is input into an injection mode-locked fiber ring laser for clock recovery. The recovered clock and the NRZ signal are input into TOAD as pump signal and probe signal, respectively, and format conversion is performed. The quality of the converted RZ signal is determined by that of the recovered clock and the NRZ signal, whereas hardly influenced by gain recovery time of the SOA. In the experimental demonstration, the obtained RZ signal has an extinction ratio of 8.7dB and low pattern dependency. After conversion, the spectrum broadens obviously and shows multimode structure with spectrum interval of 0.08nm, which matches with the bit rate 10Gbit/s. Furthermore, this format conversion method has some tolerance on the pattern dependency of the clock signal.

  17. All-Optical Wavelength Conversion by Picosecond Burst Absorption in Colloidal PbS Quantum Dots.

    PubMed

    Geiregat, Pieter; Houtepen, Arjan J; Van Thourhout, Dries; Hens, Zeger

    2016-01-26

    All-optical approaches to change the wavelength of a data signal are considered more energy- and cost-effective than current wavelength conversion schemes that rely on back and forth switching between the electrical and optical domains. However, the lack of cost-effective materials with sufficiently adequate optoelectronic properties hampers the development of this so-called all-optical wavelength conversion. Here, we show that the interplay between intraband and band gap absorption in colloidal quantum dots leads to a very strong and ultrafast modulation of the light absorption after photoexcitation in which slow components linked to exciton recombination are eliminated. This approach enables all-optical wavelength conversion at rates matching state-of-the-art convertors in speed, yet with cost-effective solution-processable materials. Moreover, the stronger light-matter interaction allows for implementation in small-footprint devices with low switching energies. Being a generic property, the demonstrated effect opens a pathway toward low-power integrated photonics based on colloidal quantum dots as the enabling material. PMID:26692112

  18. Software Defined Networking (SDN) controlled all optical switching networks with multi-dimensional switching architecture

    NASA Astrophysics Data System (ADS)

    Zhao, Yongli; Ji, Yuefeng; Zhang, Jie; Li, Hui; Xiong, Qianjin; Qiu, Shaofeng

    2014-08-01

    Ultrahigh throughout capacity requirement is challenging the current optical switching nodes with the fast development of data center networks. Pbit/s level all optical switching networks need to be deployed soon, which will cause the high complexity of node architecture. How to control the future network and node equipment together will become a new problem. An enhanced Software Defined Networking (eSDN) control architecture is proposed in the paper, which consists of Provider NOX (P-NOX) and Node NOX (N-NOX). With the cooperation of P-NOX and N-NOX, the flexible control of the entire network can be achieved. All optical switching network testbed has been experimentally demonstrated with efficient control of enhanced Software Defined Networking (eSDN). Pbit/s level all optical switching nodes in the testbed are implemented based on multi-dimensional switching architecture, i.e. multi-level and multi-planar. Due to the space and cost limitation, each optical switching node is only equipped with four input line boxes and four output line boxes respectively. Experimental results are given to verify the performance of our proposed control and switching architecture.

  19. All-optical arithmetic unit with the help of terahertz-optical-asymmetric-demultiplexer-based tree architecture

    NASA Astrophysics Data System (ADS)

    Gayen, Dilip Kumar; Nath Roy, Jitendra

    2008-03-01

    An all-optical arithmetic unit with the help of terahertz-optical-asymmetric-demultiplexer (TOAD)-based tree architecture is proposed. We describe the all-optical arithmetic unit by using a set of all-optical multiplexer, all-optical full-adder, and optical switch. The all-optical arithmetic unit can be used to perform a fast central processor unit using optical hardware components. We have tried to exploit the advantages of both optical tree architecture and TOAD-based switch to design an integrated all-optical circuit that can perform binary addition, addition with carry, subtract with borrow, subtract (2's complement), double, increment, decrement, and transfer operations.

  20. Finite Feedback Cycling in Structural Equation Models

    ERIC Educational Resources Information Center

    Hayduk, Leslie A.

    2009-01-01

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

  1. Simple Optoelectronic Feedback in Microwave Oscillators

    NASA Technical Reports Server (NTRS)

    Maleki, Lute; Iltchenko, Vladimir

    2009-01-01

    A proposed method of stabilizing microwave and millimeter-wave oscillators calls for the use of feedback in optoelectronic delay lines characterized by high values of the resonance quality factor (Q). The method would extend the applicability of optoelectronic feedback beyond the previously reported class of optoelectronic oscillators that comprise two-port electronic amplifiers in closed loops with high-Q feedback circuits.

