Plasmids as stochastic model systems
NASA Astrophysics Data System (ADS)
Paulsson, Johan
2003-05-01
Plasmids are self-replicating gene clusters present in on average 2-100 copies per bacterial cell. To reduce random fluctuations and thereby avoid extinction, they ubiquitously autoregulate their own synthesis using negative feedback loops. Here I use van Kampen's Ω-expansion for a two-dimensional model of negative feedback including plasmids and ther replication inhibitors. This analytically summarizes the standard perspective on replication control -- including the effects of sensitivity amplification, exponential time-delays and noisy signaling. I further review the two most common molecular sensitivity mechanisms: multistep control and cooperativity. Finally, I discuss more controversial sensitivity schemes, such as noise-enhanced sensitivity, the exploitation of small-number combinatorics and double-layered feedback loops to suppress noise in disordered environments.
Modeling gene regulatory network motifs using statecharts
2012-01-01
Background Gene regulatory networks are widely used by biologists to describe the interactions among genes, proteins and other components at the intra-cellular level. Recently, a great effort has been devoted to give gene regulatory networks a formal semantics based on existing computational frameworks. For this purpose, we consider Statecharts, which are a modular, hierarchical and executable formal model widely used to represent software systems. We use Statecharts for modeling small and recurring patterns of interactions in gene regulatory networks, called motifs. Results We present an improved method for modeling gene regulatory network motifs using Statecharts and we describe the successful modeling of several motifs, including those which could not be modeled or whose models could not be distinguished using the method of a previous proposal. We model motifs in an easy and intuitive way by taking advantage of the visual features of Statecharts. Our modeling approach is able to simulate some interesting temporal properties of gene regulatory network motifs: the delay in the activation and the deactivation of the "output" gene in the coherent type-1 feedforward loop, the pulse in the incoherent type-1 feedforward loop, the bistability nature of double positive and double negative feedback loops, the oscillatory behavior of the negative feedback loop, and the "lock-in" effect of positive autoregulation. Conclusions We present a Statecharts-based approach for the modeling of gene regulatory network motifs in biological systems. The basic motifs used to build more complex networks (that is, simple regulation, reciprocal regulation, feedback loop, feedforward loop, and autoregulation) can be faithfully described and their temporal dynamics can be analyzed. PMID:22536967
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.
Relaxation oscillations and hierarchy of feedbacks in MAPK signaling
NASA Astrophysics Data System (ADS)
Kochańczyk, Marek; Kocieniewski, Paweł; Kozłowska, Emilia; Jaruszewicz-Błońska, Joanna; Sparta, Breanne; Pargett, Michael; Albeck, John G.; Hlavacek, William S.; Lipniacki, Tomasz
2017-01-01
We formulated a computational model for a MAPK signaling cascade downstream of the EGF receptor to investigate how interlinked positive and negative feedback loops process EGF signals into ERK pulses of constant amplitude but dose-dependent duration and frequency. A positive feedback loop involving RAS and SOS, which leads to bistability and allows for switch-like responses to inputs, is nested within a negative feedback loop that encompasses RAS and RAF, MEK, and ERK that inhibits SOS via phosphorylation. This negative feedback, operating on a longer time scale, changes switch-like behavior into oscillations having a period of 1 hour or longer. Two auxiliary negative feedback loops, from ERK to MEK and RAF, placed downstream of the positive feedback, shape the temporal ERK activity profile but are dispensable for oscillations. Thus, the positive feedback introduces a hierarchy among negative feedback loops, such that the effect of a negative feedback depends on its position with respect to the positive feedback loop. Furthermore, a combination of the fast positive feedback involving slow-diffusing membrane components with slower negative feedbacks involving faster diffusing cytoplasmic components leads to local excitation/global inhibition dynamics, which allows the MAPK cascade to transmit paracrine EGF signals into spatially non-uniform ERK activity pulses.
A minimal mathematical model combining several regulatory cycles from the budding yeast cell cycle.
Sriram, K; Bernot, G; Képès, F
2007-11-01
A novel topology of regulatory networks abstracted from the budding yeast cell cycle is studied by constructing a simple nonlinear model. A ternary positive feedback loop with only positive regulations is constructed with elements that activates the subsequent element in a clockwise fashion. A ternary negative feedback loop with only negative regulations is constructed with the elements that inhibit the subsequent element in an anticlockwise fashion. Positive feedback loop exhibits bistability, whereas the negative feedback loop exhibits limit cycle oscillations. The novelty of the topology is that the corresponding elements in these two homogeneous feedback loops are linked by the binary positive feedback loops with only positive regulations. This results in the emergence of mixed feedback loops in the network that displays complex behaviour like the coexistence of multiple steady states, relaxation oscillations and chaos. Importantly, the arrangement of the feedback loops brings in the notion of checkpoint in the model. The model also exhibits domino-like behaviour, where the limit cycle oscillations take place in a stepwise fashion. As the aforementioned topology is abstracted from the budding yeast cell cycle, the events that govern the cell cycle are considered for the present study. In budding yeast, the sequential activation of the transcription factors, cyclins and their inhibitors form mixed feedback loops. The transcription factors that involve in the positive regulation in a clockwise orientation generates ternary positive feedback loop, while the cyclins and their inhibitors that involve in the negative regulation in an anticlockwise orientation generates ternary negative feedback loop. The mutual regulation between the corresponding elements in the transcription factors and the cyclins and their inhibitors generates binary positive feedback loops. The bifurcation diagram constructed for the whole system can be related to the different events of the cell cycle in terms of dynamical system theory. The checkpoint mechanism that plays an important role in different phases of the cell cycle are accounted for by silencing appropriate feedback loops in the model.
Fan, Lei; Li, Ji-Yu; Yang, Chen; Huang, A-Ji; Shao, Zhi-Ming
2011-01-01
Previous studies have shown that let-7 can repress the post-transcriptional translation of LIN28, and LIN28 in turn could block the maturation of let-7, forming a double-negative feedback loop. In this study, we investigated the effect of germline genetic variants on regulation of the homeostasis of the let-7/LIN28 loop and breast cancer risk. We initially demonstrated that the T/C variants of rs3811463, a single nucleotide polymorphism (SNP) located near the let-7 binding site in LIN28, could lead to differential regulation of LIN28 by let-7. Specifically, the C allele of rs3811463 weakened let-7–induced repression of LIN28 mRNA, resulting in increased production of LIN28 protein, which could in turn down-regulate the level of mature let-7. This effect was then validated at the tissue level in that the normal breast tissue of individuals with the rs3811463-TC genotype expressed significantly lower levels of let-7 and higher levels of LIN28 protein than those individuals with the rs3811463-TT genotype. Because previous in vitro and ex vivo experiments have consistently suggested that LIN28 could promote cellular transformation, we then systematically evaluated the relationship between rs3811463 as well as other common LIN28 SNPs and the risk of breast cancer in a stepwise manner. The first hospital-based association study (n = 2,300) demonstrated that two SNPs were significantly associated with breast cancer risk, one of which was rs3811463, while the other was rs6697410. The C allele of the rs3811463 SNP corresponded to an increased risk of breast cancer with an odds ratio (OR) of 1.25 (P = 0.0091), which was successfully replicated in a second independent study (n = 1,156) with community-based controls. The combined P-value of the two studies was 8.0×10−5. Taken together, our study demonstrates that host genetic variants could disturb the regulation of the let-7/LIN28 double-negative feedback loop and alter breast cancer risk. PMID:21912531
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.
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.
A theory of circular organization and negative feedback: defining life in a cybernetic context.
Tsokolov, Sergey
2010-12-01
All life today incorporates a variety of systems controlled by negative feedback loops and sometimes amplified by positive feedback loops. The first forms of life necessarily also required primitive versions of feedback, yet surprisingly little emphasis has been given to the question of how feedback emerged out of primarily chemical systems. One chemical system has been established that spontaneously develops autocatalytic feedback, the Belousov-Zhabotinsky (BZ) reaction. In this essay, I discuss the BZ reaction as a possible model for similar reactions that could have occurred under prebiotic Earth conditions. The main point is that the metabolism of contemporary life evolved from primitive homeostatic networks regulated by negative feedback. Because life could not exist in their absence, feedback loops should be included in definitions of life.
A Theory of Circular Organization and Negative Feedback: Defining Life in a Cybernetic Context
NASA Astrophysics Data System (ADS)
Tsokolov, Sergey
2010-12-01
All life today incorporates a variety of systems controlled by negative feedback loops and sometimes amplified by positive feedback loops. The first forms of life necessarily also required primitive versions of feedback, yet surprisingly little emphasis has been given to the question of how feedback emerged out of primarily chemical systems. One chemical system has been established that spontaneously develops autocatalytic feedback, the Belousov-Zhabotinsky (BZ) reaction. In this essay, I discuss the BZ reaction as a possible model for similar reactions that could have occurred under prebiotic Earth conditions. The main point is that the metabolism of contemporary life evolved from primitive homeostatic networks regulated by negative feedback. Because life could not exist in their absence, feedback loops should be included in definitions of life.
Mean field analysis of a spatial stochastic model of a gene regulatory network.
Sturrock, M; Murray, P J; Matzavinos, A; Chaplain, M A J
2015-10-01
A gene regulatory network may be defined as a collection of DNA segments which interact with each other indirectly through their RNA and protein products. Such a network is said to contain a negative feedback loop if its products inhibit gene transcription, and a positive feedback loop if a gene product promotes its own production. Negative feedback loops can create oscillations in mRNA and protein levels while positive feedback loops are primarily responsible for signal amplification. It is often the case in real biological systems that both negative and positive feedback loops operate in parameter regimes that result in low copy numbers of gene products. In this paper we investigate the spatio-temporal dynamics of a single feedback loop in a eukaryotic cell. We first develop a simplified spatial stochastic model of a canonical feedback system (either positive or negative). Using a Gillespie's algorithm, we compute sample trajectories and analyse their corresponding statistics. We then derive a system of equations that describe the spatio-temporal evolution of the stochastic means. Subsequently, we examine the spatially homogeneous case and compare the results of numerical simulations with the spatially explicit case. Finally, using a combination of steady-state analysis and data clustering techniques, we explore model behaviour across a subregion of the parameter space that is difficult to access experimentally and compare the parameter landscape of our spatio-temporal and spatially-homogeneous models.
Fei, Juntao; Lu, Cheng
2018-04-01
In this paper, an adaptive sliding mode control system using a double loop recurrent neural network (DLRNN) structure is proposed for a class of nonlinear dynamic systems. A new three-layer RNN is proposed to approximate unknown dynamics with two different kinds of feedback loops where the firing weights and output signal calculated in the last step are stored and used as the feedback signals in each feedback loop. Since the new structure has combined the advantages of internal feedback NN and external feedback NN, it can acquire the internal state information while the output signal is also captured, thus the new designed DLRNN can achieve better approximation performance compared with the regular NNs without feedback loops or the regular RNNs with a single feedback loop. The new proposed DLRNN structure is employed in an equivalent controller to approximate the unknown nonlinear system dynamics, and the parameters of the DLRNN are updated online by adaptive laws to get favorable approximation performance. To investigate the effectiveness of the proposed controller, the designed adaptive sliding mode controller with the DLRNN is applied to a -axis microelectromechanical system gyroscope to control the vibrating dynamics of the proof mass. Simulation results demonstrate that the proposed methodology can achieve good tracking property, and the comparisons of the approximation performance between radial basis function NN, RNN, and DLRNN show that the DLRNN can accurately estimate the unknown dynamics with a fast speed while the internal states of DLRNN are more stable.
NASA Astrophysics Data System (ADS)
Wang, Liu-Suo; Li, Ning-Xi; Chen, Jing-Jia; Zhang, Xiao-Peng; Liu, Feng; Wang, Wei
2018-04-01
A positive and a negative feedback loop can induce bistability and oscillation, respectively, in biological networks. Nevertheless, they are frequently interlinked to perform more elaborate functions in many gene regulatory networks. Coupled positive and negative feedback loops may exhibit either oscillation or bistability depending on the intensity of the stimulus in some particular networks. It is less understood how the transition between the two dynamic modes is modulated by the positive and negative feedback loops. We developed an abstract model of such systems, largely based on the core p53 pathway, to explore the mechanism for the transformation of dynamic behaviors. Our results show that enhancing the positive feedback may promote or suppress oscillations depending on the strength of both feedback loops. We found that the system oscillates with low amplitudes in response to a moderate stimulus and switches to the on state upon a strong stimulus. When the positive feedback is activated much later than the negative one in response to a strong stimulus, the system exhibits long-term oscillations before switching to the on state. We explain this intriguing phenomenon using quasistatic approximation. Moreover, early switching to the on state may occur when the system starts from a steady state in the absence of stimuli. The interplay between the positive and negative feedback plays a key role in the transitions between oscillation and bistability. Of note, our conclusions should be applicable only to some specific gene regulatory networks, especially the p53 network, in which both oscillation and bistability exist in response to a certain type of stimulus. Our work also underscores the significance of transient dynamics in determining cellular outcome.
NASA Astrophysics Data System (ADS)
Ding, Hong-sheng; Tong, Li-ge; Chen, Geng-hua
2001-08-01
A new confocal Fabry-Pérot interferometer (CFPI) has been constructed. By using both of the conjugate rays, the sensitivity of the system was doubled. Moreover, the negative feedback control loop of a single-chip microcomputer (MCS-51) was applied to stabilize the working point at an optimum position. The system has been used in detecting the piezoelectric ultrasonic vibration on the surface of an aluminium sample.
Leung, Chi K.; Wang, Ying; Deonarine, Andrew; Tang, Lanlan; Prasse, Stephanie
2013-01-01
Negative-feedback loops between transcription factors and repressors in responses to xenobiotics, oxidants, heat, hypoxia, DNA damage, and infection have been described. Although common, the function of feedback is largely unstudied. Here, we define a negative-feedback loop between the Caenorhabditis elegans detoxification/antioxidant response factor SKN-1/Nrf and its repressor wdr-23 and investigate its function in vivo. Although SKN-1 promotes stress resistance and longevity, we find that tight regulation by WDR-23 is essential for growth and reproduction. By disabling SKN-1 transactivation of wdr-23, we reveal that feedback is required to set the balance between growth/reproduction and stress resistance/longevity. We also find that feedback is required to set the sensitivity of a core SKN-1 target gene to an electrophile. Interestingly, the effect of feedback on target gene induction is greatly reduced when the stress response is strongly activated, presumably to ensure maximum activation of cytoprotective genes during potentially fatal conditions. Our work provides a framework for understanding the function of negative feedback in inducible stress responses and demonstrates that manipulation of feedback alone can shift the balance of competing animal processes toward cell protection, health, and longevity. PMID:23836880
Dynamics and control of the ERK signaling pathway: Sensitivity, bistability, and oscillations.
Arkun, Yaman; Yasemi, Mohammadreza
2018-01-01
Cell signaling is the process by which extracellular information is transmitted into the cell to perform useful biological functions. The ERK (extracellular-signal-regulated kinase) signaling controls several cellular processes such as cell growth, proliferation, differentiation and apoptosis. The ERK signaling pathway considered in this work starts with an extracellular stimulus and ends with activated (double phosphorylated) ERK which gets translocated into the nucleus. We model and analyze this complex pathway by decomposing it into three functional subsystems. The first subsystem spans the initial part of the pathway from the extracellular growth factor to the formation of the SOS complex, ShC-Grb2-SOS. The second subsystem includes the activation of Ras which is mediated by the SOS complex. This is followed by the MAPK subsystem (or the Raf-MEK-ERK pathway) which produces the double phosphorylated ERK upon being activated by Ras. Although separate models exist in the literature at the subsystems level, a comprehensive model for the complete system including the important regulatory feedback loops is missing. Our dynamic model combines the existing subsystem models and studies their steady-state and dynamic interactions under feedback. We establish conditions under which bistability and oscillations exist for this important pathway. In particular, we show how the negative and positive feedback loops affect the dynamic characteristics that determine the cellular outcome.
Systems-Level Feedbacks of NRF2 Controlling Autophagy upon Oxidative Stress Response
Kapuy, Orsolya; Papp, Diána; Bánhegyi, Gábor
2018-01-01
Although the primary role of autophagy-dependent cellular self-eating is cytoprotective upon various stress events (such as starvation, oxidative stress, and high temperatures), sustained autophagy might lead to cell death. A transcription factor called NRF2 (nuclear factor erythroid-related factor 2) seems to be essential in maintaining cellular homeostasis in the presence of either reactive oxygen or nitrogen species generated by internal metabolism or external exposure. Accumulating experimental evidence reveals that oxidative stress also influences the balance of the 5′ AMP-activated protein kinase (AMPK)/rapamycin (mammalian kinase target of rapamycin or mTOR) signaling pathway, thereby inducing autophagy. Based on computational modeling here we propose that the regulatory triangle of AMPK, NRF2 and mTOR guaranties a precise oxidative stress response mechanism comprising of autophagy. We suggest that under conditions of oxidative stress, AMPK is crucial for autophagy induction via mTOR down-regulation, while NRF2 fine-tunes the process of autophagy according to the level of oxidative stress. We claim that the cellular oxidative stress response mechanism achieves an incoherently amplified negative feedback loop involving NRF2, mTOR and AMPK. The mTOR-NRF2 double negative feedback generates bistability, supporting the proper separation of two alternative steady states, called autophagy-dependent survival (at low stress) and cell death (at high stress). In addition, an AMPK-mTOR-NRF2 negative feedback loop suggests an oscillatory characteristic of autophagy upon prolonged intermediate levels of oxidative stress, resulting in new rounds of autophagy stimulation until the stress events cannot be dissolved. Our results indicate that AMPK-, NRF2- and mTOR-controlled autophagy induction provides a dynamic adaptation to altering environmental conditions, assuming their new frontier in biomedicine. PMID:29510589
Double closed-loop cascade control for lower limb exoskeleton with elastic actuation.
Zhu, Yanhe; Zheng, Tianjiao; Jin, Hongzhe; Yang, Jixing; Zhao, Jie
2015-01-01
Unlike traditional rigid actuators, the significant features of Series Elastic Actuator (SEA) are stable torque control, lower output impedance, impact resistance and energy storage. Recently, SEA has been applied in many exoskeletons. In such applications, a key issue is how to realize the human-exoskeleton movement coordination. In this paper, double closed-loop cascade control for lower limb exoskeleton with SEA is proposed. This control method consists of inner SEA torque loop and outer contact force loop. Utilizing the SEA torque control with a motor velocity loop, actuation performances of SEA are analyzed. An integrated exoskeleton control system is designed, in which joint angles are calculated by internal encoders and resolvers and contact forces are gathered by external pressure sensors. The double closed-loop cascade control model is established based on the feedback signals of internal and external sensor. Movement experiments are accomplished in our prototype of lower limb exoskeleton. Preliminary results indicate the exoskeleton movements with pilot can be realized stably by utilizing this double closed-loop cascade control method. Feasibility of the SEA in our exoskeleton robot and effectiveness of the control method are verified.
NASA Astrophysics Data System (ADS)
Siscoe, G. L.
2012-12-01
What is a system? A group of elements interacting with each other so as to create feedback loops. A system gets complex as the number of feedback loops increases and as the feedback loops exhibit time delays. Positive and negative feedback loops with time delays can give a system intrinsic time dependence and emergent properties. A system generally has input and output flows of something (matter, energy, money), which, if time variable, add an extrinsic component to its behavior. The magnetosphere is a group of elements interacting through feedback loops, some with time delays, driven by energy and mass inflow from a variable solar wind and outflow into the atmosphere and solar wind. The magnetosphere is a complex system. With no solar wind, there is no behavior. With solar wind, there is behavior from intrinsic and extrinsic causes. As a contribution to taking a macroscopic view of magnetospheric dynamics, to treating the magnetosphere as a globally integrated, complex entity, I will discus the magnetosphere as a system, its feedback loops, time delays, emergent behavior, and intrinsic and extrinsic behavior modes.
Combined input shaping and feedback control for double-pendulum systems
NASA Astrophysics Data System (ADS)
Mar, Robert; Goyal, Anurag; Nguyen, Vinh; Yang, Tianle; Singhose, William
2017-02-01
A control system combining input shaping and feedback is developed for double-pendulum systems subjected to external disturbances. The proposed control method achieves fast point-to-point response similar to open-loop input-shaping control. It also minimizes transient deflections during the motion of the system, and disturbance-induced residual swing using the feedback control. Effects of parameter variations such as the mass ratio of the double pendulum, the suspension length ratio, and the move distance were studied via numerical simulation. The most important results were also verified with experiments on a small-scale crane. The controller effectively suppresses the disturbances and is robust to modelling uncertainties and task variations.
Analytical study of robustness of a negative feedback oscillator by multiparameter sensitivity
2014-01-01
Background One of the distinctive features of biological oscillators such as circadian clocks and cell cycles is robustness which is the ability to resume reliable operation in the face of different types of perturbations. In the previous study, we proposed multiparameter sensitivity (MPS) as an intelligible measure for robustness to fluctuations in kinetic parameters. Analytical solutions directly connect the mechanisms and kinetic parameters to dynamic properties such as period, amplitude and their associated MPSs. Although negative feedback loops are known as common structures to biological oscillators, the analytical solutions have not been presented for a general model of negative feedback oscillators. Results We present the analytical expressions for the period, amplitude and their associated MPSs for a general model of negative feedback oscillators. The analytical solutions are validated by comparing them with numerical solutions. The analytical solutions explicitly show how the dynamic properties depend on the kinetic parameters. The ratio of a threshold to the amplitude has a strong impact on the period MPS. As the ratio approaches to one, the MPS increases, indicating that the period becomes more sensitive to changes in kinetic parameters. We present the first mathematical proof that the distributed time-delay mechanism contributes to making the oscillation period robust to parameter fluctuations. The MPS decreases with an increase in the feedback loop length (i.e., the number of molecular species constituting the feedback loop). Conclusions Since a general model of negative feedback oscillators was employed, the results shown in this paper are expected to be true for many of biological oscillators. This study strongly supports that the hypothesis that phosphorylations of clock proteins contribute to the robustness of circadian rhythms. The analytical solutions give synthetic biologists some clues to design gene oscillators with robust and desired period. PMID:25605374
Lehrer, Paul; Eddie, David
2013-06-01
Systems theory has long been used in psychology, biology, and sociology. This paper applies newer methods of control systems modeling for assessing system stability in health and disease. Control systems can be characterized as open or closed systems with feedback loops. Feedback produces oscillatory activity, and the complexity of naturally occurring oscillatory patterns reflects the multiplicity of feedback mechanisms, such that many mechanisms operate simultaneously to control the system. Unstable systems, often associated with poor health, are characterized by absence of oscillation, random noise, or a very simple pattern of oscillation. This modeling approach can be applied to a diverse range of phenomena, including cardiovascular and brain activity, mood and thermal regulation, and social system stability. External system stressors such as disease, psychological stress, injury, or interpersonal conflict may perturb a system, yet simultaneously stimulate oscillatory processes and exercise control mechanisms. Resonance can occur in systems with negative feedback loops, causing high-amplitude oscillations at a single frequency. Resonance effects can be used to strengthen modulatory oscillations, but may obscure other information and control mechanisms, and weaken system stability. Positive as well as negative feedback loops are important for system function and stability. Examples are presented of oscillatory processes in heart rate variability, and regulation of autonomic, thermal, pancreatic and central nervous system processes, as well as in social/organizational systems such as marriages and business organizations. Resonance in negative feedback loops can help stimulate oscillations and exercise control reflexes, but also can deprive the system of important information. Empirical hypotheses derived from this approach are presented, including that moderate stress may enhance health and functioning.
Biocybernetic system evaluates indices of operator engagement in automated task
NASA Technical Reports Server (NTRS)
Pope, A. T.; Bogart, E. H.; Bartolome, D. S.
1995-01-01
A biocybernetic system has been developed as a method to evaluate automated flight deck concepts for compatibility with human capabilities. A biocybernetic loop is formed by adjusting the mode of operation of a task set (e.g., manual/automated mix) based on electroencephalographic (EEG) signals reflecting an operator's engagement in the task set. A critical issue for the loop operation is the selection of features of the EEG to provide an index of engagement upon which to base decisions to adjust task mode. Subjects were run in the closed-loop feedback configuration under four candidate and three experimental control definitions of an engagement index. The temporal patterning of system mode switching was observed for both positive and negative feedback of the index. The indices were judged on the basis of their relative strength in exhibiting expected feedback control system phenomena (stable operation under negative feedback and unstable operation under positive feedback). Of the candidate indices evaluated in this study, an index constructed according to the formula, beta power/(alpha power + theta power), reflected task engagement best.
NASA Astrophysics Data System (ADS)
Kruk, Marek; Kobos, Justyna; Nawrocka, Lidia; Parszuto, Katarzyna
2018-04-01
This study aims to demonstrate that factors associated with climate dynamics, such as temperature and wind, affect the ecosystem of the shallow Vistula Lagoon in the southern Baltic and cause nutrient forms phytoplankton interactions: the growth of biomass and constraints of it. This occurs through a network of direct and indirect relationships between environmental and phytoplankton factors, including interactions of positive and negative feedback loops. Path analysis supported by structural equation modeling (SEM) was used to test hypotheses regarding the impact of climate factors on algal assemblages. Increased phytoplankton biomass was affected directly by water temperature and salinity, while the wind speed effect was indirect as it resulted in increased concentrations of suspended solids (SS) in the water column. Simultaneously, the concentration of SS in the water was positively correlated with particulate organic carbon (POC), particulate nitrogen (PN), and particulate phosphorus (PP), and was negatively correlated with the total nitrogen to phosphorus (N:P) ratio. Particulate forms of C, N, and phosphorus (P), concentrations of soluble reactive phosphorus (SRP) and nitrate and nitrite nitrogen (NO3-N + NO2-N), and ratios of the total N:P and DIN:SRP, all indirectly effected Cyanobacteria C concentrations. These processes influence other phytoplankton groups (Chlorophyta, Bacillariophyceae and the picophytoplankton fraction). Increased levels of SRP associated with organic matter (POC), which stemmed from reduced DIN:SRP ratios, contributed to increased Cyanoprokaryota and picophytoplankton C concentrations, which created a positive feedback loop. However, a simultaneous reduction in the total N:P ratio could have inhibited increases in the biomass of these assemblages by limiting N, which likely formed a negative feedback loop. The study indicates that the nutrients-phytoplankton feedback loop phenomenon can intensify eutrophication in a temperate lagoon, including increases of the biomass of Cyanobacteria and picophytoplankton. However, it can also constrain this increase.
Yu, Tae Jun; Hong, Kyung-Han; Choi, Hyun-Gyug; Sung, Jae Hee; Choi, Il Woo; Ko, Do-Kyeong; Lee, Jongmin; Kim, Junwon; Kim, Dong Eon; Nam, Chang Hee
2007-06-25
We demonstrate a long-term operation with reduced phase noise in the carrier-envelope-phase (CEP) stabilization process by employing a double feedback loop and an improved signal detection in the direct locking technique [Opt. Express 13, 2969 (2005)]. A homodyne balanced detection method is employed for efficiently suppressing the dc noise in the f-2f beat signal, which is converted into the CEP noise in the direct locking loop working at around zero carrier-envelope offset frequency (f(ceo)). In order to enhance the long-term stability, we have used the double feedback scheme that modulates both the oscillator pump power for a fast control and the intracavity-prism insertion depth for a slow and high-dynamic-range control. As a result, the in-loop phase jitter is reduced from 50 mrad of the previous result to 29 mrad, corresponding to 13 as in time scale, and the long-term stable operation is achieved for more than 12 hours.
The Trade-Off Mechanism in Mammalian Circadian Clock Model with Two Time Delays
NASA Astrophysics Data System (ADS)
Yan, Jie; Kang, Xiaxia; Yang, Ling
Circadian clock is an autonomous oscillator which orchestrates the daily rhythms of physiology and behaviors. This study is devoted to explore how a positive feedback loop affects the dynamics of mammalian circadian clock. We simplify an experimentally validated mathematical model in our previous work, to a nonlinear differential equation with two time delays. This simplified mathematical model incorporates the pacemaker of mammalian circadian clock, a negative primary feedback loop, and a critical positive auxiliary feedback loop, Rev-erbα/Cry1 loop. We perform analytical studies of the system. Delay-dependent conditions for the asymptotic stability of the nontrivial positive steady state of the model are investigated. We also prove the existence of Hopf bifurcation, which leads to self-sustained oscillation of mammalian circadian clock. Our theoretical analyses show that the oscillatory regime is reduced upon the participation of the delayed positive auxiliary loop. However, further simulations reveal that the auxiliary loop can enable the circadian clock gain widely adjustable amplitudes and robust period. Thus, the positive auxiliary feedback loop may provide a trade-off mechanism, to use the small loss in the robustness of oscillation in exchange for adaptable flexibility in mammalian circadian clock. The results obtained from the model may gain new insights into the dynamics of biological oscillators with interlocked feedback loops.
Miró-Bueno, Jesús M.; Rodríguez-Patón, Alfonso
2011-01-01
Negative and positive transcriptional feedback loops are present in natural and synthetic genetic oscillators. A single gene with negative transcriptional feedback needs a time delay and sufficiently strong nonlinearity in the transmission of the feedback signal in order to produce biochemical rhythms. A single gene with only positive transcriptional feedback does not produce oscillations. Here, we demonstrate that this single-gene network in conjunction with a simple negative interaction can also easily produce rhythms. We examine a model comprised of two well-differentiated parts. The first is a positive feedback created by a protein that binds to the promoter of its own gene and activates the transcription. The second is a negative interaction in which a repressor molecule prevents this protein from binding to its promoter. A stochastic study shows that the system is robust to noise. A deterministic study identifies that the dynamics of the oscillator are mainly driven by two types of biomolecules: the protein, and the complex formed by the repressor and this protein. The main conclusion of this paper is that a simple and usual negative interaction, such as degradation, sequestration or inhibition, acting on the positive transcriptional feedback of a single gene is a sufficient condition to produce reliable oscillations. One gene is enough and the positive transcriptional feedback signal does not need to activate a second repressor gene. This means that at the genetic level an explicit negative feedback loop is not necessary. The model needs neither cooperative binding reactions nor the formation of protein multimers. Therefore, our findings could help to clarify the design principles of cellular clocks and constitute a new efficient tool for engineering synthetic genetic oscillators. PMID:22205920
Lehrer, Paul; Eddie, David
2013-01-01
Systems theory has long been applied in psychology, biology, and sociology. This paper applies newer methods of control systems modeling to the assessment of system stability in health and disease. Control systems can be characterized as open or closed systems with feedback loops. Feedback produces oscillatory activity, and the complexity of naturally occurring oscillatory patterns reflects the multiplicity of feedback mechanisms, such that many mechanisms operate simultaneously to control the system. Unstable systems, often associated with poor health, are characterized by absence of oscillation, random noise, or a very simple pattern of oscillation. This modeling approach can be applied to a diverse range of phenomena, including cardiovascular and brain activity, mood and thermal regulation, and social system stability. External system stressors such as disease, psychological stress, injury, or interpersonal conflict may perturb a system, yet simultaneously stimulate oscillatory processes and exercise control mechanisms. Resonance can occur in systems with negative feedback loops, causing high-amplitude oscillations at a single frequency. Resonance effects can be used to strengthen modulatory oscillations, but may obscure other information and control mechanisms, and weaken system stability. Positive as well as negative feedback loops are important for system function and stability. Examples are presented of oscillatory processes in heart rate variability, and regulation of autonomic, thermal, pancreatic and central nervous system processes, as well as in social/organizational systems such as marriages and business organizations. Resonance in negative feedback loops can help stimulate oscillations and exercise control reflexes, but also can deprive the system of important information. Empirical hypotheses derived from this approach are presented, including that moderate stress may enhance health and functioning. PMID:23572244
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ren, Jinqi; Cook, Aaron A.; Bergmeier, Wolfgang
The dynamic regulation of ERK1 and -2 (ERK1/2) is required for precise signal transduction controlling cell proliferation, differentiation, and survival. However, the underlying mechanisms regulating the activation of ERK1/2 are not completely understood. In this study, we show that phosphorylation of RasGRP2, a guanine nucleotide exchange factor (GEF), inhibits its ability to activate the small GTPase Rap1 that ultimately leads to decreased activation of ERK1/2 in cells. ERK2 phosphorylates RasGRP2 at Ser394 located in the linker region implicated in its autoinhibition. These studies identify RasGRP2 as a novel substrate of ERK1/2 and define a negative-feedback loop that regulates the BRaf–MEK–ERKmore » signaling cascade. This negative-feedback loop determines the amplitude and duration of active ERK1/2. -- Highlights: •ERK2 phosphorylates the guanine nucleotide exchange factor RasGRP2 at Ser394. •Phosphorylated RasGRP2 has decreased capacity to active Rap1b in vitro and in cells. •Phosphorylation of RasGRP2 by ERK1/2 introduces a negative-feedback loop into the BRaf-MEK-ERK pathway.« less
Antagonistic autoregulation speeds up a homogeneous response in Escherichia coli.
Rodrigo, Guillermo; Bajic, Djordje; Elola, Ignacio; Poyatos, Juan F
2016-10-31
By integrating positive and negative feedback loops, biological systems establish intricate gene expression patterns linked to multistability, pulsing, and oscillations. This depends on the specific characteristics of each interlinked feedback, and thus one would expect additional expression programs to be found. Here, we investigate one such program associated with an antagonistic positive and negative transcriptional autoregulatory motif derived from the multiple antibiotic resistance (mar) system of Escherichia coli. We studied the dynamics of the system by combining a predictive mathematical model with high-resolution experimental measures of the response both at the population and single-cell level. We show that in this motif the weak positive autoregulation does not slow down but rather enhances response speedup in combination with a strong negative feedback loop. This balance of feedback strengths anticipates a homogeneous population phenotype, which we corroborate experimentally. Theoretical analysis also emphasized the specific molecular properties that determine the dynamics of the mar phenotype. More broadly, response acceleration could provide a rationale for the presence of weak positive feedbacks in other biological scenarios exhibiting these interlinked regulatory architectures.
The Search for Perpetual Motion: Fatigue, Friction, and Drag in Quality Improvement.
Cumbler, Ethan; Pierce, Read
Most people who have worked on continuous quality improvement (QI) with teams in the clinical microsystem have experienced "change fatigue." Application of the "Limit-to-Growth" system archetype to QI teams within health care can be used to understand negative feedback loops generated by successful QI that can limit future progress. Awareness of these factors can result in actions designed to reduce drag on forward momentum. Leaders in health care QI can anticipate and minimize negative feedback loops that accumulate to slow subsequent progress of highly functioning improvement teams within clinical microsystems.
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.
High precision locating control system based on VCM for Talbot lithography
NASA Astrophysics Data System (ADS)
Yao, Jingwei; Zhao, Lixin; Deng, Qian; Hu, Song
2016-10-01
Aiming at the high precision and efficiency requirements of Z-direction locating in Talbot lithography, a control system based on Voice Coil Motor (VCM) was designed. In this paper, we built a math model of VCM and its moving characteristic was analyzed. A double-closed loop control strategy including position loop and current loop were accomplished. The current loop was implemented by driver, in order to achieve the rapid follow of the system current. The position loop was completed by the digital signal processor (DSP) and the position feedback was achieved by high precision linear scales. Feed forward control and position feedback Proportion Integration Differentiation (PID) control were applied in order to compensate for dynamic lag and improve the response speed of the system. And the high precision and efficiency of the system were verified by simulation and experiments. The results demonstrated that the performance of Z-direction gantry was obviously improved, having high precision, quick responses, strong real-time and easily to expend for higher precision.
Closed-loop fiber optic gyroscope with homodyne detection
NASA Astrophysics Data System (ADS)
Zhu, Yong; Qin, BingKun; Chen, Shufen
1996-09-01
Interferometric fiber optic gyroscope (IFOG) has been analyzed with autocontrol theory in this paper. An open-loop IFOG system is not able to restrain the bias drift, but a closed-loop IFOG system can do it very well using negative feedback in order to suppress zero drift. The result of our theoretic analysis and computer simulation indicate that the bias drift of a closed-loop system is smaller than an open- loop one.
Kim, Min-Sik; Hahn, Mi-Young; Cho, Yoobok; Cho, Sang-Nae; Roe, Jung-Hye
2009-09-01
Alternate sigma factors provide an effective way of diversifying bacterial gene expression in response to environmental changes. In Streptomyces coelicolor where more than 65 sigma factors are predicted, sigma(R) is the major regulator for response to thiol-oxidative stresses. sigma(R) becomes available when its bound anti-sigma factor RsrA is oxidized at sensitive cysteine thiols to form disulphide bonds. sigma(R) regulon includes genes for itself and multiple thiol-reducing systems, which constitute positive and negative feedback loops respectively. We found that the positive amplification loop involves an isoform of sigma(R) (sigma(R')) with an N-terminal extension of 55 amino acids, produced from an upstream start codon. A major difference between constitutive sigma(R) and inducible sigma(R') is that the latter is markedly unstable (t(1/2) approximately 10 min) compared with the former (> 70 min). The rapid turnover of sigma(R') is partly due to induced ClpP1/P2 proteases from the sigma(R) regulon. This represents a novel way of elaborating positive and negative feedback loops in a control circuit. Similar phenomenon may occur in other actinomycetes that harbour multiple start codons in the sigR homologous gene. We observed that sigH gene, the sigR orthologue in Mycobacterium smegmatis, produces an unstable larger isoform of sigma(H) upon induction by thiol-oxidative stress.
Feedback Synthesizes Neural Codes for Motion.
Clarke, Stephen E; Maler, Leonard
2017-05-08
In senses as diverse as vision, hearing, touch, and the electrosense, sensory neurons receive bottom-up input from the environment, as well as top-down input from feedback loops involving higher brain regions [1-4]. Through connectivity with local inhibitory interneurons, these feedback loops can exert both positive and negative control over fundamental aspects of neural coding, including bursting [5, 6] and synchronous population activity [7, 8]. Here we show that a prominent midbrain feedback loop synthesizes a neural code for motion reversal in the hindbrain electrosensory ON- and OFF-type pyramidal cells. This top-down mechanism generates an accurate bidirectional encoding of object position, despite the inability of the electrosensory afferents to generate a consistent bottom-up representation [9, 10]. The net positive activity of this midbrain feedback is additionally regulated through a hindbrain feedback loop, which reduces stimulus-induced bursting and also dampens the ON and OFF cell responses to interfering sensory input [11]. We demonstrate that synthesis of motion representations and cancellation of distracting signals are mediated simultaneously by feedback, satisfying an accepted definition of spatial attention [12]. The balance of excitatory and inhibitory feedback establishes a "focal" distance for optimized neural coding, whose connection to a classic motion-tracking behavior provides new insight into the computational roles of feedback and active dendrites in spatial localization [13, 14]. Copyright © 2017 Elsevier Ltd. All rights reserved.
2012-01-01
Background The three layer mitogen activated protein kinase (MAPK) signaling cascade exhibits different designs of interactions between its kinases and phosphatases. While the sequential interactions between the three kinases of the cascade are tightly preserved, the phosphatases of the cascade, such as MKP3 and PP2A, exhibit relatively diverse interactions with their substrate kinases. Additionally, the kinases of the MAPK cascade can also sequester their phosphatases. Thus, each topologically distinct interaction design of kinases and phosphatases could exhibit unique signal processing characteristics, and the presence of phosphatase sequestration may lead to further fine tuning of the propagated signal. Results We have built four architecturally distinct types of models of the MAPK cascade, each model with identical kinase-kinase interactions but unique kinases-phosphatases interactions. Our simulations unravelled that MAPK cascade’s robustness to external perturbations is a function of nature of interaction between its kinases and phosphatases. The cascade’s output robustness was enhanced when phosphatases were sequestrated by their target kinases. We uncovered a novel implicit/hidden negative feedback loop from the phosphatase MKP3 to its upstream kinase Raf-1, in a cascade resembling the B cell MAPK cascade. Notably, strength of the feedback loop was reciprocal to the strength of phosphatases’ sequestration and stronger sequestration abolished the feedback loop completely. An experimental method to verify the presence of the feedback loop is also proposed. We further showed, when the models were activated by transient signal, memory (total time taken by the cascade output to reach its unstimulated level after removal of signal) of a cascade was determined by the specific designs of interaction among its kinases and phosphatases. Conclusions Differences in interaction designs among the kinases and phosphatases can differentially shape the robustness and signal response behaviour of the MAPK cascade and phosphatase sequestration dramatically enhances the robustness to perturbations in each of the cascade. An implicit negative feedback loop was uncovered from our analysis and we found that strength of the negative feedback loop is reciprocally related to the strength of phosphatase sequestration. Duration of output phosphorylation in response to a transient signal was also found to be determined by the individual cascade’s kinase-phosphatase interaction design. PMID:22748295
Unifying Views of Autism Spectrum Disorders: A Consideration of Autoregulatory Feedback Loops
Mullins, Caitlin; Fishell, Gord
2017-01-01
Understanding the mechanisms underlying autism spectrum disorders (ASD) 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
Convection and the Soil-Moisture Precipitation Feedback
NASA Astrophysics Data System (ADS)
Schar, C.; Froidevaux, P.; Keller, M.; Schlemmer, L.; Langhans, W.; Schmidli, J.
2014-12-01
The soil moisture - precipitation (SMP) feedback is of key importance for climate and climate change. A positive SMP feedback tends to amplify the hydrological response to external forcings (and thereby fosters precipitation and drought extremes), while a negative SMP feedback tends to moderate the influence of external forcings (and thereby stabilizes the hydrological cycle). The sign of the SMP feedback is poorly constrained by the current literature. Theoretical, modeling and observational studies partly disagree, and have suggested both negative and positive feedback loops. Can wet soil anomalies indeed result in either an increase or a decrease of precipitation (positive or negative SMP feedback, respectively)? Here we investigate the local SMP feedback using real-case and idealized convection-resolving simulations. An idealized simulation strategy is developed, which is able to replicate both signs of the feedback loop, depending on the environmental parameters. The mechanism relies on horizontal soil moisture variations, which may develop and intensify spontaneously. The positive expression of the feedback is associated with the initiation of convection over dry soil patches, but the convective cells then propagate over wet patches, where they strengthen and preferentially precipitate. The negative feedback may occur when the wind profile is too weak to support the propagation of convective features from dry to wet areas. Precipitation is then generally weaker and falls preferentially over dry patches. The results highlight the role of the mid-tropospheric flow in determining the sign of the feedback. A key element of the positive feedback is the exploitation of both low convective inhibition (CIN) over dry patches (for the initiation of convection), and high CAPE over wet patches (for the generation of precipitation). The results of this study will also be discussed in relation to climate change scenarios that exhibit large biases in surface temperature and interannual variability over mid-latitude summer climates, both over Europe and North America. It is argued that parameterized convection may contribute towards such biases by overemphasizing a positive SMP feedback.
Temperature feedback control for long-term carrier-envelope phase locking.
Yun, Chenxia; Chen, Shouyuan; Wang, He; Chini, Michael; Chang, Zenghu
2009-09-20
We report a double feedback loop for the improvement of the carrier-envelope phase stabilization of a chirped mirror based femtosecond laser oscillator. By combining the control of the Ti:sapphire crystal temperature and the modulation of the pump power, the carrier envelope offset frequency, fCEO, was locked for close to 20 h, which is much longer than the typical phase stabilization time with only pump power modulation.
Adaptive Inner-Loop Rover Control
NASA Technical Reports Server (NTRS)
Kulkarni, Nilesh; Ippolito, Corey; Krishnakumar, Kalmanje; Al-Ali, Khalid M.
2006-01-01
Adaptive control technology is developed for the inner-loop speed and steering control of the MAX Rover. MAX, a CMU developed rover, is a compact low-cost 4-wheel drive, 4-wheel steer (double Ackerman), high-clearance agile durable chassis, outfitted with sensors and electronics that make it ideally suited for supporting research relevant to intelligent teleoperation and as a low-cost autonomous robotic test bed and appliance. The design consists of a feedback linearization based controller with a proportional - integral (PI) feedback that is augmented by an online adaptive neural network. The adaptation law has guaranteed stability properties for safe operation. The control design is retrofit in nature so that it fits inside the outer-loop path planning algorithms. Successful hardware implementation of the controller is illustrated for several scenarios consisting of actuator failures and modeling errors in the nominal design.
Wang, X G; Shang, X L; Lin, J
2016-05-01
Time-domain electromagnetic system can implement great depth detection. As for the electromagnetic system, the receiver utilized an air coil sensor, and the matching mode of the sensor employed the resistance matching method. By using the resistance matching method, the vibration of the coil in the time domain can be effectively controlled. However, the noise of the sensor, especially the noise at the resonance frequency, will be increased as well. In this paper, a novel design of a low noise induction coil sensor is proposed, and the experimental data and noise characteristics are provided. The sensor is designed based on the principle that the amplified voltage will be converted to current under the influence of the feedback resistance of the coil. The feedback loop around the induction coil exerts a magnetic field and sends the negative feedback signal to the sensor. The paper analyses the influence of the closed magnetic feedback loop on both the bandwidth and the noise of the sensor. The signal-to-noise ratio is improved dramatically.
Mode Selection Rules for a Two-Delay System with Positive and Negative Feedback Loops
NASA Astrophysics Data System (ADS)
Takahashi, Kin'ya; Kobayashi, Taizo
2018-04-01
The mode selection rules for a two-delay system, which has negative feedback with a short delay time t1 and positive feedback with a long delay time t2, are studied numerically and theoretically. We find two types of mode selection rules depending on the strength of the negative feedback. When the strength of the negative feedback |α1| (α1 < 0) is sufficiently small compared with that of the positive feedback α2 (> 0), 2m + 1-th harmonic oscillation is well sustained in a neighborhood of t1/t2 = even/odd, i.e., relevant condition. In a neighborhood of the irrelevant condition given by t1/t2 = odd/even or t1/t2 = odd/odd, higher harmonic oscillations are observed. However, if |α1| is slightly less than α2, a different mode selection rule works, where the condition t1/t2 = odd/even is relevant and the conditions t1/t2 = odd/odd and t1/t2 = even/odd are irrelevant. These mode selection rules are different from the mode selection rule of the normal two-delay system with two positive feedback loops, where t1/t2 = odd/odd is relevant and the others are irrelevant. The two types of mode selection rules are induced by individually different mechanisms controlling the Hopf bifurcation, i.e., the Hopf bifurcation controlled by the "boosted bifurcation process" and by the "anomalous bifurcation process", which occur for |α1| below and above the threshold value αth, respectively.
NASA Astrophysics Data System (ADS)
Zhong, Li-Xin; Xu, Wen-Juan; Chen, Rong-Da; Zhong, Chen-Yang; Qiu, Tian; Ren, Fei; He, Yun-Xing
2018-03-01
By incorporating market impact and momentum traders into an agent-based model, we investigate the conditions for the occurrence of self-reinforcing feedback loops and the coevolutionary mechanism of prices and strategies. For low market impact, the price fluctuations are originally large. The existence of momentum traders has little impact on the change of price fluctuations but destroys the equilibrium between the trend-following and trend-rejecting strategies. The trend-following herd behaviors become dominant. A self-reinforcing feedback loop exists. For high market impact, the existence of momentum traders leads to an increase in price fluctuations. The trend-following strategies of rational individuals are suppressed while the trend-following strategies of momentum traders are promoted. The crowd-anticrowd behaviors become dominant. A negative feedback loop exists. A theoretical analysis indicates that, for low market impact, the majority effect is beneficial for the trend-followers to earn more, which in turn promotes the trend-following strategies. For high market impact, the minority effect causes the trend-followers to suffer great losses, which in turn suppresses the trend-following strategies.
Periodic, Quasi-periodic and Chaotic Dynamics in Simple Gene Elements with Time Delays
Suzuki, Yoko; Lu, Mingyang; Ben-Jacob, Eshel; Onuchic, José N.
2016-01-01
Regulatory gene circuit motifs play crucial roles in performing and maintaining vital cellular functions. Frequently, theoretical studies of gene circuits focus on steady-state behaviors and do not include time delays. In this study, the inclusion of time delays is shown to entirely change the time-dependent dynamics for even the simplest possible circuits with one and two gene elements with self and cross regulations. These elements can give rise to rich behaviors including periodic, quasi-periodic, weak chaotic, strong chaotic and intermittent dynamics. We introduce a special power-spectrum-based method to characterize and discriminate these dynamical modes quantitatively. Our simulation results suggest that, while a single negative feedback loop of either one- or two-gene element can only have periodic dynamics, the elements with two positive/negative feedback loops are the minimalist elements to have chaotic dynamics. These elements typically have one negative feedback loop that generates oscillations, and another unit that allows frequent switches among multiple steady states or between oscillatory and non-oscillatory dynamics. Possible dynamical features of several simple one- and two-gene elements are presented in details. Discussion is presented for possible roles of the chaotic behavior in the robustness of cellular functions and diseases, for example, in the context of cancer. PMID:26876008
Periodic, Quasi-periodic and Chaotic Dynamics in Simple Gene Elements with Time Delays
NASA Astrophysics Data System (ADS)
Suzuki, Yoko; Lu, Mingyang; Ben-Jacob, Eshel; Onuchic, José N.
2016-02-01
Regulatory gene circuit motifs play crucial roles in performing and maintaining vital cellular functions. Frequently, theoretical studies of gene circuits focus on steady-state behaviors and do not include time delays. In this study, the inclusion of time delays is shown to entirely change the time-dependent dynamics for even the simplest possible circuits with one and two gene elements with self and cross regulations. These elements can give rise to rich behaviors including periodic, quasi-periodic, weak chaotic, strong chaotic and intermittent dynamics. We introduce a special power-spectrum-based method to characterize and discriminate these dynamical modes quantitatively. Our simulation results suggest that, while a single negative feedback loop of either one- or two-gene element can only have periodic dynamics, the elements with two positive/negative feedback loops are the minimalist elements to have chaotic dynamics. These elements typically have one negative feedback loop that generates oscillations, and another unit that allows frequent switches among multiple steady states or between oscillatory and non-oscillatory dynamics. Possible dynamical features of several simple one- and two-gene elements are presented in details. Discussion is presented for possible roles of the chaotic behavior in the robustness of cellular functions and diseases, for example, in the context of cancer.
Martins, Ruben; Simard, France; Provost, Jean-Sebastien; Monchi, Oury
2012-06-01
Some older individuals seem to use compensatory mechanisms to maintain high-level performance when submitted to cognitive tasks. However, whether and how these mechanisms affect fronto-striatal activity has never been explored. The purpose of this study was to investigate how aging affects brain patterns during the performance of a lexical analog of the Wisconsin Card Sorting Task, which has been shown to strongly depend on fronto-striatal activity. In the present study, both younger and older individuals revealed significant fronto-striatal loop activity associated with planning and execution of set-shifts, though age-related striatal activity reduction was observed. Most importantly, while the younger group showed the involvement of a "cognitive loop" during the receiving negative feedback period (which indicates that a set-shift will be required to perform the following trial) and the involvement of a "motor loop" during the matching after negative feedback period (when the set-shift must be performed), older participants showed significant activation of both loops during the matching after negative feedback period only. These findings are in agreement with the "load-shift" model postulated by Velanova et al. (Velanova K, Lustig C, Jacoby LL, Buckner RL. 2007. Evidence for frontally mediated controlled processing differences in older adults. Cereb Cortex. 17:1033-1046.) and indicate that the model is not limited to memory retrieval but also applies to executive processes relying on fronto-striatal regions.
Wei, Zhao; Guo, Haiyang; Liu, Zhaojian; Zhang, Xiyu; Liu, Qiao; Qian, Yanyan; Gong, Yaoqin; Shao, Changshun
2015-02-01
Tumor suppressor p53 is known to regulate the level of intracellular reactive oxygen species (ROS). It can either alleviate oxidative stress under physiological and mildly stressed conditions or exacerbate oxidative stress under highly stressed conditions. We here report that a p53-ROS positive feedback loop drives a senescence program in normal human fibroblasts (NHFs) and this senescence-driving loop is negatively regulated by CUL4B. CUL4B, which can assemble various ubiquitin E3 ligases, was found to be downregulated in stress-induced senescent cells, but not in replicative senescent cells. We observed that p53-dependent ROS production was significantly augmented and stress-induced senescence was greatly enhanced when CUL4B was absent or depleted. Ectopic expression of CUL4B, on the other hand, blunted p53 activation, reduced ROS production, and attenuated cellular senescence in cells treated with H2O2. CUL4B was shown to promote p53 ubiquitination and proteosomal degradation in NHFs exposed to oxidative stress, thus dampening the p53-dependent cellular senescence. Together, our results established a critical role of CUL4B in negatively regulating the p53-ROS positive feedback loop that drives cellular senescence. Copyright © 2014 Elsevier Inc. All rights reserved.
Impact of time delays on oscillatory dynamics of interlinked positive and negative feedback loops
NASA Astrophysics Data System (ADS)
Huang, Bo; Tian, Xinyu; Liu, Feng; Wang, Wei
2016-11-01
Interlinking a positive feedback loop (PFL) with a negative feedback loop (NFL) constitutes a typical motif in genetic networks, performing various functions in cell signaling. How time delay in feedback regulation affects the dynamics of such systems still remains unclear. Here, we investigate three systems of interlinked PFL and NFL with time delays: a synthetic genetic oscillator, a three-node circuit, and a simplified single-node model. The stability of steady states and the routes to oscillation in the single-node model are analyzed in detail. The amplitude and period of oscillations vary with a pointwise periodicity over a range of time delay. Larger-amplitude oscillations can be induced when the PFL has an appropriately long delay, in comparison with the PFL with no delay or short delay; this conclusion holds true for all the three systems. We unravel the underlying mechanism for the above effects via analytical derivation under a limiting condition. We also develop a stochastic algorithm for simulating a single reaction with two delays and show that robust oscillations can be maintained by the PFL with a properly long delay in the single-node system. This work presents an effective method for constructing robust large-amplitude oscillators and interprets why similar circuit architectures are engaged in timekeeping systems such as circadian clocks.
Lauriola, Mattia; Enuka, Yehoshua; Zeisel, Amit; D'Uva, Gabriele; Roth, Lee; Sharon-Sevilla, Michal; Lindzen, Moshit; Sharma, Kirti; Nevo, Nava; Feldman, Morris; Carvalho, Silvia; Cohen-Dvashi, Hadas; Kedmi, Merav; Ben-Chetrit, Nir; Chen, Alon; Solmi, Rossella; Wiemann, Stefan; Schmitt, Fernando; Domany, Eytan; Yarden, Yosef
2014-10-03
Signal transduction by receptor tyrosine kinases (RTKs) and nuclear receptors for steroid hormones is essential for body homeostasis, but the cross-talk between these receptor families is poorly understood. We observed that glucocorticoids inhibit signalling downstream of EGFR, an RTK. The underlying mechanism entails suppression of EGFR's positive feedback loops and simultaneous triggering of negative feedback loops that normally restrain EGFR. Our studies in mice reveal that the regulation of EGFR's feedback loops by glucocorticoids translates to circadian control of EGFR signalling: EGFR signals are suppressed by high glucocorticoids during the active phase (night-time in rodents), while EGFR signals are enhanced during the resting phase. Consistent with this pattern, treatment of animals bearing EGFR-driven tumours with a specific kinase inhibitor was more effective if administered during the resting phase of the day, when glucocorticoids are low. These findings support a circadian clock-based paradigm in cancer therapy.
Tao, Hui; Li, Xue; Qiu, Jian-Feng; Liu, Heng-Jiang; Zhang, Da-Yan; Chu, Feng; Sima, Yanghu; Xu, Shi-Qing
2017-10-01
Hatching behavior is a key target in silkworm (Bombyx mori) rearing, especially for the control of Lepidoptera pests. According to previous research, hatching rhythms appear to be controlled by a clock mechanism that restricts or "gates" hatching to a particular time. However, the underlying mechanism remains elusive. Under 12-h light:12-h dark photoperiod (LD) conditions, the transcriptional levels of the chitinase5 (Cht5) and hatching enzyme-like (Hel) genes, as well as the enzymatic activities of their gene products, oscillated in time with ambient light cycles, as did the transcriptional levels of the cryptochrome 1, cryptochrome 2, period (per), and timeless genes, which are key components of the negative feedback loop of the circadian rhythm. These changes were related to the expression profile of the ecdysteroid receptor gene and the hatching behavior of B. mori eggs. However, under continuous light or dark conditions, the hatching behavior, the expression levels of Cht5 and Hel, as well as the enzymatic activities of their gene products, were not synchronized unlike under LD conditions. In addition, immunohistochemistry experiments showed that light promoted the translocation of PER from the cytoplasm to the nucleus. In conclusion, LD cycles regulate the hatching rhythm of B. mori via negative feedback loop of the circadian oscillator. © 2017 Wiley Periodicals, Inc.