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  5. All-Optical Half-Adder Using All-Optical XOR and AND Gates for Optical Generation of "Sum" and "Carry"

    NASA Astrophysics Data System (ADS)

    Menezes, J. W. M.; Fraga, W. B.; Ferreira, A. C.; Guimarães, G. F.; Filho, A. F. G. F.; Sobrinho, C. S.; Sombra, A. S. B.

    2010-07-01

    In this article, a numerical simulation study using the symmetric planar three-core non-linear directional coupler, operating with a short light pulse (2 ps), for the implementation of an all-optical half-adder is presented. The half-adder is the key building block for many digital processing functions such as shift register, binary counter, and serial parallel data converters. Optical couplers are an important component for application in optical fiber telecommunication systems and all integrated optical circuits because of very high switching speeds (as high as the femto-second range). In this numerical simulation, the symmetric planar three-core non-linear directional coupler presents a planar symmetrical structure with three cores in a parallel equidistant arrangement, three logical inputs (CP, A, and B), and two output logic functions (C and S). The CP(ΔΦ) input is a control pulse with a phase difference ΔΦ = Δθπ (0 ≤ Δθ ≤ 2) between inputs A and B (logical inputs of the half-adder) and one amplitude discriminator circuit. The half-adder uses two output logic functions of Sum(S) and Carry(C), which can be demonstrated by using XOR and AND gates, respectively. For the half-adder, the phase [ΔΦMIN, ΔΦMAX] intervals are studied, allowing the operation of the device as a half-adder. For the selected range of CP(ΔΦBETTER), the extinction ratio was studied, the compression factors for both Sum(S) and Carry(C) outputs of the symmetric planar three-core non-linear directional coupler.

  6. Anomalous nonlinear absorption in epsilon-near-zero materials: optical limiting and all-optical control.

    PubMed

    Vincenti, M A; de Ceglia, D; Scalora, Michael

    2016-08-01

    We investigate nonlinear absorption in films of epsilon-near-zero materials. The combination of large local electric fields at the fundamental frequency and material losses at the harmonic frequencies induce unusual intensity-dependent phenomena. We predict that the second-order nonlinearity of a low-damping, epsilon-near-zero slab produces an optical limiting effect that mimics a two-photon absorption process. Anomalous absorption profiles that depend on low permittivity values at the pump frequency are also predicted for third-order nonlinearities. These findings suggest new opportunities for all-optical light control and novel ways to design reconfigurable and tunable nonlinear devices. PMID:27472631

  7. First demonstration of a staged all-optical laser wakefield acceleration

    SciTech Connect

    Kaganovich, D.; Ting, A.; Gordon, D.F.; Hubbard, R.F.; Jones, T.G.; Zigler, A.; Sprangle, P.

    2005-10-01

    A proof-of-principle experiment on staged all-optical laser wakefield acceleration was performed at the Naval Research Laboratory. Electrons with <1 MeV energy created by the interaction of a 2 TW laser beam with a nitrogen gas jet were injected and accelerated to more than 20 MeV in a plasma wakefield generated by a 10 TW laser beam in a helium gas jet. The energy gain occurred in a narrow time window of 3 ps between the injection and acceleration laser beams, and within a tight spatial alignment of {approx}10 {mu}m.

  8. All-Optical Steering of Laser-Wakefield-Accelerated Electron Beams

    SciTech Connect

    Popp, A.; Osterhoff, J.; Major, Zs.; Hoerlein, R.; Fuchs, M.; Weingartner, R.; Krausz, F.; Gruener, F.; Karsch, S.; Vieira, J.; Marti, M.; Fonseca, R. A.; Martins, S. F.; Silva, L. O.

    2010-11-19

    We investigate the influence of a tilted laser-pulse-intensity front on laser-wakefield acceleration. Such asymmetric light pulses may be exploited to obtain control over the electron-bunch-pointing direction and in our case allowed for reproducible electron-beam steering in an all-optical way within an 8 mrad opening window with respect to the initial laser axis. We also discovered evidence of collective electron-betatron oscillations due to off-axis electron injection into the wakefield induced by a pulse-front tilt. These findings are supported by 3D particle-in-cell simulations.