Psychophysiological Control of Acognitive Task Using Adaptive Automation
NASA Technical Reports Server (NTRS)
Freeman, Frederick; Pope, Alan T. (Technical Monitor)
2001-01-01
The major focus of the present proposal was to examine psychophysiological variables related to hazardous states of awareness induced by monitoring automated systems. With the increased use of automation in today's work environment, people's roles in the work place are being redefined from that of active participant to one of passive monitor. Although the introduction of automated systems has a number of benefits, there are also a number of disadvantages regarding worker performance. Byrne and Parasuraman have argued for the use of psychophysiological measures in the development and the implementation of adaptive automation. While both performance based and model based adaptive automation have been studied, the use of psychophysiological measures, especially EEG, offers the advantage of real time evaluation of the state of the subject. The current study used the closed-loop system, developed at NASA-Langley Research Center, to control the state of awareness of subjects while they performed a cognitive vigilance task. Previous research in our laboratory, supported by NASA, has demonstrated that, in an adaptive automation, closed-loop environment, subjects perform a tracking task better under a negative than a positive, feedback condition. In addition, this condition produces less subjective workload and larger P300 event related potentials to auditory stimuli presented in a concurrent oddball task. We have also recently shown that the closed-loop system used to control the level of automation in a tracking task can also be used to control the event rate of stimuli in a vigilance monitoring task. By changing the event rate based on the subject's index of arousal, we have been able to produce improved monitoring, relative to various control groups. We have demonstrated in our initial closed-loop experiments with the the vigilance paradigm that using a negative feedback contingency (i.e. increasing event rates when the EEG index is low and decreasing event rates when the EEG index is high) results in a marked decrease of the vigilance decrement over a 40 minute session. This effect is in direct contrast to performance of a positive feedback group, as well as a number of other control groups which demonstrated the typical vigilance decrement. Interestingly, however, the negative feedback group performed at virtually the same level as a yoked control group. The yoked control group received the same order of changes in event rate that were generated by the negative feedback subjects using the closed-loop system. Thus it would appear to be possible to optimize vigilance performance by controlling the stimuli which subjects are asked to process.
Gong, Bin; Wang, Zhiwei; Zhang, Min; Hu, Zhipeng; Ren, Zongli; Tang, Zheng; Jiang, Wanli; Cheng, Lianghao; Huang, Jun; Ren, Wei; Wang, Qingtao
2017-04-01
The development of thoracic aortic dissection (TAD) is attributed to a broad range of degenerative, genetic, structural, oxidative, apoptotic, and acquired disease states. In this study, we examined the role of the disturbed p53-MDM2 (murine double minute 2) feedback loop in the formation of TAD, and one of a potential feedback loop regulator, TRIM25 (tripartite motif protein-25). Surgical specimens of the aorta from TAD patients (n = 10) and controls (n = 10) were tested for α-smooth muscle actin (α-SMA), p53, MDM2, and TRIM25 by western blot, immunohistochemical staining, and quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR), respectively. When compared with controls, western blot shows that the protein levels of p53, MDM2, and TRIM25 were increased significantly in the aortic media of TAD patients. qRT-PCR further verified that the mRNA expression of MDM2 and TRIM25 was also increased 6- and 4-folds, respectively, in the TAD media of the aortic wall. Immunohistochemistry results showed significantly decreased staining of α-SMA, smooth muscle cells, and more collagen deposition in the media of the aortic wall from patients with TAD. This study provided a new insight into the disturbed p53-MDM2 feedback loop in the pathogenesis of TAD, and this may be because of the TRIM25 overexpression. Copyright © 2016 Elsevier Inc. All rights reserved.
Assessment and Innovation: One Darn Thing Leads to Another
ERIC Educational Resources Information Center
Rutz, Carol; Lauer-Glebov, Jacqulyn
2005-01-01
Using recent experience at Carleton College in Minnesota as a case history, the authors offer a model for assessment that provides more flexibility than the well-known assessment feedback loop, which assumes a linear progression within a hierarchical administrative structure. The proposed model is based on a double helix, with values and feedback…
Short and long sympathetic-sensory feedback loops in white fat
Ryu, Vitaly
2014-01-01
We previously demonstrated white adipose tissue (WAT) innervation using the established WAT retrograde sympathetic nervous system (SNS)-specific transneuronal viral tract tracer pseudorabies virus (PRV152) and showed its role in the control of lipolysis. Conversely, we demonstrated WAT sensory innervation using the established anterograde sensory system (SS)-specific transneuronal viral tracer, the H129 strain of herpes simplex virus-1, with sensory nerves showing responsiveness with increases in WAT SNS drive. Several brain areas were part of the SNS outflow to and SS inflow from WAT between these studies suggesting SNS-SS feedback loops. Therefore, we injected both PRV152 and H129 into inguinal WAT (IWAT) of Siberian hamsters. Animals were perfused on days 5 and 6 postinoculation after H129 and PRV152 injections, respectively, and brains, spinal cords, sympathetic, and dorsal root ganglia (DRG) were processed for immunohistochemical detection of each virus across the neuroaxis. The presence of H129+PRV152-colocalized neurons (∼50%) in the spinal segments innervating IWAT suggested short SNS-SS loops with significant coinfections (>60%) in discrete brain regions, signifying long SNS-SS loops. Notably, the most highly populated sites with the double-infected neurons were the medial part of medial preoptic nucleus, medial preoptic area, hypothalamic paraventricular nucleus, lateral hypothalamus, periaqueductal gray, oral part of the pontine reticular nucleus, and the nucleus of the solitary tract. Collectively, these results strongly indicate the neuroanatomical reality of the central SNS-SS feedback loops with short loops in the spinal cord and long loops in the brain, both likely involved in the control of lipolysis or other WAT pad-specific functions. PMID:24717676
2018-01-01
During active behaviours like running, swimming, whisking or sniffing, motor actions shape sensory input and sensory percepts guide future motor commands. Ongoing cycles of sensory and motor processing constitute a closed-loop feedback system which is central to motor control and, it has been argued, for perceptual processes. This closed-loop feedback is mediated by brainwide neural circuits but how the presence of feedback signals impacts on the dynamics and function of neurons is not well understood. Here we present a simple theory suggesting that closed-loop feedback between the brain/body/environment can modulate neural gain and, consequently, change endogenous neural fluctuations and responses to sensory input. We support this theory with modeling and data analysis in two vertebrate systems. First, in a model of rodent whisking we show that negative feedback mediated by whisking vibrissa can suppress coherent neural fluctuations and neural responses to sensory input in the barrel cortex. We argue this suppression provides an appealing account of a brain state transition (a marked change in global brain activity) coincident with the onset of whisking in rodents. Moreover, this mechanism suggests a novel signal detection mechanism that selectively accentuates active, rather than passive, whisker touch signals. This mechanism is consistent with a predictive coding strategy that is sensitive to the consequences of motor actions rather than the difference between the predicted and actual sensory input. We further support the theory by re-analysing previously published two-photon data recorded in zebrafish larvae performing closed-loop optomotor behaviour in a virtual swim simulator. We show, as predicted by this theory, that the degree to which each cell contributes in linking sensory and motor signals well explains how much its neural fluctuations are suppressed by closed-loop optomotor behaviour. More generally we argue that our results demonstrate the dependence of neural fluctuations, across the brain, on closed-loop brain/body/environment interactions strongly supporting the idea that brain function cannot be fully understood through open-loop approaches alone. PMID:29342146
Buckley, Christopher L; Toyoizumi, Taro
2018-01-01
During active behaviours like running, swimming, whisking or sniffing, motor actions shape sensory input and sensory percepts guide future motor commands. Ongoing cycles of sensory and motor processing constitute a closed-loop feedback system which is central to motor control and, it has been argued, for perceptual processes. This closed-loop feedback is mediated by brainwide neural circuits but how the presence of feedback signals impacts on the dynamics and function of neurons is not well understood. Here we present a simple theory suggesting that closed-loop feedback between the brain/body/environment can modulate neural gain and, consequently, change endogenous neural fluctuations and responses to sensory input. We support this theory with modeling and data analysis in two vertebrate systems. First, in a model of rodent whisking we show that negative feedback mediated by whisking vibrissa can suppress coherent neural fluctuations and neural responses to sensory input in the barrel cortex. We argue this suppression provides an appealing account of a brain state transition (a marked change in global brain activity) coincident with the onset of whisking in rodents. Moreover, this mechanism suggests a novel signal detection mechanism that selectively accentuates active, rather than passive, whisker touch signals. This mechanism is consistent with a predictive coding strategy that is sensitive to the consequences of motor actions rather than the difference between the predicted and actual sensory input. We further support the theory by re-analysing previously published two-photon data recorded in zebrafish larvae performing closed-loop optomotor behaviour in a virtual swim simulator. We show, as predicted by this theory, that the degree to which each cell contributes in linking sensory and motor signals well explains how much its neural fluctuations are suppressed by closed-loop optomotor behaviour. More generally we argue that our results demonstrate the dependence of neural fluctuations, across the brain, on closed-loop brain/body/environment interactions strongly supporting the idea that brain function cannot be fully understood through open-loop approaches alone.
Valproic acid disrupts the oscillatory expression of core circadian rhythm transcription factors.
Griggs, Chanel A; Malm, Scott W; Jaime-Frias, Rosa; Smith, Catharine L
2018-01-15
Valproic acid (VPA) is a well-established therapeutic used in treatment of seizure and mood disorders as well as migraines and a known hepatotoxicant. About 50% of VPA users experience metabolic disruptions, including weight gain, hyperlipidemia, and hyperinsulinemia, among others. Several of these metabolic abnormalities are similar to the effects of circadian rhythm disruption. In the current study, we examine the effect of VPA exposure on the expression of core circadian transcription factors that drive the circadian clock via a transcription-translation feedback loop. In cells with an unsynchronized clock, VPA simultaneously upregulated the expression of genes encoding core circadian transcription factors that regulate the positive and negative limbs of the feedback loop. Using low dose glucocorticoid, we synchronized cultured fibroblast cells to a circadian oscillatory pattern. Whether VPA was added at the time of synchronization or 12h later at CT12, we found that VPA disrupted the oscillatory expression of multiple genes encoding essential transcription factors that regulate circadian rhythm. Therefore, we conclude that VPA has a potent effect on the circadian rhythm transcription-translation feedback loop that may be linked to negative VPA side effects in humans. Furthermore, our study suggests potential chronopharmacology implications of VPA usage. Copyright © 2017. Published by Elsevier Inc.
Oncogenic B-Raf(V600E) abrogates the AKT/B-Raf/Mps1 interaction in melanoma cells.
Zhang, Ling; Shi, Ruyi; He, Chanting; Cheng, Caixia; Song, Bin; Cui, Heyang; Zhang, Yanyan; Zhao, Zhiping; Bi, Yanghui; Yang, Xiaofeng; Miao, Xiaoping; Guo, Jiansheng; Chen, Xing; Wang, Jinfen; Li, Yaoping; Cheng, Xiaolong; Liu, Jing; Cui, Yongping
2013-08-28
Activating B-Raf mutations that deregulate the mitogen-activated protein kinase (MAPK) pathway commonly occur in cancer. Although B-Raf(V600E) induces increased Mps1 protein contributing to centrosome amplification and chromosome instability, the regulatory mechanisms of Mps1 in melanoma cells is not fully understood. Here, we report that Mps1/AKT and B-Raf(WT)/ERK signaling form an auto-regulatory negative feedback loop in melanoma cells; notably, oncogenic B-Raf(V600E) abrogates the negative feedback loop, contributing the aberrant Mps1 functions and tumorigenesis. Our findings raise the possibility that targeting the oncogenic B-Raf and Mps1, especially when used in combination could potentially provide great therapeutic opportunities for cancer treatment. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.
Stabilization of self-mode-locked quantum dash lasers by symmetric dual-loop optical feedback
NASA Astrophysics Data System (ADS)
Asghar, Haroon; Wei, Wei; Kumar, Pramod; Sooudi, Ehsan; McInerney, John. G.
2018-02-01
We report experimental studies of the influence of symmetric dual-loop optical feedback on the RF linewidth and timing jitter of self-mode-locked two-section quantum dash lasers emitting at 1550 nm. Various feedback schemes were investigated and optimum levels determined for narrowest RF linewidth and low timing jitter, for single-loop and symmetric dual-loop feedback. Two symmetric dual-loop configurations, with balanced and unbalanced feedback ratios, were studied. We demonstrate that unbalanced symmetric dual loop feedback, with the inner cavity resonant and fine delay tuning of the outer loop, gives narrowest RF linewidth and reduced timing jitter over a wide range of delay, unlike single and balanced symmetric dual-loop configurations. This configuration with feedback lengths 80 and 140 m narrows the RF linewidth by 4-67x and 10-100x, respectively, across the widest delay range, compared to free-running. For symmetric dual-loop feedback, the influence of different power split ratios through the feedback loops was determined. Our results show that symmetric dual-loop feedback is markedly more effective than single-loop feedback in reducing RF linewidth and timing jitter, and is much less sensitive to delay phase, making this technique ideal for applications where robustness and alignment tolerance are essential.
Fedotchev, A I
2010-01-01
The perspective approach to non-pharmacological correction of the stress induced functional disorders in humans, based on the double negative feedback from patient's EEG was validated and experimentally tested. The approach implies a simultaneous use of narrow frequency EEG-oscillators, characteristic for each patient and recorded in real time span, in two independent contours of negative feedback--traditional contour of adaptive biomanagement and additional contour of resonance stimulation. In the last the signals of negative feedback from individual narrow frequency EEG oscillators are not recognized by the subject, but serve for an automatic modulation of the parameters of the sensory impact. Was shown that due to combination of active (conscious perception) and passive (automatic modulation) use of signals of negative feedback from narrow frequency EEG components of the patient, opens a possibility of considerable increase of efficiency of the procedures of EEG biomanagement.
Conceptual model of sedimentation in the Sacramento-San Joaquin River Delta
Schoellhamer, David H.; Wright, Scott A.; Drexler, Judith Z.
2012-01-01
Sedimentation in the Sacramento–San Joaquin River Delta builds the Delta landscape, creates benthic and pelagic habitat, and transports sediment-associated contaminants. Here we present a conceptual model of sedimentation that includes submodels for river supply from the watershed to the Delta, regional transport within the Delta and seaward exchange, and local sedimentation in open water and marsh habitats. The model demonstrates feedback loops that affect the Delta ecosystem. Submerged and emergent marsh vegetation act as ecosystem engineers that can create a positive feedback loop by decreasing suspended sediment, increasing water column light, which in turn enables more vegetation. Sea-level rise in open water is partially countered by a negative feedback loop that increases deposition if there is a net decrease in hydrodynamic energy. Manipulation of regional sediment transport is probably the most feasible method to control suspended sediment and thus turbidity. The conceptual model is used to identify information gaps that need to be filled to develop an accurate sediment transport model.
Effects of Oxytocin and Vasopressin on Preferential Brain Responses to Negative Social Feedback.
Gozzi, Marta; Dashow, Erica M; Thurm, Audrey; Swedo, Susan E; Zink, Caroline F
2017-06-01
Receiving negative social feedback can be detrimental to emotional, cognitive, and physical well-being, and fear of negative social feedback is a prominent feature of mental illnesses that involve social anxiety. A large body of evidence has implicated the neuropeptides oxytocin and vasopressin in the modulation of human neural activity underlying social cognition, including negative emotion processing; however, the influence of oxytocin and vasopressin on neural activity elicited during negative social evaluation remains unknown. Here 21 healthy men underwent functional magnetic resonance imaging in a double-blind, placebo-controlled, crossover design to determine how intranasally administered oxytocin and vasopressin modulated neural activity when receiving negative feedback on task performance from a study investigator. We found that under placebo, a preferential response to negative social feedback compared with positive social feedback was evoked in brain regions putatively involved in theory of mind (temporoparietal junction), pain processing (anterior insula and supplementary motor area), and identification of emotionally important visual cues in social perception (right fusiform). These activations weakened with oxytocin and vasopressin administration such that neural responses to receiving negative social feedback were not significantly greater than positive social feedback. Our results show effects of both oxytocin and vasopressin on the brain network involved in negative social feedback, informing the possible use of a pharmacological approach targeting these regions in multiple disorders with impairments in social information processing.
NASA Astrophysics Data System (ADS)
Stolnitz, Mikhail M.; Medvedev, Boris A.; Gribko, Tatyana V.
2004-05-01
The semi-phenomenological model of epidermal cell dynamics is submitted. The model takes into account three types of basal layer keratinocytes (stem, transient amplifying, terminally differentiated), distribution of first two types cells on mitotic cycle stages and resting states, keratinocytes-lymphocytes interactions that provide a positive feedback loop, influence of more differentiated cells on their progenitors that provide a negative feedback loop. Simplified model are developed and its stationary solutions are received. The opportunity of interpretation of some received modes as corresponding to various stages of psoriasis is discussed. Influence of UV-radiation on transitions between various modes of epidermis functioning is qualitatively analyzed.
Decorrelation of Neural-Network Activity by Inhibitory Feedback
Einevoll, Gaute T.; Diesmann, Markus
2012-01-01
Correlations in spike-train ensembles can seriously impair the encoding of information by their spatio-temporal structure. An inevitable source of correlation in finite neural networks is common presynaptic input to pairs of neurons. Recent studies demonstrate that spike correlations in recurrent neural networks are considerably smaller than expected based on the amount of shared presynaptic input. Here, we explain this observation by means of a linear network model and simulations of networks of leaky integrate-and-fire neurons. We show that inhibitory feedback efficiently suppresses pairwise correlations and, hence, population-rate fluctuations, thereby assigning inhibitory neurons the new role of active decorrelation. We quantify this decorrelation by comparing the responses of the intact recurrent network (feedback system) and systems where the statistics of the feedback channel is perturbed (feedforward system). Manipulations of the feedback statistics can lead to a significant increase in the power and coherence of the population response. In particular, neglecting correlations within the ensemble of feedback channels or between the external stimulus and the feedback amplifies population-rate fluctuations by orders of magnitude. The fluctuation suppression in homogeneous inhibitory networks is explained by a negative feedback loop in the one-dimensional dynamics of the compound activity. Similarly, a change of coordinates exposes an effective negative feedback loop in the compound dynamics of stable excitatory-inhibitory networks. The suppression of input correlations in finite networks is explained by the population averaged correlations in the linear network model: In purely inhibitory networks, shared-input correlations are canceled by negative spike-train correlations. In excitatory-inhibitory networks, spike-train correlations are typically positive. Here, the suppression of input correlations is not a result of the mere existence of correlations between excitatory (E) and inhibitory (I) neurons, but a consequence of a particular structure of correlations among the three possible pairings (EE, EI, II). PMID:23133368
Hybrid suboptimal control of multi-rate multi-loop sampled-data systems
NASA Technical Reports Server (NTRS)
Shieh, Leang S.; Chen, Gwangchywan; Tsai, Jason S. H.
1992-01-01
A hybrid state-space controller is developed for suboptimal digital control of multirate multiloop multivariable continuous-time systems. First, an LQR is designed for a continuous-time subsystem which has a large bandwidth and is connnected in the inner loop of the overall system. The designed LQR would optimally place the eigenvalues of a closed-loop subsystem in the common region of an open sector bounded by sector angles + or - pi/2k for k = 2 or 3 from the negative real axis and the left-hand side of a vertical line on the negative real axis in the s-plane. Then, the developed continuous-time state-feedback gain is converted into an equivalent fast-rate discrete-time state-feedback gain via a digital redesign technique (Tsai et al. 1989, Shieh et al. 1990) reviewed here. A real state reconstructor is redeveloped utilizing the fast-rate input-output data of the system of interest. The design procedure of multiloop multivariable systems using multirate samplers is shown, and a terminal homing missile system example is used to demonstrate the effectiveness of the proposed method.
The dissociable effects of punishment and reward on motor learning.
Galea, Joseph M; Mallia, Elizabeth; Rothwell, John; Diedrichsen, Jörn
2015-04-01
A common assumption regarding error-based motor learning (motor adaptation) in humans is that its underlying mechanism is automatic and insensitive to reward- or punishment-based feedback. Contrary to this hypothesis, we show in a double dissociation that the two have independent effects on the learning and retention components of motor adaptation. Negative feedback, whether graded or binary, accelerated learning. While it was not necessary for the negative feedback to be coupled to monetary loss, it had to be clearly related to the actual performance on the preceding movement. Positive feedback did not speed up learning, but it increased retention of the motor memory when performance feedback was withdrawn. These findings reinforce the view that independent mechanisms underpin learning and retention in motor adaptation, reject the assumption that motor adaptation is independent of motivational feedback, and raise new questions regarding the neural basis of negative and positive motivational feedback in motor learning.
Prell, Christina; Sun, Laixiang; Feng, Kuishuang; He, Jiaying; Hubacek, Klaus
2017-05-15
Land-use change is increasingly driven by global trade. The term "telecoupling" has been gaining ground as a means to describe how human actions in one part of the world can have spatially distant impacts on land and land-use in another. These interactions can, over time, create both direct and spatially distant feedback loops, in which human activity and land use mutually impact one another over great expanses. In this paper, we develop an analytical framework to clarify spatially distant feedbacks in the case of land use and global trade. We use an innovative mix of multi-regional input-output (MRIO) analysis and stochastic actor-oriented models (SAOMs) for analyzing the co-evolution of changes in trade network patterns with those of land use, as embodied in trade. Our results indicate that the formation of trade ties and changes in embodied land use mutually impact one another, and further, that these changes are linked to disparities in countries' wealth. Through identifying this feedback loop, our results support ongoing discussions about the unequal trade patterns between rich and poor countries that result in uneven distributions of negative environmental impacts. Finally, evidence for this feedback loop is present even when controlling for a number of underlying mechanisms, such as countries' land endowments, their geographical distance from one another, and a number of endogenous network tendencies. Copyright © 2017 Elsevier B.V. All rights reserved.
Takeda, Kosuke; Shao, Danying; Adler, Micha; Charest, Pascale G; Loomis, William F; Levine, Herbert; Groisman, Alex; Rappel, Wouter-Jan; Firtel, Richard A
2012-01-03
Adaptation in signaling systems, during which the output returns to a fixed baseline after a change in the input, often involves negative feedback loops and plays a crucial role in eukaryotic chemotaxis. We determined the dynamical response to a uniform change in chemoattractant concentration of a eukaryotic chemotaxis pathway immediately downstream from G protein-coupled receptors. The response of an activated Ras showed near-perfect adaptation, leading us to attempt to fit the results using mathematical models for the two possible simple network topologies that can provide perfect adaptation. Only the incoherent feedforward network accurately described the experimental results. This analysis revealed that adaptation in this Ras pathway is achieved through the proportional activation of upstream components and not through negative feedback loops. Furthermore, these results are consistent with a local excitation, global inhibition mechanism for gradient sensing, possibly with a Ras guanosine triphosphatase-activating protein acting as a global inhibitor.
NASA Astrophysics Data System (ADS)
Qiu, Kang; Wang, Li-Fang; Shen, Jian; Yousif, Alssadig A. M.; He, Peng; Shao, Dan-Dan; Zhang, Xiao-Min; Kirunda, John B.; Jia, Ya
2016-11-01
Based on a deterministic continuous model of cell populations dynamics in the colonic crypt and in colorectal cancer, we propose four combinations of feedback mechanisms in the differentiations from stem cells (SCs) to transit cells (TCs) and then to differentiated cells (DCs), the four combinations include the double linear (LL), the linear and saturating (LS), the saturating and linear (SL), and the double saturating (SS) feedbacks, respectively. The relative fluctuations of the population of SCs, TCs, and DCs around equilibrium states with four feedback mechanisms are studied by using the Langevin method. With the increasing of net growth rate of TCs, it is found that the Fano factors of TCs and DCs go to a peak in a transient phase, and then increase again to infinity in the cases of LS and SS feedbacks. The “up-down-up” characteristic on the Fano factor (like the van der Waals loop) demonstrates that there exists a transient phase between the normal and cancerous phases, our novel findings suggest that the mathematical model with LS or SS feedback might be better to elucidate the dynamics of a normal and abnormal (cancerous) phases.
Feedback, the various tasks of the doctor, and the feedforward alternative.
Kluger, Avraham N; Van Dijk, Dina
2010-12-01
This study aims to alert users of feedback to its dangers, explain some of its complexities and offer the feedforward alternative. We review the damage that feedback may cause to both motivation and performance. We provide an initial solution to the puzzle of the feedback sign (positive versus negative) using the concepts of promotion focus and prevention focus. We discuss additional open questions pertaining to feedback sign and consider implications for health care systems. Feedback that threatens the self is likely to debilitate recipients and, on average, positive and negative feedback are similar in their effects on performance. Positive feedback contributes to motivation and performance under promotion focus, but the same is true for negative feedback under prevention focus. We offer an alternative to feedback--the feedforward interview--and describe a brief protocol and suggestions on how it might be used in medical education. Feedback is a double-edged sword; its effective application includes careful consideration of regulatory focus and of threats to the self. Feedforward may be a good substitute for feedback in many settings. © Blackwell Publishing Ltd 2010.
A negative feedback signal that is triggered by peril curbs honey bee recruitment.
Nieh, James C
2010-02-23
Decision making in superorganisms such as honey bee colonies often uses self-organizing behaviors, feedback loops that allow the colony to gather information from multiple individuals and achieve reliable and agile solutions. Honey bees use positive feedback from the waggle dance to allocate colony foraging effort. However, the use of negative feedback signals by superorganisms is poorly understood. I show that conspecific attacks at a food source lead to the production of stop signals, communication that was known to reduce waggle dancing and recruitment but lacked a clear natural trigger. Signalers preferentially targeted nestmates visiting the same food source, on the basis of its odor. During aggressive food competition, attack victims increased signal production by 43 fold. Foragers that attacked competitors or experienced no aggression did not alter signal production. Biting ambush predators also attack foragers at flowers. Simulated biting of foragers or exposure to bee alarm pheromone also elicited signaling (88-fold and 14-fold increases, respectively). This provides the first clear evidence of a negative feedback signal elicited by foraging peril to counteract the positive feedback of the waggle dance. As in intra- and intercellular communication, negative feedback may play an important, though currently underappreciated, role in self-organizing behaviors within superorganisms. Copyright 2010 Elsevier Ltd. All rights reserved.
Negative feedback regulation of wild-type p53 biosynthesis.
Mosner, J; Mummenbrauer, T; Bauer, C; Sczakiel, G; Grosse, F; Deppert, W
1995-01-01
When growth-arrested mouse fibroblasts re-entered the cell-cycle, the rise in tumour suppressor p53 mRNA level markedly preceded the rise in expression of the p53 protein. Furthermore, gamma-irradiation of such cells led to a rapid increase in p53 protein biosynthesis even in the presence of the transcription inhibitor actinomycin D. Both findings strongly suggest that p53 biosynthesis in these cells is regulated at the translational level. We present evidence for an autoregulatory control of p53 expression by a negative feed-back loop: p53 mRNA has a predicted tendency to form a stable stem-loop structure that involves the 5'-untranslated region (5'-UTR) plus some 280 nucleotides of the coding sequence. p53 binds tightly to the 5'-UTR region and inhibits the translation of its own mRNA, most likely mediated by the p53-intrinsic RNA re-annealing activity. The inhibition of p53 biosynthesis requires wild-type p53, as it is not observed with MethA mutant p53, p53-catalysed translational inhibition is selective; it might be restricted to p53 mRNA and a few other mRNAs that are able to form extensive stem-loop structures. Release from negative feed-back regulation of p53 biosynthesis, e.g. after damage-induced nuclear transport of p53, might provide a means for rapidly increasing p53 protein levels when p53 is required to act as a cell-cycle checkpoint determinant after DNA damage. Images PMID:7556087
The 'sensory tolerance limit': A hypothetical construct determining exercise performance?
Hureau, Thomas J; Romer, Lee M; Amann, Markus
2018-02-01
Neuromuscular fatigue compromises exercise performance and is determined by central and peripheral mechanisms. Interactions between the two components of fatigue can occur via neural pathways, including feedback and feedforward processes. This brief review discusses the influence of feedback and feedforward mechanisms on exercise limitation. In terms of feedback mechanisms, particular attention is given to group III/IV sensory neurons which link limb muscle with the central nervous system. Central corollary discharge, a copy of the neural drive from the brain to the working muscles, provides a signal from the motor system to sensory systems and is considered a feedforward mechanism that might influence fatigue and consequently exercise performance. We highlight findings from studies supporting the existence of a 'critical threshold of peripheral fatigue', a previously proposed hypothesis based on the idea that a negative feedback loop operates to protect the exercising limb muscle from severe threats to homeostasis during whole-body exercise. While the threshold theory remains to be disproven within a given task, it is not generalisable across different exercise modalities. The 'sensory tolerance limit', a more theoretical concept, may address this issue and explain exercise tolerance in more global terms and across exercise modalities. The 'sensory tolerance limit' can be viewed as a negative feedback loop which accounts for the sum of all feedback (locomotor muscles, respiratory muscles, organs, and muscles not directly involved in exercise) and feedforward signals processed within the central nervous system with the purpose of regulating the intensity of exercise to ensure that voluntary activity remains tolerable.
A fast, robust and tunable synthetic gene oscillator.
Stricker, Jesse; Cookson, Scott; Bennett, Matthew R; Mather, William H; Tsimring, Lev S; Hasty, Jeff
2008-11-27
One defining goal of synthetic biology is the development of engineering-based approaches that enable the construction of gene-regulatory networks according to 'design specifications' generated from computational modelling. This approach provides a systematic framework for exploring how a given regulatory network generates a particular phenotypic behaviour. Several fundamental gene circuits have been developed using this approach, including toggle switches and oscillators, and these have been applied in new contexts such as triggered biofilm development and cellular population control. Here we describe an engineered genetic oscillator in Escherichia coli that is fast, robust and persistent, with tunable oscillatory periods as fast as 13 min. The oscillator was designed using a previously modelled network architecture comprising linked positive and negative feedback loops. Using a microfluidic platform tailored for single-cell microscopy, we precisely control environmental conditions and monitor oscillations in individual cells through multiple cycles. Experiments reveal remarkable robustness and persistence of oscillations in the designed circuit; almost every cell exhibited large-amplitude fluorescence oscillations throughout observation runs. The oscillatory period can be tuned by altering inducer levels, temperature and the media source. Computational modelling demonstrates that the key design principle for constructing a robust oscillator is a time delay in the negative feedback loop, which can mechanistically arise from the cascade of cellular processes involved in forming a functional transcription factor. The positive feedback loop increases the robustness of the oscillations and allows for greater tunability. Examination of our refined model suggested the existence of a simplified oscillator design without positive feedback, and we construct an oscillator strain confirming this computational prediction.
Orphanin FQ-ORL-1 regulation of reproduction and reproductive behavior in the female.
Sinchak, Kevin; Dalhousay, Lauren; Sanathara, Nayna
2015-01-01
Orphanin FQ (OFQ/N) and its receptor, opioid receptor-like receptor-1 (ORL-1), are expressed throughout steroid-responsive limbic and hypothalamic circuits that regulate female ovarian hormone feedback and reproductive behavior circuits. The arcuate nucleus of the hypothalamus (ARH) is a brain region that expresses OFQ/N and ORL-1 important for both sexual behavior and modulating estradiol feedback loops. Within the ARH, the activation of the OFQ/N-ORL-1 system facilitates sexual receptivity (lordosis) through the inhibition of β-endorphin neuronal activity. Estradiol initially activates ARH β-endorphin neurons to inhibit lordosis. Simultaneously, estradiol upregulates coexpression of OFQ/N and progesterone receptors and ORL-1 in ARH β-endorphin neurons. Ovarian hormones regulate pre- and postsynaptic coupling of ORL-1 to its G protein-coupled signaling pathways. When the steroid-primed rat is nonreceptive, estradiol acts pre- and postsynaptically to decrease the ability of the OFQ/N-ORL-1 system to inhibit ARH β-endorphin neurotransmission. Conversely, when sexually receptive, ORL-1 signaling is restored to inhibit β-endorphin neurotransmission. Although steroid signaling that facilitates lordosis converges to deactivate ARH β-endorphin neurons, estradiol-only facilitation of lordosis requires the activation of ORL-1, but estradiol+progesterone does not, indicating that multiple circuits mediate ovarian hormone signaling to deactivate ARH β-endorphin neurons. Research on the role of OFQ/N-ORL-1 in ovarian hormone feedback loops is just beginning. In the rat, OFQ/N may act to terminate gonadotropin-releasing hormone and luteinizing hormone release under positive and negative feedbacks. In the ewe, it appears to directly inhibit gonadotropin-releasing hormone release to mediate progesterone-negative feedback. As a whole, the localization and actions of OFQ/N-ORL-1 system indicate that it may mediate the actions of estradiol and progesterone to synchronize reproductive behavior and ovarian hormone feedback loops. © 2015 Elsevier Inc. All rights reserved.
Molecular genetic analysis of circadian timekeeping in Drosophila
Hardin, Paul E.
2014-01-01
A genetic screen for mutants that alter circadian rhythms in Drosophila identified the first clock gene - the period (per) gene. The per gene is a central player within a transcriptional feedback loop that represents the core mechanism for keeping circadian time in Drosophila and other animals. The per feedback loop, or core loop, is interlocked with the Clock (Clk) feedback loop, but whether the Clk feedback loop contributes to circadian timekeeping is not known. A series of distinct molecular events are thought to control transcriptional feedback in the core loop. The time it takes to complete these events should take much less than 24h, thus delays must be imposed at different steps within the core loop. As new clock genes are identified, the molecular mechanisms responsible for these delays have been revealed in ever-increasing detail, and provide an in depth accounting of how transcriptional feedback loops keep circadian time. The phase of these feedback loops shift to maintain synchrony with environmental cycles, the most reliable of which is light. Although a great deal is known about cell-autonomous mechanisms of light-induced phase shifting by CRYPTOCHROME (CRY), much less is known about non-cell autonomous mechanisms. CRY mediates phase shifts through an uncharacterized mechanism in certain brain oscillator neurons, and carries out a dual role as a photoreceptor and transcription factor in other tissues. Here I will review how transcriptional feedback loops function to keep time in Drosophila, how they impose delays to maintain a 24h cycle, and how they maintain synchrony with environmental light:dark cycles. The transcriptional feedback loops that keep time in Drosophila are well conserved in other animals, thus what we learn about these loops in Drosophila should continue to provide insight into the operation of analogous transcriptional feedback loops in other animals. PMID:21924977
Linear motor drive system for continuous-path closed-loop position control of an object
Barkman, William E.
1980-01-01
A precision numerical controlled servo-positioning system is provided for continuous closed-loop position control of a machine slide or platform driven by a linear-induction motor. The system utilizes filtered velocity feedback to provide system stability required to operate with a system gain of 100 inches/minute/0.001 inch of following error. The filtered velocity feedback signal is derived from the position output signals of a laser interferometer utilized to monitor the movement of the slide. Air-bearing slides mounted to a stable support are utilized to minimize friction and small irregularities in the slideway which would tend to introduce positioning errors. A microprocessor is programmed to read command and feedback information and converts this information into the system following error signal. This error signal is summed with the negative filtered velocity feedback signal at the input of a servo amplifier whose output serves as the drive power signal to the linear motor position control coil.
Automatic alignment of double optical paths in excimer laser amplifier
NASA Astrophysics Data System (ADS)
Wang, Dahui; Zhao, Xueqing; Hua, Hengqi; Zhang, Yongsheng; Hu, Yun; Yi, Aiping; Zhao, Jun
2013-05-01
A kind of beam automatic alignment method used for double paths amplification in the electron pumped excimer laser system is demonstrated. In this way, the beams from the amplifiers can be transferred along the designated direction and accordingly irradiate on the target with high stabilization and accuracy. However, owing to nonexistence of natural alignment references in excimer laser amplifiers, two cross-hairs structure is used to align the beams. Here, one crosshair put into the input beam is regarded as the near-field reference while the other put into output beam is regarded as the far-field reference. The two cross-hairs are transmitted onto Charge Coupled Devices (CCD) by image-relaying structures separately. The errors between intersection points of two cross-talk images and centroid coordinates of actual beam are recorded automatically and sent to closed loop feedback control mechanism. Negative feedback keeps running until preset accuracy is reached. On the basis of above-mentioned design, the alignment optical path is built and the software is compiled, whereafter the experiment of double paths automatic alignment in electron pumped excimer laser amplifier is carried through. Meanwhile, the related influencing factors and the alignment precision are analyzed. Experimental results indicate that the alignment system can achieve the aiming direction of automatic aligning beams in short time. The analysis shows that the accuracy of alignment system is 0.63μrad and the beam maximum restoration error is 13.75μm. Furthermore, the bigger distance between the two cross-hairs, the higher precision of the system is. Therefore, the automatic alignment system has been used in angular multiplexing excimer Main Oscillation Power Amplification (MOPA) system and can satisfy the requirement of beam alignment precision on the whole.
Rapid feedback processing in human nucleus accumbens and motor thalamus.
Schüller, Thomas; Gruendler, Theo O J; Jocham, Gerhard; Klein, Tilmann A; Timmermann, Lars; Visser-Vandewalle, Veerle; Kuhn, Jens; Ullsperger, Markus
2015-04-01
The nucleus accumbens (NAcc) and thalamus are integral parts in models of feedback processing. Deep brain stimulation (DBS) has been successfully employed to alleviate symptoms of psychiatric conditions including obsessive-compulsive disorder (OCD) and Tourette's syndrome (TS). Common target structures are the NAcc and the ventral anterior and ventro-lateral nuclei (VA/VL) of the thalamus, for OCD and TS, respectively. The feedback related negativity (FRN) is an event-related potential associated with feedback processing reflecting posterior medial frontal cortex (pMFC) activity. Here we report on three cases where we recorded scalp EEG and local field potentials (LFP) from externalized electrodes located in the NAcc or thalamus (VA/VL) while patients engaged in a modified time estimation task, known to engage feedback processing and elicit the FRN. Additionally, scalp EEG were recorded from 29 healthy participants (HP) engaged in the same task. The signal in all structures (pMFC, NAcc, and thalamus) was differently modulated by positive and negative feedback. LFP activity in the NAcc showed a biphasic time course after positive feedback during the FRN time interval. Negative feedback elicited a much weaker and later response. In the thalamus a monophasic modulation was recorded during the FRN time interval. Again, this modulation was more pronounced after positive performance feedback compared to negative feedback. In channels outside the target area no modulation was observed. The surface-FRN was reliably elicited on a group level in HP and showed no significant difference following negative feedback between patients and HP. German Clinical Trial Register: Neurocognitive specification of dysfunctions within basal ganglia-cortex loops and their therapeutic modulation by deep brain stimulation in patients with obsessive compulsive disorder and Tourette syndrome, http://www.drks.de/DRKS00005316. Copyright © 2015 Elsevier Ltd. All rights reserved.
Cloud-radiation interactions - Effects of cirrus optical thickness feedbacks
NASA Technical Reports Server (NTRS)
Somerville, Richard C. J.; Iacobellis, Sam
1987-01-01
The paper is concerned with a cloud-radiation feedback mechanism which may be an important component of the climate changes expected from increased atmospheric concentrations of carbon dioxide and other trace greenhouse gases. A major result of the study is that cirrus cloud optical thickness feedbacks may indeed tend to increase the surface warming due to trace gas increases. However, the positive feedback from cirrus appears to be generally weaker than the negative effects due to lower clouds. The results just confirm those of earlier research indicating that the net effect of cloud optical thickness feedbacks may be a negative feedback which may substantially (by a factor of about 2) reduce the surface warming due to the doubling of CO2, even in the presence of cirrus clouds.
Rodrat, Mayuree; Wongdee, Kannikar; Panupinthu, Nattapon; Thongbunchoo, Jirawan; Teerapornpuntakit, Jarinthorn; Krishnamra, Nateetip; Charoenphandhu, Narattaphol
2018-02-15
Overdose of oral calcium supplement and excessive intestinal calcium absorption can contribute pathophysiological conditions, e.g., nephrolithiasis, vascular calcification, dementia, and cardiovascular accident. Since our previous investigation has indicated that fibroblast growth factor (FGF)-23 could abolish the 1,25-dihydroxyvitamin D 3 [1,25(OH) 2 D 3 ]-enhanced calcium absorption, we further hypothesized that FGF-23 produced locally in the enterocytes might be part of a local negative feedback loop to regulate calcium absorption. Herein, 1,25(OH) 2 D 3 was found to enhance the transcellular calcium transport across the epithelium-like Caco-2 monolayer, and this stimulatory effect was diminished by preceding prolonged exposure to high-dose 1,25(OH) 2 D 3 or high concentration of apical ionized calcium. Pretreatment with a neutralizing antibody for FGF-23 prevented this negative feedback regulation of calcium hyperabsorption induced by 1,25(OH) 2 D 3 . FGF-23 exposure completely abolished the 1,25(OH) 2 D 3 -enhanced calcium transport. Western blot analysis revealed that FGF-23 expression was upregulated in a dose-dependent manner by 1,25(OH) 2 D 3 or apical calcium exposure. Finally, calcium-sensing receptor (CaSR) inhibitors were found to prevent the apical calcium-induced suppression of calcium transport. In conclusion, prolonged exposure to high apical calcium and calcium hyperabsorption were sensed by CaSR, which, in turn, increased FGF-23 expression to suppress calcium transport. This local negative feedback loop can help prevent unnecessary calcium uptake and its detrimental consequences. Copyright © 2018 Elsevier Inc. All rights reserved.
Klinke, David J.; Horvath, Nicholas; Cuppett, Vanessa; Wu, Yueting; Deng, Wentao; Kanj, Rania
2015-01-01
The integrity of epithelial tissue architecture is maintained through adherens junctions that are created through extracellular homotypic protein–protein interactions between cadherin molecules. Cadherins also provide an intracellular scaffold for the formation of a multiprotein complex that contains signaling proteins, including β-catenin. Environmental factors and controlled tissue reorganization disrupt adherens junctions by cleaving the extracellular binding domain and initiating a series of transcriptional events that aim to restore tissue homeostasis. However, it remains unclear how alterations in cell adhesion coordinate transcriptional events, including those mediated by β-catenin in this pathway. Here were used quantitative single-cell and population-level in vitro assays to quantify the endogenous pathway dynamics after the proteolytic disruption of the adherens junctions. Using prior knowledge of isolated elements of the overall network, we interpreted these data using in silico model-based inference to identify the topology of the regulatory network. Collectively the data suggest that the regulatory network contains interlocked network motifs consisting of a positive feedback loop, which is used to restore the integrity of adherens junctions, and a negative feedback loop, which is used to limit β-catenin–induced gene expression. PMID:26224311
Zhou, Ding'an; Wei, Zhiyun; Kuang, Zhongshu; Luo, Huangchao; Ma, Jiangshu; Zeng, Xing; Wang, Ke; Liu, Beizhong; Gong, Fang; Wang, Jing; Lei, Shanchuan; Wang, Dongsheng; Zeng, Jiawei; Wang, Teng; He, Yong; Yuan, Yongqiang; Dai, Hongying; He, Lin; Xing, Qinghe
2017-04-01
p53-Transcriptional-regulated proteins interact with a large number of other signal transduction pathways in the cell, and a number of positive and negative autoregulatory feedback loops act upon the p53 response. P53 directly controls the POMC/α-MSH productions induced by ultraviolet (UV) and is associated with UV-independent pathological pigmentation. When identifying the causative gene of dyschromatosis universalis hereditaria (DUH), we found three mutations encoding amino acid substitutions in the gene SAM and SH3 domain containing 1 (SASH1), and SASH1 was associated with guanine nucleotide-binding protein subunit-alpha isoforms short (Gαs). However, the pathological gene and pathological mechanism of DUH remain unknown for about 90 years. We demonstrate that SASH1 is physiologically induced by p53 upon UV stimulation and SASH and p53 is reciprocally induced at physiological and pathophysiological conditions. SASH1 is regulated by a novel p53/POMC/α-MSH/Gαs/SASH1 cascade to mediate melanogenesis. A novel p53/POMC/Gαs/SASH1 autoregulatory positive feedback loop is regulated by SASH1 mutations to induce pathological hyperpigmentation phenotype. Our study demonstrates that a novel p53/POMC/Gαs/SASH1 autoregulatory positive feedback loop is regulated by SASH1 mutations to induce pathological hyperpigmentation phenotype. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.
Oscillatory stimuli differentiate adapting circuit topologies
Rahi, Sahand Jamal; Larsch, Johannes; Pecani, Kresti; Katsov, Alexander Y.; Mansouri, Nahal; Tsaneva-Atanasova, Krasimira; Sontag, Eduardo D.; Cross, Frederick R.
2017-01-01
Adapting pathways consist of negative feedback loops (NFLs) or incoherent feedforward loops (IFFLs), which we show can be differentiated using oscillatory stimulation: NFLs but not IFFLs generically show ‘refractory period stabilization’ or ‘period skipping’. Using these signatures and genetic rewiring we identified the circuit dominating cell cycle timing in yeast. In C. elegans AWA neurons we uncovered a Ca2+-NFL, diffcult to find by other means, especially in wild-type, intact animals. (70 words) PMID:28846089
NF-κB regulates neuronal ankyrin-G via a negative feedback loop.
König, Hans-Georg; Schwamborn, Robert; Andresen, Silke; Kinsella, Sinéad; Watters, Orla; Fenner, Beau; Prehn, Jochen H M
2017-02-09
The axon initial segment (AIS) is a neuronal compartment defined by ankyrin-G expression. We here demonstrate that the IKK-complex co-localizes and interacts with the cytoskeletal anchor protein ankyrin-G in immunoprecipitation and proximity-ligation experiments in cortical neurons. Overexpression of the 270 kDa variant of ankyrin-G suppressed, while gene-silencing of ankyrin-G expression increased nuclear factor-κB (NF-κB) activity in primary neurons, suggesting that ankyrin-G sequesters the transcription factor in the AIS. We also found that p65 bound to the ank3 (ankyrin-G) promoter sequence in chromatin immunoprecipitation analyses thereby increasing ank3 expression and ankyrin-G levels at the AIS. Gene-silencing of p65 or ankyrin-G overexpression suppressed ank3 reporter activity. Collectively these data demonstrate that p65/NF-κB controls ankyrin-G levels via a negative feedback loop, thereby linking NF-κB signaling with neuronal polarity and axonal plasticity.
Reversal of an Epigenetic Switch Governing Cell Chaining in Bacillus subtilis by Protein Instability
Chai, Yunrong; Kolter, Roberto; Losick, Richard
2010-01-01
Bacillus subtilis forms long chains of cells during growth and biofilm formation. Cell separation is mediated by autolysins, whose genes are under the negative control of a heteromeric complex composed of the proteins SinR and SlrR. Formation of the SinR•SlrR complex is governed by a self-reinforcing, double-negative feedback loop in which SinR represses the gene for SlrR and SlrR, by forming the SinR•SlrR complex, titrates SinR and prevents it from repressing slrR. The loop is a bistable switch and exists in a SlrRLOW state in which autolysin genes are on, and a SlrRHIGH state in which autolysin genes are repressed by SinR•SlrR. Cells in the SlrRLOW state are driven into the SlrRHIGH state by SinI, an antirepressor that binds to and inhibits SinR. However, the mechanism by which cells in the SlrRHIGH state revert back to the SlrRLOW state is unknown. We report that SlrR is proteolytically unstable and present evidence that self-cleavage via a LexA-like autopeptidase and ClpC contribute to its degradation. Cells producing a self-cleavage-resistant mutant of SlrR exhibited more persistent chaining during growth and yielded biofilms with enhanced structural complexity. We propose that degradation of SlrR allows cells to switch from the SlrRHIGH to the SlrRLOW state. PMID:20923420
Strong feedback limit of the Goodwin circadian oscillator
NASA Astrophysics Data System (ADS)
Woller, Aurore; Gonze, Didier; Erneux, Thomas
2013-03-01
The three-variable Goodwin model constitutes a prototypical oscillator based on a negative feedback loop. It was used as a minimal model for circadian oscillations. Other core models for circadian clocks are variants of the Goodwin model. The Goodwin oscillator also appears in many studies of coupled oscillator networks because of its relative simplicity compared to other biophysical models involving a large number of variables and parameters. Because the synchronization properties of Goodwin oscillators still remain difficult to explore mathematically, further simplifications of the Goodwin model have been sought. In this paper, we investigate the strong negative feedback limit of Goodwin equations by using asymptotic techniques. We find that Goodwin oscillations approach a sequence of decaying exponentials that can be described in terms of a single-variable leaky integrated-and-fire model.
NASA Astrophysics Data System (ADS)
Asghar, Haroon; McInerney, John G.
2017-09-01
We demonstrate an asymmetric dual-loop feedback scheme to suppress external cavity side-modes induced in self-mode-locked quantum-dash lasers with conventional single and dual-loop feedback. In this letter, we achieved optimal suppression of spurious tones by optimizing the length of second delay time. We observed that asymmetric dual-loop feedback, with large (~8x) disparity in cavity lengths, eliminates all external-cavity side-modes and produces flat RF spectra close to the main peak with low timing jitter compared to single-loop feedback. Significant reduction in RF linewidth and reduced timing jitter was also observed as a function of increased second feedback delay time. The experimental results based on this feedback configuration validate predictions of recently published numerical simulations. This interesting asymmetric dual-loop feedback scheme provides simplest, efficient and cost effective stabilization of side-band free optoelectronic oscillators based on mode-locked lasers.
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.
H19/let-7/LIN28 reciprocal negative regulatory circuit promotes breast cancer stem cell maintenance
Peng, Fei; Li, Ting-Ting; Wang, Kai-Li; Xiao, Guo-Qing; Wang, Ju-Hong; Zhao, Hai-Dong; Kang, Zhi-Jie; Fan, Wen-Jun; Zhu, Li-Li; Li, Mei; Cui, Bai; Zheng, Fei-Meng; Wang, Hong-Jiang; Lam, Eric W-F; Wang, Bo; Xu, Jie; Liu, Quentin
2017-01-01
Long noncoding RNA-H19 (H19), an imprinted oncofetal gene, has a central role in carcinogenesis. Hitherto, the mechanism by which H19 regulates cancer stem cells, remains elusive. Here we show that breast cancer stem cells (BCSCs) express high levels of H19, and ectopic overexpression of H19 significantly promotes breast cancer cell clonogenicity, migration and mammosphere-forming ability. Conversely, silencing of H19 represses these BCSC properties. In concordance, knockdown of H19 markedly inhibits tumor growth and suppresses tumorigenesis in nude mice. Mechanistically, we found that H19 functions as a competing endogenous RNA to sponge miRNA let-7, leading to an increase in expression of a let-7 target, the core pluripotency factor LIN28, which is enriched in BCSC populations and breast patient samples. Intriguingly, this gain of LIN28 expression can also feedback to reverse the H19 loss-mediated suppression of BCSC properties. Our data also reveal that LIN28 blocks mature let-7 production and, thereby, de-represses H19 expression in breast cancer cells. Appropriately, H19 and LIN28 expression exhibits strong correlations in primary breast carcinomas. Collectively, these findings reveal that lncRNA H19, miRNA let-7 and transcriptional factor LIN28 form a double-negative feedback loop, which has a critical role in the maintenance of BCSCs. Consequently, disrupting this pathway provides a novel therapeutic strategy for breast cancer. PMID:28102845
A Role for Timely Nuclear Translocation of Clock Repressor Proteins in Setting Circadian Clock Speed
Lee, Euna
2014-01-01
By means of a circadian clock system, all the living organisms on earth including human beings can anticipate the environmental rhythmic changes such as light/dark and warm/cold periods in a daily as well as in a yearly manner. Anticipating such environmental changes provide organisms with survival benefits via manifesting behavior and physiology at an advantageous time of the day and year. Cell-autonomous circadian oscillators, governed by transcriptional feedback loop composed of positive and negative elements, are organized into a hierarchical system throughout the organisms and generate an oscillatory expression of a clock gene by itself as well as clock controlled genes (ccgs) with a 24 hr periodicity. In the feedback loop, hetero-dimeric transcription factor complex induces the expression of negative regulatory proteins, which in turn represses the activity of transcription factors to inhibit their own transcription. Thus, for robust oscillatory rhythms of the expression of clock genes as well as ccgs, the precise control of subcellular localization and/or timely translocation of core clock protein are crucial. Here, we discuss how sub-cellular localization and nuclear translocation are controlled in a time-specific manner focusing on the negative regulatory clock proteins. PMID:25258565
Magnetostatic Surface Wave Microwave Oscillator.
1981-12-18
feedback loop of a 2-4 Gigahertz (Gliz) amplifier (Ref. 13). Thin film yttrium-iron- garnet (YIG) was used as the propagation medium and the three...Theory, McGraw Hill Book Company, New York, 1964. 16. Tsai, T. and Sethares, J.C., "Band Stop Filter Using LPE -YIG Films ," Proceedings of the IEEE...and Stiglitz System Composed of YIG Film , Conducting Strips, Double Ground Plane and Dielectric Regions .......... . 11 4 Magnetic Field Strength versus
ERIC Educational Resources Information Center
Cziko, Gary A.
1992-01-01
Reiterates the author's convictions about the inadequacy of mainstream educational research. If perceptual control theory is correct in positing a closed-loop, negative feedback relationship between individuals and their environments, then current and mainstream educational research is not adequate for explaining purposeful behavior. (SLD)
Active rc filter permits easy trade-off of amplifier gain and sensitivity to gain
NASA Technical Reports Server (NTRS)
Kerwin, W. J.; Shaffer, C. V.
1968-01-01
Passive RC network was designed with zeros of transmission in the right half of the complex frequency plane in the feedback loop of a simple negative-gain amplifier. The proper positioning provides any desired trade-off between amplifier gain and sensitivity to amplifier gain.
Pathobiology and management of hypergastrinemia and the Zollinger-Ellison syndrome.
Hirschowitz, B I
1992-01-01
Gastrin is both stimulatory and trophic to the cells of the gastric fundus--parietal and peptic cells, and enterochromaffin-like (ECL) cells which are major intermediaries of the gastrin effect. Gastrin (from the antrum) and acid (from the fundus) represent the interactive positive and negative limbs of a feedback loop. The nature and extent of sub-loops, perhaps involving the vagus, acetylcholine, histamine, and other peptides and cell products are at present unclear or unknown. Loss of either gastrin or acid has predictable consequences. Absent acid, as in pernicious anemia or as a result of omeprazole, leads to hypergastrinemia. In rats, such hypergastrinemia (gastrin > 1,000 pg/ml) causes fundic ECL hyperplasia and, eventually, carcinoids; in humans with pernicious anemia, hypergastrinemia causes ECL-cell hyperplasia, which may progress to carcinoids that are reversible upon withdrawal of gastrin, illustrated by three cases described here. Loss of gastrin by antrectomy for duodenal ulcer leads to fundic involution and marked reduction in basal acid output, maximal acid output, and fundic histamine. An uncontrolled excess of gastrin, as from a gastrinoma outside the negative feedback loop, causes acid and pepsin hypersecretion with upper GI mucosal damage, the Zollinger-Ellison syndrome. This paper summarizes the abnormal regulation of gastrin and the biology, natural history, diagnosis, and management of ZE syndrome by medical and surgical means.
NASA Astrophysics Data System (ADS)
Saaltink, Rémon; Dekker, Stefan C.; Griffioen, Jasper; Wassen, Martin J.
2016-09-01
Interest is growing in using soft sediment as a foundation in eco-engineering projects. Wetland construction in the Dutch lake Markermeer is an example: here, dredging some of the clay-rich lake-bed sediment and using it to construct wetland will soon begin. Natural processes will be utilized during and after construction to accelerate ecosystem development. Knowing that plants can eco-engineer their environment via positive or negative biogeochemical plant-soil feedbacks, we conducted a 6-month greenhouse experiment to identify the key biogeochemical processes in the mud when Phragmites australis is used as an eco-engineering species. We applied inverse biogeochemical modeling to link observed changes in pore water composition to biogeochemical processes. Two months after transplantation we observed reduced plant growth and shriveling and yellowing of foliage. The N : P ratios of the plant tissue were low, and these were affected not by hampered uptake of N but by enhanced uptake of P. Subsequent analyses revealed high Fe concentrations in the leaves and roots. Sulfate concentrations rose drastically in our experiment due to pyrite oxidation; as reduction of sulfate will decouple Fe-P in reducing conditions, we argue that plant-induced iron toxicity hampered plant growth, forming a negative feedback loop, while simultaneously there was a positive feedback loop, as iron toxicity promotes P mobilization as a result of reduced conditions through root death, thereby stimulating plant growth and regeneration. Given these two feedback mechanisms, we propose the use of Fe-tolerant species rather than species that thrive in N-limited conditions. The results presented in this study demonstrate the importance of studying the biogeochemical properties of the situated sediment and the feedback mechanisms between plant and soil prior to finalizing the design of the eco-engineering project.
NASA Technical Reports Server (NTRS)
Chen, Songsheng; Yu, Jirong; Bai, Yingsin; Koch, Grady; Petros, Mulugeta; Trieu, Bo; Petzar, Paul; Singh, Upendra N.; Kavaya, Michael J.; Beyon, Jeffrey
2010-01-01
A carbon dioxide (CO2) Differential Absorption Lidar (DIAL) for accurate CO2 concentration measurement requires a frequency locking system to achieve high frequency locking precision and stability. We describe the frequency locking system utilizing Frequency Modulation (FM), Phase Sensitive Detection (PSD), and Proportional Integration Derivative (PID) feedback servo loop, and report the optimization of the sensitivity of the system for the feed back loop based on the characteristics of a variable path-length CO2 gas cell. The CO2 gas cell is characterized with HITRAN database (2004). The method can be applied for any other frequency locking systems referring to gas absorption line.
Beauchamp, Elspeth M.; Kosciuczuk, Ewa M.; Serrano, Ruth; Nanavati, Dhaval; Swindell, Elden P.; Viollet, Benoit; O'Halloran, Thomas V.; Altman, Jessica K.; Platanias, Leonidas C.
2014-01-01
Arsenic trioxide (As2O3) exhibits potent antineoplastic effects and is used extensively in clinical oncology for the treatment of a subset of patients with acute myeloid leukemia (AML). Although As2O3 is known to regulate activation of several signaling cascades, the key events, accounting for its anti-leukemic properties, remain to be defined. We provide evidence that arsenic can directly bind to cysteine 299 in AMPKα and inhibit its activity. This inhibition of AMPK by arsenic is required in part for its cytotoxic effects on primitive leukemic progenitors from patients with AML, while concomitant treatment with an AMPK activator antagonizes in vivo the arsenic-induced antileukemic effects in a xenograft AML mouse model. A consequence of AMPK inhibition is activation of the mTOR pathway as a negative regulatory feedback loop. However, when AMPK expression is lost, arsenic-dependent activation of the kinase RSK downstream of MAPK activity compensates the generation of regulatory feedback signals through phosphorylation of downstream mTOR targets. Thus, therapeutic regimens with arsenic trioxide will need to include inhibitors of both the mTOR and RSK pathways in combination to prevent engagement of negative feedback loops and maximize antineoplastic responses. PMID:25344585
Peng, Ke-Zheng; Ke, Yu; Zhao, Qi; Tian, Fei; Liu, Hong-Min; Hou, Guiqin; Lu, Zhaoming
2017-09-15
Hyperactivation of mTOR signaling pathway has been viewed as a significant molecular pathogenesis of cancer. However, inhibition of mTOR by rapamycin and its analogs could induce numerous negative feedback loops to attenuate their therapeutic efficacy. As a traditional Chinese herbal medicine, Rabdosia rubescens has been used to treat esophageal squamous cell carcinoma (ESCC) for hundreds of years, and its major effective component is oridonin. Here we reported that OP16, a novel analog of oridonin, showed potent inhibition of cell proliferation and Akt phosphorylation in ESCC cells. The combination of OP16 and rapamycin possesses synergistic anti-proliferative and pro-apoptotic effects both in ESCC cells and ESCC xenografts, and no obvious adverse effect was observed in vivo. Mechanistic analysis revealed that OP16 could inhibit rapamycin-induced Akt activation through the p70S6K-mediated negative feedback loops, and the combination of OP16 and rapamycin was more effective in activating caspase-dependent apoptotic signaling cascade. This study supports the combined use of OP16 with rapamycin as a feasible and effective therapeutic approach for future treatment of ESCC. Copyright © 2017 Elsevier Inc. All rights reserved.
NASA Astrophysics Data System (ADS)
Alam, Jubaer; Faruque, Mohammad Rashed Iqbal; Tariqul Islam, Mohammad
2018-07-01
Nested circular shaped Labyrinth double split open loop resonators (OLRs) are introduced in this article to design a triple bandpass filter for 3.01 GHz, 7.39 GHz and 12.88 GHz applications. A Rogers RT-5880 is used as a substrate to design the proposed passband filter which has a succinct structure where the attainment of the resonator is explored both integrally and experimentally. The same structure is designed on both sides of the substrate and an analysis is made on the current distribution. Based on the proposed resonator, a bandpass filter is designed and fabricated to justify the perception focusing on 3.01 GHz, 7.39 GHz and 12.88 GHz. It has also been observed by the Nicolson–Ross–Weir approach at the filtering frequencies. The effective electromagnetic parameters retrieved from the simulation of the S-parameters imply that the OLR metamaterial filter shows negative refraction bands. Having an auspicious design and double negative characteristics, this structure is suitable for triple passband filters, particularly for S, C and X-band applications.
Virtual grasping: closed-loop force control using electrotactile feedback.
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.
Moss, Britney L; Elhammali, Adnan; Fowlkes, Tiffanie; Gross, Shimon; Vinjamoori, Anant; Contag, Christopher H; Piwnica-Worms, David
2012-09-07
Full understanding of the biological significance of negative feedback processes requires interrogation at multiple scales as follows: in single cells, cell populations, and live animals in vivo. The transcriptionally coupled IκBα/NF-κB negative feedback loop, a pivotal regulatory node of innate immunity and inflammation, represents a model system for multiscalar reporters. Using a κB(5)→IκBα-FLuc bioluminescent reporter, we rigorously evaluated the dynamics of ΙκBα degradation and subsequent NF-κB transcriptional activity in response to diverse modes of TNFα stimulation. Modulating TNFα concentration or pulse duration yielded complex, reproducible, and differential ΙκBα dynamics in both cell populations and live single cells. Tremendous heterogeneity in the transcriptional amplitudes of individual responding cells was observed, which was greater than the heterogeneity in the transcriptional kinetics of responsive cells. Furthermore, administration of various TNFα doses in vivo generated ΙκBα dynamic profiles in the liver resembling those observed in single cells and populations of cells stimulated with TNFα pulses. This suggested that dose modulation of circulating TNFα was perceived by hepatocytes in vivo as pulses of increasing duration. Thus, a robust bioluminescent reporter strategy enabled rigorous quantitation of NF-κB/ΙκBα dynamics in both live single cells and cell populations and furthermore, revealed reproducible behaviors that informed interpretation of in vivo studies.
A high precision dual feedback discrete control system designed for satellite trajectory simulator
NASA Astrophysics Data System (ADS)
Liu, Ximin; Liu, Liren; Sun, Jianfeng; Xu, Nan
2005-08-01
Cooperating with the free-space laser communication terminals, the satellite trajectory simulator is used to test the acquisition, pointing, tracking and communicating performances of the terminals. So the satellite trajectory simulator plays an important role in terminal ground test and verification. Using the double-prism, Sun etc in our group designed a satellite trajectory simulator. In this paper, a high precision dual feedback discrete control system designed for the simulator is given and a digital fabrication of the simulator is made correspondingly. In the dual feedback discrete control system, Proportional- Integral controller is used in velocity feedback loop and Proportional- Integral- Derivative controller is used in position feedback loop. In the controller design, simplex method is introduced and an improvement to the method is made. According to the transfer function of the control system in Z domain, the digital fabrication of the simulator is given when it is exposed to mechanism error and moment disturbance. Typically, when the mechanism error is 100urad, the residual standard error of pitching angle, azimuth angle, x-coordinate position and y-coordinate position are 0.49urad, 6.12urad, 4.56urad, 4.09urad respectively. When the moment disturbance is 0.1rad, the residual standard error of pitching angle, azimuth angle, x-coordinate position and y-coordinate position are 0.26urad, 0.22urad, 0.16urad, 0.15urad respectively. The digital fabrication results demonstrate that the dual feedback discrete control system designed for the simulator can achieve the anticipated high precision performance.
Post-transcriptional control of DGCR8 expression by the Microprocessor.
Triboulet, Robinson; Chang, Hao-Ming; Lapierre, Robert J; Gregory, Richard I
2009-06-01
The Microprocessor, comprising the RNase III Drosha and the double-stranded RNA binding protein DGCR8, is essential for microRNA (miRNA) biogenesis. In the miRNA processing pathway certain hairpin structures within primary miRNA (pri-miRNA) transcripts are specifically cleaved by the Microprocessor to release approximately 60-70-nucleotide precursor miRNA (pre-miRNA) intermediates. Although both Drosha and DGCR8 are required for Microprocessor activity, the mechanisms regulating the expression of these proteins are unknown. Here we report that the Microprocessor negatively regulates DGCR8 expression. Using in vitro reconstitution and in vivo studies, we demonstrate that a hairpin, localized in the 5' untranslated region (5'UTR) of DGCR8 mRNA, is cleaved by the Microprocessor. Accordingly, knockdown of Drosha leads to an increase in DGCR8 mRNA and protein levels in cells. Furthermore, we found that the DGCR8 5'UTR confers Microprocessor-dependent repression of a luciferase reporter gene in vivo. Our results uncover a novel feedback loop that regulates DGCR8 levels.
Is sensorimotor BCI performance influenced differently by mono, stereo, or 3-D auditory feedback?
McCreadie, Karl A; Coyle, Damien H; Prasad, Girijesh
2014-05-01
Imagination of movement can be used as a control method for a brain-computer interface (BCI) allowing communication for the physically impaired. Visual feedback within such a closed loop system excludes those with visual problems and hence there is a need for alternative sensory feedback pathways. In the context of substituting the visual channel for the auditory channel, this study aims to add to the limited evidence that it is possible to substitute visual feedback for its auditory equivalent and assess the impact this has on BCI performance. Secondly, the study aims to determine for the first time if the type of auditory feedback method influences motor imagery performance significantly. Auditory feedback is presented using a stepped approach of single (mono), double (stereo), and multiple (vector base amplitude panning as an audio game) loudspeaker arrangements. Visual feedback involves a ball-basket paradigm and a spaceship game. Each session consists of either auditory or visual feedback only with runs of each type of feedback presentation method applied in each session. Results from seven subjects across five sessions of each feedback type (visual, auditory) (10 sessions in total) show that auditory feedback is a suitable substitute for the visual equivalent and that there are no statistical differences in the type of auditory feedback presented across five sessions.
Determinants of cell-to-cell variability in protein kinase signaling.
Jeschke, Matthias; Baumgärtner, Stephan; Legewie, Stefan
2013-01-01
Cells reliably sense environmental changes despite internal and external fluctuations, but the mechanisms underlying robustness remain unclear. We analyzed how fluctuations in signaling protein concentrations give rise to cell-to-cell variability in protein kinase signaling using analytical theory and numerical simulations. We characterized the dose-response behavior of signaling cascades by calculating the stimulus level at which a pathway responds ('pathway sensitivity') and the maximal activation level upon strong stimulation. Minimal kinase cascades with gradual dose-response behavior show strong variability, because the pathway sensitivity and the maximal activation level cannot be simultaneously invariant. Negative feedback regulation resolves this trade-off and coordinately reduces fluctuations in the pathway sensitivity and maximal activation. Feedbacks acting at different levels in the cascade control different aspects of the dose-response curve, thereby synergistically reducing the variability. We also investigated more complex, ultrasensitive signaling cascades capable of switch-like decision making, and found that these can be inherently robust to protein concentration fluctuations. We describe how the cell-to-cell variability of ultrasensitive signaling systems can be actively regulated, e.g., by altering the expression of phosphatase(s) or by feedback/feedforward loops. Our calculations reveal that slow transcriptional negative feedback loops allow for variability suppression while maintaining switch-like decision making. Taken together, we describe design principles of signaling cascades that promote robustness. Our results may explain why certain signaling cascades like the yeast pheromone pathway show switch-like decision making with little cell-to-cell variability.
Salmon runs have declined over the past two centuries in the Pacific Northwest region of North America. Reduced inputs of salmon-derived organic matter and nutrients (SDN) may limit freshwater production and thus establish a negative feedback loop affecting future generations of...
An Actomyosin-Arf-GEF Negative Feedback Loop for Tissue Elongation under Stress.
West, Junior J; Zulueta-Coarasa, Teresa; Maier, Janna A; Lee, Donghoon M; Bruce, Ashley E E; Fernandez-Gonzalez, Rodrigo; Harris, Tony J C
2017-08-07
In response to a pulling force, a material can elongate, hold fast, or fracture. During animal development, multi-cellular contraction of one region often stretches neighboring tissue. Such local contraction occurs by induced actomyosin activity, but molecular mechanisms are unknown for regulating the physical properties of connected tissue for elongation under stress. We show that cytohesins, and their Arf small G protein guanine nucleotide exchange activity, are required for tissues to elongate under stress during both Drosophila dorsal closure (DC) and zebrafish epiboly. In Drosophila, protein localization, laser ablation, and genetic interaction studies indicate that the cytohesin Steppke reduces tissue tension by inhibiting actomyosin activity at adherens junctions. Without Steppke, embryogenesis fails, with epidermal distortions and tears resulting from myosin misregulation. Remarkably, actomyosin network assembly is necessary and sufficient for local Steppke accumulation, where live imaging shows Steppke recruitment within minutes. This rapid negative feedback loop provides a molecular mechanism for attenuating the main tension generator of animal tissues. Such attenuation relaxes tissues and allows orderly elongation under stress. Copyright © 2017 Elsevier Ltd. All rights reserved.
A microRNA negative feedback loop downregulates vesicle transport and inhibits fear memory
Mathew, Rebecca S; Tatarakis, Antonis; Rudenko, Andrii; Johnson-Venkatesh, Erin M; Yang, Yawei J; Murphy, Elisabeth A; Todd, Travis P; Schepers, Scott T; Siuti, Nertila; Martorell, Anthony J; Falls, William A; Hammack, Sayamwong E; Walsh, Christopher A; Tsai, Li-Huei; Umemori, Hisashi; Bouton, Mark E; Moazed, Danesh
2016-01-01
The SNARE-mediated vesicular transport pathway plays major roles in synaptic remodeling associated with formation of long-term memories, but the mechanisms that regulate this pathway during memory acquisition are not fully understood. Here we identify miRNAs that are up-regulated in the rodent hippocampus upon contextual fear-conditioning and identify the vesicular transport and synaptogenesis pathways as the major targets of the fear-induced miRNAs. We demonstrate that miR-153, a member of this group, inhibits the expression of key components of the vesicular transport machinery, and down-regulates Glutamate receptor A1 trafficking and neurotransmitter release. MiR-153 expression is specifically induced during LTP induction in hippocampal slices and its knockdown in the hippocampus of adult mice results in enhanced fear memory. Our results suggest that miR-153, and possibly other fear-induced miRNAs, act as components of a negative feedback loop that blocks neuronal hyperactivity at least partly through the inhibition of the vesicular transport pathway. DOI: http://dx.doi.org/10.7554/eLife.22467.001 PMID:28001126
Implementing Audio Digital Feedback Loop Using the National Instruments RIO System
DOE Office of Scientific and Technical Information (OSTI.GOV)
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.
Servo control booster system for minimizing following error
Wise, William L.
1985-01-01
A closed-loop feedback-controlled servo system is disclosed which reduces command-to-response error to the system's position feedback resolution least increment, .DELTA.S.sub.R, on a continuous real-time basis for all operating speeds. The servo system employs a second position feedback control loop on a by exception basis, when the command-to-response error .gtoreq..DELTA.S.sub.R, to produce precise position correction signals. When the command-to-response error is less than .DELTA.S.sub.R, control automatically reverts to conventional control means as the second position feedback control loop is disconnected, becoming transparent to conventional servo control means. By operating the second unique position feedback control loop used herein at the appropriate clocking rate, command-to-response error may be reduced to the position feedback resolution least increment. The present system may be utilized in combination with a tachometer loop for increased stability.
2015-01-01
Health is regulated by homeostasis, a property of all living things. Homeostasis maintains equilibrium at set-points using feedback loops for optimum functioning of the organism. Imbalances in homeostasis causing overweight and obesity are evident in more than 1 billion people. In a new theory, homeostatic obesity imbalance is attributed to a hypothesized ‘Circle of Discontent’, a system of feedback loops linking weight gain, body dissatisfaction, negative affect and over-consumption. The Circle of Discontent theory is consistent with an extensive evidence base. A four-armed strategy to halt the obesity epidemic consists of (1) putting a stop to victim-blaming, stigma and discrimination; (2) devalorizing the thin-ideal; (3) reducing consumption of energy-dense, low-nutrient foods and drinks; and (4) improving access to plant-based diets. If fully implemented, interventions designed to restore homeostasis have the potential to halt the obesity epidemic. PMID:28070357
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.
Feedback Regulation and Its Efficiency in Biochemical Networks
NASA Astrophysics Data System (ADS)
Kobayashi, Tetsuya J.; Yokota, Ryo; Aihara, Kazuyuki
2016-03-01
Intracellular biochemical networks fluctuate dynamically due to various internal and external sources of fluctuation. Dissecting the fluctuation into biologically relevant components is important for understanding how a cell controls and harnesses noise and how information is transferred over apparently noisy intracellular networks. While substantial theoretical and experimental advancement on the decomposition of fluctuation was achieved for feedforward networks without any loop, we still lack a theoretical basis that can consistently extend such advancement to feedback networks. The main obstacle that hampers is the circulative propagation of fluctuation by feedback loops. In order to define the relevant quantity for the impact of feedback loops for fluctuation, disentanglement of the causally interlocked influences between the components is required. In addition, we also lack an approach that enables us to infer non-perturbatively the influence of the feedback to fluctuation in the same way as the dual reporter system does in the feedforward networks. In this work, we address these problems by extending the work on the fluctuation decomposition and the dual reporter system. For a single-loop feedback network with two components, we define feedback loop gain as the feedback efficiency that is consistent with the fluctuation decomposition for feedforward networks. Then, we clarify the relation of the feedback efficiency with the fluctuation propagation in an open-looped FF network. Finally, by extending the dual reporter system, we propose a conjugate feedback and feedforward system for estimating the feedback efficiency non-perturbatively only from the statistics of the system.
Not simply more of the same: distinguishing between patient heterogeneity and parameter uncertainty.
Vemer, Pepijn; Goossens, Lucas M A; Rutten-van Mölken, Maureen P M H
2014-11-01
In cost-effectiveness (CE) Markov models, heterogeneity in the patient population is not automatically taken into account. We aimed to compare methods of dealing with heterogeneity on estimates of CE, using a case study in chronic obstructive pulmonary disease (COPD). We first present a probabilistic sensitivity analysis (PSA) in which we sampled only from distributions representing parameter uncertainty. This ignores any heterogeneity. Next, we explored heterogeneity by presenting results for subgroups, using a method that samples parameter uncertainty simultaneously with heterogeneity in a single-loop PSA. Finally, we distinguished parameter uncertainty from heterogeneity in a double-loop PSA by performing a nested simulation within each PSA iteration. Point estimates and uncertainty differed substantially between methods. The incremental CE ratio (ICER) ranged from € 4900 to € 13,800. The single-loop PSA led to a substantially different shape of the CE plane and an overestimation of the uncertainty compared with the other 3 methods. The CE plane for the double-loop PSA showed substantially less uncertainty and a stronger negative correlation between the difference in costs and the difference in effects compared with the other methods. This came at the cost of higher calculation times. Not accounting for heterogeneity, subgroup analysis and the double-loop PSA can be viable options, depending on the decision makers' information needs. The single-loop PSA should not be used in CE research. It disregards the fundamental differences between heterogeneity and sampling uncertainty and overestimates uncertainty as a result. © The Author(s) 2014.
The MtDMI2-MtPUB2 Negative Feedback Loop Plays a Role in Nodulation Homeostasis1[OPEN
Deng, Jie; Zhu, Fugui; Lu, Zheng
2018-01-01
DOES NOT MAKE INFECTION 2 (MtDMI2) is a Leu rich repeat-type receptor kinase required for signal transduction in the Medicago truncatula/Sinorhizobium meliloti symbiosis pathway. However, the mechanisms through which MtDMI2 participates in nodulation homeostasis are poorly understood. In this study, we identified MtPUB2—a novel plant U-box (PUB)–type E3 ligase—and showed that it interacts with MtDMI2. MtDMI2 and MtPUB2 accumulation were shown to be similar in various tissues. Roots of plants in which MtPUB2 was silenced by RNAi (MtPUB2-RNAi plants) exhibited impaired infection threads, fewer nodules, and shorter primary root lengths compared to those of control plants transformed with empty vector. Using liquid chromatography-tandem mass spectrometry, we showed that MtDMI2 phosphorylates MtPUB2 at Ser-316, Ser-421, and Thr-488 residues. When MtPUB2-RNAi plants were transformed with MtPUB2S421D, which mimics the phosphorylated state, MtDMI2 was persistently ubiquitinated and degraded by MtPUB2S421D, resulting in fewer nodules than observed in MtPUB2/MtPUB2-RNAi-complemented plants. However, MtPUB2S421A/MtPUB2-RNAi-complemented plants showed no MtPUB2 ubiquitination activity, and their nodulation phenotype was similar to that of MtPUB2-RNAi plants transformed with empty vector. Further studies demonstrated that these proteins form a negative feedback loop of the prey (MtDMI2)-predator (MtPUB2) type. Our results suggest that the MtDMI2-MtPUB2 negative feedback loop, which displays crosstalk with the long-distance autoregulation of nodulation via MtNIN, plays an important role in nodulation homeostasis. PMID:29440269
Limit cycles in piecewise-affine gene network models with multiple interaction loops
NASA Astrophysics Data System (ADS)
Farcot, Etienne; Gouzé, Jean-Luc
2010-01-01
In this article, we consider piecewise affine differential equations modelling gene networks. We work with arbitrary decay rates, and under a local hypothesis expressed as an alignment condition of successive focal points. The interaction graph of the system may be rather complex (multiple intricate loops of any sign, multiple thresholds, etc.). Our main result is an alternative theorem showing that if a sequence of region is periodically visited by trajectories, then under our hypotheses, there exists either a unique stable periodic solution, or the origin attracts all trajectories in this sequence of regions. This result extends greatly our previous work on a single negative feedback loop. We give several examples and simulations illustrating different cases.
Hartmann, Cornelia; Dosen, Strahinja; Amsuess, Sebastian; Farina, Dario
2015-09-01
Electrocutaneous stimulation is a promising approach to provide sensory feedback to amputees, and thus close the loop in upper limb prosthetic systems. However, the stimulation introduces artifacts in the recorded electromyographic (EMG) signals, which may be detrimental for the control of myoelectric prostheses. In this study, artifact blanking with three data segmentation approaches was investigated as a simple method to restore the performance of pattern recognition in prosthesis control (eight motions) when EMG signals are corrupted by stimulation artifacts. The methods were tested over a range of stimulation conditions and using four feature sets, comprising both time and frequency domain features. The results demonstrated that when stimulation artifacts were present, the classification performance improved with blanking in all tested conditions. In some cases, the classification performance with blanking was at the level of the benchmark (artifact-free data). The greatest pulse duration and frequency that allowed a full performance recovery were 400 μs and 150 Hz, respectively. These results show that artifact blanking can be used as a practical solution to eliminate the negative influence of the stimulation artifact on EMG pattern classification in a broad range of conditions, thus allowing to close the loop in myoelectric prostheses using electrotactile feedback.
Chau, Michael; Forcinito, Patricia; Andrade, Anenisia C; Hegde, Anita; Ahn, Sohyun; Lui, Julian C; Baron, Jeffrey; Nilsson, Ola
2011-08-01
In embryonic growth cartilage, Indian hedgehog (Ihh) and parathyroid hormone-related protein (PTHrP) participate in a negative feedback loop that regulates chondrocyte differentiation. Postnatally, this region undergoes major structural and functional changes. To explore the organization of the Ihh–PTHrP system in postnatal growth plate, we microdissected growth plates of 7-day-old rats into their constituent zones and assessed expression of genes participating in the h–PTHrP feedback loop. Ihh, Patched 1, Smoothened, Gli1, Gli2, Gli3, and Pthr1 were expressed in regions analogous to the expression domains in embryonic growth cartilage. However, PTHrP was expressed in resting zone cartilage, a site that differs from the embryonic source, the periarticular cells. We then used mice in which lacZ has replaced coding sequences of Gli1 and thus serves as a marker for active hedgehog signaling. At 1, 4, 8, and 12 weeks of age, lacZ expression was detected in a pattern analogous to that of embryonic cartilage. The findings support the hypothesis that the embryonic Ihh–PTHrP feedback loop is maintained in the postnatal growth plate except that the source of PTHrP has shifted to a more proximal location in the resting zone.
A computerized Langmuir probe system
NASA Astrophysics Data System (ADS)
Pilling, L. S.; Bydder, E. L.; Carnegie, D. A.
2003-07-01
For low pressure plasmas it is important to record entire single or double Langmuir probe characteristics accurately. For plasmas with a depleted high energy tail, the accuracy of the recorded ion current plays a critical role in determining the electron temperature. Even for high density Maxwellian distributions, it is necessary to accurately model the ion current to obtain the correct electron density. Since the electron and ion current saturation values are, at best, orders of magnitude apart, a single current sensing resistor cannot provide the required resolution to accurately record these values. We present an automated, personal computer based data acquisition system for the determination of fundamental plasma properties in low pressure plasmas. The system is designed for single and double Langmuir probes, whose characteristics can be recorded over a bias voltage range of ±70 V with 12 bit resolution. The current flowing through the probes can be recorded within the range of 5 nA-100 mA. The use of a transimpedance amplifier for current sensing eliminates the requirement for traditional current sensing resistors and hence the need to correct the raw data. The large current recording range is realized through the use of a real time gain switching system in the negative feedback loop of the transimpedance amplifier.
Dual-circuit, multiple-effect refrigeration system and method
DeVault, Robert C.
1995-01-01
A dual circuit absorption refrigeration system comprising a high temperature single-effect refrigeration loop and a lower temperature double-effect refrigeration loop separate from one another and provided with a double-condenser coupling therebetween. The high temperature condenser of the single-effect refrigeration loop is double coupled to both of the generators in the double-effect refrigeration loop to improve internal heat recovery and a heat and mass transfer additive such as 2-ethyl-1-hexanol is used in the lower temperature double-effect refrigeration loop to improve the performance of the absorber in the double-effect refrigeration loop.
Burnout is associated with changes in error and feedback processing.
Gajewski, Patrick D; Boden, Sylvia; Freude, Gabriele; Potter, Guy G; Falkenstein, Michael
2017-10-01
Burnout is a pattern of complaints in individuals with emotionally demanding jobs that is often seen as a precursor of depression. One often reported symptom of burnout is cognitive decline. To analyze cognitive control and to differentiate between subclinical burnout and mild to moderate depression a double-blinded study was conducted that investigates changes in the processing of performance errors and feedback in a task switching paradigm. Fifty-one of 76 employees from emotionally demanding jobs showed a sufficient number of errors to be included in the analysis. The sample was subdivided into groups with low (EE-) and high (EE+) emotional exhaustion and no (DE-) and mild to moderate depression (DE+). The behavioral data did not significantly differ between the groups. In contrast, in the EE+ group, the error negativity (Ne/ERN) was enhanced while the error positivity (Pe) did not differ between the EE+ and EE- groups. After negative feedback the feedback-related negativity (FRN) was enhanced, while the subsequent positivity (FRP) was reduced in EE+ relative to EE-. None of these effects were observed in the DE+ vs. DE-. These results suggest an upregulation of error and negative feedback processing, while the later processing of negative feedback was attenuated in employees with subclinical burnout but not in mild to moderate depression. Copyright © 2017 Elsevier B.V. All rights reserved.
Kang, Yeon Hee; Kirik, Victor; Hulskamp, Martin; Nam, Kyoung Hee; Hagely, Katherine; Lee, Myeong Min; Schiefelbein, John
2009-01-01
The specification of cell fates during development requires precise regulatory mechanisms to ensure robust cell type patterns. Theoretical models of pattern formation suggest that a combination of negative and positive feedback mechanisms are necessary for efficient specification of distinct fates in a field of differentiating cells. Here, we examine the role of the R2R3-MYB transcription factor gene, AtMYB23 (MYB23), in the establishment of the root epidermal cell type pattern in Arabidopsis thaliana. MYB23 is closely related to, and is positively regulated by, the WEREWOLF (WER) MYB gene during root epidermis development. Furthermore, MYB23 is able to substitute for the function of WER and to induce its own expression when controlled by WER regulatory sequences. We also show that the MYB23 protein binds to its own promoter, suggesting a MYB23 positive feedback loop. The localization of MYB23 transcripts and MYB23-green fluorescent protein (GFP) fusion protein, as well as the effect of a chimeric MYB23-SRDX repressor construct, links MYB23 function to the developing non-hair cell type. Using mutational analyses, we find that MYB23 is necessary for precise establishment of the root epidermal pattern, particularly under conditions that compromise the cell specification process. These results suggest that MYB23 participates in a positive feedback loop to reinforce cell fate decisions and ensure robust establishment of the cell type pattern in the Arabidopsis root epidermis. PMID:19395683
Kang, Yeon Hee; Kirik, Victor; Hulskamp, Martin; Nam, Kyoung Hee; Hagely, Katherine; Lee, Myeong Min; Schiefelbein, John
2009-04-01
The specification of cell fates during development requires precise regulatory mechanisms to ensure robust cell type patterns. Theoretical models of pattern formation suggest that a combination of negative and positive feedback mechanisms are necessary for efficient specification of distinct fates in a field of differentiating cells. Here, we examine the role of the R2R3-MYB transcription factor gene, AtMYB23 (MYB23), in the establishment of the root epidermal cell type pattern in Arabidopsis thaliana. MYB23 is closely related to, and is positively regulated by, the WEREWOLF (WER) MYB gene during root epidermis development. Furthermore, MYB23 is able to substitute for the function of WER and to induce its own expression when controlled by WER regulatory sequences. We also show that the MYB23 protein binds to its own promoter, suggesting a MYB23 positive feedback loop. The localization of MYB23 transcripts and MYB23-green fluorescent protein (GFP) fusion protein, as well as the effect of a chimeric MYB23-SRDX repressor construct, links MYB23 function to the developing non-hair cell type. Using mutational analyses, we find that MYB23 is necessary for precise establishment of the root epidermal pattern, particularly under conditions that compromise the cell specification process. These results suggest that MYB23 participates in a positive feedback loop to reinforce cell fate decisions and ensure robust establishment of the cell type pattern in the Arabidopsis root epidermis.
Indirect Identification of Linear Stochastic Systems with Known Feedback Dynamics
NASA Technical Reports Server (NTRS)
Huang, Jen-Kuang; Hsiao, Min-Hung; Cox, David E.
1996-01-01
An algorithm is presented for identifying a state-space model of linear stochastic systems operating under known feedback controller. In this algorithm, only the reference input and output of closed-loop data are required. No feedback signal needs to be recorded. The overall closed-loop system dynamics is first identified. Then a recursive formulation is derived to compute the open-loop plant dynamics from the identified closed-loop system dynamics and known feedback controller dynamics. The controller can be a dynamic or constant-gain full-state feedback controller. Numerical simulations and test data of a highly unstable large-gap magnetic suspension system are presented to demonstrate the feasibility of this indirect identification method.
Feedback: A Systems Approach to Evaluation and Course Design. Working Papers No. 21.
ERIC Educational Resources Information Center
Holmes, John
Two types of feedback are examined, and their use in controlling the processes of instructional development and improvement are discussed. Closed-loop feedback, the most direct, uses immediate feedback about a process or product to make immediate adjustments in it. Open-loop feedback, in which input cannot be changed immediately, uses feedback to…
Power Scaling and Frequency Stabilization of an Injection-Locked Laser
2000-05-01
In Chapter 4,1 alter the well -documented theory of locking a laser to a Fabry- Perot by performing the PDH error signal derivation in a new manner...the well -documented modulation transfer scheme to lock the frequency-doubled NPRO to a hyperfine component of an electronic transition in I2. 33 I...generally true at very low noise frequencies, well within the feedback loop bandwidth. However, when G0L(V„) « 1 and thus GCL(vn) « 1, Equation 3.9
Stability analysis and compensation of a boost regulator with two-loop control
NASA Technical Reports Server (NTRS)
Wester, G. W.
1974-01-01
A useful stability measure has been demonstrated by Wester (1973) for switching regulators with a single feedback loop by applying the Nyquist criterion to the approximate loop gain determined by a time-averaging technique. This approach is extended and applied to the characterization, stability analysis, and compensation design of a switching regulator with two-loop control. The role and relative significance of each control loop is clarified on the basis of a description of circuit operation, and the major and minor loops are identified. In view of the inapplicability of linear feedback theory, describing functions of the feedback loops and power stage are derived, using small-signal analysis. Several phenomena revealed from an analysis of the major loop gain are discussed.
Rigid Body Rate Inference from Attitude Variation
NASA Technical Reports Server (NTRS)
Bar-Itzhack, I. Y.; Harman, Richard R.; Thienel, Julie K.
2006-01-01
In this paper we research the extraction of the angular rate vector from attitude information without differentiation, in particular from quaternion measurements. We show that instead of using a Kalman filter of some kind, it is possible to obtain good rate estimates, suitable for spacecraft attitude control loop damping, using simple feedback loops, thereby eliminating the need for recurrent covariance computation performed when a Kalman filter is used. This considerably simplifies the computations required for rate estimation in gyro-less spacecraft. Some interesting qualities of the Kalman filter gain are explored, proven and utilized. We examine two kinds of feedback loops, one with varying gain that is proportional to the well known Q matrix, which is computed using the measured quaternion, and the other type of feedback loop is one with constant coefficients. The latter type includes two kinds; namely, a proportional feedback loop, and a proportional-integral feedback loop. The various schemes are examined through simulations and their performance is compared. It is shown that all schemes are adequate for extracting the angular velocity at an accuracy suitable for control loop damping.
On the Extraction of Angular Velocity from Attitude Measurements
NASA Technical Reports Server (NTRS)
Bar-Itzhack, I. Y.; Harman, Richard R.; Thienel, Julie K.
2006-01-01
In this paper we research the extraction of the angular rate vector from attitude information without differentiation, in particular from quaternion measurements. We show that instead of using a Kalman filter of some kind, it is possible to obtain good rate estimates, suitable for spacecraft attitude control loop damping, using simple feedback loops, thereby eliminating the need for recurrent covariance computation performed when a Kalman filter is used. This considerably simplifies the computations required for rate estimation in gyro-less spacecraft. Some interesting qualities of the Kalman filter gain are explored, proven and utilized. We examine two kinds of feedback loops, one with varying gain that is proportional to the well known Q matrix, which is computed using the measured quaternion, and the other type of feedback loop is one with constant coefficients. The latter type includes two kinds; namely, a proportional feedback loop, and a proportional-integral feedback loop. The various schemes are examined through simulations and their performance is compared. It is shown that all schemes are adequate for extracting the angular velocity at an accuracy suitable for control loop damping.
Zhang, Zhaohui; Ma, Fei; Zhou, Feng; Chen, Yibing; Wang, Xiaoyan; Zhang, Hongxin; Zhu, Yong; Bi, Jianwei; Zhang, Yiguan
2014-12-01
Previous studies have demonstrated that circadian negative feedback loop genes play an important role in the development and progression of many cancers. However, the associations between single-nucleotide polymorphisms (SNPs) in these genes and the clinical outcomes of hepatocellular carcinoma (HCC) after surgical resection have not been studied so far. Thirteen functional SNPs in circadian genes were genotyped using the Sequenom iPLEX genotyping system in a cohort of 489 Chinese HCC patients who received radical resection. Multivariate Cox proportional hazards model and Kaplan-Meier curve were used for the prognosis analysis. Cumulative effect analysis and survival tree analysis were used for the multiple SNPs analysis. Four individual SNPs, including rs3027178 in PER1, rs228669 and rs2640908 in PER3 and rs3809236 in CRY1, were significantly associated with overall survival (OS) of HCC patients, and three SNPs, including rs3027178 in PER1, rs228729 in PER3 and rs3809236 in CRY1, were significantly associated with recurrence-free survival (RFS). Moreover, we observed a cumulative effect of significant SNPs on OS and RFS (P for trend < 0.001 for both). Survival tree analysis indicated that wild genotype of rs228729 in PER3 was the primary risk factor contributing to HCC patients' RFS. Our study suggests that the polymorphisms in circadian negative feedback loop genes may serve as independent prognostic biomarkers in predicting clinical outcomes for HCC patients who received radical resection. Further studies with different ethnicities are needed to validate our findings and generalize its clinical utility.
Servo control booster system for minimizing following error
Wise, W.L.
1979-07-26
A closed-loop feedback-controlled servo system is disclosed which reduces command-to-response error to the system's position feedback resolution least increment, ..delta..S/sub R/, on a continuous real-time basis, for all operational times of consequence and for all operating speeds. The servo system employs a second position feedback control loop on a by exception basis, when the command-to-response error greater than or equal to ..delta..S/sub R/, to produce precise position correction signals. When the command-to-response error is less than ..delta..S/sub R/, control automatically reverts to conventional control means as the second position feedback control loop is disconnected, becoming transparent to conventional servo control means. By operating the second unique position feedback control loop used herein at the appropriate clocking rate, command-to-response error may be reduced to the position feedback resolution least increment. The present system may be utilized in combination with a tachometer loop for increased stability.
Closing the Feedback Loop Is Not Enough: The Assessment Spiral
ERIC Educational Resources Information Center
Wehlburg, Catherine M.
2007-01-01
For quite some time, the call to close the feedback loop has been heard throughout higher education. Faculty and administrators have paid attention, and now they can more easily than ever point to the fact that at their institution, the feedback loop is almost always closed. As reviewers from accreditation teams visit campuses, they often hear…
ERIC Educational Resources Information Center
Zhang, Yili; Smolen, Paul; Alberini, Cristina M.; Baxter, Douglas A.; Byrne, John H.
2016-01-01
Inhibitory avoidance (IA) training in rodents initiates a molecular cascade within hippocampal neurons. This cascade contributes to the transition of short- to long-term memory (i.e., consolidation). Here, a differential equation-based model was developed to describe a positive feedback loop within this molecular cascade. The feedback loop begins…
NASA Technical Reports Server (NTRS)
Chen, George T.
1987-01-01
An automatic control scheme for spacecraft proximity operations is presented. The controller is capable of holding the vehicle at a prescribed location relative to a target, or maneuvering it to a different relative position using straight line-of-sight translations. The autopilot uses a feedforward loop to initiate and terminate maneuvers, and for operations at nonequilibrium set-points. A multivariate feedback loop facilitates precise position and velocity control in the presence of sensor noise. The feedback loop is formulated using the Linear Quadratic Gaussian (LQG) with Loop Transfer Recovery (LTR) design procedure. Linear models of spacecraft dynamics, adapted from Clohessey-Wiltshire Equations, are augmented and loop shaping techniques are applied to design a target feedback loop. The loop transfer recovery procedure is used to recover the frequency domain properties of the target feedback loop. The resulting compensator is integrated into an autopilot which is tested in a high fidelity Space Shuttle Simulator. The autopilot performance is evaluated for a variety of proximity operations tasks envisioned for future Shuttle flights.
Large deviation analysis of a simple information engine
NASA Astrophysics Data System (ADS)
Maitland, Michael; Grosskinsky, Stefan; Harris, Rosemary J.
2015-11-01
Information thermodynamics provides a framework for studying the effect of feedback loops on entropy production. It has enabled the understanding of novel thermodynamic systems such as the information engine, which can be seen as a modern version of "Maxwell's Dæmon," whereby a feedback controller processes information gained by measurements in order to extract work. Here, we analyze a simple model of such an engine that uses feedback control based on measurements to obtain negative entropy production. We focus on the distribution and fluctuations of the information obtained by the feedback controller. Significantly, our model allows an analytic treatment for a two-state system with exact calculation of the large deviation rate function. These results suggest an approximate technique for larger systems, which is corroborated by simulation data.
Nakamura, Takeshi; Aoki, Kazuhiro; Matsuda, Michiyuki
2008-08-01
Genetically encoded probes based on Förster resonance energy transfer (FRET) enable us to decipher spatiotemporal information encoded in complex tissues such as the brain. Firstly, this review focuses on FRET probes wherein both the donor and acceptor are fluorescence proteins and are incorporated into a single molecule, i.e. unimolecular probes. Advantages of these probes lie in their easy loading into cells, the simple acquisition of FRET images, and the clear evaluation of data. Next, we introduce our recent study which encompasses FRET imaging and in silico simulation. In nerve growth factor-induced neurite outgrowth in PC12 cells, we found positive and negative signaling feedback loops. We propose that these feedback loops determine neurite-budding sites. We would like to emphasize that it is now time to accelerate crossover research in neuroscience, optics, and computational biology.
NASA Technical Reports Server (NTRS)
Gettman, Chang-Ching LO
1993-01-01
This thesis develops and demonstrates an approach to nonlinear control system design using linearization by state feedback. The design provides improved transient response behavior allowing faster maneuvering of payloads by the SRMS. Modeling uncertainty is accounted for by using a second feedback loop designed around the feedback linearized dynamics. A classical feedback loop is developed to provide the easy implementation required for the relatively small on board computers. Feedback linearization also allows the use of higher bandwidth model based compensation in the outer loop, since it helps maintain stability in the presence of the nonlinearities typically neglected in model based designs.
Circuit for Driving Piezoelectric Transducers
NASA Technical Reports Server (NTRS)
Randall, David P.; Chapsky, Jacob
2009-01-01
The figure schematically depicts an oscillator circuit for driving a piezoelectric transducer to excite vibrations in a mechanical structure. The circuit was designed and built to satisfy application-specific requirements to drive a selected one of 16 such transducers at a regulated amplitude and frequency chosen to optimize the amount of work performed by the transducer and to compensate for both (1) temporal variations of the resonance frequency and damping time of each transducer and (2) initially unknown differences among the resonance frequencies and damping times of different transducers. In other words, the circuit is designed to adjust itself to optimize the performance of whichever transducer is selected at any given time. The basic design concept may be adaptable to other applications that involve the use of piezoelectric transducers in ultrasonic cleaners and other apparatuses in which high-frequency mechanical drives are utilized. This circuit includes three resistor-capacitor networks that, together with the selected piezoelectric transducer, constitute a band-pass filter having a peak response at a frequency of about 2 kHz, which is approximately the resonance frequency of the piezoelectric transducers. Gain for generating oscillations is provided by a power hybrid operational amplifier (U1). A junction field-effect transistor (Q1) in combination with a resistor (R4) is used as a voltage-variable resistor to control the magnitude of the oscillation. The voltage-variable resistor is part of a feedback control loop: Part of the output of the oscillator is rectified and filtered for use as a slow negative feedback to the gate of Q1 to keep the output amplitude constant. The response of this control loop is much slower than 2 kHz and, therefore, does not introduce significant distortion of the oscillator output, which is a fairly clean sine wave. The positive AC feedback needed to sustain oscillations is derived from sampling the current through the piezoelectric transducer. This positive AC feedback, in combination with the slow feedback to the voltage-variable resistors, causes the overall loop gain to be just large enough to keep the oscillator running. The positive feedback loop includes two 16-channel multiplexers, which are not shown in the figure. One multiplexer is used to select the desired piezoelectric transducer. The other multiplexer, which is provided for use in the event that there are significant differences among the damping times of the 16 piezoelectric transducers, facilitates changing the value of one of the resistors in the positive-feedback loop to accommodate the damping time of the selected transducer.
Closed-Loop Control of Vortex Formation in Separated Flows
NASA Technical Reports Server (NTRS)
Colonius, Tim; Joe, Won Tae; MacMynowski, Doug; Rowley, Clancy; Taira, Sam; Ahuja, Sunil
2010-01-01
In order to phase lock the flow at the desired shedding cycle, particularly at Phi,best, We designed a feedback compensator. (Even though the open-loop forcing at Wf below Wn can lead to phase-locked limit cycles with a high average lift,) This feedback controller resulted in the phase-locked limit cycles that the open-loop control could not achieve for alpha=30 and 40 Particularly for alpha=40, the feedback was able to stabilize the limit cycle that was not stable with any of the open-loop periodic forcing. This results in stable phase-locked limit cycles for a larger range of forcing frequencies than the open-loop control. Also, it was shown that the feedback achieved the high-lift unsteady flow states that open-loop control could not sustain even after the states have been achieved for a long period of time.
NASA Astrophysics Data System (ADS)
Saaltink, Rémon; Dekker, Stefan C.; Griffioen, Jasper; Wassen, Martin J.
2016-04-01
Interest is growing in using soft sediment as a building material in eco-engineering projects. Wetland construction in the Dutch lake Markermeer is an example: here the option of dredging some of the clay-rich lake-bed sediment and using it to construct 10.000 ha of wetland will soon go under construction. Natural processes will be utilized during and after construction to accelerate ecosystem development. Knowing that plants can eco-engineer their environment via positive or negative biogeochemical plant-soil feedbacks, we conducted a six-month greenhouse experiment to identify the key biogeochemical processes in the mud when Phragmites australis is used as an eco-engineering species. We applied inverse biogeochemical modeling to link observed changes in pore water composition to biogeochemical processes. Two months after transplantation we observed reduced plant growth and shriveling as well as yellowing of foliage. The N:P ratios of plant tissue were low and were affected not by hampered uptake of N but by enhanced uptake of P. Plant analyses revealed high Fe concentrations in the leaves and roots. Sulfate concentrations rose drastically in our experiment due to pyrite oxidation; as reduction of sulfate will decouple Fe-P in reducing conditions, we argue that plant-induced iron toxicity hampered plant growth, forming a negative feedback loop, while simultaneously there was a positive feedback loop, as iron toxicity promotes P mobilization as a result of reduced conditions through root death, thereby stimulating plant growth and regeneration. Given these two feedback mechanisms, we propose that when building wetlands from these mud deposits Fe-tolerant species are used rather than species that thrive in N-limited conditions. The results presented in this study demonstrate the importance of studying the biogeochemical properties of the building material and the feedback mechanisms between plant and soil prior to finalizing the design of the eco-engineering project.
Mesenchymal stem/stromal cells (MSCs): role as guardians of inflammation.
Prockop, Darwin J; Oh, Joo Youn
2012-01-01
Recent observations have demonstrated that one of the functions of mesenchymal stem/stromal cells (MSCs) is to serve as guardians against excessive inflammatory responses. One mode of action of the cells is that they are activated to express the interleukin (IL)-1 receptor antagonist. A second mode of action is to create a negative feedback loop in which tumor necrosis factor-α (TNF-α) and other proinflammatory cytokines from resident macrophages activate MSCs to secrete the multifunctional anti-inflammatory protein TNF-α stimulated gene/protein 6 (TSG-6). The TSG-6 then reduces nuclear factor-κB (NF-κB) signaling in the resident macrophages and thereby modulates the cascade of proinflammatory cytokines. A third mode of action is to create a second negative feedback loop whereby lipopolysaccharide, TNF-α, nitric oxide, and perhaps other damage-associated molecular patterns (DAMPs) from injured tissues and macrophages activate MSCs to secrete prostaglandin E(2) (PGE(2)). The PGE(2) converts macrophages to the phenotype that secretes IL-10. There are also suggestions that MSCs may produce anti-inflammatory effects through additional modes of action including activation to express the antireactive oxygen species protein stanniocalcin-1.
A Negative Feedback Loop Between Autophagy and Immune Responses in Mycobacterium leprae Infection.
Ma, Yuelong; Zhang, Li; Lu, Jie; Shui, Tiejun; Chen, Jia; Yang, Jun; Yuan, Joanna; Liu, Yeqiang; Yang, Degang
2017-01-01
The obligate intracellular bacterium Mycobacterium leprae is the causative agent of leprosy and primarily infects macrophages, leading to irreversible nerve damage and deformities. So far, the underlying reasons allowing M. leprae to persist and propagate in macrophages, despite the presence of cellular immunity, are still a mystery. Here, we investigated the role of autophagy, a cellular process that degrades cytosolic materials and intracellular pathogens, in M. leprae infection. We found that live M. leprae infection of macrophages resulted in significantly elevated autophagy level. However, macrophages with high autophagy levels preferentially expressed lower levels of proinflammatory cytokines, including interleukin (IL)-1β, IL-6, IL-12, and tumor necrosis factor-α, and preferentially primed anti-inflammatory T cells responses, characterized by high IL-10 and low interferon-γ, granzyme B, and perforin responses. These anti-inflammatory T cells could suppress further induction of autophagy, leading to improved survival of intracellular M. leprae in infected macrophages. Therefore, these data demonstrated that although autophagy had a role in eliminating intracellular pathogens, the induction of autophagy resulted in anti-inflammatory immune responses, which suppressed autophagy in a negative feedback loop and allowed the persistence of M. leprae.
Circuitry, systems and methods for detecting magnetic fields
Kotter, Dale K [Shelley, ID; Spencer, David F [Idaho Falls, ID; Roybal, Lyle G [Idaho Falls, ID; Rohrbaugh, David T [Idaho Falls, ID
2010-09-14
Circuitry for detecting magnetic fields includes a first magnetoresistive sensor and a second magnetoresistive sensor configured to form a gradiometer. The circuitry includes a digital signal processor and a first feedback loop coupled between the first magnetoresistive sensor and the digital signal processor. A second feedback loop which is discrete from the first feedback loop is coupled between the second magnetoresistive sensor and the digital signal processor.
Digital Phase-Locked Loop With Phase And Frequency Feedback
NASA Technical Reports Server (NTRS)
Thomas, J. Brooks
1991-01-01
Advanced design for digital phase-lock loop (DPLL) allows loop gains higher than those used in other designs. Divided into two major components: counterrotation processor and tracking processor. Notable features include use of both phase and rate-of-change-of-phase feedback instead of frequency feedback alone, normalized sine phase extractor, improved method for extracting measured phase, and improved method for "compressing" output rate.
Plate with decentralised velocity feedback loops: Power absorption and kinetic energy considerations
NASA Astrophysics Data System (ADS)
Gardonio, P.; Miani, S.; Blanchini, F.; Casagrande, D.; Elliott, S. J.
2012-04-01
This paper is focused on the vibration effects produced by an array of decentralised velocity feedback loops that are evenly distributed over a rectangular thin plate to minimise its flexural response. The velocity feedback loops are formed by collocated ideal velocity sensor and point force actuator pairs, which are unconditionally stable and produce 'sky-hook' damping on the plate. The study compares how the overall flexural vibration of the plate and the local absorption of vibration power by the feedback loops vary with the control gains. The analysis is carried out both considering a typical frequency-domain formulation based on kinetic energy and structural power physical quantities, which is normally used to study vibration and noise problems, and a time-domain formulation also based on kinetic energy and structural power, which is usually implemented to investigate control problems. The time-domain formulation shows to be much more computationally efficient and robust with reference to truncation errors. Thus it has been used to perform a parametric study to assess if, and under which conditions, the minimum of the kinetic energy and the maximum of the absorbed power cost functions match with reference to: (a) the number of feedback control loops, (b) the structural damping in the plate, (c) the mutual distance of a pair of control loops and (d) the mutual gains implemented in a pair of feedback loops.
Autoregulatory mechanisms controlling the Microprocessor.
Triboulet, Robinson; Gregory, Richard I
2010-01-01
The Microprocessor, comprising the ribonuclease Drosha and its essential cofactor, the double-stranded RNA-binding protein, DGCR8, is essential for the first step of the miRNA biogenesis pathway. It specifically cleaves double-stranded RNA within stem-loop structures of primary miRNA transcripts (pri-miRNAs) to generate precursor (pre-miRNA) intermediates. Pre-miRNAs are subsequently processed by Dicer to their mature 22 nt form. Thus, Microprocessor is essential for miRNA maturation, and pri-miRNA cleavage by this complex defines one end of the mature miRNA. Moreover, it is emerging that dysregulation of the Microprocessor is associated with various human diseases. It is therefore important to understand the mechanisms by which the expression of the subunits of the Microprocessor is regulated. Recent findings have uncovered a post-transcriptional mechanism that maintains the integrity of the Microprocessor. These studies revealed that the Microprocessor is involved in the processing of the messenger RNA (mRNA) that encodes DGCR8. This regulatory feedback loop, along with the reported role played by DGCR8 in the stabilization of Drosha protein, is part ofa newly identified regulatory mechanism controlling Microprocessor activity.
Tang, Rixin; Whitwell, Robert L; Goodale, Melvyn A
2014-01-01
Previous research (Whitwell et al. in Exp Brain Res 188:603-611, 2008; Whitwell and Goodale in Exp Brain Res 194:619-629, 2009) has shown that trial history, but not anticipatory knowledge about the presence or absence of visual feedback on an upcoming trial, plays a vital role in determining how that feedback is exploited when grasping with the right hand. Nothing is known about how the non-dominant left hand behaves under the same feedback regimens. In present study, therefore, we compared peak grip aperture (PGA) for left- and right-hand grasps executed with and without visual feedback (i.e., closed- vs. open-loop conditions) in right-handed individuals under three different trial schedules: the feedback conditions were blocked separately, they were randomly interleaved, or they were alternated. When feedback conditions were blocked, the PGA was much larger for open-loop trials as compared to closed-loop trials, although this difference was more pronounced for right-hand grasps than left-hand grasps. Like Whitwell et al., we found that mixing open- and closed-loop trials together, compared to blocking them separately, homogenized the PGA for open- and closed-loop grasping in the right hand (i.e., the PGAs became smaller on open-loop trials and larger on closed-loop trials). In addition, the PGAs for right-hand grasps were entirely determined by trial history and not by knowledge of whether or not visual feedback would be available on an upcoming trial. In contrast to grasps made with the right hand, grasps made by the left hand were affected both by trial history and by anticipatory knowledge of the upcoming visual feedback condition. But these effects were observed only on closed-loop trials, i.e., the PGAs of grasps made with the left hand on closed-loop trials were smaller when participants could anticipate the availability of feedback on an upcoming trial (alternating trials) than when they could not (randomized trials). In contrast, grasps made with the left hand on open-loop trials exhibited the same large PGAs under all feedback schedules: blocked, random, or alternating. In other words, there was no evidence for homogenization. Taken together, these results suggest that in addition to the real-time demands of the task, such as the target's size and position and the availability of visual feedback, the initial (i.e., pre-movement) programming of right-hand grasping relies on what happened on the previous trial, whereas the programming of left-hand grasping is more cognitively supervised and exploits explicit information about trial order to prepare for an upcoming trial.
Milewska, Malgorzata; Romano, David; Herrero, Ana; Guerriero, Maria Luisa; Birtwistle, Marc; Quehenberger, Franz; Hatzl, Stefan; Kholodenko, Boris N.; Segatto, Oreste; Kolch, Walter; Zebisch, Armin
2015-01-01
BRAF functions in the RAS-extracellular signal-regulated kinase (ERK) signaling cascade. Activation of this pathway is necessary to mediate the transforming potential of oncogenic BRAF, however, it may also cause a negative feedback that inhibits the epidermal growth factor receptor (EGFR). Mitogen-inducible gene-6 (MIG-6) is a potent inhibitor of the EGFR and has been demonstrated to function as a tumor suppressor. As MIG-6 can be induced via RAS-ERK signaling, we investigated its potential involvement in this negative regulatory loop. Focus formation assays were performed and demonstrated that MIG-6 significantly reduces malignant transformation induced by oncogenic BRAF. Although this genetic interaction was mirrored by a physical interaction between MIG-6 and BRAF, we did not observe a direct regulation of BRAF kinase activity by MIG-6. Interestingly, a selective chemical EGFR inhibitor suppressed transformation to a similar degree as MIG-6, whereas combining these approaches had no synergistic effect. By analyzing a range of BRAF mutated and wildtype cell line models, we could show that BRAF V600E causes a strong upregulation of MIG-6, which was mediated at the transcriptional level via the RAS-ERK pathway and resulted in downregulation of EGFR activation. This feedback loop is operational in tumors, as shown by the analysis of almost 400 patients with papillary thyroid cancer (PTC). Presence of BRAF V600E correlated with increased MIG-6 expression on the one hand, and with inactivation of the EGFR and of PI3K/AKT signaling on the other hand. Importantly, we also observed a more aggressive disease phenotype when BRAF V600E coexisted with low MIG-6 expression. Finally, analysis of methylation data was performed and revealed that higher methylation of MIG-6 correlated to its decreased expression. Taken together, we demonstrate that MIG-6 efficiently reduces cellular transformation driven by oncogenic BRAF by orchestrating a negative feedback circuit directed towards the EGFR. PMID:26065894
Frick, U; Rehm, J; Knoll, A; Reifinger, M; Hasford, J
2000-01-01
Public traffic safety campaigns in Germany have focussed on the changing risk perception of young drivers. While there is some consensus that perceptions of risk affect driving, less is understood about the relationship and interaction of alcohol consumption and risk perception on the decision to drive. We examined the influence of light alcohol consumption on risk perception and decision to drive, and the interaction of alcohol consumption and cognitive feedback on the handicapping effect of alcohol on risk perception and decision to drive. In a double-blind block-randomized experimental study of 104 young drivers between 19 and 24 years of age, with two experimentally manipulated independent factors of alcohol consumption (three levels: 0% BAC, 0.015% BAC, 0.03% BAC) and feedback (positive or negative), we assessed three dependent variables: perception of traffic accident risk, subjective judgement about driving-relevant cognitive performance, decision to drive a car. Analyses of variance and covariance were used to analyze differences between levels of experimental factors. We found that persons with 0.015 BAC performed better than persons in both other alcohol conditions on the standardized risk perception task. Perceived handicap of driving was significantly more pronounced for negative feedback compared to positive feedback with no influence of the level of alcohol consumption. No significant influence on decision to drive was found of either level of alcohol consumption, feedback or sex. Decision to drive in young drivers could not be influenced by feedback or light consumption. Public health approaches have to find better determining factors.
Watch what you type: the role of visual feedback from the screen and hands in skilled typewriting.
Snyder, Kristy M; Logan, Gordon D; Yamaguchi, Motonori
2015-01-01
Skilled typing is controlled by two hierarchically structured processing loops (Logan & Crump, 2011): The outer loop, which produces words, commands the inner loop, which produces keystrokes. Here, we assessed the interplay between the two loops by investigating how visual feedback from the screen (responses either were or were not echoed on the screen) and the hands (the hands either were or were not covered with a box) influences the control of skilled typing. Our results indicated, first, that the reaction time of the first keystroke was longer when responses were not echoed than when they were. Also, the interkeystroke interval (IKSI) was longer when the hands were covered than when they were visible, and the IKSI for responses that were not echoed was longer when explicit error monitoring was required (Exp. 2) than when it was not required (Exp. 1). Finally, explicit error monitoring was more accurate when response echoes were present than when they were absent, and implicit error monitoring (i.e., posterror slowing) was not influenced by visual feedback from the screen or the hands. These findings suggest that the outer loop adjusts the inner-loop timing parameters to compensate for reductions in visual feedback. We suggest that these adjustments are preemptive control strategies designed to execute keystrokes more cautiously when visual feedback from the hands is absent, to generate more cautious motor programs when visual feedback from the screen is absent, and to enable enough time for the outer loop to monitor keystrokes when visual feedback from the screen is absent and explicit error reports are required.
Erickson, Dana; Miles, John M.; Bowers, Cyril Y.