  9. All-optical steering of laser-wakefield-accelerated electron beams.

    PubMed

    Popp, A; Vieira, J; Osterhoff, J; Major, Zs; Hörlein, R; Fuchs, M; Weingartner, R; Rowlands-Rees, T P; Marti, M; Fonseca, R A; Martins, S F; Silva, L O; Hooker, S M; Krausz, F; Grüner, F; Karsch, S

    2010-11-19

    We investigate the influence of a tilted laser-pulse-intensity front on laser-wakefield acceleration. Such asymmetric light pulses may be exploited to obtain control over the electron-bunch-pointing direction and in our case allowed for reproducible electron-beam steering in an all-optical way within an 8 mrad opening window with respect to the initial laser axis. We also discovered evidence of collective electron-betatron oscillations due to off-axis electron injection into the wakefield induced by a pulse-front tilt. These findings are supported by 3D particle-in-cell simulations. PMID:21231309

  10. Coherent-population-trapping resonances with linearly polarized light for all-optical miniature atomic clocks

    SciTech Connect

    Zibrov, Sergei A.; Velichansky, Vladimir L.; Novikova, Irina; Phillips, David F.; Walsworth, Ronald L.; Zibrov, Alexander S.; Taichenachev, Alexey V.; Yudin, Valery I.

    2010-01-15

    We present a joint theoretical and experimental characterization of the coherent population trapping (CPT) resonance excited on the D{sub 1} line of {sup 87}Rb atoms by bichromatic linearly polarized laser light. We observe high-contrast transmission resonances (up to approx =25%), which makes this excitation scheme promising for miniature all-optical atomic clock applications. We also demonstrate cancellation of the first-order light shift by proper choice of the frequencies and relative intensities of the two laser-field components. Our theoretical predictions are in good agreement with the experimental results.

  11. Three-photon-absorption resonance for all-optical atomic clocks

    SciTech Connect

    Zibrov, Sergei; Novikova, Irina; Phillips, David F.; Taichenachev, Aleksei V.; Yudin, Valeriy I.; Walsworth, Ronald L.; Zibrov, Alexander S.

    2005-07-15

    We report an experimental study of an all-optical three-photon-absorption resonance (known as an 'N resonance') and discuss its potential application as an alternative to atomic clocks based on coherent population trapping. We present measurements of the N-resonance contrast, width and light shift for the D{sub 1} line of {sup 87}Rb with varying buffer gases, and find good agreement with an analytical model of this resonance. The results suggest that N resonances are promising for atomic clock applications.

  12. A novel ultrafast all-optical NRZ to RZ format converter based on Sagnac interferometric structure

    NASA Astrophysics Data System (ADS)

    Chen, Zhixin

    2008-11-01

    A simple novel ultrafast scheme of all-optical nonreturn-to-zero(NRZ) to return-to-zero(RZ) is proposed based on Sagnac interferometric structure. The operations of this scheme at 40Gbit/s 27-1 PRBS sequences are simulated correctly with the output extinction ratio more than 19.1dB. Through built theoretical model and numerical analysis, the operating characteristics of the scheme are illustrated. Furthermore, the carrier recovery time of the SOA is no more a crucial parameter to restrict the operation speed of this scheme.

  13. Realization of an all-optical zero to pi cross-phase modulation jump.

    PubMed

    Camacho, Ryan M; Dixon, P Ben; Glasser, Ryan T; Jordan, Andrew N; Howell, John C

    2009-01-01

    We report on the experimental demonstration of an all-optical pi cross-phase modulation jump. By performing a preselection, an optically induced unitary transformation, and then a postselection on the polarization degree of freedom, the phase of the output beam acquires either a zero or pi phase shift (with no other possible values). The postselection results in optical loss in the output beam. An input state may be chosen near the resulting phase singularity, yielding a pi phase shift even for weak interaction strengths. The scheme is experimentally demonstrated using a coherently prepared dark state in a warm atomic cesium vapor. PMID:19257193

  14. All-optical trion generation in single-walled carbon nanotubes.

    PubMed

    Santos, Silvia M; Yuma, Bertrand; Berciaud, Stéphane; Shaver, Jonah; Gallart, Mathieu; Gilliot, Pierre; Cognet, Laurent; Lounis, Brahim

    2011-10-28

    We present evidence of all-optical trion generation and emission in pristine single-walled carbon nanotubes (SWCNTs). Luminescence spectra, recorded on individual SWCNTs over a large cw excitation intensity range, show trion emission peaks redshifted with respect to the bright exciton peak. Clear chirality dependence is observed for 22 separate SWCNT species, allowing for determination of electron-hole exchange interaction and trion binding energy contributions. Luminescence data together with ultrafast pump-probe experiments on chirality-sorted bulk samples suggest that exciton-exciton annihilation processes generate dissociated carriers that allow for trion creation upon a subsequent photon absorption event. PMID:22107671

  15. Spin-based all-optical quantum computation with quantum dots: Understanding and suppressing decoherence

    SciTech Connect

    Calarco, T.; Datta, A.; Fedichev, P.; Zoller, P.; Pazy, E.