2011-01-01
To test the postulate that sex difference, sex steroids, and peptidyl secretagogues control GH autofeedback, 11 healthy postmenopausal women and 14 older men were each given 1) a single iv pulse of GH to enforce negative feedback and 2) continuous iv infusion of saline vs. combined GHRH/GHRP-2 to drive feedback escape during pharmacological estradiol (E2; women) or testosterone (T; men) supplementation vs. placebo in a double-blind, prospectively randomized crossover design. By three-way ANCOVA, sex difference, sex hormone treatment, peptide stimulation, and placebo/saline responses (covariate) controlled total (integrated) GH recovery during feedback (each P < 0.001). Both sex steroid milieu (P = 0.019) and dual-peptide stimulation (P < 0.001) determined nadir (maximally feedback-suppressed) GH concentrations. E2/T exposure elevated nadir GH concentrations during saline infusion (P = 0.003), whereas dual-peptide infusion did so independently of T/E2 and sex difference (P = 0.001). All three of sex difference (P = 0.001), sex steroid treatment (P = 0.005), and double-peptide stimulation (P < 0.001) augmented recovery of peak (maximally feedback-escaped) GH concentrations. Peak GH responses to dual-peptidyl agonists were greater in women than in men (P = 0.016). E2/T augmented peak GH recovery during saline infusion (P < 0.001). Approximate entropy analysis corroborated independent effects of sex steroid treatment (P = 0.012) and peptide infusion (P < 0.001) on GH regularity. In summary, sex difference, sex steroid supplementation, and combined peptide drive influence nadir, peak, and entropic measurements of GH release under controlled negative feedback. To the degree that the pharmacological sex steroid, GH, and dual-peptide clamps provide prephysiological regulatory insights, these outcomes suggest major determinants of pulsatile GH secretion in the feedback domain. PMID:21467302
Kwon, Yoojung; Kim, Youngmi; Eom, Sangkyung; Kim, Misun; Park, Deokbum; Kim, Hyuna; Noh, Kyeonga; Lee, Hansoo; Lee, Yun Sil; Choe, Jongseon; Kim, Young Myeong; Jeoung, Dooil
2015-01-01
Cyclooxgenase-2 (COX-2) knock-out mouse experiments showed that COX-2 was necessary for in vivo allergic inflammation, such as passive cutaneous anaphylaxis, passive systemic anaphylaxis, and triphasic cutaneous allergic reaction. TargetScan analysis predicted COX-2 as a target of miR-26a and miR-26b. miR-26a/-26b decreased luciferase activity associated with COX-2–3′-UTR. miR-26a/-26b exerted negative effects on the features of in vitro and in vivo allergic inflammation by targeting COX-2. ChIP assays showed the binding of HDAC3 and SNAIL, but not COX-2, to the promoter sequences of miR-26a and miR-26b. Cytokine array analysis showed that the induction of chemokines, such as MIP-2, in the mouse passive systemic anaphylaxis model occurred in a COX-2-dependent manner. ChIP assays showed the binding of HDAC3 and COX-2 to the promoter sequences of MIP-2. In vitro and in vivo allergic inflammation was accompanied by the increased expression of MIP-2. miR-26a/-26b negatively regulated the expression of MIP-2. Allergic inflammation enhanced the tumorigenic and metastatic potential of cancer cells and induced positive feedback involving cancer cells and stromal cells, such as mast cells, macrophages, and endothelial cells. miR-26a mimic and miR-26b mimic negatively regulated the positive feedback between cancer cells and stromal cells and the positive feedback among stromal cells. miR-26a/-26b negatively regulated the enhanced tumorigenic potential by allergic inflammation. COX-2 was necessary for the enhanced metastatic potential of cancer cells by allergic inflammation. Taken together, our results indicate that the miR26a/-26b-COX-2-MIP-2 loop regulates allergic inflammation and the feedback relationship between allergic inflammation and the enhanced tumorigenic and metastatic potential. PMID:25907560
Iterative LQG Controller Design Through Closed-Loop Identification
NASA Technical Reports Server (NTRS)
Hsiao, Min-Hung; Huang, Jen-Kuang; Cox, David E.
1996-01-01
This paper presents an iterative Linear Quadratic Gaussian (LQG) controller design approach for a linear stochastic system with an uncertain open-loop model and unknown noise statistics. This approach consists of closed-loop identification and controller redesign cycles. In each cycle, the closed-loop identification method is used to identify an open-loop model and a steady-state Kalman filter gain from closed-loop input/output test data obtained by using a feedback LQG controller designed from the previous cycle. Then the identified open-loop model is used to redesign the state feedback. The state feedback and the identified Kalman filter gain are used to form an updated LQC controller for the next cycle. This iterative process continues until the updated controller converges. The proposed controller design is demonstrated by numerical simulations and experiments on a highly unstable large-gap magnetic suspension system.
Conditions for Stabilizability of Linear Switched Systems
NASA Astrophysics Data System (ADS)
Minh, Vu Trieu
2011-06-01
This paper investigates some conditions that can provide stabilizability for linear switched systems with polytopic uncertainties via their closed loop linear quadratic state feedback regulator. The closed loop switched systems can stabilize unstable open loop systems or stable open loop systems but in which there is no solution for a common Lyapunov matrix. For continuous time switched linear systems, we show that if there exists solution in an associated Riccati equation for the closed loop systems sharing one common Lyapunov matrix, the switched linear systems are stable. For the discrete time switched systems, we derive a Linear Matrix Inequality (LMI) to calculate a common Lyapunov matrix and solution for the stable closed loop feedback systems. These closed loop linear quadratic state feedback regulators guarantee the global asymptotical stability for any switched linear systems with any switching signal sequence.
LWD-TCP complex activates the morning gene CCA1 in Arabidopsis.
Wu, Jing-Fen; Tsai, Huang-Lung; Joanito, Ignasius; Wu, Yi-Chen; Chang, Chin-Wen; Li, Yi-Hang; Wang, Ying; Hong, Jong Chan; Chu, Jhih-Wei; Hsu, Chao-Ping; Wu, Shu-Hsing
2016-10-13
A double-negative feedback loop formed by the morning genes CIRCADIAN CLOCK ASSOCIATED1 (CCA1)/LATE ELONGATED HYPOCOTYL (LHY) and the evening gene TIMING OF CAB EXPRESSION1 (TOC1) contributes to regulation of the circadian clock in Arabidopsis. A 24-h circadian cycle starts with the peak expression of CCA1 at dawn. Although CCA1 is targeted by multiple transcriptional repressors, including PSEUDO-RESPONSE REGULATOR9 (PRR9), PRR7, PRR5 and CCA1 HIKING EXPEDITION (CHE), activators of CCA1 remain elusive. Here we use mathematical modelling to infer a co-activator role for LIGHT-REGULATED WD1 (LWD1) in CCA1 expression. We show that the TEOSINTE BRANCHED 1-CYCLOIDEA-PCF20 (TCP20) and TCP22 proteins act as LWD-interacting transcriptional activators. The concomitant binding of LWD1 and TCP20/TCP22 to the TCP-binding site in the CCA1 promoter activates CCA1. Our study reveals activators of the morning gene CCA1 and provides an action mechanism that ensures elevated expression of CCA1 at dawn to sustain a robust clock.
LWD–TCP complex activates the morning gene CCA1 in Arabidopsis
Wu, Jing-Fen; Tsai, Huang-Lung; Joanito, Ignasius; Wu, Yi-Chen; Chang, Chin-Wen; Li, Yi-Hang; Wang, Ying; Hong, Jong Chan; Chu, Jhih-Wei; Hsu, Chao-Ping; Wu, Shu-Hsing
2016-01-01
A double-negative feedback loop formed by the morning genes CIRCADIAN CLOCK ASSOCIATED1 (CCA1)/LATE ELONGATED HYPOCOTYL (LHY) and the evening gene TIMING OF CAB EXPRESSION1 (TOC1) contributes to regulation of the circadian clock in Arabidopsis. A 24-h circadian cycle starts with the peak expression of CCA1 at dawn. Although CCA1 is targeted by multiple transcriptional repressors, including PSEUDO-RESPONSE REGULATOR9 (PRR9), PRR7, PRR5 and CCA1 HIKING EXPEDITION (CHE), activators of CCA1 remain elusive. Here we use mathematical modelling to infer a co-activator role for LIGHT-REGULATED WD1 (LWD1) in CCA1 expression. We show that the TEOSINTE BRANCHED 1-CYCLOIDEA-PCF20 (TCP20) and TCP22 proteins act as LWD-interacting transcriptional activators. The concomitant binding of LWD1 and TCP20/TCP22 to the TCP-binding site in the CCA1 promoter activates CCA1. Our study reveals activators of the morning gene CCA1 and provides an action mechanism that ensures elevated expression of CCA1 at dawn to sustain a robust clock. PMID:27734958
Core regulatory network motif underlies the ocellar complex patterning in Drosophila melanogaster
NASA Astrophysics Data System (ADS)
Aguilar-Hidalgo, D.; Lemos, M. C.; Córdoba, A.
2015-03-01
During organogenesis, developmental programs governed by Gene Regulatory Networks (GRN) define the functionality, size and shape of the different constituents of living organisms. Robustness, thus, is an essential characteristic that GRNs need to fulfill in order to maintain viability and reproducibility in a species. In the present work we analyze the robustness of the patterning for the ocellar complex formation in Drosophila melanogaster fly. We have systematically pruned the GRN that drives the development of this visual system to obtain the minimum pathway able to satisfy this pattern. We found that the mechanism underlying the patterning obeys to the dynamics of a 3-nodes network motif with a double negative feedback loop fed by a morphogenetic gradient that triggers the inhibition in a French flag problem fashion. A Boolean modeling of the GRN confirms robustness in the patterning mechanism showing the same result for different network complexity levels. Interestingly, the network provides a steady state solution in the interocellar part of the patterning and an oscillatory regime in the ocelli. This theoretical result predicts that the ocellar pattern may underlie oscillatory dynamics in its genetic regulation.
Locke, James C W; Kozma-Bognár, László; Gould, Peter D; Fehér, Balázs; Kevei, Éva; Nagy, Ferenc; Turner, Matthew S; Hall, Anthony; Millar, Andrew J
2006-01-01
Our computational model of the circadian clock comprised the feedback loop between LATE ELONGATED HYPOCOTYL (LHY), CIRCADIAN CLOCK ASSOCIATED 1 (CCA1) and TIMING OF CAB EXPRESSION 1 (TOC1), and a predicted, interlocking feedback loop involving TOC1 and a hypothetical component Y. Experiments based on model predictions suggested GIGANTEA (GI) as a candidate for Y. We now extend the model to include a recently demonstrated feedback loop between the TOC1 homologues PSEUDO-RESPONSE REGULATOR 7 (PRR7), PRR9 and LHY and CCA1. This three-loop network explains the rhythmic phenotype of toc1 mutant alleles. Model predictions fit closely to new data on the gi;lhy;cca1 mutant, which confirm that GI is a major contributor to Y function. Analysis of the three-loop network suggests that the plant clock consists of morning and evening oscillators, coupled intracellularly, which may be analogous to coupled, morning and evening clock cells in Drosophila and the mouse. PMID:17102804
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.
Quantifying the Relative Contributions of Divisive and Subtractive Feedback to Rhythm Generation
Tabak, Joël; Rinzel, John; Bertram, Richard
2011-01-01
Biological systems are characterized by a high number of interacting components. Determining the role of each component is difficult, addressed here in the context of biological oscillations. Rhythmic behavior can result from the interplay of positive feedback that promotes bistability between high and low activity, and slow negative feedback that switches the system between the high and low activity states. Many biological oscillators include two types of negative feedback processes: divisive (decreases the gain of the positive feedback loop) and subtractive (increases the input threshold) that both contribute to slowly move the system between the high- and low-activity states. Can we determine the relative contribution of each type of negative feedback process to the rhythmic activity? Does one dominate? Do they control the active and silent phase equally? To answer these questions we use a neural network model with excitatory coupling, regulated by synaptic depression (divisive) and cellular adaptation (subtractive feedback). We first attempt to apply standard experimental methodologies: either passive observation to correlate the variations of a variable of interest to system behavior, or deletion of a component to establish whether a component is critical for the system. We find that these two strategies can lead to contradictory conclusions, and at best their interpretive power is limited. We instead develop a computational measure of the contribution of a process, by evaluating the sensitivity of the active (high activity) and silent (low activity) phase durations to the time constant of the process. The measure shows that both processes control the active phase, in proportion to their speed and relative weight. However, only the subtractive process plays a major role in setting the duration of the silent phase. This computational method can be used to analyze the role of negative feedback processes in a wide range of biological rhythms. PMID:21533065
Complexity in built environment, health, and destination walking: a neighborhood-scale analysis.
Carlson, Cynthia; Aytur, Semra; Gardner, Kevin; Rogers, Shannon
2012-04-01
This study investigates the relationships between the built environment, the physical attributes of the neighborhood, and the residents' perceptions of those attributes. It focuses on destination walking and self-reported health, and does so at the neighborhood scale. The built environment, in particular sidewalks, road connectivity, and proximity of local destinations, correlates with destination walking, and similarly destination walking correlates with physical health. It was found, however, that the built environment and health metrics may not be simply, directly correlated but rather may be correlated through a series of feedback loops that may regulate risk in different ways in different contexts. In particular, evidence for a feedback loop between physical health and destination walking is observed, as well as separate feedback loops between destination walking and objective metrics of the built environment, and destination walking and perception of the built environment. These feedback loops affect the ability to observe how the built environment correlates with residents' physical health. Previous studies have investigated pieces of these associations, but are potentially missing the more complex relationships present. This study proposes a conceptual model describing complex feedback relationships between destination walking and public health, with the built environment expected to increase or decrease the strength of the feedback loop. Evidence supporting these feedback relationships is presented.
Generation of mechanical oscillation applicable to vibratory rate gyroscopes
NASA Technical Reports Server (NTRS)
Lemkin, Mark A. (Inventor); Juneau, Thor N. (Inventor); Clark, William A. (Inventor); Roessig, Allen W. (Inventor)
2001-01-01
To achieve a drive-axis oscillation with improved frequency and amplitude stability, additional feedback loops are used to adjust force-feedback loop parameters. An amplitude-control loop measures oscillation amplitude, compares this value to the desired level, and adjusts damping of the mechanical sense-element to grow or shrink oscillation amplitude as appropriate. A frequency-tuning loop measures the oscillation frequency, compares this value with a highly stable reference, and adjusts the gain in the force-feedback loop to keep the drive-axis oscillation frequency at the reference value. The combined topology simultaneously controls both amplitude and frequency. Advantages of the combined topology include improved stability, fast oscillation start-up, low power consumption, and excellent shock rejection.
Method and apparatus for signal compression
Carangelo, R.M.
1994-02-08
The method and apparatus of the invention effects compression of an analog electrical signal (e.g., representing an interferogram) by introducing into it a component that is a cubic function thereof, normally as a nonlinear negative signal in a feedback loop of an Op Amp. The compressed signal will most desirably be digitized and then digitally decompressed so as to produce a signal that emulates the original. 8 figures.
Method and apparatus for signal compression
Carangelo, Robert M.
1994-02-08
The method and apparatus of the invention effects compression of an analog electrical signal (e.g., representing an interferogram) by introducing into it a component that is a cubic function thereof, normally as a nonlinear negative signal in a feedback loop of an Op Amp. The compressed signal will most desirably be digitized and then digitally decompressed so as to produce a signal that emulates the original.
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.
Nakamura, Yuki; Hibino, Kayo; Yanagida, Toshio; Sako, Yasushi
2016-01-01
Son of sevenless (SOS) is a guanine nucleotide exchange factor that regulates cell behavior by activating the small GTPase RAS. Recent in vitro studies have suggested that an interaction between SOS and the GTP-bound active form of RAS generates a positive feedback loop that propagates RAS activation. However, it remains unclear how the multiple domains of SOS contribute to the regulation of the feedback loop in living cells. Here, we observed single molecules of SOS in living cells to analyze the kinetics and dynamics of SOS behavior. The results indicate that the histone fold and Grb2-binding domains of SOS concertedly produce an intermediate state of SOS on the cell surface. The fraction of the intermediated state was reduced in positive feedback mutants, suggesting that the feedback loop functions during the intermediate state. Translocation of RAF, recognizing the active form of RAS, to the cell surface was almost abolished in the positive feedback mutants. Thus, the concerted functions of multiple membrane-associating domains of SOS governed the positive feedback loop, which is crucial for cell fate decision regulated by RAS.
[Study of negative feedback between wild-type BRAF or RAFV600E and Mps1 in melanoma].
Zhang, Ling; He, Chanting; Bi, Yanghui; Liu, Feng; Cui, Heyang; Wang, Juan; Song, Bin; Shi, Ruyi; Yang, Bin; Wang, Fang; Jia, Zhiwu; Zhao, Zhenxiang; Liu, Jing
2015-04-01
To study the effect of Mps1 on BRAFWT/MEK/ERK pathway in the presence of wild type BRAF or BRAFV600E in melanoma. Melanoma cells harboring BRAFWT genotype were transfected either with pBabe-puro-GST-BRAF-WT and/or pBabe-puro-GFP-Mps1-WT or pBabe-puro-GST-BRAFV600E and/or pBabe-puro-GFP-Mps1-WT, followed by Western blot to detect Mps1 and p-ERK expression. The melanoma cells harboring BRAFWT and BRAFV600E genotype were infected with pSUPER-Mps1 retrovirus to knockdown the endogenous Mps1 protein, followed by Western blot to detect Mps1 and p-ERK expression. Meanwhile, melanoma cells harboring BRAFV600E genotype were infected with pBabe-puro-GFP-Mps1 and Western blot was performed to detect Mps1 and p-ERK expression. In melanoma cells harboring BRAFWT genotype and transfected with pBabe-puro-GST-BRAF-WT and pBabe-puro-GFP-Mps1-WT, phospho-ERK levels were notably reduced as compared to either negative control or empty vector. However, cells transfected with pBabe-puro-GST-BRAFV600E and pBabe-puro-GFP-Mps1-WT, phospho-ERK levels did not change significantly compared with either negative control or empty vector. Knockout of Mps1 in BRAF wild-type cell lines led to an increased ERK activity. However, there was no significant change of ERK activity in BRAFV600E cell lines in the absence of Mps1. The expression of p-ERK in BRAFV600E mutant cell lines infected with pBabe-puro-GFP-Mps1-WT did not show any significant difference from either negative control or empty vector. Based on these findings, it suggests that there exists an auto-regulatory negative feedback loop between the Mps1 kinase and BRAFWT/ERK signaling. Oncogenic BRAFV600E abrogates the regulatory negative feedback loop of Mps1 on the MAPK pathway.
Optimization and evaluation of a proportional derivative controller for planar arm movement.
Jagodnik, Kathleen M; van den Bogert, Antonie J
2010-04-19
In most clinical applications of functional electrical stimulation (FES), the timing and amplitude of electrical stimuli have been controlled by open-loop pattern generators. The control of upper extremity reaching movements, however, will require feedback control to achieve the required precision. Here we present three controllers using proportional derivative (PD) feedback to stimulate six arm muscles, using two joint angle sensors. Controllers were first optimized and then evaluated on a computational arm model that includes musculoskeletal dynamics. Feedback gains were optimized by minimizing a weighted sum of position errors and muscle forces. Generalizability of the controllers was evaluated by performing movements for which the controller was not optimized, and robustness was tested via model simulations with randomly weakened muscles. Robustness was further evaluated by adding joint friction and doubling the arm mass. After optimization with a properly weighted cost function, all PD controllers performed fast, accurate, and robust reaching movements in simulation. Oscillatory behavior was seen after improper tuning. Performance improved slightly as the complexity of the feedback gain matrix increased. Copyright 2009 Elsevier Ltd. All rights reserved.
Optimization and evaluation of a proportional derivative controller for planar arm movement
Jagodnik, Kathleen M.; van den Bogert, Antonie J.
2013-01-01
In most clinical applications of functional electrical stimulation (FES), the timing and amplitude of electrical stimuli have been controlled by open-loop pattern generators. The control of upper extremity reaching movements, however, will require feedback control to achieve the required precision. Here we present three controllers using proportional derivative (PD) feedback to stimulate six arm muscles, using two joint angle sensors. Controllers were first optimized and then evaluated on a computational arm model that includes musculoskeletal dynamics. Feedback gains were optimized by minimizing a weighted sum of position errors and muscle forces. Generalizability of the controllers was evaluated by performing movements for which the controller was not optimized, and robustness was tested via model simulations with randomly weakened muscles. Robustness was further evaluated by adding joint friction and doubling the arm mass. After optimization with a properly weighted cost function, all PD controllers performed fast, accurate, and robust reaching movements in simulation. Oscillatory behavior was seen after improper tuning. Performance improved slightly as the complexity of the feedback gain matrix increased. PMID:20097345
Consistency properties of chaotic systems driven by time-delayed feedback
NASA Astrophysics Data System (ADS)
Jüngling, T.; Soriano, M. C.; Oliver, N.; Porte, X.; Fischer, I.
2018-04-01
Consistency refers to the property of an externally driven dynamical system to respond in similar ways to similar inputs. In a delay system, the delayed feedback can be considered as an external drive to the undelayed subsystem. We analyze the degree of consistency in a generic chaotic system with delayed feedback by means of the auxiliary system approach. In this scheme an identical copy of the nonlinear node is driven by exactly the same signal as the original, allowing us to verify complete consistency via complete synchronization. In the past, the phenomenon of synchronization in delay-coupled chaotic systems has been widely studied using correlation functions. Here, we analytically derive relationships between characteristic signatures of the correlation functions in such systems and unequivocally relate them to the degree of consistency. The analytical framework is illustrated and supported by numerical calculations of the logistic map with delayed feedback for different replica configurations. We further apply the formalism to time series from an experiment based on a semiconductor laser with a double fiber-optical feedback loop. The experiment constitutes a high-quality replica scheme for studying consistency of the delay-driven laser and confirms the general theoretical results.
Lu, Ji; Pan, Junhao; Zhang, Qiang; Dubé, Laurette; Ip, Edward H
2015-01-01
With intensively collected longitudinal data, recent advances in the experience-sampling method (ESM) benefit social science empirical research, but also pose important methodological challenges. As traditional statistical models are not generally well equipped to analyze a system of variables that contain feedback loops, this paper proposes the utility of an extended hidden Markov model to model reciprocal the relationship between momentary emotion and eating behavior. This paper revisited an ESM data set (Lu, Huet, & Dube, 2011) that observed 160 participants' food consumption and momentary emotions 6 times per day in 10 days. Focusing on the analyses on feedback loop between mood and meal-healthiness decision, the proposed reciprocal Markov model (RMM) can accommodate both hidden ("general" emotional states: positive vs. negative state) and observed states (meal: healthier, same or less healthy than usual) without presuming independence between observations and smooth trajectories of mood or behavior changes. The results of RMM analyses illustrated the reciprocal chains of meal consumption and mood as well as the effect of contextual factors that moderate the interrelationship between eating and emotion. A simulation experiment that generated data consistent with the empirical study further demonstrated that the procedure is promising in terms of recovering the parameters.
Hao, Lijie; Yang, Zhuoqin; Bi, Yuanhong
2016-04-01
The cyclic AMP (cAMP)-response element-binding protein (CREB) family of transcription factors is crucial in regulating gene expression required for long-term memory (LTM) formation. Upon exposure of sensory neurons to the neurotransmitter serotonin (5-HT), CREB1 is activated via activation of the protein kinase A (PKA) intracellular signaling pathways, and CREB2 as a transcriptional repressor is relieved possibly via phosphorylation of CREB2 by mitogen-activated protein kinase (MAPK). Song et al. [18] proposed a minimal model with only interlinked positive and negative feedback loops of transcriptional regulation by the activator CREB1 and the repressor CREB2. Without considering feedbacks between the CREB proteins, Pettigrew et al. [8] developed a computational model characterizing complex dynamics of biochemical pathways downstream of 5-HT receptors. In this work, to describe more simply the biochemical pathways and gene regulation underlying 5-HT-induced LTM, we add the important extracellular sensitizing stimulus 5-HT as well as the product Ap-uch into the Song's minimal model. We also strive to examine dynamical properties of the gene regulatory network under the changing concentration of the stimulus, [5-HT], cooperating with the varying positive feedback strength in inducing a high state of CREB1 for the establishment of long-term memory. Different dynamics including monostability, bistability and multistability due to coexistence of stable steady states and oscillations is investigated by means of codimension-2 bifurcation analysis. At the different positive feedback strengths, comparative analysis of deterministic and stochastic dynamics reveals that codimension-1 bifurcation with respect to [5-HT] as the parameter can predict diverse stochastic behaviors resulted from the finite number of molecules, and the number of CREB1 molecules more and more preferentially resides near the high steady state with increasing [5-HT], which contributes to long-term memory formation. Copyright © 2016 Elsevier Inc. All rights reserved.
Giersch, C; Cornish-Bowden, A
1996-10-07
The double modulation method for determining the elasticities of pathway enzymes, originally devised by Kacser & Burns (Biochem. Soc. Trans. 7, 1149-1160, 1979), is extended to pathways of complex topological structure, including branching and feedback loops. An explicit system of linear equations for the unknown elasticities is derived. The constraints imposed on this linear system imply that modulations of more than one enzyme are not necessarily independent. Simple combinatorial rules are described for identifying without using any algebra the set of independent modulations that allow the determination of the elasticities of any enzyme. By repeated application, the minimum numbers of modulations required to determine the elasticities of all enzymes of a given pathway can be determined. The procedure is illustrated with numerous examples.
Hinske, Ludwig Christian; Galante, Pedro A. F.; Limbeck, Elisabeth; Möhnle, Patrick; Parmigiani, Raphael B.; Ohno-Machado, Lucila; Camargo, Anamaria A.; Kreth, Simone
2015-01-01
About half of the known miRNA genes are located within protein-coding host genes, and are thus subject to co-transcription. Accumulating data indicate that this coupling may be an intrinsic mechanism to directly regulate the host gene’s expression, constituting a negative feedback loop. Inevitably, the cell requires a yet largely unknown repertoire of methods to regulate this control mechanism. We propose APA as one possible mechanism by which negative feedback of intronic miRNA on their host genes might be regulated. Using in-silico analyses, we found that host genes that contain seed matching sites for their intronic miRNAs yield longer 32UTRs with more polyadenylation sites. Additionally, the distribution of polyadenylation signals differed significantly between these host genes and host genes of miRNAs that do not contain potential miRNA binding sites. We then transferred these in-silico results to a biological example and investigated the relationship between ZFR and its intronic miRNA miR-579 in a U87 cell line model. We found that ZFR is targeted by its intronic miRNA miR-579 and that alternative polyadenylation allows differential targeting. We additionally used bioinformatics analyses and RNA-Seq to evaluate a potential cross-talk between intronic miRNAs and alternative polyadenylation. CPSF2, a gene previously associated with alternative polyadenylation signal recognition, might be linked to intronic miRNA negative feedback by altering polyadenylation signal utilization. PMID:25799583
Vozeh, S; Steimer, J L
1985-01-01
The concept of feedback control methods for drug dosage optimisation is described from the viewpoint of control theory. The control system consists of 5 parts: (a) patient (the controlled process); (b) response (the measured feedback); (c) model (the mathematical description of the process); (d) adaptor (to update the parameters); and (e) controller (to determine optimum dosing strategy). In addition to the conventional distinction between open-loop and closed-loop control systems, a classification is proposed for dosage optimisation techniques which distinguishes between tight-loop and loose-loop methods depending on whether physician's interaction is absent or included as part of the control step. Unlike engineering problems where the process can usually be controlled by fully automated devices, therapeutic situations often require that the physician be included in the decision-making process to determine the 'optimal' dosing strategy. Tight-loop and loose-loop methods can be further divided into adaptive and non-adaptive, depending on the presence of the adaptor. The main application areas of tight-loop feedback control methods are general anaesthesia, control of blood pressure, and insulin delivery devices. Loose-loop feedback methods have been used for oral anticoagulation and in therapeutic drug monitoring. The methodology, advantages and limitations of the different approaches are reviewed. A general feature common to all application areas could be observed: to perform well under routine clinical conditions, which are characterised by large interpatient variability and sometimes also intrapatient changes, control systems should be adaptive. Apart from application in routine drug treatment, feedback control methods represent an important research tool. They can be applied for the investigation of pathophysiological and pharmacodynamic processes. A most promising application is the evaluation of the relationship between an intermediate response (e.g. drug level), which is often used as feedback for dosage adjustment, and the final therapeutic goal.
Results of adaptive feedforward on GTA
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ziomek, C.D.; Denney, P.M.; Regan, A.H.
1993-01-01
This paper presents the results of the adaptive feedforward system in use on the Ground Test Accelerator (GTA). The adaptive feedforward system was shown to correct repetitive, high-frequency errors in the amplitude and phase of the RF field of the pulsed accelerator. The adaptive feedforward system was designed as an augmentation to the RF field feedback control system and was able to extend the closed-loop bandwidth and disturbance rejection by a factor of ten. Within a second implementation, the adaptive feedforward hardware was implemented in place of the feedback control system and was shown to negate both beam transients andmore » phase droop in the klystron amplifier.« less
Results of adaptive feedforward on GTA
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ziomek, C.D.; Denney, P.M.; Regan, A.H.
1993-06-01
This paper presents the results of the adaptive feedforward system in use on the Ground Test Accelerator (GTA). The adaptive feedforward system was shown to correct repetitive, high-frequency errors in the amplitude and phase of the RF field of the pulsed accelerator. The adaptive feedforward system was designed as an augmentation to the RF field feedback control system and was able to extend the closed-loop bandwidth and disturbance rejection by a factor of ten. Within a second implementation, the adaptive feedforward hardware was implemented in place of the feedback control system and was shown to negate both beam transients andmore » phase droop in the klystron amplifier.« less
NASA Technical Reports Server (NTRS)
Dick, G. J.; Saunders, J.
1989-01-01
Oscillator configurations which reduce the effect of 1/f noise sources for both direct feedback and stabilized local oscillator (STALO) circuits are developed and analyzed. By appropriate use of carrier suppression, a small signal is generated which suffers no loss of loop phase information or signal-to-noise ratio. This small signal can be amplified without degradation by multiplicative amplifier noise, and can be detected without saturation of the detector. Together with recent advances in microwave resonator Qs, these circuit improvements will make possible lower phase noise than can be presently achieved without the use of cryogenic devices.
Lee, Sung-Hun; Chen, Tsai-Yu; Dhar, Shilpa S.; Gu, Bingnan; Chen, Kaifu; Kim, Young Zoon; Li, Wei; Lee, Min Gyu
2016-01-01
Self-renewal and pluripotency are two fundamental characteristics of embryonic stem cells (ESCs) and are controlled by diverse regulatory factors, including pluripotent factors, epigenetic regulators and microRNAs (miRNAs). Although histone methyltransferases are key epigenetic regulators, whether and how a histone methyltransferase forms a network with miRNAs and the core pluripotent factor system to regulate ESC stemness is little known. Here, we show that the protein arginine methyltransferase 7 (PRMT7) is a pluripotent factor essential for the stemness of mouse ESCs. PRMT7 repressed the miR-24-2 gene encoding miR-24-3p and miR-24-2-5p by upregulating the levels of symmetrically dimethylated H4R3. Notably, miR-24-3p targeted the 3′ untranslated regions (UTRs) of the major pluripotent factors Oct4, Nanog, Klf4 and c-Myc, whereas miR-24-2-5p silenced Klf4 and c-Myc expression. miR-24-3p and miR-24-2-5p also targeted the 3′UTR of their repressor gene Prmt7. miR-24-3p and miR-24-2-5p induced mouse ESC differentiation, and their anti-sense inhibitors substantially reversed spontaneous differentiation of PRMT7-depleted mouse ESCs. Oct4, Nanog, Klf4 and c-Myc positively regulated Prmt7 expression. These findings define miR-24-3p and miR-24-2-5p as new anti-pluripotent miRNAs and also reveal a novel epigenetic stemness-regulatory mechanism in which a double-negative feedback loop consisting of PRMT7 and miR-24-3p/miR24-2-5p interplays with Oct4, Nanog, Klf4 and c-Myc to control ESC stemness. PMID:27625395
Lee, Sung-Hun; Chen, Tsai-Yu; Dhar, Shilpa S; Gu, Bingnan; Chen, Kaifu; Kim, Young Zoon; Li, Wei; Lee, Min Gyu
2016-12-15
Self-renewal and pluripotency are two fundamental characteristics of embryonic stem cells (ESCs) and are controlled by diverse regulatory factors, including pluripotent factors, epigenetic regulators and microRNAs (miRNAs). Although histone methyltransferases are key epigenetic regulators, whether and how a histone methyltransferase forms a network with miRNAs and the core pluripotent factor system to regulate ESC stemness is little known. Here, we show that the protein arginine methyltransferase 7 (PRMT7) is a pluripotent factor essential for the stemness of mouse ESCs. PRMT7 repressed the miR-24-2 gene encoding miR-24-3p and miR-24-2-5p by upregulating the levels of symmetrically dimethylated H4R3. Notably, miR-24-3p targeted the 3' untranslated regions (UTRs) of the major pluripotent factors Oct4, Nanog, Klf4 and c-Myc, whereas miR-24-2-5p silenced Klf4 and c-Myc expression. miR-24-3p and miR-24-2-5p also targeted the 3'UTR of their repressor gene Prmt7 miR-24-3p and miR-24-2-5p induced mouse ESC differentiation, and their anti-sense inhibitors substantially reversed spontaneous differentiation of PRMT7-depleted mouse ESCs. Oct4, Nanog, Klf4 and c-Myc positively regulated Prmt7 expression. These findings define miR-24-3p and miR-24-2-5p as new anti-pluripotent miRNAs and also reveal a novel epigenetic stemness-regulatory mechanism in which a double-negative feedback loop consisting of PRMT7 and miR-24-3p/miR24-2-5p interplays with Oct4, Nanog, Klf4 and c-Myc to control ESC stemness. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.
Alk1 and Alk5 inhibition by Nrp1 controls vascular sprouting downstream of Notch.
Aspalter, Irene Maria; Gordon, Emma; Dubrac, Alexandre; Ragab, Anan; Narloch, Jarek; Vizán, Pedro; Geudens, Ilse; Collins, Russell Thomas; Franco, Claudio Areias; Abrahams, Cristina Luna; Thurston, Gavin; Fruttiger, Marcus; Rosewell, Ian; Eichmann, Anne; Gerhardt, Holger
2015-06-17
Sprouting angiogenesis drives blood vessel growth in healthy and diseased tissues. Vegf and Dll4/Notch signalling cooperate in a negative feedback loop that specifies endothelial tip and stalk cells to ensure adequate vessel branching and function. Current concepts posit that endothelial cells default to the tip-cell phenotype when Notch is inactive. Here we identify instead that the stalk-cell phenotype needs to be actively repressed to allow tip-cell formation. We show this is a key endothelial function of neuropilin-1 (Nrp1), which suppresses the stalk-cell phenotype by limiting Smad2/3 activation through Alk1 and Alk5. Notch downregulates Nrp1, thus relieving the inhibition of Alk1 and Alk5, thereby driving stalk-cell behaviour. Conceptually, our work shows that the heterogeneity between neighbouring endothelial cells established by the lateral feedback loop of Dll4/Notch utilizes Nrp1 levels as the pivot, which in turn establishes differential responsiveness to TGF-β/BMP signalling.
Alk1 and Alk5 inhibition by Nrp1 controls vascular sprouting downstream of Notch
Aspalter, Irene Maria; Gordon, Emma; Dubrac, Alexandre; Ragab, Anan; Narloch, Jarek; Vizán, Pedro; Geudens, Ilse; Collins, Russell Thomas; Franco, Claudio Areias; Abrahams, Cristina Luna; Thurston, Gavin; Fruttiger, Marcus; Rosewell, Ian; Eichmann, Anne; Gerhardt, Holger
2015-01-01
Sprouting angiogenesis drives blood vessel growth in healthy and diseased tissues. Vegf and Dll4/Notch signalling cooperate in a negative feedback loop that specifies endothelial tip and stalk cells to ensure adequate vessel branching and function. Current concepts posit that endothelial cells default to the tip-cell phenotype when Notch is inactive. Here we identify instead that the stalk-cell phenotype needs to be actively repressed to allow tip-cell formation. We show this is a key endothelial function of neuropilin-1 (Nrp1), which suppresses the stalk-cell phenotype by limiting Smad2/3 activation through Alk1 and Alk5. Notch downregulates Nrp1, thus relieving the inhibition of Alk1 and Alk5, thereby driving stalk-cell behaviour. Conceptually, our work shows that the heterogeneity between neighbouring endothelial cells established by the lateral feedback loop of Dll4/Notch utilizes Nrp1 levels as the pivot, which in turn establishes differential responsiveness to TGF-β/BMP signalling. PMID:26081042
The circadian clock of Neurospora crassa.
Baker, Christopher L; Loros, Jennifer J; Dunlap, Jay C
2012-01-01
Circadian clocks organize our inner physiology with respect to the external world, providing life with the ability to anticipate and thereby better prepare for major fluctuations in its environment. Circadian systems are widely represented in nearly all major branches of life, except archaebacteria, and within the eukaryotes, the filamentous fungus Neurospora crassa has served for nearly half a century as a durable model organism for uncovering the basic circadian physiology and molecular biology. Studies using Neurospora have clarified our fundamental understanding of the clock as nested positive and negative feedback loops regulated through transcriptional and post-transcriptional processes. These feedback loops are centered on a limited number of proteins that form molecular complexes, and their regulation provides a physical explanation for nearly all clock properties. This review will introduce the basics of circadian rhythms, the model filamentous fungus N. crassa, and provide an overview of the molecular components and regulation of the circadian clock. © 2011 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.
CK1/Doubletime activity delays transcription activation in the circadian clock
O'Neil, Jenna L; Merz, Gregory E; Dusad, Kritika; Crane, Brian R; Young, Michael W
2018-01-01
In the Drosophila circadian clock, Period (PER) and Timeless (TIM) proteins inhibit Clock-mediated transcription of per and tim genes until PER is degraded by Doubletime/CK1 (DBT)-mediated phosphorylation, establishing a negative feedback loop. Multiple regulatory delays within this feedback loop ensure ~24 hr periodicity. Of these delays, the mechanisms that regulate delayed PER degradation (and Clock reactivation) remain unclear. Here we show that phosphorylation of certain DBT target sites within a central region of PER affect PER inhibition of Clock and the stability of the PER/TIM complex. Our results indicate that phosphorylation of PER residue S589 stabilizes and activates PER inhibitory function in the presence of TIM, but promotes PER degradation in its absence. The role of DBT in regulating PER activity, stabilization and degradation ensures that these events are chronologically and biochemically linked, and contributes to the timing of an essential delay that influences the period of the circadian clock. PMID:29611807
A portable expression resource for engineering cross-species genetic circuits and pathways
Kushwaha, Manish; Salis, Howard M.
2015-01-01
Genetic circuits and metabolic pathways can be reengineered to allow organisms to process signals and manufacture useful chemicals. However, their functions currently rely on organism-specific regulatory parts, fragmenting synthetic biology and metabolic engineering into host-specific domains. To unify efforts, here we have engineered a cross-species expression resource that enables circuits and pathways to reuse the same genetic parts, while functioning similarly across diverse organisms. Our engineered system combines mixed feedback control loops and cross-species translation signals to autonomously self-regulate expression of an orthogonal polymerase without host-specific promoters, achieving nontoxic and tuneable gene expression in diverse Gram-positive and Gram-negative bacteria. Combining 50 characterized system variants with mechanistic modelling, we show how the cross-species expression resource's dynamics, capacity and toxicity are controlled by the control loops' architecture and feedback strengths. We also demonstrate one application of the resource by reusing the same genetic parts to express a biosynthesis pathway in both model and non-model hosts. PMID:26184393
Homeostatic systems, biocybernetics, and autonomic neuroscience.
Goldstein, David S; Kopin, Irwin J
2017-12-01
In this review we describe a series of major concepts introduced during the past 150years that have contributed to our current understanding about how physiological processes required for well-being and survival are regulated. One can theorize that hierarchical networks involving input-output relationships continuously orchestrate and learn adaptive patterns of observable behaviors, cognition, memory, mood, and autonomic systems. Taken together, these networks function as "good regulators" determining levels of internal variables and act as if there were homeostatic comparators ("homeostats"). The consequences of models with vs. without homeostats remain the same in terms of allostatic load and the eventual switch from stabilizing negative feedback loops to destabilizing, pathogenic positive feedback loops. Understanding this switch seems important for comprehending senescence-related, neurodegenerative disorders that involve the autonomic nervous system. Our general proposal is that disintegration of homeostatic systems causes disorders of regulation in degenerative diseases and that medical cybernetics can inspire and rationalize new approaches to treatment and prevention. Published by Elsevier B.V.
Electron emission controller with pulsed heating of filament
NASA Astrophysics Data System (ADS)
Durakiewicz, Tomasz
1996-11-01
A novel circuit has been invented for the versatile and safe stabilization of the electron emission current (Ie) produced by a hot filament in mass spectrometers or in ionization gauges. The voltage signal, which is directly proportional to Ie, is provided to the inverting input of a comparator, whereas the noninverting input is connected to the reference voltage. In addition to the commonly used negative feedback loop, a positive feedback loop was introduced by siting a resistor between the noninverting input and the output of the comparator, which results in a pulsation of the filament voltage. The pulses are rectangular, so that the power dissipated by the transistor in the filament power supply circuit is radically reduced. To refine the switching action of the transistor, the output of the comparator is connected through a capacitor to the transistor gate. A concise discussion of the phase shift between Ie, the filament temperature Tf, and the filament voltage Vf, including time constants for different modes of power dissipation, is included.
Flatness-based adaptive fuzzy control of chaotic finance dynamics
NASA Astrophysics Data System (ADS)
Rigatos, G.; Siano, P.; Loia, V.; Tommasetti, A.; Troisi, O.
2017-11-01
A flatness-based adaptive fuzzy control is applied to the problem of stabilization of the dynamics of a chaotic finance system, describing interaction between the interest rate, the investment demand and the price exponent. By proving that the system is differentially flat and by applying differential flatness diffeomorphisms, its transformation to the linear canonical (Brunovsky) is performed. For the latter description of the system, the design of a stabilizing state feedback controller becomes possible. A first problem in the design of such a controller is that the dynamic model of the finance system is unknown and thus it has to be identified with the use neurofuzzy approximators. The estimated dynamics provided by the approximators is used in the computation of the control input, thus establishing an indirect adaptive control scheme. The learning rate of the approximators is chosen from the requirement the system's Lyapunov function to have always a negative first-order derivative. Another problem that has to be dealt with is that the control loop is implemented only with the use of output feedback. To estimate the non-measurable state vector elements of the finance system, a state observer is implemented in the control loop. The computation of the feedback control signal requires the solution of two algebraic Riccati equations at each iteration of the control algorithm. Lyapunov stability analysis demonstrates first that an H-infinity tracking performance criterion is satisfied. This signifies elevated robustness against modelling errors and external perturbations. Moreover, the global asymptotic stability is proven for the control loop.
Diz-Muñoz, Alba; Thurley, Kevin; Chintamen, Sana; Altschuler, Steven J.; Fletcher, Daniel A.; Weiner, Orion D.
2016-01-01
For efficient polarity and migration, cells need to regulate the magnitude and spatial distribution of actin assembly. This process is coordinated by reciprocal interactions between the actin cytoskeleton and mechanical forces. Actin polymerization-based protrusion increases tension in the plasma membrane, which in turn acts as a long-range inhibitor of actin assembly. These interactions form a negative feedback circuit that limits the magnitude of membrane tension in neutrophils and prevents expansion of the existing front and the formation of secondary fronts. It has been suggested that the plasma membrane directly inhibits actin assembly by serving as a physical barrier that opposes protrusion. Here we show that efficient control of actin polymerization-based protrusion requires an additional mechanosensory feedback cascade that indirectly links membrane tension with actin assembly. Specifically, elevated membrane tension acts through phospholipase D2 (PLD2) and the mammalian target of rapamycin complex 2 (mTORC2) to limit actin nucleation. In the absence of this pathway, neutrophils exhibit larger leading edges, higher membrane tension, and profoundly defective chemotaxis. Mathematical modeling suggests roles for both the direct (mechanical) and indirect (biochemical via PLD2 and mTORC2) feedback loops in organizing cell polarity and motility—the indirect loop is better suited to enable competition between fronts, whereas the direct loop helps spatially organize actin nucleation for efficient leading edge formation and cell movement. This circuit is essential for polarity, motility, and the control of membrane tension. PMID:27280401
Simulating closed- and open-loop voluntary movement: a nonlinear control-systems approach.
Davidson, Paul R; Jones, Richard D; Andreae, John H; Sirisena, Harsha R
2002-11-01
In many recent human motor control models, including feedback-error learning and adaptive model theory (AMT), feedback control is used to correct errors while an inverse model is simultaneously tuned to provide accurate feedforward control. This popular and appealing hypothesis, based on a combination of psychophysical observations and engineering considerations, predicts that once the tuning of the inverse model is complete the role of feedback control is limited to the correction of disturbances. This hypothesis was tested by looking at the open-loop behavior of the human motor system during adaptation. An experiment was carried out involving 20 normal adult subjects who learned a novel visuomotor relationship on a pursuit tracking task with a steering wheel for input. During learning, the response cursor was periodically blanked, removing all feedback about the external system (i.e., about the relationship between hand motion and response cursor motion). Open-loop behavior was not consistent with a progressive transfer from closed- to open-loop control. Our recently developed computational model of the brain--a novel nonlinear implementation of AMT--was able to reproduce the observed closed- and open-loop results. In contrast, other control-systems models exhibited only minimal feedback control following adaptation, leading to incorrect open-loop behavior. This is because our model continues to use feedback to control slow movements after adaptation is complete. This behavior enhances the internal stability of the inverse model. In summary, our computational model is currently the only motor control model able to accurately simulate the closed- and open-loop characteristics of the experimental response trajectories.
de las Heras, Aitor; Fraile, Sofia; de Lorenzo, Victor
2012-01-01
Prokaryotic transcription factors (TFs) that bind small xenobiotic molecules (e.g., TFs that drive genes that respond to environmental pollutants) often display a promiscuous effector profile for analogs of the bona fide chemical signals. XylR, the master TF for expression of the m-xylene biodegradation operons encoded in the TOL plasmid pWW0 of Pseudomonas putida, responds not only to the aromatic compound but also, albeit to a lesser extent, to many other aromatic compounds, such as 3-methylbenzylalcohol (3MBA). We have examined whether such a relaxed regulatory scenario can be reshaped into a high-capacity/high-specificity regime by changing the connectivity of this effector-sensing TF within the rest of the circuit rather than modifying XylR structure itself. To this end, the natural negative feedback loop that operates on xylR transcription was modified with a translational attenuator that brings down the response to 3MBA while maintaining the transcriptional output induced by m-xylene (as measured with a luxCDABE reporter system). XylR expression was then subject to a positive feedback loop in which the TF was transcribed from its own target promoters, each known to hold different input/output transfer functions. In the first case (xylR under the strong promoter of the upper TOL operon, Pu), the reporter system displayed an increased transcriptional capacity in the resulting network for both the optimal and the suboptimal XylR effectors. In contrast, when xylR was expressed under the weaker Ps promoter, the resulting circuit unmistakably discriminated m-xylene from 3MBA. The non-natural connectivity engineered in the network resulted both in a higher promoter activity and also in a much-increased signal-to-background ratio. These results indicate that the working regimes of given genetic circuits can be dramatically altered through simple changes in the way upstream transcription factors are self-regulated by positive or negative feedback loops. PMID:23071444
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.
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…
How securely is the testicular artery occluded in the spermatic cord by using a ligature?
Rijkenhuizen, A B M; Sommerauer, S; Fasching, M; Velde, K; Peham, C
2013-09-01
There are no studies on the ideal ligature technique for the spermatic cord. To compare the maximal resistance pressure in the testicular artery and the maximal tensile forces to produce failure of 2 different ligature techniques used for ligation of the equine spermatic cord. The capabilities of 2 types of ligatures, single knot loop and double knot loop, were assessed using a pressure-resistance test in testicular arteries and with an in vitro mechanical evaluation of the tensile strength by single cycle-to-failure testing. In the pressure-resistance test, the mean ± s.d. peak force at failure of the single knot loop was 354.4 ± 91.7 mmHg and for the double knot loop 303.2 ± 62.0 mmHg. There was no significant difference between the maximal load to failure of the single knot loop and double knot loop technique. The pressure needed for rupture was significantly higher (P = 0.001) than for leakage. The maximal tensile force at failure of the single knot loop was significantly higher than the double knot loop (P = 0.028). There was no significant difference in load elongation properties to failure between the single knot loop and double knot loop. Although no significant differences were obtained in the pressure-resistance test, the single knot loop sustained significantly greater load to failure than the double knot loop in single cycle-to-failure testing. Based on these findings, it would appear that the performance of the single knot loop should be superior to the double knot loop. Both ligature techniques are able to withstand the normal physiological intravascular pressure. The single knot loop has the greater breaking strength of the 2 ligatures tested and is less time consuming to perform and may therefore have advantages during equine castration. © 2012 EVJ Ltd.
Near Real-Time Closed-Loop Optimal Control Feedback for Spacecraft Attitude Maneuvers
2009-03-01
60 3.8 Positive ωi Static Thrust Fan Characterization Polynomial Coefficients . . 62 3.9 Negative ωi Static Thrust Fan...Characterization Polynomial Coefficients . 62 4.1 Coefficients for SimSAT II’s Air Drag Polynomial Function . . . . . . . . . . . 78 5.1 OLOC Simulation...maneuver. Researchers using OCT identified that naturally occurring aerodynamic drag and gravity forces could be exploited in such a way that the CMGs
Chaotic dynamics and diffusion in a piecewise linear equation
NASA Astrophysics Data System (ADS)
Shahrear, Pabel; Glass, Leon; Edwards, Rod
2015-03-01
Genetic interactions are often modeled by logical networks in which time is discrete and all gene activity states update simultaneously. However, there is no synchronizing clock in organisms. An alternative model assumes that the logical network is preserved and plays a key role in driving the dynamics in piecewise nonlinear differential equations. We examine dynamics in a particular 4-dimensional equation of this class. In the equation, two of the variables form a negative feedback loop that drives a second negative feedback loop. By modifying the original equations by eliminating exponential decay, we generate a modified system that is amenable to detailed analysis. In the modified system, we can determine in detail the Poincaré (return) map on a cross section to the flow. By analyzing the eigenvalues of the map for the different trajectories, we are able to show that except for a set of measure 0, the flow must necessarily have an eigenvalue greater than 1 and hence there is sensitive dependence on initial conditions. Further, there is an irregular oscillation whose amplitude is described by a diffusive process that is well-modeled by the Irwin-Hall distribution. There is a large class of other piecewise-linear networks that might be analyzed using similar methods. The analysis gives insight into possible origins of chaotic dynamics in periodically forced dynamical systems.
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.
NASA Astrophysics Data System (ADS)
Deng, Chao; Ren, Wei; Mao, Yao; Ren, Ge
2017-08-01
A plug-in module acceleration feedback control (Plug-In AFC) strategy based on the disturbance observer (DOB) principle is proposed for charge-coupled device (CCD)-based fast steering mirror (FSM) stabilization systems. In classical FSM tracking systems, dual-loop control (DLC), including velocity feedback and position feedback, is usually utilized to enhance the closed-loop performance. Due to the mechanical resonance of the system and CCD time delay, the closed-loop bandwidth is severely restricted. To solve this problem, cascade acceleration feedback control (AFC), which is a kind of high-precision robust control method, is introduced to strengthen the disturbance rejection property. However, in practical applications, it is difficult to realize an integral algorithm in an acceleration controller to compensate for the quadratic differential contained in the FSM acceleration model, resulting in a challenging controller design and a limited improvement. To optimize the acceleration feedback framework in the FSM system, different from the cascade AFC, the accelerometers are used to construct DOB to compensate for the platform vibrations directly. The acceleration nested loop can be plugged into the velocity loop without changing the system stability, and the controller design is quite simple. A series of comparative experimental results demonstrate that the disturbance rejection property of the CCD-based FSM can be effectively improved by the proposed approach.
NASA Astrophysics Data System (ADS)
Bruns, Tim M.; Wagenaar, Joost B.; Bauman, Matthew J.; Gaunt, Robert A.; Weber, Douglas J.
2013-04-01
Objective. Functional electrical stimulation (FES) approaches often utilize an open-loop controller to drive state transitions. The addition of sensory feedback may allow for closed-loop control that can respond effectively to perturbations and muscle fatigue. Approach. We evaluated the use of natural sensory nerve signals obtained with penetrating microelectrode arrays in lumbar dorsal root ganglia (DRG) as real-time feedback for closed-loop control of FES-generated hind limb stepping in anesthetized cats. Main results. Leg position feedback was obtained in near real-time at 50 ms intervals by decoding the firing rates of more than 120 DRG neurons recorded simultaneously. Over 5 m of effective linear distance was traversed during closed-loop stepping trials in each of two cats. The controller compensated effectively for perturbations in the stepping path when DRG sensory feedback was provided. The presence of stimulation artifacts and the quality of DRG unit sorting did not significantly affect the accuracy of leg position feedback obtained from the linear decoding model as long as at least 20 DRG units were included in the model. Significance. This work demonstrates the feasibility and utility of closed-loop FES control based on natural neural sensors. Further work is needed to improve the controller and electrode technologies and to evaluate long-term viability.
Bruns, Tim M; Wagenaar, Joost B; Bauman, Matthew J; Gaunt, Robert A; Weber, Douglas J
2013-01-01
Objective Functional electrical stimulation (FES) approaches often utilize an open-loop controller to drive state transitions. The addition of sensory feedback may allow for closed-loop control that can respond effectively to perturbations and muscle fatigue. Approach We evaluated the use of natural sensory nerve signals obtained with penetrating microelectrode arrays in lumbar dorsal root ganglia (DRG) as real-time feedback for closed-loop control of FES-generated hind limb stepping in anesthetized cats. Main results Leg position feedback was obtained in near real-time at 50 ms intervals by decoding the firing rates of more than 120 DRG neurons recorded simultaneously. Over 5 m of effective linear distance was traversed during closed-loop stepping trials in each of two cats. The controller compensated effectively for perturbations in the stepping path when DRG sensory feedback was provided. The presence of stimulation artifacts and the quality of DRG unit sorting did not significantly affect the accuracy of leg position feedback obtained from the linear decoding model as long as at least 20 DRG units were included in the model. Significance This work demonstrates the feasibility and utility of closed-loop FES control based on natural neural sensors. Further work is needed to improve the controller and electrode technologies and to evaluate long-term viability. PMID:23503062
An open source digital servo for atomic, molecular, and optical physics experiments
DOE Office of Scientific and Technical Information (OSTI.GOV)
Leibrandt, D. R., E-mail: david.leibrandt@nist.gov; Heidecker, J.
2015-12-15
We describe a general purpose digital servo optimized for feedback control of lasers in atomic, molecular, and optical physics experiments. The servo is capable of feedback bandwidths up to roughly 1 MHz (limited by the 320 ns total latency); loop filter shapes up to fifth order; multiple-input, multiple-output control; and automatic lock acquisition. The configuration of the servo is controlled via a graphical user interface, which also provides a rudimentary software oscilloscope and tools for measurement of system transfer functions. We illustrate the functionality of the digital servo by describing its use in two example scenarios: frequency control of themore » laser used to probe the narrow clock transition of {sup 27}Al{sup +} in an optical atomic clock, and length control of a cavity used for resonant frequency doubling of a laser.« less
An open source digital servo for atomic, molecular, and optical physics experiments.
Leibrandt, D R; Heidecker, J
2015-12-01
We describe a general purpose digital servo optimized for feedback control of lasers in atomic, molecular, and optical physics experiments. The servo is capable of feedback bandwidths up to roughly 1 MHz (limited by the 320 ns total latency); loop filter shapes up to fifth order; multiple-input, multiple-output control; and automatic lock acquisition. The configuration of the servo is controlled via a graphical user interface, which also provides a rudimentary software oscilloscope and tools for measurement of system transfer functions. We illustrate the functionality of the digital servo by describing its use in two example scenarios: frequency control of the laser used to probe the narrow clock transition of (27)Al(+) in an optical atomic clock, and length control of a cavity used for resonant frequency doubling of a laser.
An open source digital servo for atomic, molecular, and optical physics experiments
NASA Astrophysics Data System (ADS)
Leibrandt, D. R.; Heidecker, J.
2015-12-01
We describe a general purpose digital servo optimized for feedback control of lasers in atomic, molecular, and optical physics experiments. The servo is capable of feedback bandwidths up to roughly 1 MHz (limited by the 320 ns total latency); loop filter shapes up to fifth order; multiple-input, multiple-output control; and automatic lock acquisition. The configuration of the servo is controlled via a graphical user interface, which also provides a rudimentary software oscilloscope and tools for measurement of system transfer functions. We illustrate the functionality of the digital servo by describing its use in two example scenarios: frequency control of the laser used to probe the narrow clock transition of 27Al+ in an optical atomic clock, and length control of a cavity used for resonant frequency doubling of a laser.
An open source digital servo for atomic, molecular, and optical physics experiments
Leibrandt, D. R.; Heidecker, J.
2016-01-01
We describe a general purpose digital servo optimized for feedback control of lasers in atomic, molecular, and optical physics experiments. The servo is capable of feedback bandwidths up to roughly 1 MHz (limited by the 320 ns total latency); loop filter shapes up to fifth order; multiple-input, multiple-output control; and automatic lock acquisition. The configuration of the servo is controlled via a graphical user interface, which also provides a rudimentary software oscilloscope and tools for measurement of system transfer functions. We illustrate the functionality of the digital servo by describing its use in two example scenarios: frequency control of the laser used to probe the narrow clock transition of 27Al+ in an optical atomic clock, and length control of a cavity used for resonant frequency doubling of a laser. PMID:26724014
Grunseich, Christopher; Wang, Isabel X; Watts, Jason A; Burdick, Joshua T; Guber, Robert D; Zhu, Zhengwei; Bruzel, Alan; Lanman, Tyler; Chen, Kelian; Schindler, Alice B; Edwards, Nancy; Ray-Chaudhury, Abhik; Yao, Jianhua; Lehky, Tanya; Piszczek, Grzegorz; Crain, Barbara; Fischbeck, Kenneth H; Cheung, Vivian G
2018-02-01
R-loops are three-stranded nucleic acid structures found abundantly and yet often viewed as by-products of transcription. Studying cells from patients with a motor neuron disease (amyotrophic lateral sclerosis 4 [ALS4]) caused by a mutation in senataxin, we uncovered how R-loops promote transcription. In ALS4 patients, the senataxin mutation depletes R-loops with a consequent effect on gene expression. With fewer R-loops in ALS4 cells, the expression of BAMBI, a negative regulator of transforming growth factor β (TGF-β), is reduced; that then leads to the activation of the TGF-β pathway. We uncovered that genome-wide R-loops influence promoter methylation of over 1,200 human genes. DNA methyl-transferase 1 favors binding to double-stranded DNA over R-loops. Thus, in forming R-loops, nascent RNA blocks DNA methylation and promotes further transcription. Hence, our results show that nucleic acid structures, in addition to sequences, influence the binding and activity of regulatory proteins. Copyright © 2017 Elsevier Inc. All rights reserved.
Nakamura, Yuki; Hibino, Kayo; Yanagida, Toshio; Sako, Yasushi
2016-01-01
Son of sevenless (SOS) is a guanine nucleotide exchange factor that regulates cell behavior by activating the small GTPase RAS. Recent in vitro studies have suggested that an interaction between SOS and the GTP-bound active form of RAS generates a positive feedback loop that propagates RAS activation. However, it remains unclear how the multiple domains of SOS contribute to the regulation of the feedback loop in living cells. Here, we observed single molecules of SOS in living cells to analyze the kinetics and dynamics of SOS behavior. The results indicate that the histone fold and Grb2-binding domains of SOS concertedly produce an intermediate state of SOS on the cell surface. The fraction of the intermediated state was reduced in positive feedback mutants, suggesting that the feedback loop functions during the intermediate state. Translocation of RAF, recognizing the active form of RAS, to the cell surface was almost abolished in the positive feedback mutants. Thus, the concerted functions of multiple membrane-associating domains of SOS governed the positive feedback loop, which is crucial for cell fate decision regulated by RAS. PMID:27924253
Closing the Feedback Loop: Ensuring Effective Action from Student Feedback
ERIC Educational Resources Information Center
Watson, Sarah
2003-01-01
Feedback from students can inform improvement in higher education institutions and be part of the students' role in university management. To be effective it is important to"close the loop": from student views, through identifying issues and delegating responsibility for action, to informing students of the action resulting from their expressed…
The macaque midbrain reticular formation sends side-specific feedback to the superior colliculus.
Wang, Niping; Warren, Susan; May, Paul J
2010-04-01
The central mesencephalic reticular formation (cMRF) likely plays a role in gaze control, as cMRF neurons receive tectal input and provide a bilateral projection back to the superior colliculus (SC). We examined the important question of whether this feedback is excitatory or inhibitory. Biotinylated dextran amine (BDA) was injected into the cMRF of M. fascicularis monkeys to anterogradely label reticulotectal terminals and retrogradely label tectoreticular neurons. BDA labeled profiles in the ipsi- and contralateral intermediate gray layer (SGI) were examined electron microscopically. Postembedding GABA immunochemistry was used to identify putative inhibitory profiles. Nearly all (94.7%) of the ipsilateral BDA labeled terminals were GABA positive, but profiles postsynaptic to these labeled terminals were exclusively GABA negative. In addition, BDA labeled terminals were observed to contact BDA labeled dendrites, indicating the presence of a monosynaptic feedback loop connecting the cMRF and ipsilateral SC. In contrast, within the contralateral SGI, half of the BDA labeled terminals were GABA positive, while more than a third were GABA negative. All the postsynaptic profiles were GABA negative. These results indicate the cMRF provides inhibitory feedback to the ipsilateral side of the SC, but it has more complex effects on the contralateral side. The ipsilateral projection may help tune the "winner-take-all" mechanism that produces a unified saccade signal, while the contralateral projections may contribute to the coordination of activity between the two colliculi.
Software feedback for monochromator tuning at UNICAT (abstract)
NASA Astrophysics Data System (ADS)
Jemian, Pete R.
2002-03-01
Automatic tuning of double-crystal monochromators presents an interesting challenge in software. The goal is to either maximize, or hold constant, the throughput of the monochromator. An additional goal of the software feedback is to disable itself when there is no beam and then, at the user's discretion, re-enable itself when the beam returns. These and other routine goals, such as adherence to limits of travel for positioners, are maintained by software controls. Many solutions exist to lock in and maintain a fixed throughput. Among these include a hardware solution involving a wave form generator, and a lock-in amplifier to autocorrelate the movement of a piezoelectric transducer (PZT) providing fine adjustment of the second crystal Bragg angle. This solution does not work when the positioner is a slow acting device such as a stepping motor. Proportional integral differential (PID) loops have been used to provide feedback through software but additional controls must be provided to maximize the monochromator throughput. Presented here is a software variation of the PID loop which meets the above goals. By using two floating point variables as inputs, representing the intensity of x rays measured before and after the monochromator, it attempts to maximize (or hold constant) the ratio of these two inputs by adjusting an output floating point variable. These floating point variables are connected to hardware channels corresponding to detectors and positioners. When the inputs go out of range, the software will stop making adjustments to the control output. Not limited to monochromator feedback, the software could be used, with beam steering positioners, to maintain a measure of beam position. Advantages of this software feedback are the flexibility of its various components. It has been used with stepping motors and PZTs as positioners. Various devices such as ion chambers, scintillation counters, photodiodes, and photoelectron collectors have been used as detectors. The software provides significant cost savings over hardware feedback methods. Presently implemented in EPICS, the software is sufficiently general to any automated instrument control system.
Autoregulatory mechanisms controlling the microprocessor.
Triboulet, Robinson; Gregory, Richard I
2011-01-01
The Microprocessor, comprising the ribonuclease Drosha and its essential cofactor, the double-stranded RNA-binding protein, DGCR8, is essential for the first step of the miRNA biogenesis pathway. It specifically cleaves double-stranded RNA within stem-loop structures of primary miRNA transcripts (pri-miRNAs) to generate precursor (pre-miRNA) intermediates. Pre-miRNAs are subsequently processed by Dicer to their mature ∼22 nt form. Thus, Microprocessor is essential for miRNA maturation, and pri-miRNA cleavage by this complex defines one end of the mature miRNA. Moreover, it is emerging that dysregulation of the Microprocessor is associated with various human diseases. It is therefore important to understand the mechanisms by which the expression of the subunits of the Microprocessor is regulated. Recent findings have uncovered a post-transcriptional mechanism that maintains the integrity of the Microprocessor. These studies revealed that the Microprocessor is involved in the processing of the messenger RNA (mRNA) that encodes DGCR8. This regulatory feedback loop, along with the reported role played by DGCR8 in the stabilization of Drosha protein, is part of a newly identified regulatory mechanism controlling Microprocessor activity.
Arizmendi, Luis; Ambite, Emilio J
2012-02-20
We used a digital feedback control loop system to produce reproducible fixed volume transmission holograms of high diffraction efficiency. Different strategies were investigated to obtain holograms of good quality and the highest refractive index modulation depth. Using this control system, we were able to record holograms with stationary fringes. Additionally to using the stationary fringe recording, a double recording-fixing schedule resulted in being the most appropriate one to produce reproducible holograms of better characteristics. This strategy is discussed and compared with other already established ones. © 2012 Optical Society of America
Mathematical modeling in chronobiology.
Bordyugov, G; Westermark, P O; Korenčič, A; Bernard, S; Herzel, H
2013-01-01
Circadian clocks are autonomous oscillators entrained by external Zeitgebers such as light-dark and temperature cycles. On the cellular level, rhythms are generated by negative transcriptional feedback loops. In mammals, the suprachiasmatic nucleus (SCN) in the anterior part of the hypothalamus plays the role of the central circadian pacemaker. Coupling between individual neurons in the SCN leads to precise self-sustained oscillations even in the absence of external signals. These neuronal rhythms orchestrate the phasing of circadian oscillations in peripheral organs. Altogether, the mammalian circadian system can be regarded as a network of coupled oscillators. In order to understand the dynamic complexity of these rhythms, mathematical models successfully complement experimental investigations. Here we discuss basic ideas of modeling on three different levels (1) rhythm generation in single cells by delayed negative feedbacks, (2) synchronization of cells via external stimuli or cell-cell coupling, and (3) optimization of chronotherapy.
Normalization for sparse encoding of odors by a wide-field interneuron.
Papadopoulou, Maria; Cassenaer, Stijn; Nowotny, Thomas; Laurent, Gilles
2011-05-06
Sparse coding presents practical advantages for sensory representations and memory storage. In the insect olfactory system, the representation of general odors is dense in the antennal lobes but sparse in the mushroom bodies, only one synapse downstream. In locusts, this transformation relies on the oscillatory structure of antennal lobe output, feed-forward inhibitory circuits, intrinsic properties of mushroom body neurons, and connectivity between antennal lobe and mushroom bodies. Here we show the existence of a normalizing negative-feedback loop within the mushroom body to maintain sparse output over a wide range of input conditions. This loop consists of an identifiable "giant" nonspiking inhibitory interneuron with ubiquitous connectivity and graded release properties.
Open-loop-feedback control of serum drug concentrations: pharmacokinetic approaches to drug therapy.
Jelliffe, R W
1983-01-01
Recent developments to optimize open-loop-feedback control of drug dosage regimens, generally applicable to pharmacokinetically oriented therapy with many drugs, involve computation of patient-individualized strategies for obtaining desired serum drug concentrations. Analyses of past therapy are performed by least squares, extended least squares, and maximum a posteriori probability Bayesian methods of fitting pharmacokinetic models to serum level data. Future possibilities for truly optimal open-loop-feedback therapy with full Bayesian methods, and conceivably for optimal closed-loop therapy in such data-poor clinical situations, are also discussed. Implementation of these various therapeutic strategies, using automated, locally controlled infusion devices, has also been achieved in prototype form.
Log amplifier with pole-zero compensation
Brookshier, William
1987-01-01
A logarithmic amplifier circuit provides pole-zero compensation for improved stability and response time over 6-8 decades of input signal frequency. The amplifier circuit includes a first operational amplifier with a first feedback loop which includes a second, inverting operational amplifier in a second feedback loop. The compensated output signal is provided by the second operational amplifier with the log elements, i.e., resistors, and the compensating capacitors in each of the feedback loops having equal values so that each break point or pole is offset by a compensating break point or zero.
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.
Offset quadrature communications with decision-feedback carrier synchronization
NASA Technical Reports Server (NTRS)
Simon, M. K.; Smith, J. G.
1974-01-01
In order to accommodate a quadrature amplitude-shift-keyed (QASK) signal, Simon and Smith (1974) have modified the decision-feedback loop which tracks a quadrature phase-shift-keyed (QPSK). In the investigation reported approaches are considered to modify the loops in such a way that offset QASK signals can be tracked, giving attention to the special case of an offset QPSK. The development of the stochastic integro-differential equation of operation for a decision-feedback offset QASK loop is discussed along with the probability density function of the phase error process.
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.
Generalized fast feedback system in the SLC
DOE Office of Scientific and Technical Information (OSTI.GOV)
Hendrickson, L.; Allison, S.; Gromme, T.
A generalized fast feedback system has been developed to stabilize beams at various locations in the SLC. The system is designed to perform measurements and change actuator settings to control beam states such as position, angle and energy on a pulse to pulse basis. The software design is based on the state space formalism of digital control theory. The system is database-driven, facilitating the addition of new loops without requiring additional software. A communications system, KISNet, provides fast communications links between microprocessors for feedback loops which involve multiple micros. Feedback loops have been installed in seventeen locations throughout the SLCmore » and have proven to be invaluable in stabilizing the machine.« less
A Review of Control Strategies in Closed-Loop Neuroprosthetic Systems
Wright, James; Macefield, Vaughan G.; van Schaik, André; Tapson, Jonathan C.
2016-01-01
It has been widely recognized that closed-loop neuroprosthetic systems achieve more favorable outcomes for users then equivalent open-loop devices. Improved performance of tasks, better usability, and greater embodiment have all been reported in systems utilizing some form of feedback. However, the interdisciplinary work on neuroprosthetic systems can lead to miscommunication due to similarities in well-established nomenclature in different fields. Here we present a review of control strategies in existing experimental, investigational and clinical neuroprosthetic systems in order to establish a baseline and promote a common understanding of different feedback modes and closed-loop controllers. The first section provides a brief discussion of feedback control and control theory. The second section reviews the control strategies of recent Brain Machine Interfaces, neuromodulatory implants, neuroprosthetic systems, and assistive neurorobotic devices. The final section examines the different approaches to feedback in current neuroprosthetic and neurorobotic systems. PMID:27462202
10 W single-mode Er/Yb co-doped all-fiber amplifier with suppressed Yb-ASE
NASA Astrophysics Data System (ADS)
Sobon, G.; Sliwinska, D.; Abramski, K. M.; Kaczmarek, P.
2014-02-01
In this work we demonstrate a single-frequency, single-mode all-fiber master oscillator power amplifier (MOPA) source, based on erbium-ytterbium co-doped double-clad fiber emitting 10 W of continuous wave power at 1565 nm. In the power amplifier stage, the amplified spontaneous emission from Yb3+ ions (Yb-ASE) is forced to recirculate in a loop resonator in order to provide stable lasing at 1060 nm. The generated signal acts as an additional pump source for the amplifier and is reabsorbed by the Yb3+ ions in the active fiber, allowing an increase in the efficiency and boosting the output power. The feedback loop also protects the amplifier from parasitic lasing or self-pulsing at a wavelength of 1 μm. This allows one to significantly scale the output power in comparison to a conventional setup without any Yb-ASE control.
Magnetic field line reconnection experiments. V - Current disruptions and double layers
NASA Technical Reports Server (NTRS)
Stenzel, R. L.; Gekelman, W.; Wild, N.
1983-01-01
An investigation is conducted of the stability of a large laboratory plasma current sheet, which has been generated in the process of magnetic field line reconnection, with respect to local current increases. Magnetic flux variations in regions remote from the current sheet generate an inductive voltage in the current loop that drops off inside the plasma in the form of a potential double layer, leading to particle acceleration with velocities much larger than those expected from the steady state electric fields in the plasma. A model for the mechanism of the current disruptions is formulated in which the potential structure leads to ion expulsion, creating a localized density drop. The associated current drop in an inductive circuit drives the potential structure, providing feedback for the disruptive instability. Similarities to, and differences from, magnetospheric substorm phenomena are noted.
Depression as a systemic syndrome: mapping the feedback loops of major depressive disorder.
Wittenborn, A K; Rahmandad, H; Rick, J; Hosseinichimeh, N
2016-02-01
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. 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. 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. 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.
Depression as a systemic syndrome: mapping the feedback loops of major depressive disorder
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
A Comparison of Climate Feedback Strength between CO2 Doubling and LGM Experiments
NASA Astrophysics Data System (ADS)
Yoshimori, M.; Yokohata, T.; Abe-Ouchi, A.
2008-12-01
Studies of past climate potentially provide a constraint on the uncertainty of climate sensitivity, but previous studies warn against a simple scaling to the future. The climate sensitivity is determined by various feedback processes and they may vary with climate states and forcings. In this study, we investigate similarities and differences of feedbacks for a CO2 doubling, a last glacial maximum (LGM), and LGM greenhouse gas (GHG) forcing experiments, using an atmospheric general circulation model coupled to a slab ocean model. After computing the radiative forcing, the individual feedback strengths: water vapor, lapse rate, albedo, and cloud feedbacks, are evaluated explicitly. For this particular model, the difference in the climate sensitivity among experiments is attributed to the shortwave cloud feedback in which there is a tendency that it becomes weaker or even negative in the cooling experiments. No significant difference is found in the water vapor feedback between warming and cooling experiments by GHGs despite the nonlinear dependence of the Clausius-Clapeyron relation on temperature. The weaker water vapor feedback in the LGM experiment due to a relatively weaker tropical forcing is compensated by the stronger lapse rate feedback due to a relatively stronger extratropical forcing. A hypothesis is proposed which explains the asymmetric cloud response between warming and cooling experiments associated with a displacement of the region of mixed- phase clouds. The difference in the total feedback strength between experiments is, however, relatively small compared to the current intermodel spread, and does not necessarily preclude the use of LGM climate as a future constraint.
Roe, S C
1997-01-01
Evaluate the mechanical properties of twist, loop, double loop, double-wrap and loop/twist cerclage. The initial tension generated by 18 cerclage of each type was determined using a materials testing machine after tying around a testing jig. Six wires from each type were distracted and the initial stiffness and yield load were determined. Yield behavior was further investigated in six wires of each type by determining the load required to reduce cerclage tension below 30 Newton (N) following and incremental (50 N) stepwise load and unload regimen. The amount of collapse of the simulated bone fragments that resulted in the reduction of initial tension to 30 N was measured for the final six wires of each group. Data were analyzed by analysis of variance and a multiple comparison test. Twist type cerclage generated less tension than loop-type cerclage. The yield load of these two types was similar. Double-loop and double-wrap cerclage generated superior tension and resisted a greater load before loosening. Loop/twist cerclage had an intermediate initial tension but had the greatest resistance to loading. In the collapse test, the greater the initial tension, the more collapse could occur before the wire was loose. For all types of cerclage wire fixation, a reduction of diameter of the testing jig of more than 1% caused loosening. Double-loop and double-wrap cerclage provide greater compression of fragments and resist loads associated with weight-bearing better than the twist and loop methods. Loop/twist cerclage may have advantages because of their superior resistance to loading. All cerclage will loosen if fracture fragments collapse.
Design and Implementation of a Biomolecular Concentration Tracker
2015-01-01
As a field, synthetic biology strives to engineer increasingly complex artificial systems in living cells. Active feedback in closed loop systems offers a dynamic and adaptive way to ensure constant relative activity independent of intrinsic and extrinsic noise. In this work, we use synthetic protein scaffolds as a modular and tunable mechanism for concentration tracking through negative feedback. Input to the circuit initiates scaffold production, leading to colocalization of a two-component system and resulting in the production of an inhibitory antiscaffold protein. Using a combination of modeling and experimental work, we show that the biomolecular concentration tracker circuit achieves dynamic protein concentration tracking in Escherichia coli and that steady state outputs can be tuned. PMID:24847683
Tang, Rixin; Whitwell, Robert L; Goodale, Melvyn A
2015-05-01
Goal-directed movements, such as reaching out to grasp an object, are necessarily constrained by the spatial properties of the target such as its size, shape, and position. For example, during a reach-to-grasp movement, the peak width of the aperture formed by the thumb and fingers in flight (peak grip aperture, PGA) is linearly related to the target's size. Suppressing vision throughout the movement (visual open loop) has a small though significant effect on this relationship. Visual open loop conditions also produce a large increase in the PGA compared to when vision is available throughout the movement (visual closed loop). Curiously, this differential effect of the availability of visual feedback is influenced by the presentation order: the difference in PGA between closed- and open-loop trials is smaller when these trials are intermixed (an effect we have called 'homogenization'). Thus, grasping movements are affected not only by the availability of visual feedback (closed loop or open loop) but also by what happened on the previous trial. It is not clear, however, whether this carry-over effect is mediated through motor (or sensorimotor) memory or through the interference of different task sets for closed-loop and open-loop feedback that determine when the movements are fully specified. We reasoned that sensorimotor memory, but not a task set for closed and open loop feedback, would be specific to the type of response. We tested this prediction in a condition in which pointing to targets was alternated with grasping those same targets. Critically, in this condition, when pointing was performed in open loop, grasping was always performed in closed loop (and vice versa). Despite the fact that closed- and open-loop trials were alternating in this condition, we found no evidence for homogenization of the PGA. Homogenization did occur, however, in a follow-up experiment in which grasping movements and visual feedback were alternated between the left and the right hand, indicating that sensorimotor (or motor) memory can operate both within and between hands when the response type is kept the same. In a final experiment, we ruled out the possibility that simply alternating the hand used to perform the grasp interferes with motor or sensorimotor memory. We did this by showing that when the hand was alternated within a block of exclusively closed- or open-loop trials, homogenization of the PGA did not occur. Taken together, the results suggest that (1) interference from simply switching between task sets for closed or open-loop feedback or from switching between the hands cannot account homogenization in the PGA and that (2) the programming and execution of grasps can borrow not only from grasping movements executed in the past by the same hand, but also from grasping movements executed with the other hand. Copyright © 2015 Elsevier B.V. All rights reserved.
NASA Technical Reports Server (NTRS)
Thomas, Jr., Jess B. (Inventor)
1991-01-01
An improved digital phase lock loop incorporates several distinctive features that attain better performance at high loop gain and better phase accuracy. These features include: phase feedback to a number-controlled oscillator in addition to phase rate; analytical tracking of phase (both integer and fractional cycles); an amplitude-insensitive phase extractor; a more accurate method for extracting measured phase; a method for changing loop gain during a track without loss of lock; and a method for avoiding loss of sampled data during computation delay, while maintaining excellent tracking performance. The advantages of using phase and phase-rate feedback are demonstrated by comparing performance with that of rate-only feedback. Extraction of phase by the method of modeling provides accurate phase measurements even when the number-controlled oscillator phase is discontinuously updated.
Lu, Ji; Pan, Junhao; Zhang, Qiang; Dubé, Laurette; Ip, Edward H.
2015-01-01
With intensively collected longitudinal data, recent advances in Experience Sampling Method (ESM) benefit social science empirical research, but also pose important methodological challenges. As traditional statistical models are not generally well-equipped to analyze a system of variables that contain feedback loops, this paper proposes the utility of an extended hidden Markov model to model reciprocal relationship between momentary emotion and eating behavior. This paper revisited an ESM data set (Lu, Huet & Dube, 2011) that observed 160 participants’ food consumption and momentary emotions six times per day in 10 days. Focusing on the analyses on feedback loop between mood and meal healthiness decision, the proposed Reciprocal Markov Model (RMM) can accommodate both hidden (“general” emotional states: positive vs. negative state) and observed states (meal: healthier, same or less healthy than usual) without presuming independence between observations and smooth trajectories of mood or behavior changes. The results of RMM analyses illustrated the reciprocal chains of meal consumption and mood as well as the effect of contextual factors that moderate the interrelationship between eating and emotion. A simulation experiment that generated data consistent to the empirical study further demonstrated that the procedure is promising in terms of recovering the parameters. PMID:26717120
A DFIG Islanding Detection Scheme Based on Reactive Power Infusion
NASA Astrophysics Data System (ADS)
Wang, M.; Liu, C.; He, G. Q.; Li, G. H.; Feng, K. H.; Sun, W. W.
2017-07-01
A lot of research has been done on photovoltaic (the “PV”) power system islanding detection in recent years. As a comparison, much less attention has been paid to islanding in wind turbines. Meanwhile, wind turbines can work in islanding conditions for quite a long period, which can be harmful to equipments and cause safety hazards. This paper presents and examines a double fed introduction generation (the “DFIG”) islanding detection scheme based on feedback of reactive power and frequency and uses a trigger signal of reactive power infusion which can be obtained by dividing the voltage total harmonic distortion (the "THD") by the voltage THD of last cycle to avoid the deterioration of power quality. This DFIG islanding detection scheme uses feedback of reactive power current loop to amplify the frequency differences in islanding and normal conditions. Simulation results show that the DFIG islanding detection scheme is effective.
NASA Technical Reports Server (NTRS)
Simon, Marvin; Valles, Esteban; Jones, Christopher
2008-01-01
This paper addresses the carrier-phase estimation problem under low SNR conditions as are typical of turbo- and LDPC-coded applications. In previous publications by the first author, closed-loop carrier synchronization schemes for error-correction coded BPSK and QPSK modulation were proposed that were based on feeding back hard data decisions at the input of the loop, the purpose being to remove the modulation prior to attempting to track the carrier phase as opposed to the more conventional decision-feedback schemes that incorporate such feedback inside the loop. In this paper, we consider an alternative approach wherein the extrinsic soft information from the iterative decoder of turbo or LDPC codes is instead used as the feedback.
Numerical Simulation of the Oscillations in a Mixer: An Internal Aeroacoustic Feedback System
NASA Technical Reports Server (NTRS)
Jorgenson, Philip C. E.; Loh, Ching Y.
2004-01-01
The space-time conservation element and solution element method is employed to numerically study the acoustic feedback system in a high temperature, high speed wind tunnel mixer. The computation captures the self-sustained feedback loop between reflecting Mach waves and the shear layer. This feedback loop results in violent instabilities that are suspected of causing damage to some tunnel components. The computed frequency is in good agreement with the available experimental data. The physical phenomena are explained based on the numerical results.
Monitoring Digital Closed-Loop Feedback Systems
NASA Technical Reports Server (NTRS)
Katz, Richard; Kleyner, Igor
2011-01-01
A technique of monitoring digital closed-loop feedback systems has been conceived. The basic idea is to obtain information on the performances of closed-loop feedback circuits in such systems to aid in the determination of the functionality and integrity of the circuits and of performance margins. The need for this technique arises as follows: Some modern digital systems include feedback circuits that enable other circuits to perform with precision and are tolerant of changes in environment and the device s parameters. For example, in a precision timing circuit, it is desirable to make the circuit insensitive to variability as a result of the manufacture of circuit components and to the effects of temperature, voltage, radiation, and aging. However, such a design can also result in masking the indications of damaged and/or deteriorating components. The present technique incorporates test circuitry and associated engineering-telemetry circuitry into an embedded system to monitor the closed-loop feedback circuits, using spare gates that are often available in field programmable gate arrays (FPGAs). This technique enables a test engineer to determine the amount of performance margin in the system, detect out of family circuit performance, and determine one or more trend(s) in the performance of the system. In one system to which the technique has been applied, an ultra-stable oscillator is used as a reference for internal adjustment of 12 time-to-digital converters (TDCs). The feedback circuit produces a pulse-width-modulated signal that is fed as a control input into an amplifier, which controls the circuit s operating voltage. If the circuit s gates are determined to be operating too slowly or rapidly when their timing is compared with that of the reference signal, then the pulse width increases or decreases, respectively, thereby commanding the amplifier to increase or reduce, respectively, its output level, and "adjust" the speed of the circuits. The nominal frequency of the TDC s pulse width modulated outputs is approximately 40 kHz. In this system, the technique is implemented by means of a monitoring circuit that includes a 20-MHz sampling circuit and a 24-bit accumulator with a gate time of 10 ms. The monitoring circuit measures the duty cycle of each of the 12 TDCs at a repetition rate of 28 Hz. The accumulator content is reset to all zeroes at the beginning of each measurement period and is then incremented or decremented based of the value of the state of the pulse width modulated signal. Positive or negative values in the accumulator correspond to duty cycles greater or less, respectively, than 50 percent.
Francisco-Velilla, Rosario; Fernandez-Chamorro, Javier; Dotu, Ivan; Martinez-Salas, Encarnación
2018-05-16
Gemin5 is a predominantly cytoplasmic protein that downregulates translation, beyond controlling snRNPs assembly. The C-terminal region harbors a non-canonical RNA-binding site consisting of two domains, RBS1 and RBS2, which differ in RNA-binding capacity and the ability to modulate translation. Here, we show that these domains recognize distinct RNA targets in living cells. Interestingly, the most abundant and exclusive RNA target of the RBS1 domain was Gemin5 mRNA. Biochemical and functional characterization of this target demonstrated that RBS1 polypeptide physically interacts with a predicted thermodynamically stable stem-loop upregulating mRNA translation, thereby counteracting the negative effect of Gemin5 protein on global protein synthesis. In support of this result, destabilization of the stem-loop impairs the stimulatory effect on translation. Moreover, RBS1 stimulates translation of the endogenous Gemin5 mRNA. Hence, although the RBS1 domain downregulates global translation, it positively enhances translation of RNA targets carrying thermodynamically stable secondary structure motifs. This mechanism allows fine-tuning the availability of Gemin5 to play its multiple roles in gene expression control.
Analysis of Network Topologies Underlying Ethylene Growth Response Kinetics
Prescott, Aaron M.; McCollough, Forest W.; Eldreth, Bryan L.; Binder, Brad M.; Abel, Steven M.
2016-01-01
Most models for ethylene signaling involve a linear pathway. However, measurements of seedling growth kinetics when ethylene is applied and removed have resulted in more complex network models that include coherent feedforward, negative feedback, and positive feedback motifs. The dynamical responses of the proposed networks have not been explored in a quantitative manner. Here, we explore (i) whether any of the proposed models are capable of producing growth-response behaviors consistent with experimental observations and (ii) what mechanistic roles various parts of the network topologies play in ethylene signaling. To address this, we used computational methods to explore two general network topologies: The first contains a coherent feedforward loop that inhibits growth and a negative feedback from growth onto itself (CFF/NFB). In the second, ethylene promotes the cleavage of EIN2, with the product of the cleavage inhibiting growth and promoting the production of EIN2 through a positive feedback loop (PFB). Since few network parameters for ethylene signaling are known in detail, we used an evolutionary algorithm to explore sets of parameters that produce behaviors similar to experimental growth response kinetics of both wildtype and mutant seedlings. We generated a library of parameter sets by independently running the evolutionary algorithm many times. Both network topologies produce behavior consistent with experimental observations, and analysis of the parameter sets allows us to identify important network interactions and parameter constraints. We additionally screened these parameter sets for growth recovery in the presence of sub-saturating ethylene doses, which is an experimentally-observed property that emerges in some of the evolved parameter sets. Finally, we probed simplified networks maintaining key features of the CFF/NFB and PFB topologies. From this, we verified observations drawn from the larger networks about mechanisms underlying ethylene signaling. Analysis of each network topology results in predictions about changes that occur in network components that can be experimentally tested to give insights into which, if either, network underlies ethylene responses. PMID:27625669
Sparse, decorrelated odor coding in the mushroom body enhances learned odor discrimination.
Lin, Andrew C; Bygrave, Alexei M; de Calignon, Alix; Lee, Tzumin; Miesenböck, Gero
2014-04-01
Sparse coding may be a general strategy of neural systems for augmenting memory capacity. In Drosophila melanogaster, sparse odor coding by the Kenyon cells of the mushroom body is thought to generate a large number of precisely addressable locations for the storage of odor-specific memories. However, it remains untested how sparse coding relates to behavioral performance. Here we demonstrate that sparseness is controlled by a negative feedback circuit between Kenyon cells and the GABAergic anterior paired lateral (APL) neuron. Systematic activation and blockade of each leg of this feedback circuit showed that Kenyon cells activated APL and APL inhibited Kenyon cells. Disrupting the Kenyon cell-APL feedback loop decreased the sparseness of Kenyon cell odor responses, increased inter-odor correlations and prevented flies from learning to discriminate similar, but not dissimilar, odors. These results suggest that feedback inhibition suppresses Kenyon cell activity to maintain sparse, decorrelated odor coding and thus the odor specificity of memories.
General theory of feedback control of a nuclear spin ensemble in quantum dots
NASA Astrophysics Data System (ADS)
Yang, Wen; Sham, L. J.
2013-12-01
We present a microscopic theory of the nonequilibrium nuclear spin dynamics driven by the electron and/or hole under continuous-wave pumping in a quantum dot. We show the correlated dynamics of the nuclear spin ensemble and the electron and/or hole under optical excitation as a quantum feedback loop and investigate the dynamics of the many nuclear spins as a nonlinear collective motion. This gives rise to three observable effects: (i) hysteresis, (ii) locking (avoidance) of the pump absorption strength to (from) the natural resonance, and (iii) suppression (amplification) of the fluctuation of weakly polarized nuclear spins, leading to prolonged (shortened) electron-spin coherence time. A single nonlinear feedback function is constructed which determines the different outcomes of the three effects listed above depending on the feedback being negative or positive. The general theory also helps to put in perspective the wide range of existing theories on the problem of a single electron spin in a nuclear spin bath.
Arzouan, Yossi; Solomon, Sorin; Faust, Miriam; Goldstein, Abraham
2011-04-27
Language comprehension is a complex task that involves a wide network of brain regions. We used topological measures to qualify and quantify the functional connectivity of the networks used under various comprehension conditions. To that aim we developed a technique to represent functional networks based on EEG recordings, taking advantage of their excellent time resolution in order to capture the fast processes that occur during language comprehension. Networks were created by searching for a specific causal relation between areas, the negative feedback loop, which is ubiquitous in many systems. This method is a simple way to construct directed graphs using event-related activity, which can then be analyzed topologically. Brain activity was recorded while subjects read expressions of various types and indicated whether they found them meaningful. Slightly different functional networks were obtained for event-related activity evoked by each expression type. The differences reflect the special contribution of specific regions in each condition and the balance of hemispheric activity involved in comprehending different types of expressions and are consistent with the literature in the field. Our results indicate that representing event-related brain activity as a network using a simple temporal relation, such as the negative feedback loop, to indicate directional connectivity is a viable option for investigation which also derives new information about aspects not reflected in the classical methods for investigating brain activity.
Reiterer, Veronika; Grossniklaus, Lars; Tschon, Therese; Kasper, Christoph Alexander; Sorg, Isabel; Arrieumerlou, Cécile
2011-07-01
Shigella flexneri type III secreted effector OspF harbors a phosphothreonine lyase activity that irreversibly dephosphorylates MAP kinases (MAPKs) p38 and ERK in infected epithelial cells and thereby, dampens innate immunity. Whereas this activity has been well characterized, the impact of OspF on other host signaling pathways that control inflammation was unknown. Here we report that OspF potentiates the activation of the MAPK JNK and the transcription factor NF-κB during S. flexneri infection. This unexpected effect of OspF was dependent on the phosphothreonine lyase activity of OspF on p38, and resulted from the disruption of a negative feedback loop regulation between p38 and TGF-beta activated kinase 1 (TAK1), mediated via the phosphorylation of TAK1-binding protein 1. Interestingly, potentiated JNK activation was not associated with enhanced c-Jun signaling as OspF also inhibits c-Jun expression at the transcriptional level. Altogether, our data reveal the impact of OspF on the activation of NF-κB, JNK and c-Jun, and demonstrate the existence of a negative feedback loop regulation between p38 and TAK1 during S. flexneri infection. Furthermore, this study validates the use of bacterial effectors as molecular tools to identify the crosstalks that connect important host signaling pathways induced upon bacterial infection. Copyright © 2011 Elsevier Inc. All rights reserved.
ERIC Educational Resources Information Center
Lee, Eun Jeong
2017-01-01
The author in this study introduces an integrated corrective feedback (CF) loop to schematize the interplay between CF and independent practice in L2 oral English learning among advanced-level adult ESL students. The CF loop integrates insights from the Interaction, Output, and Noticing Hypotheses to show how CF can help or harm L2 learners'…
On the Minimization of Fluctuations in the Response Times of Autoregulatory Gene Networks
Murugan, Rajamanickam; Kreiman, Gabriel
2011-01-01
The temporal dynamics of the concentrations of several proteins are tightly regulated, particularly for critical nodes in biological networks such as transcription factors. An important mechanism to control transcription factor levels is through autoregulatory feedback loops where the protein can bind its own promoter. Here we use theoretical tools and computational simulations to further our understanding of transcription-factor autoregulatory loops. We show that the stochastic dynamics of feedback and mRNA synthesis can significantly influence the speed of response of autoregulatory genetic networks toward external stimuli. The fluctuations in the response-times associated with the accumulation of the transcription factor in the presence of negative or positive autoregulation can be minimized by confining the ratio of mRNA/protein lifetimes within 1:10. This predicted range of mRNA/protein lifetime agrees with ranges observed empirically in prokaryotes and eukaryotes. The theory can quantitatively and systematically account for the influence of regulatory element binding and unbinding dynamics on the transcription-factor concentration rise-times. The simulation results are robust against changes in several system parameters of the gene expression machinery. PMID:21943410
NASA Technical Reports Server (NTRS)
Mielke, R. R.; Tung, L. J.; Carraway, P. I., III
1984-01-01
The feasibility of using reduced order models and reduced order observers with eigenvalue/eigenvector assignment procedures is investigated. A review of spectral assignment synthesis procedures is presented. Then, a reduced order model which retains essential system characteristics is formulated. A constant state feedback matrix which assigns desired closed loop eigenvalues and approximates specified closed loop eigenvectors is calculated for the reduced order model. It is shown that the eigenvalue and eigenvector assignments made in the reduced order system are retained when the feedback matrix is implemented about the full order system. In addition, those modes and associated eigenvectors which are not included in the reduced order model remain unchanged in the closed loop full order system. The full state feedback design is then implemented by using a reduced order observer. It is shown that the eigenvalue and eigenvector assignments of the closed loop full order system rmain unchanged when a reduced order observer is used. The design procedure is illustrated by an actual design problem.
A social feedback loop for speech development and its reduction in autism
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
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.
NASA Technical Reports Server (NTRS)
Mielke, R. R.; Tung, L. J.; Carraway, P. I., III
1985-01-01
The feasibility of using reduced order models and reduced order observers with eigenvalue/eigenvector assignment procedures is investigated. A review of spectral assignment synthesis procedures is presented. Then, a reduced order model which retains essential system characteristics is formulated. A constant state feedback matrix which assigns desired closed loop eigenvalues and approximates specified closed loop eigenvectors is calculated for the reduced order model. It is shown that the eigenvalue and eigenvector assignments made in the reduced order system are retained when the feedback matrix is implemented about the full order system. In addition, those modes and associated eigenvectors which are not included in the reduced order model remain unchanged in the closed loop full order system. The fulll state feedback design is then implemented by using a reduced order observer. It is shown that the eigenvalue and eigenvector assignments of the closed loop full order system remain unchanged when a reduced order observer is used. The design procedure is illustrated by an actual design problem.
An evaluation of the feedback loops in the poverty focus of world bank operations.
Fardoust, Shahrokh; Kanbur, Ravi; Luo, Xubei; Sundberg, Mark
2018-04-01
The World Bank Group in 2013 made the elimination of extreme poverty by 2030 a central institutional focus and purpose. This paper, based on an evaluation conducted by the Independent Evaluation Group of the World Bank Group, examines how, and how well, the Bank uses feedback loops to enhance the poverty focus of its operations. Feedback loops are important for every element of the results chain running from data, to diagnostics, to strategy formulation and finally to strategy implementation. The evaluation uses a range of instruments, including surveys of stakeholders and World Bank staff, focus group meetings, country case studies and systematic reviews of Bank lending and non-lending operations. We find that while the Bank generates useful information on poverty reduction from its projects and programs, the feedback loops - from outcomes to data analysis to diagnostics to strategy formulation and implementation - have generally been weak, with sizable variation across countries. Copyright © 2017 The World Bank. Published by Elsevier Ltd.. All rights reserved.
NASA Technical Reports Server (NTRS)
Joshi, S. M.
1985-01-01
Robustness properties are investigated for two types of controllers for large flexible space structures, which use collocated sensors and actuators. The first type is an attitude controller which uses negative definite feedback of measured attitude and rate, while the second type is a damping enhancement controller which uses only velocity (rate) feedback. It is proved that collocated attitude controllers preserve closed loop global asymptotic stability when linear actuator/sensor dynamics satisfying certain phase conditions are present, or monotonic increasing nonlinearities are present. For velocity feedback controllers, the global asymptotic stability is proved under much weaker conditions. In particular, they have 90 phase margin and can tolerate nonlinearities belonging to the (0,infinity) sector in the actuator/sensor characteristics. The results significantly enhance the viability of both types of collocated controllers, especially when the available information about the large space structure (LSS) parameters is inadequate or inaccurate.
Switching LPV Control with Double-Layer LPV Model for Aero-Engines
NASA Astrophysics Data System (ADS)
Tang, Lili; Huang, Jinquan; Pan, Muxuan
2017-11-01
To cover the whole range of operating conditions of aero-engine, a double-layer LPV model is built so as to take into account of the variability due to the flight altitude, Mach number and the rotational speed. With this framework, the problem of designing LPV state-feedback robust controller that guarantees desired bounds on both H_∞ and H_2 performances is considered. Besides this, to reduce the conservativeness caused by a single LPV controller of the whole flight envelope and the common Lyapunov function method, a new method is proposed to design a family of LPV switching controllers. The switching LPV controllers can ensure that the closed-loop system remains stable in the sense of Lyapunov under arbitrary switching logic. Meanwhile, the switching LPV controllers can ensure the parameters change smoothly. The validity and performance of the theoretical results are demonstrated through a numerical example.
Processing of double-R-loops in (CAG)·(CTG) and C9orf72 (GGGGCC)·(GGCCCC) repeats causes instability
Reddy, Kaalak; Schmidt, Monika H.M.; Geist, Jaimie M.; Thakkar, Neha P.; Panigrahi, Gagan B.; Wang, Yuh-Hwa; Pearson, Christopher E.
2014-01-01
R-loops, transcriptionally-induced RNA:DNA hybrids, occurring at repeat tracts (CTG)n, (CAG)n, (CGG)n, (CCG)n and (GAA)n, are associated with diseases including myotonic dystrophy, Huntington's disease, fragile X and Friedreich's ataxia. Many of these repeats are bidirectionally transcribed, allowing for single- and double-R-loop configurations, where either or both DNA strands may be RNA-bound. R-loops can trigger repeat instability at (CTG)·(CAG) repeats, but the mechanism of this is unclear. We demonstrate R-loop-mediated instability through processing of R-loops by HeLa and human neuron-like cell extracts. Double-R-loops induced greater instability than single-R-loops. Pre-treatment with RNase H only partially suppressed instability, supporting a model in which R-loops directly generate instability by aberrant processing, or via slipped-DNA formation upon RNA removal and its subsequent aberrant processing. Slipped-DNAs were observed to form following removal of the RNA from R-loops. Since transcriptionally-induced R-loops can occur in the absence of DNA replication, R-loop processing may be a source of repeat instability in the brain. Double-R-loop formation and processing to instability was extended to the expanded C9orf72 (GGGGCC)·(GGCCCC) repeats, known to cause amyotrophic lateral sclerosis and frontotemporal dementia, providing the first suggestion through which these repeats may become unstable. These findings provide a mechanistic basis for R-loop-mediated instability at disease-associated repeats. PMID:25147206
Zhao, Chunnian; Sun, GuoQiang; Li, Shengxiu; Shi, Yanhong
2009-04-01
MicroRNAs have been implicated as having important roles in stem cell biology. MicroRNA-9 (miR-9) is expressed specifically in neurogenic areas of the brain and may be involved in neural stem cell self-renewal and differentiation. We showed previously that the nuclear receptor TLX is an essential regulator of neural stem cell self-renewal. Here we show that miR-9 suppresses TLX expression to negatively regulate neural stem cell proliferation and accelerate neural differentiation. Introducing a TLX expression vector that is not prone to miR-9 regulation rescued miR-9-induced proliferation deficiency and inhibited precocious differentiation. In utero electroporation of miR-9 in embryonic brains led to premature differentiation and outward migration of the transfected neural stem cells. Moreover, TLX represses expression of the miR-9 pri-miRNA. By forming a negative regulatory loop with TLX, miR-9 provides a model for controlling the balance between neural stem cell proliferation and differentiation.
Zhao, Chunnian; Sun, GuoQiang; Li, Shengxiu; Shi, Yanhong
2009-01-01
Summary MicroRNAs are important players in stem cell biology. Among them, microRNA-9 (miR-9) is expressed specifically in neurogenic areas of the brain. Whether miR-9 plays a role in neural stem cell self-renewal and differentiation is unknown. We showed previously that nuclear receptor TLX is an essential regulator of neural stem cell self-renewal. Here we show that miR-9 suppresses TLX expression to negatively regulate neural stem cell proliferation and accelerate neural differentiation. Introducing a TLX expression vector lacking the miR-9 recognition site rescued miR-9-induced proliferation deficiency and inhibited precocious differentiation. In utero electroporation of miR-9 in embryonic brains led to premature differentiation and outward migration of the transfected neural stem cells. Moreover, TLX represses miR-9 pri-miRNA expression. MiR-9, by forming a negative regulatory loop with TLX, establishes a model for controlling the balance between neural stem cell proliferation and differentiation. PMID:19330006
SRC-2 is an essential coactivator for orchastrating metabolism and circadian rhythm
USDA-ARS?s Scientific Manuscript database
Synchrony of the mammalian circadian clock is achieved by complex transcriptional and translational feedback loops centered on the BMAL1:CLOCK heterodimer. Modulation of circadian feedback loops is essential for maintaining rhythmicity, yet the role of transcriptional coactivators in driving BMAL1:C...
Wang, Gaowei; Zhu, Xiaomei; Gu, Jianren; Ao, Ping
2014-06-06
A quantitative hypothesis for cancer genesis and progression-the endogenous molecular-cellular network hypothesis, intended to include both genetic and epigenetic causes of cancer-has been proposed recently. Using this hypothesis, here we address the molecular basis for maintaining normal liver and hepatocellular carcinoma (HCC), and the potential strategy to cure or relieve HCC. First, we elaborate the basic assumptions of the hypothesis and establish a core working network of HCC according to the hypothesis. Second, we quantify the working network by a nonlinear dynamical system. We show that the working network reproduces the main known features of normal liver and HCC at both the modular and molecular levels. Lastly, the validated working network reveals that (i) specific positive feedback loops are responsible for the maintenance of normal liver and HCC; (ii) inhibiting proliferation and inflammation-related positive feedback loops and simultaneously inducing a liver-specific positive feedback loop is predicated as a potential strategy to cure or relieve HCC; and (iii) the genesis and regression of HCC are asymmetric. In light of the characteristic properties of the nonlinear dynamical system, we demonstrate that positive feedback loops must exist as a simple and general molecular basis for the maintenance of heritable phenotypes, such as normal liver and HCC, and regulating the positive feedback loops directly or indirectly provides potential strategies to cure or relieve HCC.
Houl, Jerry H; Ng, Fanny; Taylor, Pete; Hardin, Paul E
2008-12-18
The Drosophila circadian oscillator is composed of transcriptional feedback loops in which CLOCK-CYCLE (CLK-CYC) heterodimers activate their feedback regulators period (per) and timeless (tim) via E-box mediated transcription. These feedback loop oscillators are present in distinct clusters of dorsal and lateral neurons in the adult brain, but how this pattern of expression is established during development is not known. Since CLK is required to initiate feedback loop function, defining the pattern of CLK expression in embryos and larvae will shed light on oscillator neuron development. A novel CLK antiserum is used to show that CLK expression in the larval CNS and adult brain is limited to circadian oscillator cells. CLK is initially expressed in presumptive small ventral lateral neurons (s-LNvs), dorsal neurons 2 s (DN2s), and dorsal neuron 1 s (DN1s) at embryonic stage (ES) 16, and this CLK expression pattern persists through larval development. PER then accumulates in all CLK-expressing cells except presumptive DN2s during late ES 16 and ES 17, consistent with the delayed accumulation of PER in adult oscillator neurons and antiphase cycling of PER in larval DN2s. PER is also expressed in non-CLK-expressing cells in the embryonic CNS starting at ES 12. Although PER expression in CLK-negative cells continues in ClkJrk embryos, PER expression in cells that co-express PER and CLK is eliminated. These data demonstrate that brain oscillator neurons begin development during embryogenesis, that PER expression in non-oscillator cells is CLK-independent, and that oscillator phase is an intrinsic characteristic of brain oscillator neurons. These results define the temporal and spatial coordinates of factors that initiate Clk expression, imply that circadian photoreceptors are not activated until the end of embryogenesis, and suggest that PER functions in a different capacity before oscillator cell development is initiated.
Briat, Corentin; Gupta, Ankit; Khammash, Mustafa
2018-06-01
The ability of a cell to regulate and adapt its internal state in response to unpredictable environmental changes is called homeostasis and this ability is crucial for the cell's survival and proper functioning. Understanding how cells can achieve homeostasis, despite the intrinsic noise or randomness in their dynamics, is fundamentally important for both systems and synthetic biology. In this context, a significant development is the proposed antithetic integral feedback (AIF) motif, which is found in natural systems, and is known to ensure robust perfect adaptation for the mean dynamics of a given molecular species involved in a complex stochastic biomolecular reaction network. From the standpoint of applications, one drawback of this motif is that it often leads to an increased cell-to-cell heterogeneity or variance when compared to a constitutive (i.e. open-loop) control strategy. Our goal in this paper is to show that this performance deterioration can be countered by combining the AIF motif and a negative feedback strategy. Using a tailored moment closure method, we derive approximate expressions for the stationary variance for the controlled network that demonstrate that increasing the strength of the negative feedback can indeed decrease the variance, sometimes even below its constitutive level. Numerical results verify the accuracy of these results and we illustrate them by considering three biomolecular networks with two types of negative feedback strategies. Our computational analysis indicates that there is a trade-off between the speed of the settling-time of the mean trajectories and the stationary variance of the controlled species; i.e. smaller variance is associated with larger settling-time. © 2018 The Author(s).
Dynamic Mesoscale Land-Atmosphere Feedbacks in Fragmented Forests in Amazonia
NASA Astrophysics Data System (ADS)
Rastogi, D.; Baidya Roy, S.
2011-12-01
This paper investigates land-atmosphere feedbacks in disturbed rainforests of Amazonia. Deforestation along the rapidly expanding highways and road network has created the unique fishbone land cover pattern in Rondonia, a state in southwestern Amazonia. Numerical experiments and observations show that sharp gradients in land cover due to the fishbone heterogeneity triggers mesoscale circulations. These circulations significantly change the spatial pattern of local hydrometeorology, especially convection, clouds and precipitation. The primary research question now is can these changes in local hydrometeorology affect vegetation growth in the clearings. If so, that would be a clear indication that land-atmosphere feedbacks can affect vegetation recovery in fragmented forests. A computationally-efficient modeling tool consisting of a mesoscale atmospheric model dynamically coupled with a plant growth model has been specifically developed to identify the atmospheric feedback pathways. Preliminary experiments focus on the seasonal-scale feedbacks during the dry season. Results show that temperature, incoming shortwave and precipitation are the three primary drivers through which the feedbacks operate. Increasing temperature increases respiratory losses generating a positive feedback. Increased cloud cover reduces incoming PAR and photosynthesis, resulting in a positive feedback. Increased precipitation reduces water stress and promotes growth resulting in a negative feedback. The net effect is a combination of these 3 feedback loops. These findings can significantly improve our understanding of ecosystem resiliency in disturbed tropical forests.
Smart Braid Feedback for the Closed-Loop Control of Soft Robotic Systems.
Felt, Wyatt; Chin, Khai Yi; Remy, C David
2017-09-01
This article experimentally investigates the potential of using flexible, inductance-based contraction sensors in the closed-loop motion control of soft robots. Accurate motion control remains a highly challenging task for soft robotic systems. Precise models of the actuation dynamics and environmental interactions are often unavailable. This renders open-loop control impossible, while closed-loop control suffers from a lack of suitable feedback. Conventional motion sensors, such as linear or rotary encoders, are difficult to adapt to robots that lack discrete mechanical joints. The rigid nature of these sensors runs contrary to the aspirational benefits of soft systems. As truly soft sensor solutions are still in their infancy, motion control of soft robots has so far relied on laboratory-based sensing systems such as motion capture, electromagnetic (EM) tracking, or Fiber Bragg Gratings. In this article, we used embedded flexible sensors known as Smart Braids to sense the contraction of McKibben muscles through changes in inductance. We evaluated closed-loop control on two systems: a revolute joint and a planar, one degree of freedom continuum manipulator. In the revolute joint, our proposed controller compensated for elasticity in the actuator connections. The Smart Braid feedback allowed motion control with a steady-state root-mean-square (RMS) error of [1.5]°. In the continuum manipulator, Smart Braid feedback enabled tracking of the desired tip angle with a steady-state RMS error of [1.25]°. This work demonstrates that Smart Braid sensors can provide accurate position feedback in closed-loop motion control suitable for field applications of soft robotic systems.
Neelly, Kurt R; Terry, Joseph G; Morris, Martin J
2010-01-01
A relatively new and scarcely researched technique to increase strength is the use of supplemental heavy chain resistance (SHCR) in conjunction with plate weights to provide variable resistance to free weight exercises. The purpose of this case study was to determine the actual resistance being provided by a double-looped versus a linear hung SHCR to the back squat exercise. The linear technique simply hangs the chain directly from the bar, whereas the double-looped technique uses a smaller chain to adjust the height of the looped chain. In both techniques, as the squat descends, chain weight is unloaded onto the floor, and as the squat ascends, chain weight is progressively loaded back as resistance. One experienced and trained male weight lifter (age = 33 yr; height = 1.83 m; weight = 111.4 kg) served as the subject. Plate weight was set at 84.1 kg, approximately 50% of the subject's 1 repetition maximum. The SHCR was affixed to load cells, sampling at a frequency of 500 Hz, which were affixed to the Olympic bar. Data were collected as the subject completed the back squat under the following conditions: double-looped 1 chain (9.6 kg), double-looped 2 chains (19.2 kg), linear 1 chain, and linear 2 chains. The double-looped SHCR resulted in a 78-89% unloading of the chain weight at the bottom of the squat, whereas the linear hanging SHCR resulted in only a 36-42% unloading. The double-looped technique provided nearly 2 times the variable resistance at the top of the squat compared with the linear hanging technique, showing that attention must be given to the technique used to hang SHCR.
A boosted negative bit-line SRAM with write-assisted cell in 45 nm CMOS technology
NASA Astrophysics Data System (ADS)
Bhatnagar, Vipul; Kumar, Pradeep; Pandey, Neeta; Pandey, Sujata
2018-02-01
A new 11 T SRAM cell with write-assist is proposed to improve operation at low supply voltage. In this technique, a negative bit-line voltage is applied to one of the write bit-lines, while a boosted voltage is applied to the other write bit-line where transmission gate access is used in proposed 11 T cell. Supply voltage to one of the inverters is interrupted to weaken the feedback. Improved write feature is attributed to strengthened write access devices and weakened feedback loop of cell at the same time. Amount of boosting required for write performance improvement is also reduced due to feedback weakening, solving the persistent problem of half-selected cells and reliability reduction of access devices with the other suggested boosted and negative bit-line techniques. The proposed design improves write time by 79%, 63% and slower by 52% with respect to LP 10 T, WRE 8 T and 6 T cells respectively. It is found that write margin for the proposed cell is improved by about 4×, 2.4× and 5.37× compared to WRE8 T, LP10 T and 6 T respectively. The proposed cell with boosted negative bit line (BNBL) provides 47%, 31%, and 68.4% improvement in write margin with respect to no write-assist, negative bit line (NBL) and boosted bit line (BBL) write-assist respectively. Also, new sensing circuit with replica bit-line is proposed to give a more precise timing of applying boosted voltages for improved results. All simulations are done on TSMC 45 nm CMOS technology.
Jukam, David; Viets, Kayla; Anderson, Caitlin; Zhou, Cyrus; DeFord, Peter; Yan, Jenny; Cao, Jinshuai; Johnston, Robert J
2016-07-01
The Hippo pathway is crucial for not only normal growth and apoptosis but also cell fate specification during development. What controls Hippo pathway activity during cell fate specification is incompletely understood. In this article, we identify the insulator protein BEAF-32 as a regulator of Hippo pathway activity in Drosophila photoreceptor differentiation. Though morphologically uniform, the fly eye is composed of two subtypes of R8 photoreceptor neurons defined by expression of light-detecting Rhodopsin proteins. In one R8 subtype, active Hippo signaling induces Rhodopsin 6 (Rh6) and represses Rhodopsin 5 (Rh5), whereas in the other subtype, inactive Hippo signaling induces Rh5 and represses Rh6. The activity state of the Hippo pathway in R8 cells is determined by the expression of warts, a core pathway kinase, which interacts with the growth regulator melted in a double-negative feedback loop. We show that BEAF-32 is required for expression of warts and repression of melted Furthermore, BEAF-32 plays a second role downstream of Warts to induce Rh6 and prevent Rh5 fate. BEAF-32 is dispensable for Warts feedback, indicating that BEAF-32 differentially regulates warts and Rhodopsins. Loss of BEAF-32 does not noticeably impair the functions of the Hippo pathway in eye growth regulation. Our study identifies a context-specific regulator of Hippo pathway activity in post-mitotic neuronal fate, and reveals a developmentally specific role for a broadly expressed insulator protein. © 2016. Published by The Company of Biologists Ltd.
Sánchez-Pérez, Ana M; Arnal-Vicente, Isabel; Santos, Fabio N; Pereira, Celia W; ElMlili, Nisrin; Sanjuan, Julio; Ma, Sherie; Gundlach, Andrew L; Olucha-Bordonau, Francisco E
2015-03-01
Projections from the nucleus incertus (NI) to the septum have been implicated in the modulation of hippocampal theta rhythm. In this study we describe a previously uncharacterized projection from the septum to the NI, which may provide feedback modulation of the ascending circuitry. Fluorogold injections into the NI resulted in retrograde labeling in the septum that was concentrated in the horizontal diagonal band and areas of the posterior septum including the septofimbrial and triangular septal nuclei. Double-immunofluorescent staining indicated that the majority of NI-projecting septal neurons were calretinin-positive and some were parvalbumin-, calbindin-, or glutamic acid decarboxylase (GAD)-67-positive. Choline acetyltransferase-positive neurons were Fluorogold-negative. Injection of anterograde tracers into medial septum, or triangular septal and septofimbrial nuclei, revealed fibers descending to the supramammillary nucleus, median raphe, and the NI. These anterogradely labeled varicosities displayed synaptophysin immunoreactivity, indicating septal inputs form synapses on NI neurons. Anterograde tracer also colocalized with GAD-67-positive puncta in labeled fibers, which in some cases made close synaptic contact with GAD-67-labeled NI neurons. These data provide evidence for the existence of an inhibitory descending projection from medial and posterior septum to the NI that provides a "feedback loop" to modulate the comparatively more dense ascending NI projections to medial septum and hippocampus. Neural processes and associated behaviors activated or modulated by changes in hippocampal theta rhythm may depend on reciprocal connections between ascending and descending pathways rather than on unidirectional regulation via the medial septum. © 2014 Wiley Periodicals, Inc.