    2003-07-01

    We present an all-optical implementation of quantum computation using semiconductor quantum dots. Quantum memory is represented by the spin of an excess electron stored in each dot. Two-qubit gates are realized by switching on trion-trion interactions between different dots. State selectivity is achieved via conditional laser excitation exploiting Pauli exclusion principle. Read out is performed via a quantum-jump technique. We analyze the effect on our scheme's performance of the main imperfections present in real quantum dots: exciton decay, hole mixing, and phonon decoherence. We introduce an adiabatic gate procedure that allows one to circumvent these effects and evaluate quantitatively its fidelity.

  16. Single Shot Radiography Using an All-optical Compton Backscattering Source

    NASA Astrophysics Data System (ADS)

    Döpp, A.; Guillaume, E.; Thaury, C.; Gautier, J.; Lifschitz, A.; Conejero, E.; Ruiz, C.; Malka, V.; Rousse, A.; Phuoc, K. Ta

    The development of compact laser-based synchrotron sources is a field of active research. Here we present recent results on an all-optical Compton backscattering source using laser-accelerated electrons and a plasma mirror, as introduced in [K. Ta Phuoc et al., Nature Photonics 6 (5) (2012) 308-311]. Scattering of quasi-monoenergetic electrons of up to 200 MeV energy with their proper drive-beam leads to emission of femtosecond X-ray pulses, whose energies exceed 100 keV. We demonstrate that the photon yield from the source is sufficient to illuminate a centimeter-size sample placed 90 centimeters behind the source.

  17. Polarization insensitive all-optical wavelength conversion of polarization multiplexed signals using co-polarized pumps.

    PubMed

    Anthur, Aravind P; Zhou, Rui; O'Duill, Sean; Walsh, Anthony J; Martin, Eamonn; Venkitesh, Deepa; Barry, Liam P

    2016-05-30

    We study and experimentally validate the vector theory of four-wave mixing (FWM) in semiconductor optical amplifiers (SOA). We use the vector theory of FWM to design a polarization insensitive all-optical wavelength converter, suitable for advanced modulation formats, using non-degenerate FWM in SOAs and parallelly polarized pumps. We demonstrate the wavelength conversion of polarization-multiplexed (PM)-QPSK, PM-16QAM and a Nyquist WDM super-channel modulated with PM-QPSK signals at a baud rate of 12.5 GBaud, with total data rates of 50 Gbps, 100 Gbps and 200 Gbps respectively. PMID:27410100

  18. All-optical flip-flop operation based on bistability in V-cavity laser.

    PubMed

    Wu, Yingchen; Zhu, Yu; Liao, Xiaolu; Meng, Jianjun; He, Jian-Jun

    2016-06-13

    We theoretically analyzed and experimentally demonstrated an injection-locking based all-optical flip-flop memory using a simple and compact tunable V-cavity laser (VCL). A bistable region in the tuning characteristics of the VCL is employed for the flip-flop operation. The state of the VCL can be set and reset by injecting signal pulses at two different wavelengths. The pulse power for both set and reset signal is only about 1 pJ. Short response times of about 150 ps are measured for storing and erasing. PMID:27410271

  19. All-optical transistor based on a cavity optomechanical system with a Bose-Einstein condensate

    SciTech Connect

    Chen, Bin; Jiang, Cheng; Li, Jin-Jin; Zhu, Ka-Di

    2011-11-15

    We propose a scheme of an all-optical transistor based on a coupled Bose-Einstein condensate cavity system. The calculated results show that, in such an optomechanical system, the transmission of the probe beam is strongly dependent on the optical pump power. Therefore, the optical pump field can serve as a ''gate'' field of the transistor, effectively controlling the propagation of the probe field (the ''signal'' field). The scheme proposed here may have potential applications in optical communication and quantum information processing.

  20. All-optical atom surface traps implemented with one-dimensional planar diffractive microstructures.

    PubMed

    Alloschery, O; Mathevet, R; Weiner, J; Lezec, H J

    2006-12-25

    We characterize the loading, containment and optical properties of all-optical atom traps implemented by diffractive focusing with one-dimensional (1D) microstructures milled on gold films. These on-chip Fresnel lenses with focal lengths of the order of a few hundred microns produce optical-gradient-dipole traps. Cold atoms are loaded from a mirror magneto-optical trap (MMOT) centered a few hundred microns above the gold mirror surface. Details of loading optimization are reported and perspectives for future development of these structures are discussed. PMID:19532148