Dynamics of nonlinear feedback control.
Snippe, H P; van Hateren, J H
2007-05-01
Feedback control in neural systems is ubiquitous. Here we study the mathematics of nonlinear feedback control. We compare models in which the input is multiplied by a dynamic gain (multiplicative control) with models in which the input is divided by a dynamic attenuation (divisive control). The gain signal (resp. the attenuation signal) is obtained through a concatenation of an instantaneous nonlinearity and a linear low-pass filter operating on the output of the feedback loop. For input steps, the dynamics of gain and attenuation can be very different, depending on the mathematical form of the nonlinearity and the ordering of the nonlinearity and the filtering in the feedback loop. Further, the dynamics of feedback control can be strongly asymmetrical for increment versus decrement steps of the input. Nevertheless, for each of the models studied, the nonlinearity in the feedback loop can be chosen such that immediately after an input step, the dynamics of feedback control is symmetric with respect to increments versus decrements. Finally, we study the dynamics of the output of the control loops and find conditions under which overshoots and undershoots of the output relative to the steady-state output occur when the models are stimulated with low-pass filtered steps. For small steps at the input, overshoots and undershoots of the output do not occur when the filtering in the control path is faster than the low-pass filtering at the input. For large steps at the input, however, results depend on the model, and for some of the models, multiple overshoots and undershoots can occur even with a fast control path.
Alagoz, Baris Baykant; Deniz, Furkan Nur; Keles, Cemal; Tan, Nusret
2015-03-01
This study investigates disturbance rejection capacity of closed loop control systems by means of reference to disturbance ratio (RDR). The RDR analysis calculates the ratio of reference signal energy to disturbance signal energy at the system output and provides a quantitative evaluation of disturbance rejection performance of control systems on the bases of communication channel limitations. Essentially, RDR provides a straightforward analytical method for the comparison and improvement of implicit disturbance rejection capacity of closed loop control systems. Theoretical analyses demonstrate us that RDR of the negative feedback closed loop control systems are determined by energy spectral density of controller transfer function. In this manner, authors derived design criteria for specifications of disturbance rejection performances of PID and fractional order PID (FOPID) controller structures. RDR spectra are calculated for investigation of frequency dependence of disturbance rejection capacity and spectral RDR analyses are carried out for PID and FOPID controllers. For the validation of theoretical results, simulation examples are presented. Copyright © 2014 ISA. Published by Elsevier Ltd. All rights reserved.
Watkins, Arthur D.; Smartt, Herschel B.; Taylor, Paul L.
1994-01-01
An integrated optical sensor for arc welding having multifunction feedback control. The sensor, comprising generally a CCD camera and diode laser, is positioned behind the arc torch for measuring weld pool position and width, standoff distance, and post-weld centerline cooling rate. Computer process information from this sensor is passed to a controlling computer for use in feedback control loops to aid in the control of the welding process. Weld pool position and width are used in a feedback loop, by the weld controller, to track the weld pool relative to the weld joint. Sensor standoff distance is used in a feedback loop to control the contact tip to base metal distance during the welding process. Cooling rate information is used to determine the final metallurgical state of the weld bead and heat affected zone, thereby controlling post-weld mechanical properties.
Watkins, A.D.; Smartt, H.B.; Taylor, P.L.
1994-01-04
An integrated optical sensor for arc welding having multifunction feedback control is described. The sensor, comprising generally a CCD camera and diode laser, is positioned behind the arc torch for measuring weld pool position and width, standoff distance, and post-weld centerline cooling rate. Computer process information from this sensor is passed to a controlling computer for use in feedback control loops to aid in the control of the welding process. Weld pool position and width are used in a feedback loop, by the weld controller, to track the weld pool relative to the weld joint. Sensor standoff distance is used in a feedback loop to control the contact tip to base metal distance during the welding process. Cooling rate information is used to determine the final metallurgical state of the weld bead and heat affected zone, thereby controlling post-weld mechanical properties. 6 figures.
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.
NASA Astrophysics Data System (ADS)
Sejas, S.; Cai, M.
2012-12-01
Surfing warming due to CO2 doubling is a robust feature of coupled general circulation models (GCM), as noted in the IPCC AR4 assessment report. In this study, the contributions of different climate feedbacks to the magnitude, spatial distribution, and seasonality of the surface warming is examined using data from NCAR's CCSM4. In particular, a focus is placed on polar regions to see which feedbacks play a role in polar amplification and its seasonal pattern. A new climate feedback analysis method is used to isolate the surface warming or cooling contributions of both radiative and non-radiative (dynamical) climate feedbacks to the total (actual) surface temperature change given by the CCSM4. These contributions (or partial surface temperature changes) are additive and their total is approximately equal to the actual surface temperature change. What is found is that the effects of CO2 doubling alone warms the surface throughout with a maximum in polar regions, which indicates the CO2 forcing alone has a degree of polar warming amplification. Water vapor feedback is a positive feedback throughout but is most responsible for the surface warming found in the tropics. Polar warming amplification is found to be strongest away from summer (especially in NH), which is primarily caused by a positive feedback due to cloud feedbacks but with the surface temperature change due to the CO2 forcing alone and the ocean dynamics and storage feedback also playing an important role. Contrary to popular belief, surface albedo feedback (SAF) does not account for much of the polar amplification. SAF tries to amplify polar warming, but in summer. No major polar amplification is seen in summer for the actual surface temperature, so SAF is not the feedback responsible for polar amplification. This is actually a consequence of the ocean dynamics and storage feedback, which negates the effects of SAF to a large degree.
An Adapting Auditory-motor Feedback Loop Can Contribute to Generating Vocal Repetition
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
Study on real-time force feedback for a master-slave interventional surgical robotic system.
Guo, Shuxiang; Wang, Yuan; Xiao, Nan; Li, Youxiang; Jiang, Yuhua
2018-04-13
In robot-assisted catheterization, haptic feedback is important, but is currently lacking. In addition, conventional interventional surgical robotic systems typically employ a master-slave architecture with an open-loop force feedback, which results in inaccurate control. We develop herein a novel real-time master-slave (RTMS) interventional surgical robotic system with a closed-loop force feedback that allows a surgeon to sense the true force during remote operation, provide adequate haptic feedback, and improve control accuracy in robot-assisted catheterization. As part of this system, we also design a unique master control handle that measures the true force felt by a surgeon, providing the basis for the closed-loop control of the entire system. We use theoretical and empirical methods to demonstrate that the proposed RTMS system provides a surgeon (using the master control handle) with a more accurate and realistic force sensation, which subsequently improves the precision of the master-slave manipulation. The experimental results show a substantial increase in the control accuracy of the force feedback and an increase in operational efficiency during surgery.
General, database-driven fast-feedback system for the Stanford Linear Collider
DOE Office of Scientific and Technical Information (OSTI.GOV)
Rouse, F.; Allison, S.; Castillo, S.
A new feedback system has been developed for stabilizing the SLC beams at many locations. The feedback loops are designed to sample and correct at the 60 Hz repetition rate of the accelerator. Each loop can be distributed across several of the standard 80386 microprocessors which control the SLC hardware. A new communications system, KISNet, has been implemented to pass signals between the microprocessors at this rate. The software is written in a general fashion using the state space formalism of digital control theory. This allows a new loop to be implemented by just setting up the online database andmore » perhaps installing a communications link. 3 refs., 4 figs.« less
Strbac, Matija; Isakovic, Milica; Belic, Minja; Popovic, Igor; Simanic, Igor; Farina, Dario; Keller, Thierry; Dosen, Strahinja
2017-11-01
Human motor control relies on a combination of feedback and feedforward strategies. The aim of this study was to longitudinally investigate artificial somatosensory feedback and feedforward control in the context of grasping with myoelectric prosthesis. Nine amputee subjects performed routine grasping trials, with the aim to produce four levels of force during four blocks of 60 trials across five days. The electrotactile force feedback was provided in the second and third block using multipad electrode and spatial coding. The first baseline and last validation block (open-loop control) evaluated the effects of long- (across sessions) and short-term (within session) learning, respectively. The outcome measures were the absolute error between the generated and target force, and the number of force saturations. The results demonstrated that the electrotactile feedback improved the performance both within and across sessions. In the validation block, the performance did not significantly decrease and the quality of open-loop control (baseline) improved across days, converging to the performance characterizing closed-loop control. This paper provides important insights into the feedback and feedforward processes in prosthesis control, contributing to the better understanding of the role and design of feedback in prosthetic systems.
Symposium Proceedings on Quantitative Feedback Theory Held in Fairborn, Ohio on 2-4 August 1992.
1992-08-01
modification. This permits a drastic reduction in the cost of feedback, in terms of loop bandwidth and effect of sensor noise . This is the first...High- frequency Bound ( UHB ) but its main use is to ensure that at high frequencies the controlled system cannot go unstable and has sufficient noise ...a 5-cascaded multiple-loop feedback system giving significant reductions in sensor noise amplification (peak reduced by a factor of 4), is
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…
A social feedback loop for speech development and its reduction in autism.
Warlaumont, Anne S; Richards, Jeffrey A; Gilkerson, Jill; Oller, D Kimbrough
2014-07-01
We analyzed the microstructure of child-adult interaction during naturalistic, daylong, automatically labeled audio recordings (13,836 hr total) of children (8- to 48-month-olds) with and without autism. We found that an adult was more likely to respond when the child's vocalization was speech related rather than not speech related. In turn, a child's vocalization was more likely to be speech related if the child's previous speech-related vocalization had received an immediate adult response rather than no response. Taken together, these results are consistent with the idea that there is a social feedback loop between child and caregiver that promotes speech development. Although this feedback loop applies in both typical development and autism, children with autism produced proportionally fewer speech-related vocalizations, and the responses they received were less contingent on whether their vocalizations were speech related. We argue that such differences will diminish the strength of the social feedback loop and have cascading effects on speech development over time. Differences related to socioeconomic status are also reported. © The Author(s) 2014.
Analysis and application of a velocity command motor as a reaction mass actuator
NASA Technical Reports Server (NTRS)
Sulla, Jeffrey L.; Juang, Jer-Nan; Horta, Lucas G.
1990-01-01
A commercially available linear stepper motor is applied as a reaction mass (RM) actuator. With the actuator operating in the (RM) relative-velocity command mode, open-loop and closed-loop testing is performed to determine operational limits. With the actuator mounted on a simple beam structure, root strain, RM acceleration, or beam acceleration is used in the feedback loop to augment the structural damping. The RM relative position is also used as feedback to ensure that the RM remains centered.
Adams, Scott D; Kouzani, Abbas Z; Tye, Susannah J; Bennet, Kevin E; Berk, Michael
2018-02-13
Dynamic feedback based closed-loop medical devices offer a number of advantages for treatment of heterogeneous neurological conditions. Closed-loop devices integrate a level of neurobiological feedback, which allows for real-time adjustments to be made with the overarching aim of improving treatment efficacy and minimizing risks for adverse events. One target which has not been extensively explored as a potential feedback component in closed-loop therapies is mitochondrial function. Several neurodegenerative and psychiatric disorders including Parkinson's disease, Major Depressive disorder and Bipolar disorder have been linked to perturbations in the mitochondrial respiratory chain. This paper investigates the potential to monitor this mitochondrial function as a method of feedback for closed-loop neuromodulation treatments. A generic model of the closed-loop treatment is developed to describe the high-level functions of any system designed to control neural function based on mitochondrial response to stimulation, simplifying comparison and future meta-analysis. This model has four key functional components including: a sensor, signal manipulator, controller and effector. Each of these components are described and several potential technologies for each are investigated. While some of these candidate technologies are quite mature, there are still technological gaps remaining. The field of closed-loop medical devices is rapidly evolving, and whilst there is a lot of interest in this area, widespread adoption has not yet been achieved due to several remaining technological hurdles. However, the significant therapeutic benefits offered by this technology mean that this will be an active area for research for years to come.
Sensory feedback in prosthetics: a standardized test bench for closed-loop control.
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.
von Borries, A K L; Verkes, R J; Bulten, B H; Cools, R; de Bruijn, E R A
2013-12-01
Optimal behavior depends on the ability to assess the predictive value of events and to adjust behavior accordingly. Outcome processing can be studied by using its electrophysiological signatures--that is, the feedback-related negativity (FRN) and the P300. A prominent reinforcement-learning model predicts an FRN on negative prediction errors, as well as implying a role for the FRN in learning and the adaptation of behavior. However, these predictions have recently been challenged. Notably, studies so far have used tasks in which the outcomes have been contingent on the response. In these paradigms, the need to adapt behavioral responses is present only for negative, not for positive feedback. The goal of the present study was to investigate the effects of positive as well as negative violations of expectancy on FRN amplitudes, without the usual confound of behavioral adjustments. A reversal-learning task was employed in which outcome value and outcome expectancy were orthogonalized; that is, both positive and negative outcomes were equally unexpected. The results revealed a double dissociation, with effects of valence but not expectancy on the FRN and, conversely, effects of expectancy but not valence on the P300. While FRN amplitudes were largest for negative-outcome trials, irrespective of outcome expectancy, P300 amplitudes were largest for unexpected-outcome trials, irrespective of outcome valence. These FRN effects were interpreted to reflect an evaluation along a good-bad dimension, rather than reflecting a negative prediction error or a role in behavioral adaptation. By contrast, the P300 reflects the updating of information relevant for behavior in a changing context.
Screech tones from free and ducted supersonic jets
NASA Technical Reports Server (NTRS)
Tam, C. K. W.; Ahuja, K. K.; Jones, R. R., III
1994-01-01
It is well known that screech tones from supersonic jets are generated by a feedback loop. The loop consists of three main components. They are the downstream propagating instability wave, the shock cell structure in the jet plume, and the feedback acoustic waves immediately outside the jet. Evidence will be presented to show that the screech frequency is largely controlled by the characteristics of the feedback acoustic waves. The feedback loop is driven by the instability wave of the jet. Thus the tone intensity and its occurrence are dictated by the characteristics of the instability wave. In this paper the dependence of the instability wave spectrum on the azimuthal mode number (axisymmetric or helical/flapping mode, etc.), the jet-to-ambient gas temperature ratio, and the jet Mach number are studied. The results of this study provide an explanation for the observed screech tone mode switch phenomenon (changing from axisymmetric to helical mode as Mach number increases) and the often-cited experimental observation that tone intensity reduces with increase in jet temperature. For ducted supersonic jets screech tones can also be generated by feedback loops formed by the coupling of normal duct modes to instability waves of the jet. The screech frequencies are dictated by the frequencies of the duct modes. Super resonance, resonance involving very large pressure oscillations, can occur when the feedback loop is powered by the most amplified instability wave. It is proposed that the observed large amplitude pressure fluctuations and tone in the test cells of Arnold Engineering Development Center were generated by super resonance. Estimated super-resonance frequency for a Mach 1.3 axisymmetric jet tested in the facility agrees well with measurement.
Lee, Chien-kuo; Raz, Regina; Gimeno, Ramon; Gertner, Rachel; Wistinghausen, Birte; Takeshita, Kenichi; DePinho, Ronald A; Levy, David E
2002-07-01
STAT3 has been described as an essential component of G-CSF-driven cell proliferation and granulopoiesis. This notion was tested by conditional gene ablation in transgenic mice. Contrary to expectation, granulocytes developed from STAT3 null bone marrow progenitors, and STAT3 null neutrophils displayed mature effector functions. Rather than a deficit in granulopoiesis, mice lacking STAT3 in their hematopoietic progenitors developed neutrophilia, and bone marrow cells were hyperresponsive to G-CSF stimulation. These studies provide direct evidence for STAT3-independent granulopoiesis and suggest that STAT3 directs a negative feedback loop necessary for controlling neutrophil numbers, possibly through induced expression of the signaling inhibitor, SOCS3.
Complex food webs prevent competitive exclusion among producer species.
Brose, Ulrich
2008-11-07
Herbivorous top-down forces and bottom-up competition for nutrients determine the coexistence and relative biomass patterns of producer species. Combining models of predator-prey and producer-nutrient interactions with a structural model of complex food webs, I investigated these two aspects in a dynamic food-web model. While competitive exclusion leads to persistence of only one producer species in 99.7% of the simulated simple producer communities without consumers, embedding the same producer communities in complex food webs generally yields producer coexistence. In simple producer communities, the producers with the most efficient nutrient-intake rates increase in biomass until they competitively exclude inferior producers. In food webs, herbivory predominantly reduces the biomass density of those producers that dominated in producer communities, which yields a more even biomass distribution. In contrast to prior analyses of simple modules, this facilitation of producer coexistence by herbivory does not require a trade-off between the nutrient-intake efficiency and the resistance to herbivory. The local network structure of food webs (top-down effects of the number of herbivores and the herbivores' maximum consumption rates) and the nutrient supply (bottom-up effect) interactively determine the relative biomass densities of the producer species. A strong negative feedback loop emerges in food webs: factors that increase producer biomasses also increase herbivory, which reduces producer biomasses. This negative feedback loop regulates the coexistence and biomass patterns of the producers by balancing biomass increases of producers and biomass fluxes to herbivores, which prevents competitive exclusion.
Bellebaum, Christian; Kuchinke, Lars; Roser, Patrik
2017-02-01
Modafinil is becoming increasingly popular as a cognitive enhancer. Research on the effects of modafinil on cognitive function have yielded mixed results, with negative findings for simple memory and attention tasks and enhancing effects for more complex tasks. In the present study we examined whether modafinil, due to its known effect on the dopamine level in the striatum, alters feedback-related choice behaviour. We applied a task that separately tests the choice of previously rewarded behaviours (approach) and avoidance of previously punished behaviours. 18 participants received a single dose of 200 mg modafinil. Their performance was compared to a group of 22 participants who received placebo in a double-blind design. Modafinil but not placebo induced a significant bias towards approach behaviour as compared to the frequency of avoidance behaviour. General attention, overall feedback-based acquisition of choice behaviour and reaction times in high vs low conflict choices were not significantly affected by modafinil. This finding suggests that modafinil has a specific effect on dopamine-mediated choice behaviour based on the history of feedback, while a contribution of noradrenaline is also conceivable. The described change in decision making cannot be considered as cognitive enhancement, but might rather have detrimental effects on decisions in everyday life.
Pulsatile desynchronizing delayed feedback for closed-loop deep brain stimulation
Lysyansky, Borys; Rosenblum, Michael; Pikovsky, Arkady; Tass, Peter A.
2017-01-01
High-frequency (HF) deep brain stimulation (DBS) is the gold standard for the treatment of medically refractory movement disorders like Parkinson’s disease, essential tremor, and dystonia, with a significant potential for application to other neurological diseases. The standard setup of HF DBS utilizes an open-loop stimulation protocol, where a permanent HF electrical pulse train is administered to the brain target areas irrespectively of the ongoing neuronal dynamics. Recent experimental and clinical studies demonstrate that a closed-loop, adaptive DBS might be superior to the open-loop setup. We here combine the notion of the adaptive high-frequency stimulation approach, that aims at delivering stimulation adapted to the extent of appropriately detected biomarkers, with specifically desynchronizing stimulation protocols. To this end, we extend the delayed feedback stimulation methods, which are intrinsically closed-loop techniques and specifically designed to desynchronize abnormal neuronal synchronization, to pulsatile electrical brain stimulation. We show that permanent pulsatile high-frequency stimulation subjected to an amplitude modulation by linear or nonlinear delayed feedback methods can effectively and robustly desynchronize a STN-GPe network of model neurons and suggest this approach for desynchronizing closed-loop DBS. PMID:28273176
Optical feedback technique extends frequency response of photoconductors
NASA Technical Reports Server (NTRS)
Katzberg, S. J.
1975-01-01
Feedback circuit consists of high-gain light-to-voltage converter with frequency-limited nonlinear photoconductor inside feedback loop. Feedback element is visible light-emitting diode with light-out versus current-in characteristic that is linear over several decades.
Integration of Haptics in Agricultural Robotics
NASA Astrophysics Data System (ADS)
Kannan Megalingam, Rajesh; Sreekanth, M. M.; Sivanantham, Vinu; Sai Kumar, K.; Ghanta, Sriharsha; Surya Teja, P.; Reddy, Rajesh G.
2017-08-01
Robots can differentiate with open loop system and closed loop system robots. We face many problems when we do not have a feedback from robots. In this research paper, we are discussing all possibilities to achieve complete closed loop system for Multiple-DOF Robotic Arm, which is used in a coconut tree climbing and cutting robot by introducing a Haptic device. We are working on various sensors like tactile, vibration, force and proximity sensors for getting feedback. For monitoring the robotic arm achieved by graphical user interference software which simulates the working of the robotic arm, send the feedback of all the real time analog values which are produced by various sensors and provide real-time graphs for estimate the efficiency of the Robot.
Performance of a modified feedback loop adaptive array with TVRO satellite signals
NASA Technical Reports Server (NTRS)
Steadman, Karl N.; Gupta, Inder J.; Walton, Eric K.
1990-01-01
Performance of an experimental adaptive antenna array system is evaluated using television receive-only (TVRO) satellite signals. The experimental system is a sidelobe canceller with two auxiliary channels. Modified feedback loops are used to enhance the suppression of weak interfering signals. The modified feedback loops used two spatialy separated antennas, each with an individual amplifier for each auxiliary channel. Thus, the experimental system uses five antenna elements. Instead of using five separate antennas, a reflector antenna with multiple feeds is used to receive signals from various TVRO satellites. The details of the earth station are given. It is shown that the experimental system can null up to two signals originating from interfering TVRO satellites while receiving the signals from a desired TVRO satellite.
Cell Pattern in the Arabidopsis Root Epidermis Determined by Lateral Inhibition with Feedback
Lee, Myeong Min; Schiefelbein, John
2002-01-01
In the root epidermis of Arabidopsis, hair and nonhair cell types are specified in a distinct position-dependent pattern. Here, we show that transcriptional feedback loops between the WEREWOLF (WER), CAPRICE (CPC), and GLABRA2 (GL2) genes help to establish this pattern. Positional cues bias the expression of the WER MYB gene, leading to the induction of CPC and GL2 in cells located in a particular position (N) and adoption of the nonhair fate. The truncated MYB encoded by CPC mediates a lateral inhibition mechanism to negatively regulate WER, GL2, and its own gene in the alternative position (H) to induce the hair fate. These results provide a molecular genetic framework for understanding the determination of a cell-type pattern in plants. PMID:11910008
Cell pattern in the Arabidopsis root epidermis determined by lateral inhibition with feedback.
Lee, Myeong Min; Schiefelbein, John
2002-03-01
In the root epidermis of Arabidopsis, hair and nonhair cell types are specified in a distinct position-dependent pattern. Here, we show that transcriptional feedback loops between the WEREWOLF (WER), CAPRICE (CPC), and GLABRA2 (GL2) genes help to establish this pattern. Positional cues bias the expression of the WER MYB gene, leading to the induction of CPC and GL2 in cells located in a particular position (N) and adoption of the nonhair fate. The truncated MYB encoded by CPC mediates a lateral inhibition mechanism to negatively regulate WER, GL2, and its own gene in the alternative position (H) to induce the hair fate. These results provide a molecular genetic framework for understanding the determination of a cell-type pattern in plants.
Some Properties and Stability Results for Sector-Bounded LTI Systems
NASA Technical Reports Server (NTRS)
Gupta, Sandeep; Joshi, Suresh M.
1994-01-01
This paper presents necessary and sufficient conditions for a linear, time-invariant (LTI) system to be inside sector (n, b) in terms of linear matrix inequalities in its state-space realization matrices, which represents a generalization of similar conditions for bounded H(sub infinity)-norm systems. Further, a weaker definition of LTI systems strictly inside closed sector (a, b) is proposed, and state-space characterization of such systems is presented. Sector conditions for stability of the negative feedback interconnection of two LTI systems and for stability of LTI systems with feedback nonlinearities are investigated using the Lyapunov function approach. It is shown that the proposed weaker conditions for an LTI system to be strictly inside a sector are sufficient to establish closed-loop stability of these systems.
Multiple Scenarios of Transition to Chaos in the Alternative Splicing Model
NASA Astrophysics Data System (ADS)
Kogai, Vladislav V.; Likhoshvai, Vitaly A.; Fadeev, Stanislav I.; Khlebodarova, Tamara M.
We have investigated the scenarios of transition to chaos in the mathematical model of a genetic system constituted by a single transcription factor-encoding gene, the expression of which is self-regulated by a feedback loop that involves protein isoforms. Alternative splicing results in the synthesis of protein isoforms providing opposite regulatory outcomes — activation or repression. The model is represented by a differential equation with two delayed arguments. The possibility of transition to chaos dynamics via all classical scenarios: a cascade of period-doubling bifurcations, quasiperiodicity and type-I, type-II and type-III intermittencies, has been numerically demonstrated. The parametric features of each type of transition to chaos have been described.
Interactive Information Seeking and Retrieving: A Third Feedback Framework.
ERIC Educational Resources Information Center
Spink, Amanda
1996-01-01
Presents an overview of feedback within the cybernetics and social frameworks. These feedback concepts are then compared with the interactive feedback concept evolving within the framework of information seeking and retrieving, based on their conceptualization of the feedback loop and notion of information. (Author/AEF)
Electronically Tunable Differential Integrator: Linear Voltage Controlled Quadrature Oscillator.
Nandi, Rabindranath; Pattanayak, Sandhya; Venkateswaran, Palaniandavar; Das, Sagarika
2015-01-01
A new electronically tunable differential integrator (ETDI) and its extension to voltage controlled quadrature oscillator (VCQO) design with linear tuning law are proposed; the active building block is a composite current feedback amplifier with recent multiplication mode current conveyor (MMCC) element. Recently utilization of two different kinds of active devices to form a composite building block is being considered since it yields a superior functional element suitable for improved quality circuit design. The integrator time constant (τ) and the oscillation frequency (ω o ) are tunable by the control voltage (V) of the MMCC block. Analysis indicates negligible phase error (θ e ) for the integrator and low active ω o -sensitivity relative to the device parasitic capacitances. Satisfactory experimental verifications on electronic tunability of some wave shaping applications by the integrator and a double-integrator feedback loop (DIFL) based sinusoid oscillator with linear f o variation range of 60 KHz~1.8 MHz at low THD of 2.1% are verified by both simulation and hardware tests.
Surgeon Training in Telerobotic Surgery via a Hardware-in-the-Loop Simulator
Alemzadeh, Homa; Chen, Daniel; Kalbarczyk, Zbigniew; Iyer, Ravishankar K.; Kesavadas, Thenkurussi
2017-01-01
This work presents a software and hardware framework for a telerobotic surgery safety and motor skill training simulator. The aims are at providing trainees a comprehensive simulator for acquiring essential skills to perform telerobotic surgery. Existing commercial robotic surgery simulators lack features for safety training and optimal motion planning, which are critical factors in ensuring patient safety and efficiency in operation. In this work, we propose a hardware-in-the-loop simulator directly introducing these two features. The proposed simulator is built upon the Raven-II™ open source surgical robot, integrated with a physics engine and a safety hazard injection engine. Also, a Fast Marching Tree-based motion planning algorithm is used to help trainee learn the optimal instrument motion patterns. The main contributions of this work are (1) reproducing safety hazards events, related to da Vinci™ system, reported to the FDA MAUDE database, with a novel haptic feedback strategy to provide feedback to the operator when the underlying dynamics differ from the real robot's states so that the operator will be aware and can mitigate the negative impact of the safety-critical events, and (2) using motion planner to generate semioptimal path in an interactive robotic surgery training environment. PMID:29065635
Use of Double-Loop Learning to Combat Advanced Persistent Threat: Multiple Case Studies
ERIC Educational Resources Information Center
Lamb, Christopher J.
2013-01-01
The Advanced Persistent Threat (APT) presents an ever present and more growing threat to organizations across the globe. Traditional Information Technology (IT) incident response falls short in effectively addressing this threat. This researcher investigated the use of single-loop and double-loop learning in two organizations with internal…
NASA Astrophysics Data System (ADS)
Ugon, B.; Nandong, J.; Zang, Z.
2017-06-01
The presence of unstable dead-time systems in process plants often leads to a daunting challenge in the design of standard PID controllers, which are not only intended to provide close-loop stability but also to give good performance-robustness overall. In this paper, we conduct stability analysis on a double-loop control scheme based on the Routh-Hurwitz stability criteria. We propose to use this unstable double-loop control scheme which employs two P/PID controllers to control first-order or second-order unstable dead-time processes typically found in process industries. Based on the Routh-Hurwitz stability necessary and sufficient criteria, we establish several stability regions which enclose within them the P/PID parameter values that guarantee close-loop stability of the double-loop control scheme. A systematic tuning rule is developed for the purpose of obtaining the optimal P/PID parameter values within the established regions. The effectiveness of the proposed tuning rule is demonstrated using several numerical examples and the result are compared with some well-established tuning methods reported in the literature.
LIN28 expression in malignant germ cell tumors down-regulates let-7 and increases oncogene levels
Murray, Matthew J.; Saini, Harpreet K.; Siegler, Charlotte A.; Hanning, Jennifer E.; Barker, Emily M.; van Dongen, Stijn; Ward, Dawn M.; Raby, Katie L.; Groves, Ian J.; Scarpini, Cinzia G.; Pett, Mark R.; Thornton, Claire M.; Enright, Anton J.; Nicholson, James C.; Coleman, Nicholas
2013-01-01
Despite their clinico-pathologic heterogeneity, malignant germ-cell-tumors (GCTs) share molecular abnormalities that are likely to be functionally important. In this study, we investigated the potential significance of down-regulation of the let-7 family of tumor-suppressor microRNAs in malignant-GCTs. Microarray results from pediatric and adult samples (n=45) showed that LIN28, the negative-regulator of let-7 biogenesis, was abundant in malignant-GCTs, regardless of patient age, tumor site or histologic subtype. Indeed, a strong negative-correlation existed between LIN28 and let-7 levels in specimens with matched datasets. Low let-7 levels were biologically significant, since the sequence complementary to the 2-7nt common let-7 seed ‘GAGGUA’ was enriched in the 3′untranslated regions of mRNAs up-regulated in pediatric and adult malignant-GCTs, compared with normal gonads (a mixture of germ cells and somatic cells). We identified 27 mRNA targets of let-7 that were up-regulated in malignant-GCT cells, confirming significant negative-correlations with let-7 levels. Among 16 mRNAs examined in a largely independent set of specimens by qRT-PCR, we defined negative-associations with let-7e levels for six oncogenes, including MYCN, AURKB, CCNF, RRM2, MKI67 and C12orf5 (when including normal control tissues). Importantly, LIN28 depletion in malignant-GCT cells restored let-7 levels and repressed all of these oncogenic let-7 mRNA targets, with LIN28 levels correlating with cell proliferation and MYCN levels. Conversely, ectopic expression of let-7e was sufficient to reduce proliferation and down-regulate MYCN, AURKB and LIN28, the latter via a double-negative feedback loop. We concluded that the LIN28/let-7 pathway has a critical pathobiological role in malignant-GCTs and therefore offers a promising target for therapeutic intervention. PMID:23774216
DOE Office of Scientific and Technical Information (OSTI.GOV)
Bakry, A.; Abdulrhmann, S.; Ahmed, M., E-mail: mostafa.farghal@mu.edu.eg
2016-06-15
We theoretically model the dynamics of semiconductor lasers subject to the double-reflector feedback. The proposed model is a new modification of the time-delay rate equations of semiconductor lasers under the optical feedback to account for this type of the double-reflector feedback. We examine the influence of adding the second reflector to dynamical states induced by the single-reflector feedback: periodic oscillations, period doubling, and chaos. Regimes of both short and long external cavities are considered. The present analyses are done using the bifurcation diagram, temporal trajectory, phase portrait, and fast Fourier transform of the laser intensity. We show that adding themore » second reflector attracts the periodic and perioddoubling oscillations, and chaos induced by the first reflector to a route-to-continuous-wave operation. During this operation, the periodic-oscillation frequency increases with strengthening the optical feedback. We show that the chaos induced by the double-reflector feedback is more irregular than that induced by the single-reflector feedback. The power spectrum of this chaos state does not reflect information on the geometry of the optical system, which then has potential for use in chaotic (secure) optical data encryption.« less
Log amplifier with pole-zero compensation
Brookshier, W.
1985-02-08
A logarithmic amplifier circuit provides pole-zero compensation for improved stability and response time over 6-8 decades of input signal frequency. The amplifer circuit includes a first operational amplifier with a first feedback loop which includes a second, inverting operational amplifier in a second feedstock loop. The compensated output signal is provided by the second operational amplifier with the log elements, i.e., resistors, and the compensating capacitors in each of the feedback loops having equal values so that each break point is offset by a compensating break point or zero.
A hidden oncogenic positive feedback loop caused by crosstalk between Wnt and ERK pathways.
Kim, D; Rath, O; Kolch, W; Cho, K-H
2007-07-05
The Wnt and the extracellular signal regulated-kinase (ERK) pathways are both involved in the pathogenesis of various kinds of cancers. Recently, the existence of crosstalk between Wnt and ERK pathways was reported. Gathering all reported results, we have discovered a positive feedback loop embedded in the crosstalk between the Wnt and ERK pathways. We have developed a plausible model that represents the role of this hidden positive feedback loop in the Wnt/ERK pathway crosstalk based on the integration of experimental reports and employing established basic mathematical models of each pathway. Our analysis shows that the positive feedback loop can generate bistability in both the Wnt and ERK signaling pathways, and this prediction was further validated by experiments. In particular, using the commonly accepted assumption that mutations in signaling proteins contribute to cancerogenesis, we have found two conditions through which mutations could evoke an irreversible response leading to a sustained activation of both pathways. One condition is enhanced production of beta-catenin, the other is a reduction of the velocity of MAP kinase phosphatase(s). This enables that high activities of Wnt and ERK pathways are maintained even without a persistent extracellular signal. Thus, our study adds a novel aspect to the molecular mechanisms of carcinogenesis by showing that mutational changes in individual proteins can cause fundamental functional changes well beyond the pathway they function in by a positive feedback loop embedded in crosstalk. Thus, crosstalk between signaling pathways provides a vehicle through which mutations of individual components can affect properties of the system at a larger scale.
Topology and Dynamics of the Zebrafish Segmentation Clock Core Circuit
Schröter, Christian; Isakova, Alina; Hens, Korneel; Soroldoni, Daniele; Gajewski, Martin; Jülicher, Frank; Maerkl, Sebastian J.; Deplancke, Bart; Oates, Andrew C.
2012-01-01
During vertebrate embryogenesis, the rhythmic and sequential segmentation of the body axis is regulated by an oscillating genetic network termed the segmentation clock. We describe a new dynamic model for the core pace-making circuit of the zebrafish segmentation clock based on a systematic biochemical investigation of the network's topology and precise measurements of somitogenesis dynamics in novel genetic mutants. We show that the core pace-making circuit consists of two distinct negative feedback loops, one with Her1 homodimers and the other with Her7:Hes6 heterodimers, operating in parallel. To explain the observed single and double mutant phenotypes of her1, her7, and hes6 mutant embryos in our dynamic model, we postulate that the availability and effective stability of the dimers with DNA binding activity is controlled in a “dimer cloud” that contains all possible dimeric combinations between the three factors. This feature of our model predicts that Hes6 protein levels should oscillate despite constant hes6 mRNA production, which we confirm experimentally using novel Hes6 antibodies. The control of the circuit's dynamics by a population of dimers with and without DNA binding activity is a new principle for the segmentation clock and may be relevant to other biological clocks and transcriptional regulatory networks. PMID:22911291
2012-06-01
the open-loop path is established, the feedback system can be treated as a set of SISO feedback loops and a single SISO control law can be applied...Zernike polynomials are commonly referred to by the names, such as focus, coma, astigmatism , and etc. Zernike polynomials can be transformed into
Zamora-Chimal, Criseida; Santillán, Moisés; Rodríguez-González, Jesús
2012-10-07
In this paper we introduce a mathematical model for the tryptophan operon regulatory pathway in Bacillus subtilis. This model considers the transcription-attenuation, and the enzyme-inhibition regulatory mechanisms. Special attention is paid to the estimation of all the model parameters from reported experimental data. With the aid of this model we investigate, from a mathematical-modeling point of view, whether the existing multiplicity of regulatory feedback loops is advantageous in some sense, regarding the dynamic response and the biochemical noise in the system. The tryptophan operon dynamic behavior is studied by means of deterministic numeric simulations, while the biochemical noise is analyzed with the aid of stochastic simulations. The model feasibility is tested comparing its stochastic and deterministic results with experimental reports. Our results for the wildtype and for a couple of mutant bacterial strains suggest that the enzyme-inhibition feedback loop, dynamically accelerates the operon response, and plays a major role in the reduction of biochemical noise. Also, the transcription-attenuation feedback loop makes the trp operon sensitive to changes in the endogenous tryptophan level, and increases the amplitude of the biochemical noise. Copyright © 2012 Elsevier Ltd. All rights reserved.
Pant, Vinod; Xiong, Shunbin; Jackson, James G.; Post, Sean M.; Abbas, Hussein A.; Quintás-Cardama, Alfonso; Hamir, Amirali N.; Lozano, Guillermina
2013-01-01
The p53–Mdm2 feedback loop is perceived to be critical for regulating stress-induced p53 activity and levels. However, this has never been tested in vivo. Using a genetically engineered mouse with mutated p53 response elements in the Mdm2 P2 promoter, we show that feedback loop-deficient Mdm2P2/P2 mice are viable and aphenotypic and age normally. p53 degradation kinetics after DNA damage in radiosensitive tissues remains similar to wild-type controls. Nonetheless, DNA damage response is elevated in Mdm2P2/P2 mice. Enhanced p53-dependent apoptosis sensitizes hematopoietic stem cells (HSCs), causing drastic myeloablation and lethality. These results suggest that while basal Mdm2 levels are sufficient to regulate p53 in most tissues under homeostatic conditions, the p53–Mdm2 feedback loop is critical for regulating p53 activity and sustaining HSC function after DNA damage. Therefore, transient disruption of p53–Mdm2 interaction could be explored as a potential adjuvant/therapeutic strategy for targeting stem cells in hematological malignancies. PMID:23973961
Asymmetry in Signal Oscillations Contributes to Efficiency of Periodic Systems.
Bae, Seul-A; Acevedo, Alison; Androulakis, Ioannis P
2016-01-01
Oscillations are an important feature of cellular signaling that result from complex combinations of positive- and negative-feedback loops. The encoding and decoding mechanisms of oscillations based on amplitude and frequency have been extensively discussed in the literature in the context of intercellular and intracellular signaling. However, the fundamental questions of whether and how oscillatory signals offer any competitive advantages-and, if so, what-have not been fully answered. We investigated established oscillatory mechanisms and designed a study to analyze the oscillatory characteristics of signaling molecules and system output in an effort to answer these questions. Two classic oscillators, Goodwin and PER, were selected as the model systems, and corresponding no-feedback models were created for each oscillator to discover the advantage of oscillating signals. Through simulating the original oscillators and the matching no-feedback models, we show that oscillating systems have the capability to achieve better resource-to-output efficiency, and we identify oscillatory characteristics that lead to improved efficiency.
NASA Astrophysics Data System (ADS)
Pandey, Saurabh; Majhi, Somanath; Ghorai, Prasenjit
2017-07-01
In this paper, the conventional relay feedback test has been modified for modelling and identification of a class of real-time dynamical systems in terms of linear transfer function models with time-delay. An ideal relay and unknown systems are connected through a negative feedback loop to bring the sustained oscillatory output around the non-zero setpoint. Thereafter, the obtained limit cycle information is substituted in the derived mathematical equations for accurate identification of unknown plants in terms of overdamped, underdamped, critically damped second-order plus dead time and stable first-order plus dead time transfer function models. Typical examples from the literature are included for the validation of the proposed identification scheme through computer simulations. Subsequently, the comparisons between estimated model and true system are drawn through integral absolute error criterion and frequency response plots. Finally, the obtained output responses through simulations are verified experimentally on real-time liquid level control system using Yokogawa Distributed Control System CENTUM CS3000 set up.
Imran, Tayyab; Lee, Yong S; Nam, Chang H; Hong, Kyung-Han; Yu, Tae J; Sung, Jae H
2007-01-08
We have stabilized and electronically controlled the carrier-envelope phase (CEP) of high-power femtosecond laser pulses, generated in a grating-based chirped-pulse amplification kHz Ti:sapphire laser, using the direct locking technique [Opt. Express 13, 2969 (2005)] combined with a slow feedback loop. An f-2f spectral interferometer has shown the CEP stabilities of 1.2 rad with the direct locking loop applied to the oscillator and of 180 mrad with an additional slow feedback loop, respectively. The electronic CEP modulations that can be easily realized in the direct locking loop are also demonstrated with the amplified pulses.
Hybrid force-velocity sliding mode control of a prosthetic hand.
Engeberg, Erik D; Meek, Sanford G; Minor, Mark A
2008-05-01
Four different methods of hand prosthesis control are developed and examined experimentally. Open-loop control is shown to offer the least sensitivity when manipulating objects. Force feedback substantially improves upon open-loop control. However, it is shown that the inclusion of velocity and/or position feedback in a hybrid force-velocity control scheme can further improve the functionality of hand prostheses. Experimental results indicate that the sliding mode controller with force, position, and velocity feedback is less prone to unwanted force overshoot when initially grasping objects than the other controllers.
Performance of a modified feedback loop adaptive array with TVRO satellite signals
NASA Technical Reports Server (NTRS)
Steadman, K.; Gupta, I. J.; Walton, E. K.
1990-01-01
The performance of an experimental adaptive antenna array system is evaluated using television-receive-only (TVRO) satellite signals. The experimental system is a sidelobe canceler with two auxiliary channels. Modified feedback loops are used to enhance the suppression of weak interfering signals. The modified feedback loops use two spatially separate antennas, each with an individual amplifier for each auxiliary channel. Thus, the experimental system uses five antenna elements. Instead of using five separate antennas, a reflector antenna with multiple feeds is used to receive signals from various TVRO satellites. The details of the earth station are given. It is shown that the experimental system can null up to two signals originating from interfering TVRO satellites while receiving the signals from a desired TVRO satellite.
Causal Loop Analysis of coastal geomorphological systems
NASA Astrophysics Data System (ADS)
Payo, Andres; Hall, Jim W.; French, Jon; Sutherland, James; van Maanen, Barend; Nicholls, Robert J.; Reeve, Dominic E.
2016-03-01
As geomorphologists embrace ever more sophisticated theoretical frameworks that shift from simple notions of evolution towards single steady equilibria to recognise the possibility of multiple response pathways and outcomes, morphodynamic modellers are facing the problem of how to keep track of an ever-greater number of system feedbacks. Within coastal geomorphology, capturing these feedbacks is critically important, especially as the focus of activity shifts from reductionist models founded on sediment transport fundamentals to more synthesist ones intended to resolve emergent behaviours at decadal to centennial scales. This paper addresses the challenge of mapping the feedback structure of processes controlling geomorphic system behaviour with reference to illustrative applications of Causal Loop Analysis at two study cases: (1) the erosion-accretion behaviour of graded (mixed) sediment beds, and (2) the local alongshore sediment fluxes of sand-rich shorelines. These case study examples are chosen on account of their central role in the quantitative modelling of geomorphological futures and as they illustrate different types of causation. Causal loop diagrams, a form of directed graph, are used to distil the feedback structure to reveal, in advance of more quantitative modelling, multi-response pathways and multiple outcomes. In the case of graded sediment bed, up to three different outcomes (no response, and two disequilibrium states) can be derived from a simple qualitative stability analysis. For the sand-rich local shoreline behaviour case, two fundamentally different responses of the shoreline (diffusive and anti-diffusive), triggered by small changes of the shoreline cross-shore position, can be inferred purely through analysis of the causal pathways. Explicit depiction of feedback-structure diagrams is beneficial when developing numerical models to explore coastal morphological futures. By explicitly mapping the feedbacks included and neglected within a model, the modeller can readily assess if critical feedback loops are included.
Cushing's syndrome: from physiological principles to diagnosis and clinical care
Raff, Hershel; Carroll, Ty
2015-01-01
The physiological control of cortisol synthesis in the adrenal cortex involves stimulation of adrenocorticotrophic hormone (ACTH) by hypothalamic corticotrophin-releasing hormone (CRH) and then stimulation of the adrenal by ACTH. The control loop of the hypothalamic–pituitary–adrenal (HPA) axis is closed by negative feedback of cortisol on the hypothalamus and pituitary. Understanding this system is required to master the diagnosis, differential diagnosis and treatment of endogenous hypercortisolism – Cushing's syndrome. Endogenous Cushing's syndrome is caused either by excess ACTH secretion or by autonomous cortisol release from the adrenal cortex. Diagnosis of cortisol excess exploits three physiological principles: failure to achieve the normal nadir in the cortisol diurnal rhythm, loss of sensitivity of ACTH-secreting tumours to cortisol negative feedback, and increased excretion of free cortisol in the urine. Differentiating a pituitary source of excess ACTH (Cushing's disease) from an ectopic source is accomplished by imaging the pituitary and sampling for ACTH in the venous drainage of the pituitary. With surgical removal of ACTH or cortisol-secreting tumours, secondary adrenal insufficiency ensues because of the prior suppression of the HPA axis by glucocorticoid negative feedback. Medical therapy is targeted to the anatomical location of the dysregulated component of the HPA axis. Future research will focus on new diagnostics and treatments of Cushing's syndrome. These are elegant examples of translational research: understanding basic physiology informs the development of new approaches to diagnosis and treatment. Appreciating pathophysiology generates new areas for inquiry of basic physiological and biochemical mechanisms. PMID:25480800
Blind lineup administration as a prophylactic against the postidentification feedback effect.
Dysart, Jennifer E; Lawson, Victoria Z; Rainey, Anna
2012-08-01
Confidence and other testimony-relevant judgments may be distorted when witnesses are given confirming postidentification feedback, and double-blind procedures-wherein the lineup administrator does not know the identity of the suspect-are a commonly proposed, but untested, remedy for this effect. In the current study, mock witnesses viewed a staged crime video followed by a target-present or target-absent lineup where the administrator was or was not presumed to know the identity of the suspect. After making an identification decision, witnesses were or were not given realistic, but nonidentification-specific, feedback, and then confidence and other judgments were assessed. A significant interaction was found between blind condition and feedback such that feedback inflated confidence and other judgments in presumed nonblind conditions only; feedback had no effect on participants in presumed blind conditions. As predicted by the selective cue integration framework-a theoretical model suggested to explain the interaction between presumed blind administration and feedback-this interaction was significant only for inaccurate participants. These results suggest that blind administration may serve as a prophylactic against the negative effects of postidentification feedback. In addition, the effectiveness of our subtle feedback in influencing judgments suggests that lineup administrators should take care not to provide any feedback to eyewitnesses. (PsycINFO Database Record (c) 2012 APA, all rights reserved).
Performance constraints and compensation for teleoperation with delay
NASA Technical Reports Server (NTRS)
Mclaughlin, J. S.; Staunton, B. D.
1989-01-01
A classical control perspective is used to characterize performance constraints and evaluate compensation techniques for teleoperation with delay. Use of control concepts such as open and closed loop performance, stability, and bandwidth yield insight to the delay problem. Teleoperator performance constraints are viewed as an open loop time delay lag and as a delay-induced closed loop bandwidth constraint. These constraints are illustrated with a simple analytical tracking example which is corroborated by a real time, 'man-in-the-loop' tracking experiment. The experiment also provides insight to those controller characteristics which are unique to a human operator. Predictive displays and feedforward commands are shown to provide open loop compensation for delay lag. Low pass filtering of telemetry or feedback signals is interpreted as closed loop compensation used to maintain a sufficiently low bandwidth for stability. A new closed loop compensation approach is proposed that uses a reactive (or force feedback) hand controller to restrict system bandwidth by impeding operator inputs.
Investigation of Inner Loop Flight Control Strategies for High-Speed Research
NASA Technical Reports Server (NTRS)
Newman, Brett; Kassem, Ayman
1999-01-01
This report describes the activities and findings conducted under contract NAS1-19858 with NASA Langley Research Center. Subject matter is the investigation of suitable flight control design methodologies and solutions for large, flexible high-speed vehicles. Specifically, methodologies are to address the inner control loops used for stabilization and augmentation of a highly coupled airframe system possibly involving rigid-body motion, structural vibrations, unsteady aerodynamics, and actuator dynamics. Techniques considered in this body of work are primarily conventional-based, and the vehicle of interest is the High-Speed Civil Transport (HSCT). Major findings include 1) current aeroelastic vehicle modeling procedures require further emphasis and refinement, 2) traditional and nontraditional inner loop flight control strategies employing a single feedback loop do not appear sufficient for highly flexible HSCT class vehicles, 3) inner loop flight control systems will, in all likelihood, require multiple interacting feedback loops, and 4) Ref. H HSCT configuration presents major challenges to designing acceptable closed-loop flight dynamics.
NASA Astrophysics Data System (ADS)
Morecroft, John
System dynamics is an approach for thinking about and simulating situations and organisations of all kinds and sizes by visualising how the elements fit together, interact and change over time. This chapter, written by John Morecroft, describes modern system dynamics which retains the fundamentals developed in the 1950s by Jay W. Forrester of the MIT Sloan School of Management. It looks at feedback loops and time delays that affect system behaviour in a non-linear way, and illustrates how dynamic behaviour depends upon feedback loop structures. It also recognises improvements as part of the ongoing process of managing a situation in order to achieve goals. Significantly it recognises the importance of context, and practitioner skills. Feedback systems thinking views problems and solutions as being intertwined. The main concepts and tools: feedback structure and behaviour, causal loop diagrams, dynamics, are practically illustrated in a wide variety of contexts from a hot water shower through to a symphony orchestra and the practical application of the approach is described through several real examples of its use for strategic planning and evaluation.
Marzullo, Timothy Charles; Lehmkuhle, Mark J; Gage, Gregory J; Kipke, Daryl R
2010-04-01
Closed-loop neural interface technology that combines neural ensemble decoding with simultaneous electrical microstimulation feedback is hypothesized to improve deep brain stimulation techniques, neuromotor prosthetic applications, and epilepsy treatment. Here we describe our iterative results in a rat model of a sensory and motor neurophysiological feedback control system. Three rats were chronically implanted with microelectrode arrays in both the motor and visual cortices. The rats were subsequently trained over a period of weeks to modulate their motor cortex ensemble unit activity upon delivery of intra-cortical microstimulation (ICMS) of the visual cortex in order to receive a food reward. Rats were given continuous feedback via visual cortex ICMS during the response periods that was representative of the motor cortex ensemble dynamics. Analysis revealed that the feedback provided the animals with indicators of the behavioral trials. At the hardware level, this preparation provides a tractable test model for improving the technology of closed-loop neural devices.
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.
NASA Technical Reports Server (NTRS)
Simon, M.; Tkacenko, A.
2006-01-01
In a previous publication [1], an iterative closed-loop carrier synchronization scheme for binary phase-shift keyed (BPSK) modulation was proposed that was based on feeding back data decisions to the input of the loop, the purpose being to remove the modulation prior to carrier synchronization as opposed to the more conventional decision-feedback schemes that incorporate such feedback inside the loop. The idea there was that, with sufficient independence between the received data and the decisions on it that are fed back (as would occur in an error-correction coding environment with sufficient decoding delay), a pure tone in the presence of noise would ultimately be produced (after sufficient iteration and low enough error probability) and thus could be tracked without any squaring loss. This article demonstrates that, with some modification, the same idea of iterative information reduction through decision feedback can be applied to quadrature phase-shift keyed (QPSK) modulation, something that was mentioned in the previous publication but never pursued.
A double torsion pendulum with two cascade soft degrees of freedom
NASA Astrophysics Data System (ADS)
Marconi, L.; Stanga, R.; Bassan, M.
2012-06-01
We report on a double torsion pendulum, where motion along two degrees of freedom (DoFs) is almost free. The Test Mass (TM) is enclosed in a replica of the LISA-Pathfinder electrostatic readout and actuation system. This apparatus is designed to perform extensive ground testing of undesired effects such as leakage of the readout noise from one DoF to another, or actuation cross talks with closed feedback loop. Such investigation is relevant to the noise budget of LISA and LISA-Pathfinder missions, as the TM will be sensitive to weak forces along all 6 degrees of freedom (DoFs). The instrument being developed in Firenze is capable of measuring the forces and stiffnesses acting simultaneously along the 2 soft DoFs. We have completed an upgrade of the apparatus to a definitive configuration and we report on both advances in the commissioning tests and on measurements of residual charge, with the first DoF released.
Loop corrections in double field theory: non-trivial dilaton potentials
NASA Astrophysics Data System (ADS)
Lv, Songlin; Wu, Houwen; Yang, Haitang
2014-10-01
It is believed that the invariance of the generalised diffeomorphisms prevents any non-trivial dilaton potential from double field theory. It is therefore difficult to include loop corrections in the formalism. We show that by redefining a non-local dilaton field, under strong constraint which is necessary to preserve the gauge invariance of double field theory, the theory does permit non-constant dilaton potentials and loop corrections. If the fields have dependence on only one single coordinate, the non-local dilaton is identical to the ordinary one with an additive constant.
PREDICT: Privacy and Security Enhancing Dynamic Information Monitoring
2015-08-03
consisting of global server-side probabilistic assignment by an untrusted server using cloaked locations, followed by feedback-loop guided local...12], consisting of global server-side probabilistic assignment by an untrusted server using cloaked locations, followed by feedback-loop guided...these methods achieve high sensing coverage with low cost using cloaked locations [3]. In follow-on work, the issue of mobility is addressed. Task
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kerns, Q.A.; Jackson, G.; Kerns, C.R.
This paper describes the damper design for 6 proton on 6 pbar bunches in the Tevatron collider. Signal pickup, transient phase detection, derivative networks, and phase correction via the high-level rf are covered. Each rf station is controlled by a slow feedback loop. In addition, global feedback loops control each set of four cavities, one set for protons and one set for antiprotons. Operational experience with these systems is discussed. 7 refs., 9 figs.
Mathematical modeling of planar cell polarity signaling in the Drosophila melanogaster wing
NASA Astrophysics Data System (ADS)
Amonlirdviman, Keith
Planar cell polarity (PCP) signaling refers to the coordinated polarization of cells within the plane of various epithelial tissues to generate sub-cellular asymmetry along an axis orthogonal to their apical-basal axes. For example, in the Drosophila wing, PCP is seen in the parallel orientation of hairs that protrude from each of the approximately 30,000 epithelial cells to robustly point toward the wing tip. Through a poorly understood mechanism, cell clones mutant for some PCP signaling components, including some, but not all alleles of the receptor frizzled, cause polarity disruptions of neighboring, wild-type cells, a phenomenon referred to as domineering nonautonomy. Previous models have proposed diffusible factors to explain nonautonomy, but no such factors have yet been found. This dissertation describes the mathematical modeling of PCP in the Drosophila wing, based on a contact dependent signaling hypothesis derived from experimental results. Intuition alone is insufficient to deduce that this hypothesis, which relies on a local feedback loop acting at the cell membrane, underlies the complex patterns observed in large fields of cells containing mutant clones, and others have argued that it cannot account for observed phenotypes. Through reaction-diffusion, partial differential equation modeling and simulation, the feedback loop is shown to fully reproduce PCP phenotypes, including domineering nonautonomy. The sufficiency of this model and the experimental validation of model predictions argue that previously proposed diffusible factors need not be invoked to explain PCP signaling and reveal how specific protein-protein interactions lead to autonomy or domineering nonautonomy. Based on these results, an ordinary differential equation model is derived to study the relationship of the feedback loop with upstream signaling components. The cadherin Fat transduces a cue to the local feedback loop, biasing the polarity direction of each cell toward the wing tip. The feedback loop then amplifies and propagates PCP across the pupal wing, but polarity information does not always propagate correctly across cells lacking Fat function. Using the simplified model, the presence and severity of polarity defects in fat clones is shown to be an inherent consequence of the feedback loop when confronted with irregular variations in cell geometry.
Soares, Heloisa P.; Ming, Ming; Mellon, Michelle; Young, Steven H.; Han, Liang; Sinnet-Smith, James; Rozengurt, Enrique
2015-01-01
PI3K/AKT/mTOR pathway which is aberrantly stimulated in many cancer cells, has emerged as a target for therapy. However, mTORC1/S6K also mediates negative feedback loops that attenuate upstream signaling. Suppression of these feedback loops opposes the growth-suppressive effects of mTOR inhibitors and leads to drug resistance. Here, we demonstrate that treatment of PANC-1 or MiaPaCa-2 pancreatic ductal adenocarcinoma (PDAC) cells with the dual PI3K/mTOR kinase inhibitor (PI3K/TOR-KI) NPV-BEZ235 blocked mTORC1/S6K activation (scored by S6 phosphorylation at Ser240/244), mTORC1/4E-BP1 (assayed by 4E-BP1 phosphorylation at Thr37/46) and mTORC2-mediated AKT phosphorylation at Ser473, in a concentration-dependent manner. Strikingly, NPV-BEZ235 markedly enhanced the MEK/ERK pathway in a dose-dependent manner. Maximal ERK over-activation coincided with complete inhibition of phosphorylation of AKT and 4E-BP1. ERK over-activation was induced by other PI3K/TOR-KIs, including PKI-587 and GDC-0980. The MEK inhibitors U126 or PD0325901 prevented ERK over-activation induced by PI3K/TOR-KIs. The combination of NPV-BEZ235 and PD0325901 caused a more pronounced inhibition of cell growth than that produced by each inhibitor individually. Mechanistic studies assessing PI3K activity in single PDAC cells indicate that PI3K/TOR-KIs act through a PI3K-independent pathway. Doses of PI3K/TOR-KIs that enhanced MEK/ERK activation coincided with those that inhibited mTORC2-mediated AKT phosphorylation on Ser473, suggesting a role of mTORC2. Knockdown of Rictor via transfection of siRNA markedly attenuated the enhancing effect of NVP-BEZ235 on ERK phosphorylation. We propose that dual PI3K/mTOR inhibitors suppress a novel negative feedback loop mediated by mTORC2 thereby leading to enhanced MEK/ERK pathway activity in pancreatic cancer cells. PMID:25673820
Picker, Alexander; Scholpp, Steffen; Böhli, Heike; Takeda, Hiroyuki; Brand, Michael
2002-07-01
The pax2.1 gene encodes a paired-box transcription factor that is one of the earliest genes to be specifically activated in development of the midbrain and midbrain-hindbrain boundary (MHB), and is required for the development and organizer activity of this territory. To understand how this spatially restricted transcriptional activity of pax2.1 is achieved, we have isolated and characterized the pax2.1-promoter using a lacZ and a GFP reporter gene in transient injection assays and transgenic lines. Stable transgenic expression of this reporter gene shows that a 5.3-kb fragment of the 5' region contains most, but not all, elements required for driving pax2.1 expression. The expressing tissues include the MHB, hindbrain, spinal cord, ear and pronephros. Transgene activation in the pronephros and developing ear suggests that these pax2.1-expressing tissues are composed of independently regulated subdomains. In addition, ectopic but spatially restricted activation of the reporter genes in rhombomeres 3 and 5 and in the forebrain, which do not normally express endogenous pax2.1, demonstrates the importance of negative regulation of pax2.1. Comparison of transgene expression in wild-type and homozygous pax2.1 mutant no isthmus (noi) embryos reveals that the transgene contains control element(s) for a novel, positive transcriptional feedback loop in MHB development. Transcription of endogenous pax2.1 at the MHB is known to be initially Pax2.1 independent, during activation in late gastrulation. In contrast, transgene expression requires the endogenous Pax2.1 function. Transplantations, mRNA injections and morpholino knock-down experiments show that this feedback regulation of pax2.1 transcription occurs cell-autonomously, and that it requires eng2 and eng3 as known targets for Pax2.1 regulation. We suggest that this novel feedback loop may allow continuation of pax2.1 expression, and hence development of the MHB organizer, to become independent of the patterning machinery of the gastrula embryo.
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.
Preliminary demonstration of a robust controller design method
NASA Technical Reports Server (NTRS)
Anderson, L. R.
1980-01-01
Alternative computational procedures for obtaining a feedback control law which yields a control signal based on measurable quantitites are evaluated. The three methods evaluated are: (1) the standard linear quadratic regulator design model; (2) minimization of the norm of the feedback matrix, k via nonlinear programming subject to the constraint that the closed loop eigenvalues be in a specified domain in the complex plane; and (3) maximize the angles between the closed loop eigenvectors in combination with minimizing the norm of K also via the constrained nonlinear programming. The third or robust design method was chosen to yield a closed loop system whose eigenvalues are insensitive to small changes in the A and B matrices. The relationship between orthogonality of closed loop eigenvectors and the sensitivity of closed loop eigenvalues is described. Computer programs are described.
Millet, Caroline; Yamashita, Motozo; Heller, Mary; Yu, Li-Rong; Veenstra, Timothy D; Zhang, Ying E
2009-07-24
Through the action of its membrane-bound type I receptor, transforming growth factor-beta (TGF-beta) elicits a wide range of cellular responses that regulate cell proliferation, differentiation, and apo ptosis. Many of these signaling responses are mediated by Smad proteins. As such, controlling Smad activity is crucial for proper signaling by TGF-beta and its related factors. Here, we show that TGF-beta induces phosphorylation at three sites in the Smad3 linker region in addition to the two C-terminal residues, and glycogen synthase kinase 3 is responsible for phosphorylation at one of these sites, namely Ser-204. Alanine substitution at Ser-204 and/or the neighboring Ser-208, the priming site for glycogen synthase kinase 3 in vivo activity, strengthened the affinity of Smad3 to CREB-binding protein, suggesting that linker phosphorylation may be part of a negative feedback loop that modulates Smad3 transcriptional activity. Thus, our findings reveal a novel aspect of the Smad3 signaling mechanism that controls the final amplitude of cellular responses to TGF-beta.
Design of Tunable Oscillatory Dynamics in a Synthetic NF-κB Signaling Circuit.
Zhang, Zhi-Bo; Wang, Qiu-Yue; Ke, Yu-Xi; Liu, Shi-Yu; Ju, Jian-Qi; Lim, Wendell A; Tang, Chao; Wei, Ping
2017-11-22
Although oscillatory circuits are prevalent in transcriptional regulation, it is unclear how a circuit's structure and the specific parameters that describe its components determine the shape of its oscillations. Here, we engineer a minimal, inducible human nuclear factor κB (NF-κB)-based system that is composed of NF-κB (RelA) and degradable inhibitor of NF-κB (IκBα), into the yeast, Saccharomyces cerevisiae. We define an oscillation's waveform quantitatively as a function of signal amplitude, rest time, rise time, and decay time; by systematically tuning RelA concentration, the strength of negative feedback, and the degradation rate of IκBα, we demonstrate that peak shape and frequency of oscillations can be controlled in vivo and predicted mathematically. In addition, we show that nested negative feedback loops can be employed to specifically tune the frequency of oscillations while leaving their peak shape unchanged. In total, this work establishes design principles that enable function-guided design of oscillatory signaling controllers in diverse synthetic biology applications. Copyright © 2017 Elsevier Inc. All rights reserved.
Effects of the fluid flows on enzymatic chemical oscillations
NASA Astrophysics Data System (ADS)
Shklyaev, Oleg; Yashin, Victor; Balazs, Anna
2017-11-01
Chemical oscillations are ubiquitous in nature and have a variety of promising applications. Usually, oscillating chemical systems are analyzed within the context of a reaction-diffusion framework. Here, we examine how fluid flows carrying the reactants can be utilized to modulate the negative feedback loops and time delays that promote chemical oscillations. We consider a model where a chemical reaction network involves two species, X and Y, which undergo transformations catalyzed by respective enzymes immobilized at the bottom wall of a fluid-filled microchamber. The reactions with the enzymes provide a negative feedback in the chemically oscillating system. In particular, the first enzyme, localized on the first patch, promotes production of chemical X, while the second enzyme, immobilized on the second patch, promotes production of chemical Y, which inhibits the production of chemical X. The separation distance between the enzyme-coated patches sets the time delay required for the transportation of X and Y. The chemical transport is significantly enhanced if convective fluxes accompany the diffusive ones. Therefore, the parameter region where oscillations are present is modified. The findings provide guidance to designing micro-scale chemical reactors with improved functionalities.
Active Control of Thermal Convection in a Rectangular Loop by Changing its Spatial Orientation
NASA Astrophysics Data System (ADS)
Bratsun, Dmitry A.; Krasnyakov, Ivan V.; Zyuzgin, Alexey V.
2018-02-01
The problem of the automatic control of the fluid flow in a rectangular convective loop heated from below is studied theoretically and experimentally. The control is performed by using a feedback subsystem which changes the convection regimes by introducing small discrete changes in the spatial orientation of the loop with respect to gravity. We focus on effects that arise when the feedback controller operates with an unavoidable time delay, which is cause by the thermal inertia of the medium. The mathematical model of the phenomenon is developed. The dynamic regimes of the convection in the thermosyphon loop under control are studied. It is shown that the proposed control method can successfully stabilize not only a no-motion state of the fluid, but also time-dependent modes of convection including the irregular fluid flow at high values of the Rayleigh number. It is shown that the excessive gain of the proportional feedback can result in oscillations in the loop orientation exciting the unsteady convection modes. The comparison of the experimental data obtained for dielectric oil and dodecane with theory is given, and their good agreement is demonstrated.
Active Control of Thermal Convection in a Rectangular Loop by Changing its Spatial Orientation
NASA Astrophysics Data System (ADS)
Bratsun, Dmitry A.; Krasnyakov, Ivan V.; Zyuzgin, Alexey V.
2017-12-01
The problem of the automatic control of the fluid flow in a rectangular convective loop heated from below is studied theoretically and experimentally. The control is performed by using a feedback subsystem which changes the convection regimes by introducing small discrete changes in the spatial orientation of the loop with respect to gravity. We focus on effects that arise when the feedback controller operates with an unavoidable time delay, which is cause by the thermal inertia of the medium. The mathematical model of the phenomenon is developed. The dynamic regimes of the convection in the thermosyphon loop under control are studied. It is shown that the proposed control method can successfully stabilize not only a no-motion state of the fluid, but also time-dependent modes of convection including the irregular fluid flow at high values of the Rayleigh number. It is shown that the excessive gain of the proportional feedback can result in oscillations in the loop orientation exciting the unsteady convection modes. The comparison of the experimental data obtained for dielectric oil and dodecane with theory is given, and their good agreement is demonstrated.
Neuromimetic Event-Based Detection for Closed-Loop Tactile Feedback Control of Upper Limb Prostheses
Osborn, Luke; Kaliki, Rahul; Soares, Alcimar; Thakor, Nitish
2016-01-01
Upper limb amputees lack the valuable tactile sensing that helps provide context about the surrounding environment. Here we utilize tactile information to provide active touch feedback to a prosthetic hand. First, we developed fingertip tactile sensors for producing biomimetic spiking responses for monitoring contact, release, and slip of an object grasped by a prosthetic hand. We convert the sensor output into pulses, mimicking the rapid and slowly adapting spiking responses of receptor afferents found in the human body. Second, we designed and implemented two neuromimetic event-based algorithms, Compliant Grasping and Slip Prevention, on a prosthesis to create a local closed-loop tactile feedback control system (i.e. tactile information is sent to the prosthesis). Grasping experiments were designed to assess the benefit of this biologically inspired neuromimetic tactile feedback to a prosthesis. Results from able-bodied and amputee subjects show the average number of objects that broke or slipped during grasping decreased by over 50% and the average time to complete a grasping task decreased by at least 10% for most trials when comparing neuromimetic tactile feedback with no feedback on a prosthesis. Our neuromimetic method of closed-loop tactile sensing is a novel approach to improving the function of upper limb prostheses. PMID:27777640
Zeng, Hong; Wang, Yanxin; Wu, Changcheng; Song, Aiguo; Liu, Jia; Ji, Peng; Xu, Baoguo; Zhu, Lifeng; Li, Huijun; Wen, Pengcheng
2017-01-01
Brain-machine interface (BMI) can be used to control the robotic arm to assist paralysis people for performing activities of daily living. However, it is still a complex task for the BMI users to control the process of objects grasping and lifting with the robotic arm. It is hard to achieve high efficiency and accuracy even after extensive trainings. One important reason is lacking of sufficient feedback information for the user to perform the closed-loop control. In this study, we proposed a method of augmented reality (AR) guiding assistance to provide the enhanced visual feedback to the user for a closed-loop control with a hybrid Gaze-BMI, which combines the electroencephalography (EEG) signals based BMI and the eye tracking for an intuitive and effective control of the robotic arm. Experiments for the objects manipulation tasks while avoiding the obstacle in the workspace are designed to evaluate the performance of our method for controlling the robotic arm. According to the experimental results obtained from eight subjects, the advantages of the proposed closed-loop system (with AR feedback) over the open-loop system (with visual inspection only) have been verified. The number of trigger commands used for controlling the robotic arm to grasp and lift the objects with AR feedback has reduced significantly and the height gaps of the gripper in the lifting process have decreased more than 50% compared to those trials with normal visual inspection only. The results reveal that the hybrid Gaze-BMI user can benefit from the information provided by the AR interface, improving the efficiency and reducing the cognitive load during the grasping and lifting processes. PMID:29163123
Regulation of aldosterone secretion by mineralocorticoid receptor-mediated signaling.
Chong, Cherish; Hamid, Anis; Yao, Tham; Garza, Amanda E; Pojoga, Luminita H; Adler, Gail K; Romero, Jose R; Williams, Gordon H
2017-03-01
We posit the existence of a paracrine/autocrine negative feedback loop, mediated by the mineralocorticoid receptor (MR), regulating aldosterone secretion. To assess this hypothesis, we asked whether altering MR activity in zona glomerulosa (ZG) cells affects aldosterone production. To this end, we studied ex vivo ZG cells isolated from male Wistar rats fed chow containing either high (1.6% Na + (HS)) or low (0.03% Na + (LS)) amount of sodium. Western blot analyses demonstrated that MR was present in both the ZG and zona fasciculata/zona reticularis (ZF/ZR/ZR). In ZG cells isolated from rats on LS chow, MR activation by fludrocortisone produced a 20% and 60% reduction in aldosterone secretion basally and in response to angiotensin II (ANGII) stimulation, respectively. Corticosterone secretion was increased in these cells suggesting that aldosterone synthase activity was being reduced by fludrocortisone. In contrast, canrenoic acid, an MR antagonist, enhanced aldosterone production by up to 30% both basally and in response to ANGII. Similar responses were observed in ZG cells from rats fed HS. Modulating glucocorticoid receptor (GR) activity did not alter aldosterone production by ZG cells; however, altering GR activity did modify corticosterone production from ZF/ZR/ZR cells both basally and in response to adrenocorticotropic hormone (ACTH). Additionally, activating the MR in ZF/ZR/ZR cells strikingly reduced corticosterone secretion. In summary, these data support the hypothesis that negative ultra-short feedback loops regulate adrenal steroidogenesis. In the ZG, aldosterone secretion is regulated by the MR, but not the GR, an effect that appears to be secondary to a change in aldosterone synthase activity. © 2017 Society for Endocrinology.
Closed-loop model identification of cooperative manipulators holding deformable objects
NASA Astrophysics Data System (ADS)
Alkathiri, A. A.; Akmeliawati, R.; Azlan, N. Z.
2017-11-01
This paper presents system identification to obtain the closed-loop models of a couple of cooperative manipulators in a system, which function to hold deformable objects. The system works using the master-slave principle. In other words, one of the manipulators is position-controlled through encoder feedback, while a force sensor gives feedback to the other force-controlled manipulator. Using the closed-loop input and output data, the closed-loop models, which are useful for model-based control design, are estimated. The criteria for model validation are a 95% fit between the measured and simulated output of the estimated models and residual analysis. The results show that for both position and force control respectively, the fits are 95.73% and 95.88%.
Biomechanical performance of different cable and wire cerclage configurations.
Lenz, Mark; Perren, Stephan Marcel; Richards, Robert Geoff; Mückley, Thomas; Hofmann, Gunther Olaf; Gueorguiev, Boyko; Windolf, Markus
2013-01-01
Cerclage technology is regaining interest due to the increasing number of periprosthetic fractures. Different wiring techniques have been formerly proposed and have hibernated over years. Hereby, they are compared to current cerclage technology. Seven groups (n = 6) of different cable cerclage (Ø1.7 mm, crimp closure) configurations (one single cerclage looped once around the shells, one single cerclage looped twice, two cerclages each looped once) and solid wire cerclages (Ø1.5 mm, twist closure) (same configurations as cable cerclages, and two braided wires, twisted around each other looped once) fixed two cortical half shells of human femoral shaft mounted on a testing jig. Sinusoidal cyclic loading with constantly increasing force (0.1 N/cycle) was applied starting at 50 N peak load. Cerclage pretension (P), load leading to onset of plastic deformation (D) and load at total failure (T) were identified. Statistical differences between the groups were detected by univariate ANOVA. Double looped cables (P442N ± 129; D1334N ± 319; T2734N ± 330) performed significantly better (p < 0.05) than single looped cables (P292N ± 56; D646N ± 108; T1622N ± 171) and were comparable to two single cables (P392N ± 154; D1191N ± 334; T2675N ± 361). Double looped wires (P335N ± 49; D752N ± 119; T1359N ± 80) were significantly better (p < 0.05) than single looped wires (P181N ± 16; D343N ± 33; T606N ± 109) and performed similarly to single looped cables. Braided wires (P119N ± 26; D225N ± 55; T919N ± 197) exhibited early loss of pretension and plastic deformation. Double looped cerclages provided a better fixation stability compared to a single looped cerclage. Double looped wires were comparable to a single looped cable. The use of braided wires could not be recommended mechanically.
Zhang, Yu'e; Xu, Wenying; Li, Zhonghui; Deng, Xing Wang; Wu, Weihua; Xue, Yongbiao
2008-12-01
Guard cells, which form stoma in leaf epidermis, sense and integrate environmental signals to modulate stomatal aperture in response to diverse conditions. Under drought stress, plants synthesize abscisic acid (ABA), which in turn induces a rapid closing of stoma, to prevent water loss by transpiration. However, many aspects of the molecular mechanism for ABA-mediated stomatal closure are still not understood. Here, we report a novel negative regulator of guard cell ABA signaling, DOR, in Arabidopsis (Arabidopsis thaliana). The DOR gene encodes a putative F-box protein, a member of the S-locus F-box-like family related to AhSLF-S(2) and specifically interacting with ASK14 and CUL1. A null mutation in DOR resulted in a hypersensitive ABA response of stomatal closing and a substantial increase of drought tolerance; in contrast, the transgenic plants overexpressing DOR were more susceptible to the drought stress. DOR is strongly expressed in guard cells and suppressed by ABA treatment, suggesting a negative feedback loop of DOR in ABA responses. Double-mutant analyses of dor with ABA-insensitive mutant abi1-1 showed that abi1-1 is epistatic to dor, but no apparent change of phospholipase Dalpha1 was detected between the wild type and dor. Affymetrix GeneChip analysis showed that DOR likely regulates ABA biosynthesis under drought stress. Taken together, our results demonstrate that DOR acts independent of phospholipase Dalpha1 in an ABA signaling pathway to inhibit the ABA-induced stomatal closure under drought stress.
ASDTIC: A feedback control innovation
NASA Technical Reports Server (NTRS)
Lalli, V. R.; Schoenfeld, A. D.
1972-01-01
The ASDTIC (Analog Signal to Discrete Time Interval Converter) control subsystem provides precise output control of high performance aerospace power supplies. The key to ASDTIC operation is that it stably controls output by sensing output energy change as well as output magnitude. The ASDTIC control subsystem and control module were developed to improve power supply performance during static and dynamic input voltage and output load variations, to reduce output voltage or current regulation due to component variations or aging, to maintain a stable feedback control with variations in the loop gain or loop time constants, and to standardize the feedback control subsystem for power conditioning equipment.
ASDTIC - A feedback control innovation.
NASA Technical Reports Server (NTRS)
Lalli, V. R.; Schoenfeld, A. D.
1972-01-01
The ASDTIC (analog signal to discrete time interval converter) control subsystem provides precise output control of high performance aerospace power supplies. The key to ASDTIC operation is that it stably controls output by sensing output energy change as well as output magnitude. The ASDTIC control subsystem and control module were developed to improve power supply performance during static and dynamic input voltage and output load variations, to reduce output voltage or current regulation due to component variations or aging, to maintain a stable feedback control with variations in the loop gain or loop time constants, and to standardize the feedback control subsystem for power conditioning equipment.
Tower Based Load Measurements for Individual Pitch Control and Tower Damping of Wind Turbines
NASA Astrophysics Data System (ADS)
Kumar, A. A.; Hugues-Salas, O.; Savini, B.; Keogh, W.
2016-09-01
The cost of IPC has hindered adoption outside of Europe despite significant loading advantages for large wind turbines. In this work we presented a method for applying individual pitch control (including for higher-harmonics) using tower-top strain gauge feedback instead of blade-root strain gauge feedback. Tower-top strain gauges offer hardware savings of approximately 50% in addition to the possibility of easier access for maintenance and installation and requiring a less specialised skill-set than that required for applying strain gauges to composite blade roots. A further advantage is the possibility of using the same tower-top sensor array for tower damping control. This method is made possible by including a second order IPC loop in addition to the tower damping loop to reduce the typically dominating 3P content in tower-top load measurements. High-fidelity Bladed simulations show that the resulting turbine spectral characteristics from tower-top feedback IPC and from the combination of tower-top IPC and damping loops largely match those of blade-root feedback IPC and nacelle- velocity feedback damping. Lifetime weighted fatigue analysis shows that the methods allows load reductions within 2.5% of traditional methods.
Electrotactile Feedback Improves Performance and Facilitates Learning in the Routine Grasping Task.
Isaković, Milica; Belić, Minja; Štrbac, Matija; Popović, Igor; Došen, Strahinja; Farina, Dario; Keller, Thierry
2016-06-13
Aim of this study was to investigate the feasibility of electrotactile feedback in closed loop training of force control during the routine grasping task. The feedback was provided using an array electrode and a simple six-level spatial coding, and the experiment was conducted in three amputee subjects. The psychometric tests confirmed that the subjects could perceive and interpret the electrotactile feedback with a high success rate. The subjects performed the routine grasping task comprising 4 blocks of 60 grasping trials. In each trial, the subjects employed feedforward control to close the hand and produce the desired grasping force (four levels). First (baseline) and the last (validation) session were performed in open loop, while the second and the third session (training) included electrotactile feedback. The obtained results confirmed that using the feedback improved the accuracy and precision of the force control. In addition, the subjects performed significantly better in the validation vs. baseline session, therefore suggesting that electrotactile feedback can be used for learning and training of myoelectric control.
System and method of designing models in a feedback loop
Gosink, Luke C.; Pulsipher, Trenton C.; Sego, Landon H.
2017-02-14
A method and system for designing models is disclosed. The method includes selecting a plurality of models for modeling a common event of interest. The method further includes aggregating the results of the models and analyzing each model compared to the aggregate result to obtain comparative information. The method also includes providing the information back to the plurality of models to design more accurate models through a feedback loop.
Modeling Aggressive Medulloblastoma Using Human Induced Pluripotent Stem Cells
2017-09-01
and Myc in turn induces expression of AT1R creating a positive feedback loop and development of aggression tumor phenotype. The therapeutic...strengths are the relevant expertise of the applicant and his collaborating team, the novel paracrine positive feedback loop in EC-tumor cell...to as MYC-driven MB. The molecular mechanisms that drive MYC hyper -activation in MB remain incompletely understood. MB cells in actual tumors interact
Sp1-CD147 positive feedback loop promotes the invasion ability of ovarian cancer.
Zhao, Jing; Ye, Wei; Wu, Juan; Liu, Lijuan; Yang, Lina; Gao, Lu; Chen, Biliang; Zhang, Fanglin; Yang, Hong; Li, Yu
2015-07-01
CD147 is a novel cancer biomarker that has been confirmed to be overexpressed in ovarian carcinoma, which is significantly associated with poor prognosis. Although the Sp1 protein regulates the expression level of CD147, it remains unclear whether Sp1 phosphorylation plays a role in this regulation. A dual-luciferase assay revealed that T453 and T739 mutations decreased the activity of Sp1 binding to the promoter of CD147, followed by a decrease in CD147 mRNA and protein expression. Western blot analysis showed that CD147 promoted Sp1 phosphorylation at T453 and T739 through the PI3K/AKT and MAPK/ERK pathways. In addition, blocking the Sp1-CD147 positive feedback loop reduced the invasion ability of HO-8910pm cells. Immunohistochemical staining showed that the components of the feedback loop were overexpressed in ovarian cancer tissues. The correlation analysis revealed a significant correlation between phospho-Sp1 (T453), phospho-Sp1 (T739) and CD147 expression levels, with correlation coefficients of r=0.477 and r=0.461, respectively. Collectively, our results suggest that a Sp1-CD147 positive feedback loop plays a critical role in the invasion ability of ovarian cancer cells.
Coherent feedback control of a single qubit in diamond
NASA Astrophysics Data System (ADS)
Hirose, Masashi; Cappellaro, Paola
2016-04-01
Engineering desired operations on qubits subjected to the deleterious effects of their environment is a critical task in quantum information processing, quantum simulation and sensing. The most common approach relies on open-loop quantum control techniques, including optimal-control algorithms based on analytical or numerical solutions, Lyapunov design and Hamiltonian engineering. An alternative strategy, inspired by the success of classical control, is feedback control. Because of the complications introduced by quantum measurement, closed-loop control is less pervasive in the quantum setting and, with exceptions, its experimental implementations have been mainly limited to quantum optics experiments. Here we implement a feedback-control algorithm using a solid-state spin qubit system associated with the nitrogen vacancy centre in diamond, using coherent feedback to overcome the limitations of measurement-based feedback, and show that it can protect the qubit against intrinsic dephasing noise for milliseconds. In coherent feedback, the quantum system is connected to an auxiliary quantum controller (ancilla) that acquires information about the output state of the system (by an entangling operation) and performs an appropriate feedback action (by a conditional gate). In contrast to open-loop dynamical decoupling techniques, feedback control can protect the qubit even against Markovian noise and for an arbitrary period of time (limited only by the coherence time of the ancilla), while allowing gate operations. It is thus more closely related to quantum error-correction schemes, although these require larger and increasing qubit overheads. Increasing the number of fresh ancillas enables protection beyond their coherence time. We further evaluate the robustness of the feedback protocol, which could be applied to quantum computation and sensing, by exploring a trade-off between information gain and decoherence protection, as measurement of the ancilla-qubit correlation after the feedback algorithm voids the protection, even if the rest of the dynamics is unchanged.
Cheong, Rachel Y; Czieselsky, Katja; Porteous, Robert; Herbison, Allan E
2015-10-28
Circulating estradiol exerts a profound influence on the activity of the gonadotropin-releasing hormone (GnRH) neuronal network controlling fertility. Using genetic strategies enabling neuron-specific deletion of estrogen receptor α (Esr1), we examine here whether estradiol-modulated GABA and glutamate transmission are critical for the functioning of the GnRH neuron network in the female mouse. Using Vgat- and Vglut2-ires-Cre knock-in mice and ESR1 immunohistochemistry, we demonstrate that subpopulations of GABA and glutamate neurons throughout the limbic forebrain express ESR1, with ESR1-GABAergic neurons being more widespread and numerous than ESR1-glutamatergic neurons. We crossed Vgat- and Vglut2-ires-Cre mice with an Esr1(lox/lox) line to generate animals with GABA-neuron-specific or glutamate-neuron-specific deletion of Esr1. Vgat-ires-Cre;Esr1(lox/lox) mice were infertile, with abnormal estrous cycles, and exhibited a complete failure of the estrogen positive feedback mechanism responsible for the preovulatory GnRH surge. However, puberty onset and estrogen negative feedback were normal. Vglut2-ires-Cre;Esr1(lox/lox) mice were also infertile but displayed a wider range of deficits, including advanced puberty onset, abnormal negative feedback, and abolished positive feedback. Whereas <25% of preoptic kisspeptin neurons expressed Cre in Vgat- and Vglut2-ires-Cre lines, ∼70% of arcuate kisspeptin neurons were targeted in Vglut2-ires-Cre;Esr1(lox/lox) mice, possibly contributing to their advanced puberty phenotype. These observations show that, unexpectedly, ESR1-GABA neurons are only essential for the positive feedback mechanism. In contrast, we reveal the key importance of ESR1 in glutamatergic neurons for multiple estrogen feedback loops within the GnRH neuronal network required for fertility in the female mouse. Copyright © 2015 the authors 0270-6474/15/3514533-11$15.00/0.
Cherry-Bukowiec, Jill R; Machado-Aranda, David; To, Kathleen; Englesbe, Michael; Ryszawa, Susan; Napolitano, Lena M
2015-11-01
The unpredictable and sometimes chaotic environment present in acute care surgery services (trauma, burn, surgical critical care, and nontrauma emergency surgery) can cause high levels of anxiety and stress that could impact a medical students' experience during their third year of medical school surgical clerkship. This negative perception perhaps is a determinant influence in diverting talented students into other medical subspecialties. We sought out to objectively identify potential areas of improvement through direct feedback and implement programmatic changes to address these areas. We hypothesized that as the changes were made, students' perception of the rotation would improve. Review of end of clerkship third year of medical school trauma burn surgery rotation evaluations and comments was performed for the 2010-2011 academic year. Trends in negative feedback were identified and categorized into five areas for improvement as follows: logistics, student expectations, communication, team integration, and feedback. A plan was designed and implemented for each category. Feedback on improvements to the rotation was monitored via surveys and during monthly end of rotation face-to-face student feedback sessions with the rotation faculty facilitator and surgery clerkship director. Data were compiled and reviewed. Perceptions of the rotation markedly improved within the first month of the changes and continued to improve over the study time frame (2011-2013) in all five categories. We also observed an increase in the number of students selecting a surgical residency in the National Resident Matching Program match from a low of 8% in 2009-2010 before any interventions to 25% after full implementation of the improvement measures in 2011-2012. A systematic approach using direct feedback from students to address service-specific issues improves perceptions of students on the educational value of a busy trauma-burn acute care surgery service and may have a positive influence on students considering surgical careers to pursue a surgical specialty. Published by Elsevier Inc.
Autopilot for frequency-modulation atomic force microscopy.
Kuchuk, Kfir; Schlesinger, Itai; Sivan, Uri
2015-10-01
One of the most challenging aspects of operating an atomic force microscope (AFM) is finding optimal feedback parameters. This statement applies particularly to frequency-modulation AFM (FM-AFM), which utilizes three feedback loops to control the cantilever excitation amplitude, cantilever excitation frequency, and z-piezo extension. These loops are regulated by a set of feedback parameters, tuned by the user to optimize stability, sensitivity, and noise in the imaging process. Optimization of these parameters is difficult due to the coupling between the frequency and z-piezo feedback loops by the non-linear tip-sample interaction. Four proportional-integral (PI) parameters and two lock-in parameters regulating these loops require simultaneous optimization in the presence of a varying unknown tip-sample coupling. Presently, this optimization is done manually in a tedious process of trial and error. Here, we report on the development and implementation of an algorithm that computes the control parameters automatically. The algorithm reads the unperturbed cantilever resonance frequency, its quality factor, and the z-piezo driving signal power spectral density. It analyzes the poles and zeros of the total closed loop transfer function, extracts the unknown tip-sample transfer function, and finds four PI parameters and two lock-in parameters for the frequency and z-piezo control loops that optimize the bandwidth and step response of the total system. Implementation of the algorithm in a home-built AFM shows that the calculated parameters are consistently excellent and rarely require further tweaking by the user. The new algorithm saves the precious time of experienced users, facilitates utilization of FM-AFM by casual users, and removes the main hurdle on the way to fully automated FM-AFM.
Autopilot for frequency-modulation atomic force microscopy
NASA Astrophysics Data System (ADS)
Kuchuk, Kfir; Schlesinger, Itai; Sivan, Uri
2015-10-01
One of the most challenging aspects of operating an atomic force microscope (AFM) is finding optimal feedback parameters. This statement applies particularly to frequency-modulation AFM (FM-AFM), which utilizes three feedback loops to control the cantilever excitation amplitude, cantilever excitation frequency, and z-piezo extension. These loops are regulated by a set of feedback parameters, tuned by the user to optimize stability, sensitivity, and noise in the imaging process. Optimization of these parameters is difficult due to the coupling between the frequency and z-piezo feedback loops by the non-linear tip-sample interaction. Four proportional-integral (PI) parameters and two lock-in parameters regulating these loops require simultaneous optimization in the presence of a varying unknown tip-sample coupling. Presently, this optimization is done manually in a tedious process of trial and error. Here, we report on the development and implementation of an algorithm that computes the control parameters automatically. The algorithm reads the unperturbed cantilever resonance frequency, its quality factor, and the z-piezo driving signal power spectral density. It analyzes the poles and zeros of the total closed loop transfer function, extracts the unknown tip-sample transfer function, and finds four PI parameters and two lock-in parameters for the frequency and z-piezo control loops that optimize the bandwidth and step response of the total system. Implementation of the algorithm in a home-built AFM shows that the calculated parameters are consistently excellent and rarely require further tweaking by the user. The new algorithm saves the precious time of experienced users, facilitates utilization of FM-AFM by casual users, and removes the main hurdle on the way to fully automated FM-AFM.
Repicky, Sarah; Broadie, Kendal
2009-02-01
Loss of the mRNA-binding protein FMRP results in the most common inherited form of both mental retardation and autism spectrum disorders: fragile X syndrome (FXS). The leading FXS hypothesis proposes that metabotropic glutamate receptor (mGluR) signaling at the synapse controls FMRP function in the regulation of local protein translation to modulate synaptic transmission strength. In this study, we use the Drosophila FXS disease model to test the relationship between Drosophila FMRP (dFMRP) and the sole Drosophila mGluR (dmGluRA) in regulation of synaptic function, using two-electrode voltage-clamp recording at the glutamatergic neuromuscular junction (NMJ). Null dmGluRA mutants show minimal changes in basal synapse properties but pronounced defects during sustained high-frequency stimulation (HFS). The double null dfmr1;dmGluRA mutant shows repression of enhanced augmentation and delayed onset of premature long-term facilitation (LTF) and strongly reduces grossly elevated post-tetanic potentiation (PTP) phenotypes present in dmGluRA-null animals. Null dfmr1 mutants show features of synaptic hyperexcitability, including multiple transmission events in response to a single stimulus and cyclic modulation of transmission amplitude during prolonged HFS. The double null dfmr1;dmGluRA mutant shows amelioration of these defects but does not fully restore wildtype properties in dfmr1-null animals. These data suggest that dmGluRA functions in a negative feedback loop in which excess glutamate released during high-frequency transmission binds the glutamate receptor to dampen synaptic excitability, and dFMRP functions to suppress the translation of proteins regulating this synaptic excitability. Removal of the translational regulator partially compensates for loss of the receptor and, similarly, loss of the receptor weakly compensates for loss of the translational regulator.
Method for spinning up a three-axis controlled spacecraft
NASA Technical Reports Server (NTRS)
Vorlicek, Preston L. (Inventor)
1988-01-01
A three-axis controlled spacecraft (1), typically a satellite, is spun up about its roll axis (20) prior to firing a motor (2), i.e., a perigee kick motor, to achieve the requisite degree of angular momentum stiffness. Thrusters (21) for imparting rotation about the roll axis (20) are activated in open-loop fashion, typically at less than full duty cycle. Cross-axis torques induced by this rotational motion are compensated for by means of closed control loops for each of the pitch and yaw axes (30, 40, respectively). Each closed control loop combines a prebias torque (72) with torques (75, 74) representative of position and rate feedback information, respectively. A deadband (52) within each closed control loop can be widened during the spinup, to conserve fuel. Position feedback information (75) in each of the control loops is disabled upon saturation of the gyroscope associated with the roll axis (20).
NASA Astrophysics Data System (ADS)
Del Vescovo, D.; D'Ambrogio, W.
1995-01-01
A frequency domain method is presented to design a closed-loop control for vibration reduction flexible mechanisms. The procedure is developed on a single-link flexible arm, driven by one rotary degree of freedom servomotor, although the same technique may be applied to similar systems such as supports for aerospace antennae or solar panels. The method uses the structural frequency response functions (FRFs), thus avoiding system identification, that produces modeling uncertainties. Two closed-loops are implemented: the inner loop uses acceleration feedback with the aim of making the FRF similar to that of an equivalent rigid link; the outer loop feeds back displacements to achieve a fast positioning response and null steady state error. In both cases, the controller type is established a priori, while actual characteristics are defined by an optimisation procedure in which the relevant FRF is constrained into prescribed bounds and stability is taken into account.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ravishankar, A.S. Ghosal, A.
1999-01-01
The dynamics of a feedback-controlled rigid robot is most commonly described by a set of nonlinear ordinary differential equations. In this paper, the authors analyze these equations, representing the feedback-controlled motion of two- and three-degrees-of-freedom rigid robots with revolute (R) and prismatic (P) joints in the absence of compliance, friction, and potential energy, for the possibility of chaotic motions. The authors first study the unforced or inertial motions of the robots, and show that when the Gaussian or Riemannian curvature of the configuration space of a robot is negative, the robot equations can exhibit chaos. If the curvature is zeromore » or positive, then the robot equations cannot exhibit chaos. The authors show that among the two-degrees-of-freedom robots, the PP and the PR robot have zero Gaussian curvature while the RP and RR robots have negative Gaussian curvatures. For the three-degrees-of-freedom robots, they analyze the two well-known RRP and RRR configurations of the Stanford arm and the PUMA manipulator, respectively, and derive the conditions for negative curvature and possible chaotic motions. The criteria of negative curvature cannot be used for the forced or feedback-controlled motions. For the forced motion, the authors resort to the well-known numerical techniques and compute chaos maps, Poincare maps, and bifurcation diagrams. Numerical results are presented for the two-degrees-of-freedom RP and RR robots, and the authors show that these robot equations can exhibit chaos for low controller gains and for large underestimated models. From the bifurcation diagrams, the route to chaos appears to be through period doubling.« less
NASA Technical Reports Server (NTRS)
Wu, Te-Kao (Inventor)
1994-01-01
A multireflector antenna utilizes a frequency-selective surface (FSS) in a subreflector to allow signals in two different RF bands to be selectively reflected back into a main reflector and to allow signals in other RF bands to be transmitted through it to the main reflector for primary focus transmission. A first approach requires only one FSS at the subreflector which may be an array of double-square-loop conductive elements. A second approach uses two FSS's at the subreflector which may be an array of either double-square-loop (DSL) or double-ring (DR). In the case of DR elements, they may be advantageously arranged in a triangular array instead of the rectangular array for the DSL elements.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Levine, Paul A.; Randerson, James T.; Swenson, Sean C.
The relationship between terrestrial water storage (TWS) and atmospheric processes has important implications for predictability of climatic extremes and projection of future climate change. In places where moisture availability limits evapotranspiration (ET), variability in TWS has the potential to influence surface energy fluxes and atmospheric conditions. Where atmospheric conditions, in turn, influence moisture availability, a full feedback loop exists. Here we developed a novel approach for measuring the strength of both components of this feedback loop, i.e., the forcing of the atmosphere by variability in TWS and the response of TWS to atmospheric variability, using satellite observations of TWS, precipitation,more » solar radiation, and vapor pressure deficit during 2002–2014. Our approach defines metrics to quantify the relationship between TWS anomalies and climate globally on a seasonal to interannual timescale. Metrics derived from the satellite data were used to evaluate the strength of the feedback loop in 38 members of the Community Earth System Model (CESM) Large Ensemble (LENS) and in six models that contributed simulations to phase 5 of the Coupled Model Intercomparison Project (CMIP5). We found that both forcing and response limbs of the feedback loop in LENS were stronger than in the satellite observations in tropical and temperate regions. Feedbacks in the selected CMIP5 models were not as strong as those found in LENS, but were still generally stronger than those estimated from the satellite measurements. Consistent with previous studies conducted across different spatial and temporal scales, our analysis suggests that models may overestimate the strength of the feedbacks between the land surface and the atmosphere. Lastly, we describe several possible mechanisms that may contribute to this bias, and discuss pathways through which models may overestimate ET or overestimate the sensitivity of ET to TWS.« less
An adaptive molecular timer in p53-meidated cell fate decision
NASA Astrophysics Data System (ADS)
Zhang, Xiao-Peng; Wang, Ping; Liu, Feng; Wang, Wei
The tumor suppressor p53 decides cellular outcomes in the DNA damage response. It is intriguing to explore the link between p53 dynamics and cell fates. We developed a theoretical model of p53 signaling network to clarify the mechanism of cell fate decision mediated by its dynamics. We found that the interplay between p53-Mdm2 negative feedback loop and p53-PTEN-Mdm2 positive feedback loop shapes p53 dynamics. Depending on the intensity of DNA damage, p53 shows three modes of dynamics: persistent pulses, two-phase dynamics with pulses followed by sustained high levels and straightforward high levels. Especially, p53 shows two-phase dynamics upon moderated damage and the required number of p53 pulses before apoptosis induction decreases with increasing DNA damage. Our results suggested there exists an adaptive molecular timer that determines whether and when the apoptosis switch should be triggered. We clarified the mechanism behind the switching of p53 dynamical modes by bifurcation analysis. Moreover, we reproduced the experimental results that drug additions alter p53 pulses to sustained p53 activation and leads to senescence. Our work may advance the understanding the significance of p53 dynamics in tumor suppression. This work was supported by National Natural Science Foundation of China (Nos. 11175084, 11204126 and 31361163003).
The Cerebellum and Premenstrual Dysphoric Disorder
Rapkin, Andrea J.; Berman, Steven M.; London, Edythe D.
2017-01-01
The cerebellum constitutes ten percent of brain volume and contains the majority of brain neurons. Although it was historically viewed primarily as processing motoric computations, current evidence supports a more comprehensive role, where cerebro-cerebellar feedback loops also modulate various forms of cognitive and affective processing. Here we present evidence for a role of the cerebellum in premenstrual dysphoric disorder (PMDD), which is characterized by severe negative mood symptoms during the luteal phase of the menstrual cycle. Although a link between menstruation and cyclical dysphoria has long been recognized, neuroscientific investigations of this common disorder have only recently been explored. This article reviews functional and structural brain imaging studies of PMDD and the similar but less well defined condition of premenstrual syndrome (PMS). The most consistent findings are that women with premenstrual dysphoria exhibit greater relative activity than other women in the dorsolateral prefrontal cortex and posterior lobules VI and VII of the neocerebellum. Since both brain areas have been implicated in emotional processing and mood disorders, working memory and executive functions, this greater activity probably represents coactivation within a cerebro-cerebellar feedback loop regulating emotional and cognitive processing. Some of the evidence suggests that increased activity within this circuit may preserve cerebellar structure during aging, and possible mechanisms and implications of this finding are discussed. PMID:28275721
The Cerebellum and Premenstrual Dysphoric Disorder.
Rapkin, Andrea J; Berman, Steven M; London, Edythe D
2014-01-01
The cerebellum constitutes ten percent of brain volume and contains the majority of brain neurons. Although it was historically viewed primarily as processing motoric computations, current evidence supports a more comprehensive role, where cerebro-cerebellar feedback loops also modulate various forms of cognitive and affective processing. Here we present evidence for a role of the cerebellum in premenstrual dysphoric disorder (PMDD), which is characterized by severe negative mood symptoms during the luteal phase of the menstrual cycle. Although a link between menstruation and cyclical dysphoria has long been recognized, neuroscientific investigations of this common disorder have only recently been explored. This article reviews functional and structural brain imaging studies of PMDD and the similar but less well defined condition of premenstrual syndrome (PMS). The most consistent findings are that women with premenstrual dysphoria exhibit greater relative activity than other women in the dorsolateral prefrontal cortex and posterior lobules VI and VII of the neocerebellum. Since both brain areas have been implicated in emotional processing and mood disorders, working memory and executive functions, this greater activity probably represents coactivation within a cerebro-cerebellar feedback loop regulating emotional and cognitive processing. Some of the evidence suggests that increased activity within this circuit may preserve cerebellar structure during aging, and possible mechanisms and implications of this finding are discussed.
Differential flatness properties and multivariable adaptive control of ovarian system dynamics
NASA Astrophysics Data System (ADS)
Rigatos, Gerasimos
2016-12-01
The ovarian system exhibits nonlinear dynamics which is modeled by a set of coupled nonlinear differential equations. The paper proposes adaptive fuzzy control based on differential flatness theory for the complex dynamics of the ovarian system. It is proven that the dynamic model of the ovarian system, having as state variables the LH and the FSH hormones and their derivatives, is a differentially flat one. This means that all its state variables and its control inputs can be described as differential functions of the flat output. By exploiting differential flatness properties the system's dynamic model is written in the multivariable linear canonical (Brunovsky) form, for which the design of a state feedback controller becomes possible. After this transformation, the new control inputs of the system contain unknown nonlinear parts, which are identified with the use of neurofuzzy approximators. The learning procedure for these estimators is determined by the requirement the first derivative of the closed-loop's Lyapunov function to be a negative one. Moreover, Lyapunov stability analysis shows that H-infinity tracking performance is succeeded for the feedback control loop and this assures improved robustness to the aforementioned model uncertainty as well as to external perturbations. The efficiency of the proposed adaptive fuzzy control scheme is confirmed through simulation experiments.
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
Digital control of a direct current converter for a hybrid vehicle
NASA Astrophysics Data System (ADS)
Hernandez, Juan Manuel
The nonlinear feedback loops permitting the large signal control of pulse width modulators in direct current converters are discussed. A digital feedback loop on a converter controlling the coupling of a direct current machine is described. It is used in the propulsion of a hybrid vehicle (thermal-electric) with regenerative braking. The protection of the power switches is also studied. An active protection of the MOST bipolar transistor association is proposed.
Power supply with air core transformer and seperated power supplies for high dynamic range
NASA Technical Reports Server (NTRS)
Orient, Otto (Inventor); Chutjian, Ara (Inventor); Aalami, Dean (Inventor); Darrach, Murray (Inventor)
2001-01-01
A power supply for a quadrupole mass spectrometer which operates using an RF signal. The RF signal is controllable via a feedback loop. The feedback loop is from the output, through a comparator, and compared to a digital signal. An air core transformer is used to minimize the weight. The air core transformer is driven via two out of phase sawtooth signals which drive opposite ends of the transformer.
Dual-range linearized transimpedance amplifier system
Wessendorf, Kurt O.
2010-11-02
A transimpedance amplifier system is disclosed which simultaneously generates a low-gain output signal and a high-gain output signal from an input current signal using a single transimpedance amplifier having two different feedback loops with different amplification factors to generate two different output voltage signals. One of the feedback loops includes a resistor, and the other feedback loop includes another resistor in series with one or more diodes. The transimpedance amplifier system includes a signal linearizer to linearize one or both of the low- and high-gain output signals by scaling and adding the two output voltage signals from the transimpedance amplifier. The signal linearizer can be formed either as an analog device using one or two summing amplifiers, or alternately can be formed as a digital device using two analog-to-digital converters and a digital signal processor (e.g. a microprocessor or a computer).
DOE Office of Scientific and Technical Information (OSTI.GOV)
Li Dan; Chao Kuangta; He Zhiguo
2009-12-01
We study the production of C=+ charmonium states X in e{sup +}e{sup -}{yields}{gamma}+X at B factories with X={eta}{sub c}(nS) (n=1, 2, 3), {chi}{sub cJ}(mP) (m=1, 2), and {sup 1}D{sub 2}(1D). In the S- and P-wave case, contributions of QED with one-loop QCD corrections are calculated within the framework of nonrelativistic QCD (NRQCD), and in the D-wave case only the QED contribution is considered. We find that in most cases the one-loop QCD corrections are negative and moderate, in contrast to the case of double charmonium production e{sup +}e{sup -}{yields}J/{psi}+X, where one-loop QCD corrections are positive and large in most cases.more » We also find that the production cross sections of some of these states in e{sup +}e{sup -}{yields}{gamma}+X are larger than that in e{sup +}e{sup -}{yields}J/{psi}+X by an order of magnitude even after the negative one-loop QCD corrections are included. We then argue that search for the X(3872), X(3940), Y(3940), and X(4160) in e{sup +}e{sup -}{yields}{gamma}+X at B factories may be helpful to clarify the nature of these states. For completeness, the production of bottomonium states in e{sup +}e{sup -} annihilation is also discussed.« less
Circuit Regulates Speed Of dc Motor
NASA Technical Reports Server (NTRS)
Weaver, Charles; Padden, Robin; Brown, Floyd A., Jr.
1990-01-01
Driving circuit regulates speed of small dc permanent-magnet motor in tape recorder. Two nested feedback loops maintain speed within 1 percent of constant value. Inner loop provides coarse regulation, while outer loop removes most of variation in speed that remains in the presence of regulation by the inner loop. Compares speed of motor with commanded speed and adjusts current supplied to motor accordingly.
Runtime Assurance Framework Development for Highly Adaptive Flight Control Systems
2015-12-01
performing a surveillance mission. The demonstration platform consisted of RTA systems for the inner- loop control, outer- loop guidance, ownship flight...For the inner- loop , the concept of employing multiple transition controllers in the reversionary control system was studied. For all feedback levels...5 RTA Protection Applied to Inner- Loop Control Systems .................................................61 5.1 General Description of Morphing Wing
Clinical Results of Flexor Tendon Repair in Zone II Using a six Strand Double Loop Technique.
Savvidou, Christiana; Tsai, Tsu-Min
2015-06-01
The purpose of this study is to report the clinical results after repair of flexor tendon zone II injuries utilizing a 6-strand double-loop technique and early post-operative active rehabilitation. We retrospectively reviewed 22 patients involving 51 cases with zone II flexor tendon repair using a six strand double loop technique from September 1996 to December 2012. Most common mechanism of injuries was sharp lacerations (86.5 %). Tendon injuries occurred equally in manual and non-manual workers and were work-related in 33 % of the cases. The Strickland score for active range of motion (ROM) postoperatively was excellent and good in the majority of the cases (81 %). The rupture rate was 1.9 %. The six strand double loop technique for Zone II flexor tendon repair leads to good and excellent motion in the majority of patients and low re- rupture rate. It is clinically effective and allows for early postoperative active rehabilitation.
Cushing's syndrome: from physiological principles to diagnosis and clinical care.
Raff, Hershel; Carroll, Ty
2015-02-01
The physiological control of cortisol synthesis in the adrenal cortex involves stimulation of adrenocorticotrophic hormone (ACTH) by hypothalamic corticotrophin-releasing hormone (CRH) and then stimulation of the adrenal by ACTH. The control loop of the hypothalamic-pituitary-adrenal (HPA) axis is closed by negative feedback of cortisol on the hypothalamus and pituitary. Understanding this system is required to master the diagnosis, differential diagnosis and treatment of endogenous hypercortisolism--Cushing's syndrome. Endogenous Cushing's syndrome is caused either by excess ACTH secretion or by autonomous cortisol release from the adrenal cortex. Diagnosis of cortisol excess exploits three physiological principles: failure to achieve the normal nadir in the cortisol diurnal rhythm, loss of sensitivity of ACTH-secreting tumours to cortisol negative feedback, and increased excretion of free cortisol in the urine. Differentiating a pituitary source of excess ACTH (Cushing's disease) from an ectopic source is accomplished by imaging the pituitary and sampling for ACTH in the venous drainage of the pituitary. With surgical removal of ACTH or cortisol-secreting tumours, secondary adrenal insufficiency ensues because of the prior suppression of the HPA axis by glucocorticoid negative feedback. Medical therapy is targeted to the anatomical location of the dysregulated component of the HPA axis. Future research will focus on new diagnostics and treatments of Cushing's syndrome. These are elegant examples of translational research: understanding basic physiology informs the development of new approaches to diagnosis and treatment. Appreciating pathophysiology generates new areas for inquiry of basic physiological and biochemical mechanisms. © 2014 The Authors. The Journal of Physiology © 2014 The Physiological Society.
Levine, Paul A.; Randerson, James T.; Swenson, Sean C.; ...
2016-12-09
The relationship between terrestrial water storage (TWS) and atmospheric processes has important implications for predictability of climatic extremes and projection of future climate change. In places where moisture availability limits evapotranspiration (ET), variability in TWS has the potential to influence surface energy fluxes and atmospheric conditions. Where atmospheric conditions, in turn, influence moisture availability, a full feedback loop exists. Here we developed a novel approach for measuring the strength of both components of this feedback loop, i.e., the forcing of the atmosphere by variability in TWS and the response of TWS to atmospheric variability, using satellite observations of TWS, precipitation,more » solar radiation, and vapor pressure deficit during 2002–2014. Our approach defines metrics to quantify the relationship between TWS anomalies and climate globally on a seasonal to interannual timescale. Metrics derived from the satellite data were used to evaluate the strength of the feedback loop in 38 members of the Community Earth System Model (CESM) Large Ensemble (LENS) and in six models that contributed simulations to phase 5 of the Coupled Model Intercomparison Project (CMIP5). We found that both forcing and response limbs of the feedback loop in LENS were stronger than in the satellite observations in tropical and temperate regions. Feedbacks in the selected CMIP5 models were not as strong as those found in LENS, but were still generally stronger than those estimated from the satellite measurements. Consistent with previous studies conducted across different spatial and temporal scales, our analysis suggests that models may overestimate the strength of the feedbacks between the land surface and the atmosphere. Lastly, we describe several possible mechanisms that may contribute to this bias, and discuss pathways through which models may overestimate ET or overestimate the sensitivity of ET to TWS.« less
Invasive plants may promote predator-mediated feedback that inhibits further invasion
Smith, Lauren M; Schmitz, Oswald J
2015-01-01
Understanding the impacts of invasive species requires placing invasion within a full community context. Plant invaders are often considered in the context of herbivores that may drive invasion by avoiding invaders while consuming natives (enemy escape), or inhibit invasion by consuming invaders (biotic resistance). However, predators that attack those herbivores are rarely considered as major players in invasion. Invasive plants often promote predators, generally by providing improved habitat. Here, we show that predator-promoting invaders may initiate a negative feedback loop that inhibits invasion. By enabling top-down control of herbivores, predator-promoting invaders lose any advantage gained through enemy escape, indirectly favoring natives. In cases where palatable invaders encounter biotic resistance, predator promotion may allow an invader to persist, but not dominate. Overall, results indicate that placing invaders in a full community context may reveal reduced impacts of invaders compared to expectations based on simple plant–plant or plant–herbivore subsystems. PMID:26120430
Closed Loop Vibrational Control: Theory and Applications
1993-10-01
the open loop system dynamics will be close to that of Bit. However, in general, in a closed loop system with a specified feedback co-’ - oller , for...Juang, and G. Rodriguez , "Formulations and Applications of Large Structure Actuator and Sensor Placements," Second VPI & SU/AIAA Symposium on Dynamics
OncomiR Addiction Is Generated by a miR-155 Feedback Loop in Theileria-Transformed Leukocytes
Medjkane, Souhila; Perichon, Martine; Yin, Qinyan; Flemington, Erik; Weitzman, Matthew D.; Weitzman, Jonathan B.
2013-01-01
The intracellular parasite Theileria is the only eukaryote known to transform its mammalian host cells. We investigated the host mechanisms involved in parasite-induced transformation phenotypes. Tumour progression is a multistep process, yet ‘oncogene addiction’ implies that cancer cell growth and survival can be impaired by inactivating a single gene, offering a rationale for targeted molecular therapies. Furthermore, feedback loops often act as key regulatory hubs in tumorigenesis. We searched for microRNAs involved in addiction to regulatory loops in leukocytes infected with Theileria parasites. We show that Theileria transformation involves induction of the host bovine oncomiR miR-155, via the c-Jun transcription factor and AP-1 activity. We identified a novel miR-155 target, DET1, an evolutionarily-conserved factor involved in c-Jun ubiquitination. We show that miR-155 expression led to repression of DET1 protein, causing stabilization of c-Jun and driving the promoter activity of the BIC transcript containing miR-155. This positive feedback loop is critical to maintain the growth and survival of Theileria-infected leukocytes; transformation is reversed by inhibiting AP-1 activity or miR-155 expression. This is the first demonstration that Theileria parasites induce the expression of host non-coding RNAs and highlights the importance of a novel feedback loop in maintaining the proliferative phenotypes induced upon parasite infection. Hence, parasite infection drives epigenetic rewiring of the regulatory circuitry of host leukocytes, placing miR-155 at the crossroads between infection, regulatory circuits and transformation. PMID:23637592
Direct laser additive fabrication system with image feedback control
Griffith, Michelle L.; Hofmeister, William H.; Knorovsky, Gerald A.; MacCallum, Danny O.; Schlienger, M. Eric; Smugeresky, John E.
2002-01-01
A closed-loop, feedback-controlled direct laser fabrication system is disclosed. The feedback refers to the actual growth conditions obtained by real-time analysis of thermal radiation images. The resulting system can fabricate components with severalfold improvement in dimensional tolerances and surface finish.
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.
Negative autoregulation matches production and demand in synthetic transcriptional networks.
Franco, Elisa; Giordano, Giulia; Forsberg, Per-Ola; Murray, Richard M
2014-08-15
We propose a negative feedback architecture that regulates activity of artificial genes, or "genelets", to meet their output downstream demand, achieving robustness with respect to uncertain open-loop output production rates. In particular, we consider the case where the outputs of two genelets interact to form a single assembled product. We show with analysis and experiments that negative autoregulation matches the production and demand of the outputs: the magnitude of the regulatory signal is proportional to the "error" between the circuit output concentration and its actual demand. This two-device system is experimentally implemented using in vitro transcriptional networks, where reactions are systematically designed by optimizing nucleic acid sequences with publicly available software packages. We build a predictive ordinary differential equation (ODE) model that captures the dynamics of the system and can be used to numerically assess the scalability of this architecture to larger sets of interconnected genes. Finally, with numerical simulations we contrast our negative autoregulation scheme with a cross-activation architecture, which is less scalable and results in slower response times.
Does Double Loop Learning Create Reliable Knowledge?
ERIC Educational Resources Information Center
Blackman, Deborah; Connelly, James; Henderson, Steven
2004-01-01
This paper addresses doubts concerning the reliability of knowledge being created by double loop learning processes. Popper's ontological worlds are used to explore the philosophical basis of the way that individual experiences are turned into organisational knowledge, and such knowledge is used to generate organisational learning. The paper…
Metabolism and acetylation contribute to leucine-mediated inhibition of cardiac glucose uptake.
Renguet, Edith; Ginion, Audrey; Gélinas, Roselle; Bultot, Laurent; Auquier, Julien; Robillard Frayne, Isabelle; Daneault, Caroline; Vanoverschelde, Jean-Louis; Des Rosiers, Christine; Hue, Louis; Horman, Sandrine; Beauloye, Christophe; Bertrand, Luc
2017-08-01
High plasma leucine levels strongly correlate with type 2 diabetes. Studies of muscle cells have suggested that leucine alters the insulin response for glucose transport by activating an insulin-negative feedback loop driven by the mammalian target of rapamycin/p70 ribosomal S6 kinase (mTOR/p70S6K) pathway. Here, we examined the molecular mechanism involved in leucine's action on cardiac glucose uptake. Leucine was indeed able to curb glucose uptake after insulin stimulation in both cultured cardiomyocytes and perfused hearts. Although leucine activated mTOR/p70S6K, the mTOR inhibitor rapamycin did not prevent leucine's inhibitory action on glucose uptake, ruling out the contribution of the insulin-negative feedback loop. α-Ketoisocaproate, the first metabolite of leucine catabolism, mimicked leucine's effect on glucose uptake. Incubation of cardiomyocytes with [ 13 C]leucine ascertained its metabolism to ketone bodies (KBs), which had a similar negative impact on insulin-stimulated glucose transport. Both leucine and KBs reduced glucose uptake by affecting translocation of glucose transporter 4 (GLUT4) to the plasma membrane. Finally, we found that leucine elevated the global protein acetylation level. Pharmacological inhibition of lysine acetyltransferases counteracted this increase in protein acetylation and prevented leucine's inhibitory action on both glucose uptake and GLUT4 translocation. Taken together, these results indicate that leucine metabolism into KBs contributes to inhibition of cardiac glucose uptake by hampering the translocation of GLUT4-containing vesicles via acetylation. They offer new insights into the establishment of insulin resistance in the heart. NEW & NOTEWORTHY Catabolism of the branched-chain amino acid leucine into ketone bodies efficiently inhibits cardiac glucose uptake through decreased translocation of glucose transporter 4 to the plasma membrane. Leucine increases protein acetylation. Pharmacological inhibition of acetylation reverses leucine's action, suggesting acetylation involvement in this phenomenon.Listen to this article's corresponding podcast at http://ajpheart.podbean.com/e/leucine-metabolism-inhibits-cardiac-glucose-uptake/. Copyright © 2017 the American Physiological Society.
Effects of explicit convection on global land-atmosphere coupling in the superparameterized CAM
Sun, Jian; Pritchard, Michael S.
2016-07-25
Here, conventional global climate models are prone to producing unrealistic land-atmosphere coupling signals. Cumulus and convection parameterizations are natural culprits but the effect of bypassing them with explicitly resolved convection on global land-atmosphere coupling dynamics has not been explored systematically. We apply a suite of modern land-atmosphere coupling diagnostics to isolate the effect of cloud Superparameterization in the Community Atmosphere Model (SPCAM) v3.5, focusing on both the terrestrial segment (i.e., soil moisture and surface turbulent fluxes interaction) and atmospheric segment (i.e., surface turbulent fluxes and precipitation interaction) in the water pathway of the landatmosphere feedback loop. At daily timescales, SPCAMmore » produces stronger uncoupled terrestrial signals (negative sign) over tropical rainforests in wet seasons, reduces the terrestrial coupling strength in the Central Great Plain in American, and reverses the coupling sign (from negative to positive) over India in the boreal summer season—all favorable improvements relative to reanalysis-forced land modeling. Analysis of the triggering feedback strength (TFS) and amplification feedback strength (AFS) shows that SPCAM favorably reproduces the observed geographic patterns of these indices over North America, with the probability of afternoon precipitation enhanced by high evaporative fraction along the eastern United States and Mexico, while conventional CAM does not capture this signal. We introduce a new diagnostic called the Planetary Boundary Layer (PBL) Feedback Strength (PFS), which reveals that SPCAM exhibits a tight connection between the responses of the lifting condensation level, the PBL height, and the rainfall triggering to surface turbulent fluxes; a triggering disconnect is found in CAM.« less
Effects of explicit convection on global land-atmosphere coupling in the superparameterized CAM
NASA Astrophysics Data System (ADS)
Sun, Jian; Pritchard, Michael S.
2016-09-01
Conventional global climate models are prone to producing unrealistic land-atmosphere coupling signals. Cumulus and convection parameterizations are natural culprits but the effect of bypassing them with explicitly resolved convection on global land-atmosphere coupling dynamics has not been explored systematically. We apply a suite of modern land-atmosphere coupling diagnostics to isolate the effect of cloud Superparameterization in the Community Atmosphere Model (SPCAM) v3.5, focusing on both the terrestrial segment (i.e., soil moisture and surface turbulent fluxes interaction) and atmospheric segment (i.e., surface turbulent fluxes and precipitation interaction) in the water pathway of the land-atmosphere feedback loop. At daily timescales, SPCAM produces stronger uncoupled terrestrial signals (negative sign) over tropical rainforests in wet seasons, reduces the terrestrial coupling strength in the Central Great Plain in American, and reverses the coupling sign (from negative to positive) over India in the boreal summer season—all favorable improvements relative to reanalysis-forced land modeling. Analysis of the triggering feedback strength (TFS) and amplification feedback strength (AFS) shows that SPCAM favorably reproduces the observed geographic patterns of these indices over North America, with the probability of afternoon precipitation enhanced by high evaporative fraction along the eastern United States and Mexico, while conventional CAM does not capture this signal. We introduce a new diagnostic called the Planetary Boundary Layer (PBL) Feedback Strength (PFS), which reveals that SPCAM exhibits a tight connection between the responses of the lifting condensation level, the PBL height, and the rainfall triggering to surface turbulent fluxes; a triggering disconnect is found in CAM.
Effects of explicit convection on global land-atmosphere coupling in the superparameterized CAM
DOE Office of Scientific and Technical Information (OSTI.GOV)
Sun, Jian; Pritchard, Michael S.
Here, conventional global climate models are prone to producing unrealistic land-atmosphere coupling signals. Cumulus and convection parameterizations are natural culprits but the effect of bypassing them with explicitly resolved convection on global land-atmosphere coupling dynamics has not been explored systematically. We apply a suite of modern land-atmosphere coupling diagnostics to isolate the effect of cloud Superparameterization in the Community Atmosphere Model (SPCAM) v3.5, focusing on both the terrestrial segment (i.e., soil moisture and surface turbulent fluxes interaction) and atmospheric segment (i.e., surface turbulent fluxes and precipitation interaction) in the water pathway of the landatmosphere feedback loop. At daily timescales, SPCAMmore » produces stronger uncoupled terrestrial signals (negative sign) over tropical rainforests in wet seasons, reduces the terrestrial coupling strength in the Central Great Plain in American, and reverses the coupling sign (from negative to positive) over India in the boreal summer season—all favorable improvements relative to reanalysis-forced land modeling. Analysis of the triggering feedback strength (TFS) and amplification feedback strength (AFS) shows that SPCAM favorably reproduces the observed geographic patterns of these indices over North America, with the probability of afternoon precipitation enhanced by high evaporative fraction along the eastern United States and Mexico, while conventional CAM does not capture this signal. We introduce a new diagnostic called the Planetary Boundary Layer (PBL) Feedback Strength (PFS), which reveals that SPCAM exhibits a tight connection between the responses of the lifting condensation level, the PBL height, and the rainfall triggering to surface turbulent fluxes; a triggering disconnect is found in CAM.« less
Polarization switching in undoped and La-doped TlInS2 ferroelectric-semiconductors
NASA Astrophysics Data System (ADS)
Seyidov, MirHasan Yu.; Mikailzade, Faik A.; Suleymanov, Rauf A.; Aliyeva, Vafa B.; Mammadov, Tofig G.; Sharifov, Galib M.
2017-12-01
Dielectric hysteresis loops of pure and lanthanum doped TlInS2 ferroelectric-semiconductors were studied at the frequency 50 Hz for different temperatures below the Curie temperature (Tc). It has been revealed that, without any poling procedure, pure TlInS2 exhibits normal single hysteresis loops at T < Tc. After electric field-cooled treatment of TlInS2 the shape of hysteresis loops was strongly affected by corresponding charged deep level defects which were previously activated during the poling process. As a result, an additional defect polarization state from space charges accumulated on the intrinsic deep level defects has been revealed in pure TlInS2 at the temperatures below Tc. Besides, unusual multiple hysteresis loops were observed in La doped TlInS2 at T < Tc after application of different external perturbations (electric field, exposition and memory effect) to the sample. Measurements of the hysteresis loops in TlInS2:La revealed the slim single, double and even triple polarization-electric field (P-E) hysteresis loops. This intriguing phenomenon is attributed to the domain pinning by photo- and electrically active La-impurity centers. The temperature variation of double-hysteresis loop was also investigated. Due to the heat elimination of the random local defect polar moments, the double-hysteresis loops were transformed into a normal single hysteresis loops on increasing the temperature.
Höhne, Klaus; Shirahama, Hiroyuki; Choe, Chol-Ung; Benner, Hartmut; Pyragas, Kestutis; Just, Wolfram
2007-05-25
We demonstrate by electronic circuit experiments the feasibility of an unstable control loop to stabilize torsion-free orbits by time-delayed feedback control. Corresponding analytical normal form calculations and numerical simulations reveal a severe dependence of the basin of attraction on the particular coupling scheme of the control force. Such theoretical predictions are confirmed by the experiments and emphasize the importance of the coupling scheme for the global control performance.
Gunawardhana, Kushan L; Hardin, Paul E
2017-11-20
In Drosophila, the circadian clock is comprised of transcriptional feedback loops that control rhythmic gene expression responsible for daily rhythms in physiology, metabolism, and behavior. The core feedback loop, which employs CLOCK-CYCLE (CLK-CYC) activators and PERIOD-TIMELESS (PER-TIM) repressors to drive rhythmic transcription peaking at dusk, is required for circadian timekeeping and overt behavioral rhythms. CLK-CYC also activates an interlocked feedback loop, which uses the PAR DOMAIN PROTEIN 1ε (PDP1ε) activator and the VRILLE (VRI) repressor to drive rhythmic transcription peaking at dawn. Although Pdp1ε mutants disrupt activity rhythms without eliminating clock function, whether vri is required for clock function and/or output is not known. Using a conditionally inactivatable transgene to rescue vri developmental lethality, we show that clock function persists after vri inactivation but that activity rhythms are abolished. The inactivation of vri disrupts multiple output pathways thought to be important for activity rhythms, including PDF accumulation and arborization rhythms in the small ventrolateral neuron (sLN v ) dorsal projection. These results demonstrate that vri acts as a key regulator of clock output and suggest that the primary function of the interlocked feedback loop in Drosophila is to drive rhythmic transcription required for overt rhythms. Copyright © 2017 Elsevier Ltd. All rights reserved.
Turcotte, Martin M; Reznick, David N; Daniel Hare, J
2013-05-01
An eco-evolutionary feedback loop is defined as the reciprocal impacts of ecology on evolutionary dynamics and evolution on ecological dynamics on contemporary timescales. We experimentally tested for an eco-evolutionary feedback loop in the green peach aphid, Myzus persicae, by manipulating initial densities and evolution. We found strong evidence that initial aphid density alters the rate and direction of evolution, as measured by changes in genotype frequencies through time. We also found that evolution of aphids within only 16 days, or approximately three generations, alters the rate of population growth and predicts density compared to nonevolving controls. The impact of evolution on population dynamics also depended on density. In one evolution treatment, evolution accelerated population growth by up to 10.3% at high initial density or reduced it by up to 6.4% at low initial density. The impact of evolution on population growth was as strong as or stronger than that caused by a threefold change in intraspecific density. We found that, taken together, ecological condition, here intraspecific density, alters evolutionary dynamics, which in turn alter concurrent population growth rate (ecological dynamics) in an eco-evolutionary feedback loop. Our results suggest that ignoring evolution in studies predicting population dynamics might lead us to over- or underestimate population density and that we cannot predict the evolutionary outcome within aphid populations without considering population size.
Evaluating Land-Atmosphere Moisture Feedbacks in Earth System Models With Spaceborne Observations
NASA Astrophysics Data System (ADS)
Levine, P. A.; Randerson, J. T.; Lawrence, D. M.; Swenson, S. C.
2016-12-01
We have developed a set of metrics for measuring the feedback loop between the land surface moisture state and the atmosphere globally on an interannual time scale. These metrics consider both the forcing of terrestrial water storage (TWS) on subsequent atmospheric conditions as well as the response of TWS to antecedent atmospheric conditions. We designed our metrics to take advantage of more than one decade's worth of satellite observations of TWS from the Gravity Recovery and Climate Experiment (GRACE) along with atmospheric variables from the Atmospheric Infrared Sounder (AIRS), the Global Precipitation Climatology Project (GPCP), and Clouds and the Earths Radiant Energy System (CERES). Metrics derived from spaceborne observations were used to evaluate the strength of the feedback loop in the Community Earth System Model (CESM) Large Ensemble (LENS) and in several models that contributed simulations to Phase 5 of the Coupled Model Intercomparison Project (CMIP5). We found that both forcing and response limbs of the feedback loop were generally stronger in tropical and temperate regions in CMIP5 models and even more so in LENS compared to satellite observations. Our analysis suggests that models may overestimate the strength of the feedbacks between the land surface and the atmosphere, which is consistent with previous studies conducted across different spatial and temporal scales.
Mathematical Modeling of RNA-Based Architectures for Closed Loop Control of Gene Expression.
Agrawal, Deepak K; Tang, Xun; Westbrook, Alexandra; Marshall, Ryan; Maxwell, Colin S; Lucks, Julius; Noireaux, Vincent; Beisel, Chase L; Dunlop, Mary J; Franco, Elisa
2018-05-08
Feedback allows biological systems to control gene expression precisely and reliably, even in the presence of uncertainty, by sensing and processing environmental changes. Taking inspiration from natural architectures, synthetic biologists have engineered feedback loops to tune the dynamics and improve the robustness and predictability of gene expression. However, experimental implementations of biomolecular control systems are still far from satisfying performance specifications typically achieved by electrical or mechanical control systems. To address this gap, we present mathematical models of biomolecular controllers that enable reference tracking, disturbance rejection, and tuning of the temporal response of gene expression. These controllers employ RNA transcriptional regulators to achieve closed loop control where feedback is introduced via molecular sequestration. Sensitivity analysis of the models allows us to identify which parameters influence the transient and steady state response of a target gene expression process, as well as which biologically plausible parameter values enable perfect reference tracking. We quantify performance using typical control theory metrics to characterize response properties and provide clear selection guidelines for practical applications. Our results indicate that RNA regulators are well-suited for building robust and precise feedback controllers for gene expression. Additionally, our approach illustrates several quantitative methods useful for assessing the performance of biomolecular feedback control systems.
Kolesnikoff, Natasha; Attema, Joanne L; Roslan, Suraya; Bert, Andrew G; Schwarz, Quenten P; Gregory, Philip A; Goodall, Gregory J
2014-04-18
Epithelial-mesenchymal transition (EMT) is required for the specification of tissues during embryonic development and is recapitulated during the metastatic progression of tumors. The miR-200 family plays a critical role in enforcing the epithelial state with their expression lost in cells undergoing EMT. EMT can be mediated by activation of the ZEB1 and ZEB2 (ZEB) transcription factors, which repress miR-200 expression via a self-reinforcing double negative feedback loop to promote the mesenchymal state. However, it remains unclear what factors drive and maintain epithelial-specific expression of miR-200 in the absence of EMT-inducing factors. Here, we show that the transcription factor Specificity Protein 1 (Sp1) binds to the miR-200b∼200a∼429 proximal promoter and activates miR-200 expression in epithelial cells. In mesenchymal cells, Sp1 expression is maintained, but its ability to activate the miR-200 promoter is perturbed by ZEB-mediated repression. Reduction of Sp1 expression caused changes in EMT-associated markers in epithelial cells. Furthermore, we observed co-expression of Sp1 and miR-200 during mouse embryonic development wherein miR-200 expression was only lost in regions with high ZEB expression. Together, these findings indicate that miR-200 family members require Sp1 to drive basal expression and to maintain an epithelial state.
Beaulieu, M L; Palmieri-Smith, R M
2014-08-01
Excessive knee abduction loading is a contributing factor to anterior cruciate ligament (ACL) injury risk. The purpose of this study was to determine whether a double-leg landing training program with real-time visual feedback improves frontal-plane mechanics during double- and single-leg landings. Knee abduction angles and moments and vertical ground reaction forces (GRF) of 21 recreationally active women were quantified for double- and single-leg landings before and after the training program. This program consisted of two sessions of double-leg jump landings with real-time visual feedback on knee abduction moments for the experimental group and without real-time feedback for the control group. No significant differences were found between training groups. In comparison with pre-training data, peak knee abduction moments decreased 12% post-training for both double- and single-leg landings; whereas peak vertical GRF decreased 8% post-training for double-leg landings only, irrespective of training group. Real-time feedback on knee abduction moments, therefore, did not significantly improve frontal-plane knee mechanics during landings. The effect of the training program on knee abduction moments, however, transferred from the double-leg landings (simple task) to single-leg landings (more complex task). Consequently, ACL injury prevention efforts may not need to focus on complex tasks during which injury occurs. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Feedback Augmented Sub-Ranging (FASR) Quantizer
NASA Technical Reports Server (NTRS)
Guilligan, Gerard
2012-01-01
This innovation is intended to reduce the size, power, and complexity of pipeline analog-to-digital converters (ADCs) that require high resolution and speed along with low power. Digitizers are important components in any application where analog signals (such as light, sound, temperature, etc.) need to be digitally processed. The innovation implements amplification of a sampled residual voltage in a switched capacitor amplifier stage that does not depend on charge redistribution. The result is less sensitive to capacitor mismatches that cause gain errors, which are the main limitation of such amplifiers in pipeline ADCs. The residual errors due to mismatch are reduced by at least a factor of 16, which is equivalent to at least 4 bits of improvement. The settling time is also faster because of a higher feedback factor. In traditional switched capacitor residue amplifiers, closed-loop amplification of a sampled and held residue signal is achieved by redistributing sampled charge onto a feedback capacitor around a high-gain transconductance amplifier. The residual charge that was sampled during the acquisition or sampling phase is stored on two or more capacitors, often equal in value or integral multiples of each other. During the hold or amplification phase, all of the charge is redistributed onto one capacitor in the feedback loop of the amplifier to produce an amplified voltage. The key error source is the non-ideal ratios of feedback and input capacitors caused by manufacturing tolerances, called mismatches. The mismatches cause non-ideal closed-loop gain, leading to higher differential non-linearity. Traditional solutions to the mismatch errors are to use larger capacitor values (than dictated by thermal noise requirements) and/or complex calibration schemes, both of which increase the die size and power dissipation. The key features of this innovation are (1) the elimination of the need for charge redistribution to achieve an accurate closed-loop gain of two, (2) a higher feedback factor in the amplifier stage giving a higher closed-loop bandwidth compared to the prior art, and (3) reduced requirement for calibration. The accuracy of the new amplifier is mainly limited by the sampling networks parasitic capacitances, which should be minimized in relation to the sampling capacitors.
HER2 in Breast Cancer Stemness: A Negative Feedback Loop towards Trastuzumab Resistance
Nami, Babak; Wang, Zhixiang
2017-01-01
HER2 receptor tyrosine kinase that is overexpressed in approximately 20% of all breast cancers (BCs) is a poor prognosis factor and a precious target for BC therapy. Trastuzumab is approved by FDA to specifically target HER2 for treating HER2+ BC. However, about 60% of patients with HER2+ breast tumor develop de novo resistance to trastuzumab, partially due to the loss of expression of HER2 extracellular domain on their tumor cells. This is due to shedding/cleavage of HER2 by metalloproteinases (ADAMs and MMPs). HER2 shedding results in the accumulation of intracellular carboxyl-terminal HER2 (p95HER2), which is a common phenomenon in trastuzumab-resistant tumors and is suggested as a predictive marker for trastuzumab resistance. Up-regulation of the metalloproteinases is a poor prognosis factor and is commonly seen in mesenchymal-like cancer stem cells that are risen during epithelial to mesenchymal transition (EMT) of tumor cells. HER2 cleavage during EMT can explain why secondary metastatic tumors with high percentage of mesenchymal-like cancer stem cells are mostly resistant to trastuzumab but still sensitive to lapatinib. Importantly, many studies report HER2 interaction with oncogenic/stemness signaling pathways including TGF-β/Smad, Wnt/β-catenin, Notch, JAK/STAT and Hedgehog. HER2 overexpression promotes EMT and the emergence of cancer stem cell properties in BC. Increased expression and activation of metalloproteinases during EMT leads to proteolytic cleavage and shedding of HER2 receptor, which downregulates HER2 extracellular domain and eventually increases trastuzumab resistance. Here, we review the hypothesis that a negative feedback loop between HER2 and stemness signaling drives resistance of BC to trastuzumab. PMID:28445439
Comprehensive Logic Based Analyses of Toll-Like Receptor 4 Signal Transduction Pathway
Padwal, Mahesh Kumar; Sarma, Uddipan; Saha, Bhaskar
2014-01-01
Among the 13 TLRs in the vertebrate systems, only TLR4 utilizes both Myeloid differentiation factor 88 (MyD88) and Toll/Interleukin-1 receptor (TIR)-domain-containing adapter interferon-β-inducing Factor (TRIF) adaptors to transduce signals triggering host-protective immune responses. Earlier studies on the pathway combined various experimental data in the form of one comprehensive map of TLR signaling. But in the absence of adequate kinetic parameters quantitative mathematical models that reveal emerging systems level properties and dynamic inter-regulation among the kinases/phosphatases of the TLR4 network are not yet available. So, here we used reaction stoichiometry-based and parameter independent logical modeling formalism to build the TLR4 signaling network model that captured the feedback regulations, interdependencies between signaling kinases and phosphatases and the outcome of simulated infections. The analyses of the TLR4 signaling network revealed 360 feedback loops, 157 negative and 203 positive; of which, 334 loops had the phosphatase PP1 as an essential component. The network elements' interdependency (positive or negative dependencies) in perturbation conditions such as the phosphatase knockout conditions revealed interdependencies between the dual-specific phosphatases MKP-1 and MKP-3 and the kinases in MAPK modules and the role of PP2A in the auto-regulation of Calmodulin kinase-II. Our simulations under the specific kinase or phosphatase gene-deficiency or inhibition conditions corroborated with several previously reported experimental data. The simulations to mimic Yersinia pestis and E. coli infections identified the key perturbation in the network and potential drug targets. Thus, our analyses of TLR4 signaling highlights the role of phosphatases as key regulatory factors in determining the global interdependencies among the network elements; uncovers novel signaling connections; identifies potential drug targets for infections. PMID:24699232
A Low noise, Non-contact Capacitive Cardiac Sensor*
Peng, GuoChen; Bocko, Mark F.
2014-01-01
The development of sensitive, non-contact electric field sensors to measure weak bioelectric signals will be useful for the development of a number of unobtrusive health sensors. In this paper we summarize our recent work on a number of specific challenges in the development of non-contact ECG sensors. First, we considered the design of a low noise sensor preamplifier. We have adapted circuit designs that incorporate a double feedback loop to cancel the input transistor leakage current while providing stable operation, fast settling time and good low frequency response without the need for ultrahigh value resistors. The measured input referred noise of the preamplifier in the frequency band 0.05–100 Hz is 0.76 μVrms, which is several times lower than existing ECG preamplifiers. PMID:23367049
A low noise, non-contact capacitive cardiac sensor.
Peng, GuoChen; Bocko, Mark F
2012-01-01
The development of sensitive, non-contact electric field sensors to measure weak bioelectric signals will be useful for the development of a number of unobtrusive health sensors. In this paper we summarize our recent work on a number of specific challenges in the development of non-contact ECG sensors. First, we considered the design of a low noise sensor preamplifier. We have adapted circuit designs that incorporate a double feedback loop to cancel the input transistor leakage current while providing stable operation, fast settling time and good low frequency response without the need for ultrahigh value resistors. The measured input referred noise of the preamplifier in the frequency band 0.05-100 Hz is 0.76 µV(rms), which is several times lower than existing ECG preamplifiers.
Quantifying the ice-albedo feedback through decoupling
NASA Astrophysics Data System (ADS)
Kravitz, B.; Rasch, P. J.
2017-12-01
The ice-albedo feedback involves numerous individual components, whereby warming induces sea ice melt, inducing reduced surface albedo, inducing increased surface shortwave absorption, causing further warming. Here we attempt to quantify the sea ice albedo feedback using an analogue of the "partial radiative perturbation" method, but where the governing mechanisms are directly decoupled in a climate model. As an example, we can isolate the insulating effects of sea ice on surface energy and moisture fluxes by allowing sea ice thickness to change but fixing Arctic surface albedo, or vice versa. Here we present results from such idealized simulations using the Community Earth System Model in which individual components are successively fixed, effectively decoupling the ice-albedo feedback loop. We isolate the different components of this feedback, including temperature change, sea ice extent/thickness, and air-sea exchange of heat and moisture. We explore the interactions between these different components, as well as the strengths of the total feedback in the decoupled feedback loop, to quantify contributions from individual pieces. We also quantify the non-additivity of the effects of the components as a means of investigating the dominant sources of nonlinearity in the ice-albedo feedback.
Feedback and Sentence Learning.
ERIC Educational Resources Information Center
Guthrie, John T.
The theoretical functions of external feedback in SR and closed loop models of verbal learning are presented. Contradictory predictions from the models are tested with a three by three factorial experiment including three types of feedback and three amounts of rehearsal. There were 90 adult students run individually and they were required to learn…
A new discrete dynamic model of ABA-induced stomatal closure predicts key feedback loops
Acharya, Biswa R.; Jeon, Byeong Wook; Zañudo, Jorge G. T.; Zhu, Mengmeng; Osman, Karim; Assmann, Sarah M.
2017-01-01
Stomata, microscopic pores in leaf surfaces through which water loss and carbon dioxide uptake occur, are closed in response to drought by the phytohormone abscisic acid (ABA). This process is vital for drought tolerance and has been the topic of extensive experimental investigation in the last decades. Although a core signaling chain has been elucidated consisting of ABA binding to receptors, which alleviates negative regulation by protein phosphatases 2C (PP2Cs) of the protein kinase OPEN STOMATA 1 (OST1) and ultimately results in activation of anion channels, osmotic water loss, and stomatal closure, over 70 additional components have been identified, yet their relationships with each other and the core components are poorly elucidated. We integrated and processed hundreds of disparate observations regarding ABA signal transduction responses underlying stomatal closure into a network of 84 nodes and 156 edges and, as a result, established those relationships, including identification of a 36-node, strongly connected (feedback-rich) component as well as its in- and out-components. The network’s domination by a feedback-rich component may reflect a general feature of rapid signaling events. We developed a discrete dynamic model of this network and elucidated the effects of ABA plus knockout or constitutive activity of 79 nodes on both the outcome of the system (closure) and the status of all internal nodes. The model, with more than 1024 system states, is far from fully determined by the available data, yet model results agree with existing experiments in 82 cases and disagree in only 17 cases, a validation rate of 75%. Our results reveal nodes that could be engineered to impact stomatal closure in a controlled fashion and also provide over 140 novel predictions for which experimental data are currently lacking. Noting the paucity of wet-bench data regarding combinatorial effects of ABA and internal node activation, we experimentally confirmed several predictions of the model with regard to reactive oxygen species, cytosolic Ca2+ (Ca2+c), and heterotrimeric G-protein signaling. We analyzed dynamics-determining positive and negative feedback loops, thereby elucidating the attractor (dynamic behavior) repertoire of the system and the groups of nodes that determine each attractor. Based on this analysis, we predict the likely presence of a previously unrecognized feedback mechanism dependent on Ca2+c. This mechanism would provide model agreement with 10 additional experimental observations, for a validation rate of 85%. Our research underscores the importance of feedback regulation in generating robust and adaptable biological responses. The high validation rate of our model illustrates the advantages of discrete dynamic modeling for complex, nonlinear systems common in biology. PMID:28937978
Multiple feedback control apparatus for power conditioning equipment
NASA Technical Reports Server (NTRS)
Biess, John (Inventor); Yu, Yuan (Inventor)
1977-01-01
An improved feedback control system to govern the cyclic operation of the power switch of a non-dissipative power conditioning equipment. The apparatus includes two or three control loops working in unison. The first causes the output DC level to be compared with a reference, and the error amplified for control purposes. The second utilizes the AC component of the voltage across the output filter inductor or the current through the output filter capacitor, and the third loop senses the output transients.
Kalibjian, R.; Perez-Mendez, V.
1957-08-20
An improved circuit for forming square pulses having substantially short and precise durations is described. The gate forming circuit incorporates a secondary emission R. F. pentode adapted to receive input trigger pulses amd having a positive feedback loop comnected from the dynode to the control grid to maintain conduction in response to trigger pulses. A short circuited pulse delay line is employed to precisely control the conducting time of the tube and a circuit for squelching spurious oscillations is provided in the feedback loop.
Agyepong, Irene Akua; Kodua, Augustina; Adjei, Sam; Adam, Taghreed
2012-10-01
Implementation of policies (decisions) in the health sector is sometimes defeated by the system's response to the policy itself. This can lead to counter-intuitive, unanticipated, or more modest effects than expected by those who designed the policy. The health sector fits the characteristics of complex adaptive systems (CAS) and complexity is at the heart of this phenomenon. Anticipating both positive and negative effects of policy decisions, understanding the interests, power and interaction between multiple actors; and planning for the delayed and distal impact of policy decisions are essential for effective decision making in CAS. Failure to appreciate these elements often leads to a series of reductionist approach interventions or 'fixes'. This in turn can initiate a series of negative feedback loops that further complicates the situation over time. In this paper we use a case study of the Additional Duty Hours Allowance (ADHA) policy in Ghana to illustrate these points. Using causal loop diagrams, we unpack the intended and unintended effects of the policy and how these effects evolved over time. The overall goal is to advance our understanding of decision making in complex adaptive systems; and through this process identify some essential elements in formulating, updating and implementing health policy that can help to improve attainment of desired outcomes and minimize negative unintended effects.
Closed-loop and robust control of quantum systems.
Chen, Chunlin; Wang, Lin-Cheng; Wang, Yuanlong
2013-01-01
For most practical quantum control systems, it is important and difficult to attain robustness and reliability due to unavoidable uncertainties in the system dynamics or models. Three kinds of typical approaches (e.g., closed-loop learning control, feedback control, and robust control) have been proved to be effective to solve these problems. This work presents a self-contained survey on the closed-loop and robust control of quantum systems, as well as a brief introduction to a selection of basic theories and methods in this research area, to provide interested readers with a general idea for further studies. In the area of closed-loop learning control of quantum systems, we survey and introduce such learning control methods as gradient-based methods, genetic algorithms (GA), and reinforcement learning (RL) methods from a unified point of view of exploring the quantum control landscapes. For the feedback control approach, the paper surveys three control strategies including Lyapunov control, measurement-based control, and coherent-feedback control. Then such topics in the field of quantum robust control as H(∞) control, sliding mode control, quantum risk-sensitive control, and quantum ensemble control are reviewed. The paper concludes with a perspective of future research directions that are likely to attract more attention.
Beyond R0 Maximisation: On Pathogen Evolution and Environmental Dimensions.
Lion, Sébastien; Metz, Johan A J
2018-06-01
A widespread tenet is that evolution of pathogens maximises their basic reproduction ratio, R 0 . The breakdown of this principle is typically discussed as exception. Here, we argue that a radically different stance is needed, based on evolutionarily stable strategy (ESS) arguments that take account of the 'dimension of the environmental feedback loop'. The R 0 maximisation paradigm requires this feedback loop to be one-dimensional, which notably excludes pathogen diversification. By contrast, almost all realistic ecological ingredients of host-pathogen interactions (density-dependent mortality, multiple infections, limited cross-immunity, multiple transmission routes, host heterogeneity, and spatial structure) will lead to multidimensional feedbacks. Copyright © 2018 Elsevier Ltd. All rights reserved.
NASA Astrophysics Data System (ADS)
Sun, Shu-Ting; Li, Xiao-Dong; Zhong, Ren-Xin
2017-10-01
For nonlinear switched discrete-time systems with input constraints, this paper presents an open-closed-loop iterative learning control (ILC) approach, which includes a feedforward ILC part and a feedback control part. Under a given switching rule, the mathematical induction is used to prove the convergence of ILC tracking error in each subsystem. It is demonstrated that the convergence of ILC tracking error is dependent on the feedforward control gain, but the feedback control can speed up the convergence process of ILC by a suitable selection of feedback control gain. A switched freeway traffic system is used to illustrate the effectiveness of the proposed ILC law.
Closed-loop stability of linear quadratic optimal systems in the presence of modeling errors
NASA Technical Reports Server (NTRS)
Toda, M.; Patel, R.; Sridhar, B.
1976-01-01
The well-known stabilizing property of linear quadratic state feedback design is utilized to evaluate the robustness of a linear quadratic feedback design in the presence of modeling errors. Two general conditions are obtained for allowable modeling errors such that the resulting closed-loop system remains stable. One of these conditions is applied to obtain two more particular conditions which are readily applicable to practical situations where a designer has information on the bounds of modeling errors. Relations are established between the allowable parameter uncertainty and the weighting matrices of the quadratic performance index, thereby enabling the designer to select appropriate weighting matrices to attain a robust feedback design.
Voltage regulator/amplifier is self-regulated
NASA Technical Reports Server (NTRS)
Day, W. E.; Phillips, D. E.
1967-01-01
Signal modulated, self-regulating voltage regulator/amplifier controls the output b-plus voltage in modulated regulator systems. It uses self-oscillation with feedback to a control circuit with a discontinuous amplitude action feedback loop.
A program to evaluate a control system based on feedback of aerodynamic pressure differentials
NASA Technical Reports Server (NTRS)
Levy, D. W.; Finn, P.; Roskam, J.
1981-01-01
The use of aerodynamic pressure differentials to position a control surface is evaluated. The system is a differential pressure command loop, analogous to a position command loop, where the surface is commanded to move until a desired differential pressure across the surface is achieved. This type of control is more direct and accurate because it is the differential pressure which causes the control forces and moments. A frequency response test was performed in a low speed wind tunnel to measure the performance of the system. Both pressure and position feedback were tested. The pressure feedback performed as well as position feedback implying that the actuator, with a break frequency on the order of 10 Rad/sec, was the limiting component. Theoretical considerations indicate that aerodynamic lags will not appear below frequencies of 50 Rad/sec, or higher.
Drive-amplitude-modulation atomic force microscopy: From vacuum to liquids
Jaafar, Miriam; Cuenca, Mariano; Melcher, John; Raman, Arvind
2012-01-01
Summary We introduce drive-amplitude-modulation atomic force microscopy as a dynamic mode with outstanding performance in all environments from vacuum to liquids. As with frequency modulation, the new mode follows a feedback scheme with two nested loops: The first keeps the cantilever oscillation amplitude constant by regulating the driving force, and the second uses the driving force as the feedback variable for topography. Additionally, a phase-locked loop can be used as a parallel feedback allowing separation of the conservative and nonconservative interactions. We describe the basis of this mode and present some examples of its performance in three different environments. Drive-amplutide modulation is a very stable, intuitive and easy to use mode that is free of the feedback instability associated with the noncontact-to-contact transition that occurs in the frequency-modulation mode. PMID:22563531
Ninu, Andrei; Dosen, Strahinja; Muceli, Silvia; Rattay, Frank; Dietl, Hans; Farina, Dario
2014-09-01
In closed-loop control of grasping by hand prostheses, the feedback information sent to the user is usually the actual controlled variable, i.e., the grasp force. Although this choice is intuitive and logical, the force production is only the last step in the process of grasping. Therefore, this study evaluated the performance in controlling grasp strength using a hand prosthesis operated through a complete grasping sequence while varying the feedback variables (e.g., closing velocity, grasping force), which were provided to the user visually or through vibrotactile stimulation. The experiments were conducted on 13 volunteers who controlled the Otto Bock Sensor Hand Speed prosthesis. Results showed that vibrotactile patterns were able to replace the visual feedback. Interestingly, the experiments demonstrated that direct force feedback was not essential for the control of grasping force. The subjects were indeed able to control the grip strength, predictively, by estimating the grasping force from the prosthesis velocity of closing. Therefore, grasping without explicit force feedback is not completely blind, contrary to what is usually assumed. In our study we analyzed grasping with a specific prosthetic device, but the outcomes are also applicable for other devices, with one or more degrees-of-freedom. The necessary condition is that the electromyography (EMG) signal directly and proportionally controls the velocity/grasp force of the hand, which is a common approach among EMG controlled prosthetic devices. The results provide important indications on the design of closed-loop EMG controlled prosthetic systems.
van Duijvenvoorde, Anna C. K.; Bakermans-Kranenburg, Marian J.; Crone, Eveline A.
2016-01-01
Abstract Negative social feedback often generates aggressive feelings and behavior. Prior studies have investigated the neural basis of negative social feedback, but the underlying neural mechanisms of aggression regulation following negative social feedback remain largely undiscovered. In the current study, participants viewed pictures of peers with feedback (positive, neutral or negative) to the participant’s personal profile. Next, participants responded to the peer feedback by pressing a button, thereby producing a loud noise toward the peer, as an index of aggression. Behavioral analyses showed that negative feedback led to more aggression (longer noise blasts). Conjunction neuroimaging analyses revealed that both positive and negative feedback were associated with increased activity in the medial prefrontal cortex (PFC) and bilateral insula. In addition, more activation in the right dorsal lateral PFC (dlPFC) during negative feedback vs neutral feedback was associated with shorter noise blasts in response to negative social feedback, suggesting a potential role of dlPFC in aggression regulation, or top-down control over affective impulsive actions. This study demonstrates a role of the dlPFC in the regulation of aggressive social behavior. PMID:26755768
Electrothermal feedback in kinetic inductance detectors
NASA Astrophysics Data System (ADS)
Guruswamy, T.; Thomas, C. N.; Withington, S.; Goldie, D. J.
2017-06-01
In kinetic inductance detectors (KIDs) and other similar applications of superconducting microresonators, both the large and small-signal behaviour of the device may be affected by electrothermal feedback. Microwave power applied to read out the device is absorbed by and heats the superconductor quasiparticles, changing the superconductor conductivity and hence the readout power absorbed in a positive or negative feedback loop. In this work, we explore numerically the implications of an extensible theoretical model of a generic superconducting microresonator device for a typical KID, incorporating recent work on the power flow between superconductor quasiparticles and phonons. This model calculates the large-signal (changes in operating point) and small-signal behaviour of a device, allowing us to determine the effect of electrothermal feedback on device responsivity and noise characteristics under various operating conditions. We also investigate how thermally isolating the device from the bath, for example by designing the device on a membrane only connected to the bulk substrate by thin legs, affects device performance. We find that at a typical device operating point, positive electrothermal feedback reduces the effective thermal conductance from the superconductor quasiparticles to the bath, and so increases responsivity to signal (pair-breaking) power, increases noise from temperature fluctuations, and decreases the noise equivalent power (NEP). Similarly, increasing the thermal isolation of the device while keeping the quasiparticle temperature constant decreases the NEP, but also decreases the device response bandwidth.
Limit Cycle Bifurcations by Perturbing a Piecewise Hamiltonian System with a Double Homoclinic Loop
NASA Astrophysics Data System (ADS)
Xiong, Yanqin
2016-06-01
This paper is concerned with the bifurcation problem of limit cycles by perturbing a piecewise Hamiltonian system with a double homoclinic loop. First, the derivative of the first Melnikov function is provided. Then, we use it, together with the analytic method, to derive the asymptotic expansion of the first Melnikov function near the loop. Meanwhile, we present the first coefficients in the expansion, which can be applied to study the limit cycle bifurcation near the loop. We give sufficient conditions for this system to have 14 limit cycles in the neighborhood of the loop. As an application, a piecewise polynomial Liénard system is investigated, finding six limit cycles with the help of the obtained method.
Optimized tokamak power exhaust with double radiative feedback in ASDEX Upgrade
NASA Astrophysics Data System (ADS)
Kallenbach, A.; Bernert, M.; Eich, T.; Fuchs, J. C.; Giannone, L.; Herrmann, A.; Schweinzer, J.; Treutterer, W.; the ASDEX Upgrade Team
2012-12-01
A double radiative feedback technique has been developed on the ASDEX Upgrade tokamak for optimization of power exhaust with a standard vertical target divertor. The main chamber radiation is measured in real time by a subset of three foil bolometer channels and controlled by argon injection in the outer midplane. The target heat flux is in addition controlled by nitrogen injection in the divertor private flux region using either a thermoelectric sensor or the scaled divertor radiation obtained by a bolometer channel in the outer divertor. No negative interference of the two radiation controllers has been observed so far. The combination of main chamber and divertor radiative cooling extends the operational space of a standard divertor configuration towards high values of P/R. Pheat/R = 14 MW m-1 has been achieved so far with nitrogen seeding alone as well as with combined N + Ar injection, with the time-averaged divertor peak heat flux below 5 MW m-2. Good plasma performance can be maintained under these conditions, namely H98(y,2) = 1 and βN = 3.
Autopilot for frequency-modulation atomic force microscopy
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kuchuk, Kfir; Schlesinger, Itai; Sivan, Uri, E-mail: phsivan@tx.technion.ac.il
2015-10-15
One of the most challenging aspects of operating an atomic force microscope (AFM) is finding optimal feedback parameters. This statement applies particularly to frequency-modulation AFM (FM-AFM), which utilizes three feedback loops to control the cantilever excitation amplitude, cantilever excitation frequency, and z-piezo extension. These loops are regulated by a set of feedback parameters, tuned by the user to optimize stability, sensitivity, and noise in the imaging process. Optimization of these parameters is difficult due to the coupling between the frequency and z-piezo feedback loops by the non-linear tip-sample interaction. Four proportional-integral (PI) parameters and two lock-in parameters regulating these loopsmore » require simultaneous optimization in the presence of a varying unknown tip-sample coupling. Presently, this optimization is done manually in a tedious process of trial and error. Here, we report on the development and implementation of an algorithm that computes the control parameters automatically. The algorithm reads the unperturbed cantilever resonance frequency, its quality factor, and the z-piezo driving signal power spectral density. It analyzes the poles and zeros of the total closed loop transfer function, extracts the unknown tip-sample transfer function, and finds four PI parameters and two lock-in parameters for the frequency and z-piezo control loops that optimize the bandwidth and step response of the total system. Implementation of the algorithm in a home-built AFM shows that the calculated parameters are consistently excellent and rarely require further tweaking by the user. The new algorithm saves the precious time of experienced users, facilitates utilization of FM-AFM by casual users, and removes the main hurdle on the way to fully automated FM-AFM.« less
Learning from ISS-modular adaptive NN control of nonlinear strict-feedback systems.
Wang, Cong; Wang, Min; Liu, Tengfei; Hill, David J
2012-10-01
This paper studies learning from adaptive neural control (ANC) for a class of nonlinear strict-feedback systems with unknown affine terms. To achieve the purpose of learning, a simple input-to-state stability (ISS) modular ANC method is first presented to ensure the boundedness of all the signals in the closed-loop system and the convergence of tracking errors in finite time. Subsequently, it is proven that learning with the proposed stable ISS-modular ANC can be achieved. The cascade structure and unknown affine terms of the considered systems make it very difficult to achieve learning using existing methods. To overcome these difficulties, the stable closed-loop system in the control process is decomposed into a series of linear time-varying (LTV) perturbed subsystems with the appropriate state transformation. Using a recursive design, the partial persistent excitation condition for the radial basis function neural network (NN) is established, which guarantees exponential stability of LTV perturbed subsystems. Consequently, accurate approximation of the closed-loop system dynamics is achieved in a local region along recurrent orbits of closed-loop signals, and learning is implemented during a closed-loop feedback control process. The learned knowledge is reused to achieve stability and an improved performance, thereby avoiding the tremendous repeated training process of NNs. Simulation studies are given to demonstrate the effectiveness of the proposed method.
Zhang, Yixuan; Li, Qiang; Youn, Ji Youn; Cai, Hua
2017-01-01
The VEGF/VEGFR2/Akt/eNOS/NO pathway is essential to VEGF-induced angiogenesis. We have previously discovered a novel role of calpain in mediating VEGF-induced PI3K/AMPK/Akt/eNOS activation through Ezrin. Here, we sought to identify possible feedback regulation of VEGFR2 by calpain via its substrate protein phosphotyrosine phosphatase 1B (PTP1B), and the relevance of this pathway to VEGF-induced angiogenesis, especially in diabetic wound healing. Overexpression of PTP1B inhibited VEGF-induced VEGFR2 and Akt phosphorylation in bovine aortic endothelial cells, while PTP1B siRNA increased both, implicating negative regulation of VEGFR2 by PTP1B. Calpain inhibitor ALLN induced VEGFR2 activation, which can be completely blocked by PTP1B overexpression. Calpain activation induced by overexpression or Ca/A23187 resulted in PTP1B cleavage, which can be blocked by ALLN. Moreover, calpain activation inhibited VEGF-induced VEGFR2 phosphorylation, which can be restored by PTP1B siRNA. These data implicate calpain/PTP1B negative feedback regulation of VEGFR2, in addition to the primary signaling pathway of VEGF/VEGFR2/calpain/PI3K/AMPK/Akt/eNOS. We next examined a potential role of PTP1B in VEGF-induced angiogenesis. Endothelial cells transfected with PTP1B siRNA showed faster wound closure in response to VEGF. Aortic discs isolated from PTP1B siRNA-transfected mice also had augmented endothelial outgrowth. Importantly, PTP1B inhibition and/or calpain overexpression significantly accelerated wound healing in STZ-induced diabetic mice. In conclusion, our data for the first time demonstrate a calpain/PTP1B/VEGFR2 negative feedback loop in the regulation of VEGF-induced angiogenesis. Modulation of local PTP1B and/or calpain activities may prove beneficial in the treatment of impaired wound healing in diabetes. PMID:27872190
Faruque, Imraan A; Muijres, Florian T; Macfarlane, Kenneth M; Kehlenbeck, Andrew; Humbert, J Sean
2018-06-01
This paper presents "optimal identification," a framework for using experimental data to identify the optimality conditions associated with the feedback control law implemented in the measurements. The technique compares closed loop trajectory measurements against a reduced order model of the open loop dynamics, and uses linear matrix inequalities to solve an inverse optimal control problem as a convex optimization that estimates the controller optimality conditions. In this study, the optimal identification technique is applied to two examples, that of a millimeter-scale micro-quadrotor with an engineered controller on board, and the example of a population of freely flying Drosophila hydei maneuvering about forward flight. The micro-quadrotor results show that the performance indices used to design an optimal flight control law for a micro-quadrotor may be recovered from the closed loop simulated flight trajectories, and the Drosophila results indicate that the combined effect of the insect longitudinal flight control sensing and feedback acts principally to regulate pitch rate.
Power flow control based solely on slow feedback loop for heart pump applications.
Wang, Bob; Hu, Aiguo Patrick; Budgett, David
2012-06-01
This paper proposes a new control method for regulating power flow via transcutaneous energy transfer (TET) for implantable heart pumps. Previous work on power flow controller requires a fast feedback loop that needs additional switching devices and resonant capacitors to be added to the primary converter. The proposed power flow controller eliminates these additional components, and it relies solely on a slow feedback loop to directly drive the primary converter to meet the heart pump power demand and ensure zero voltage switching. A controlled change in switching frequency varies the resonant tank shorting period of a current-fed push-pull resonant converter, thus changing the magnitude of the primary resonant voltage, as well as the tuning between primary and secondary resonant tanks. The proposed controller has been implemented successfully using an analogue circuit and has reached an end-to-end power efficiency of 79.6% at 10 W with a switching frequency regulation range of 149.3 kHz to 182.2 kHz.
Complete analog control of the carrier-envelope-phase of a high-power laser amplifier.
Feng, C; Hergott, J-F; Paul, P-M; Chen, X; Tcherbakoff, O; Comte, M; Gobert, O; Reduzzi, M; Calegari, F; Manzoni, C; Nisoli, M; Sansone, G
2013-10-21
In this work we demonstrate the development of a complete analog feedback loop for the control of the carrier-envelope phase (CEP) of a high-average power (20 W) laser operating at 10 kHz repetition rate. The proposed method combines a detection scheme working on a single-shot basis at the full-repetition-rate of the laser system with a fast actuator based either on an acousto-optic or on an electro-optic crystal. The feedback loop is used to correct the CEP fluctuations introduced by the amplification process demonstrating a CEP residual noise of 320 mrad measured on a single-shot basis. The comparison with a feedback loop operating at a lower sampling rate indicates an improvement up to 45% in the residual noise. The measurement of the CEP drift for different integration times clearly evidences the importance of the single-shot characterization of the residual CEP drift. The demonstrated scheme could be efficiently applied for systems approaching the 100 kHz repetition rate regime.
Forster, Sarah E; Zirnheld, Patrick; Shekhar, Anantha; Steinhauer, Stuart R; O'Donnell, Brian F; Hetrick, William P
2017-09-01
Signals carried by the mesencephalic dopamine system and conveyed to anterior cingulate cortex are critically implicated in probabilistic reward learning and performance monitoring. A common evaluative mechanism purportedly subserves both functions, giving rise to homologous medial frontal negativities in feedback- and response-locked event-related brain potentials (the feedback-related negativity (FRN) and the error-related negativity (ERN), respectively), reflecting dopamine-dependent prediction error signals to unexpectedly negative events. Consistent with this model, the dopamine receptor antagonist, haloperidol, attenuates the ERN, but effects on FRN have not yet been evaluated. ERN and FRN were recorded during a temporal interval learning task (TILT) following randomized, double-blind administration of haloperidol (3 mg; n = 18), diphenhydramine (an active control for haloperidol; 25 mg; n = 20), or placebo (n = 21) to healthy controls. Centroparietal positivities, the Pe and feedback-locked P300, were also measured and correlations between ERP measures and behavioral indices of learning, overall accuracy, and post-error compensatory behavior were evaluated. We hypothesized that haloperidol would reduce ERN and FRN, but that ERN would uniquely track automatic, error-related performance adjustments, while FRN would be associated with learning and overall accuracy. As predicted, ERN was reduced by haloperidol and in those exhibiting less adaptive post-error performance; however, these effects were limited to ERNs following fast timing errors. In contrast, the FRN was not affected by drug condition, although increased FRN amplitude was associated with improved accuracy. Significant drug effects on centroparietal positivities were also absent. Our results support a functional and neurobiological dissociation between the ERN and FRN.
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. Copyright © 2015 Elsevier Ltd. All rights reserved.
NASA Technical Reports Server (NTRS)
Thompson, P. M.; Stein, G.
1980-01-01
The behavior of the closed loop eigenstructure of a linear system with output feedback is analyzed as a single parameter multiplying the feedback gain is varied. An algorithm is presented that computes the asymptotically infinite eigenstructure, and it is shown how a system with high gain, feedback decouples into single input, single output systems. Then a synthesis algorithm is presented which uses full state feedback to achieve a desired asymptotic eigenstructure.
Zhang, Qiang; Pi, Jingbo; Woods, Courtney G; Andersen, Melvin E
2009-06-15
Hormetic responses to xenobiotic exposure likely occur as a result of overcompensation by the homeostatic control systems operating in biological organisms. However, the mechanisms underlying overcompensation that leads to hormesis are still unclear. A well-known homeostatic circuit in the cell is the gene induction network comprising phase I, II and III metabolizing enzymes, which are responsible for xenobiotic detoxification, and in many cases, bioactivation. By formulating a differential equation-based computational model, we investigated in this study whether hormesis can arise from the operation of this gene/enzyme network. The model consists of two feedback and one feedforward controls. With the phase I negative feedback control, xenobiotic X activates nuclear receptors to induce cytochrome P450 enzyme, which bioactivates X into a reactive metabolite X'. With the phase II negative feedback control, X' activates transcription factor Nrf2 to induce phase II enzymes such as glutathione S-transferase and glutamate cysteine ligase, etc., which participate in a set of reactions that lead to the metabolism of X' into a less toxic conjugate X''. The feedforward control involves phase I to II cross-induction, in which the parent chemical X can also induce phase II enzymes directly through the nuclear receptor and indirectly through transcriptionally upregulating Nrf2. As a result of the active feedforward control, a steady-state hormetic relationship readily arises between the concentrations of the reactive metabolite X' and the extracellular parent chemical X to which the cell is exposed. The shape of dose-response evolves over time from initially monotonically increasing to J-shaped at the final steady state-a temporal sequence consistent with adaptation-mediated hormesis. The magnitude of the hormetic response is enhanced by increases in the feedforward gain, but attenuated by increases in the bioactivation or phase II feedback loop gains. Our study suggests a possibly common mechanism for the hormetic responses observed with many mutagens/carcinogens whose activities require bioactivation by phase I enzymes. Feedforward control, often operating in combination with negative feedback regulation in a homeostatic system, may be a general control theme responsible for steady-state hormesis.
NASA Astrophysics Data System (ADS)
Fang, B.; Sushama, L.; Diro, G. T.
2015-12-01
Snow characteristics and snow albedo feedback (SAF) over North America, as simulated by the fifth-generation Canadian Regional Climate Model (CRCM5), when driven by ERA-40/ERA-Interim, CanESM2 and MPI-ESM-LR at the lateral boundaries, are analyzed in this study. Validation of snow characteristics is performed by comparing simulations against available observations from MODIS, ISCCP and CMC. Results show that the model is able to represent the main spatial distribution of snow characteristics with some overestimation in snow mass and snow depth over the Canadian high Arctic. Some overestimation in surface albedo is also noted for the boreal region which is believed to be related to the snow unloading parameterization, as well as the overestimation of snow albedo. SAF is assessed both in seasonal and climate change contexts when possible. The strength of SAF is quantified as the amount of additional net shortwave radiation at the top of the atmosphere as surface albedo decreases in association with a 1°C increase in surface temperature. Following Qu and Hall (2007), this is expressed as the product of the variation in planetary albedo with surface albedo and the change in surface albedo for 1°C change in surface air temperature during the season, which in turn is determined by the strength of the snow cover and snowpack metamorphosis feedback loops. Analysis of the latter term in the seasonal cycle suggests that for CRCM5 simulations, the snow cover feedback loop is more dominant compared to the snowpack metamorphosis feedback loop, whereas for MODIS, the two feedback loops have more or less similar strength. Moreover, the SAF strength in the climate change context appears to be weaker than in the seasonal cycle and is sensitive to the driving GCM and the RCP scenario.
A technique for sequential segmental neuromuscular stimulation with closed loop feedback control.
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.
Yao, Li-Qing; Tan, Chang-Jun; Huang, Xiao-Yong; Ke, Ai-Wu; Dai, Zhi; Fan, Jia; Zhou, Jian
2012-01-01
Background Rapamycin is an attractive approach for the treatment and prevention of HCC recurrence after liver transplantation. However, the objective response rates of rapamycin achieved with single-agent therapy were modest, supporting that rapamycin resistance is a frequently observed characteristic of many cancers. Some studies have been devoted to understanding the mechanisms of rapamycin resistance, however, the mechanisms are cell-type-dependent and studies on rapamycin resistance in HCC are extremely limited. Methodology/Principal Findings The anti-tumor sensitivity of rapamycin was modest in vitro and in vivo. In both human and rat HCC cells, rapamycin up-regulated the expression and phosphorylation of PDGFRβ in a time and dose-dependent manner as assessed by RT-PCR and western blot analysis. Using siRNA mediated knockdown of PDGFRβ, we confirmed that subsequent activation of AKT and ERK was PDGFRβ-dependent and compromised the anti-tumor activity of rapamycin. Then, blockade of this PDGFRβ-dependent feedback loop by sorafenib enhanced the anti-tumor sensitivity of rapamycin in vitro and in an immunocompetent orthotopic rat model of HCC. Conclusions Activation of PI3K/AKT and MAPK pathway through a PDGFRβ-dependent feedback loop compromises the anti-tumor activity of rapamycin in HCC, and blockade of this feedback loop by sorafenib is an attractive approach to improve the anti-tumor effect of rapamycin, particularly in preventing or treating HCC recurrence after liver transplantation. PMID:22428038
Pregnenolone can protect the brain from cannabis intoxication.
Vallée, Monique; Vitiello, Sergio; Bellocchio, Luigi; Hébert-Chatelain, Etienne; Monlezun, Stéphanie; Martin-Garcia, Elena; Kasanetz, Fernando; Baillie, Gemma L; Panin, Francesca; Cathala, Adeline; Roullot-Lacarrière, Valérie; Fabre, Sandy; Hurst, Dow P; Lynch, Diane L; Shore, Derek M; Deroche-Gamonet, Véronique; Spampinato, Umberto; Revest, Jean-Michel; Maldonado, Rafael; Reggio, Patricia H; Ross, Ruth A; Marsicano, Giovanni; Piazza, Pier Vincenzo
2014-01-03
Pregnenolone is considered the inactive precursor of all steroid hormones, and its potential functional effects have been largely uninvestigated. The administration of the main active principle of Cannabis sativa (marijuana), Δ(9)-tetrahydrocannabinol (THC), substantially increases the synthesis of pregnenolone in the brain via activation of the type-1 cannabinoid (CB1) receptor. Pregnenolone then, acting as a signaling-specific inhibitor of the CB1 receptor, reduces several effects of THC. This negative feedback mediated by pregnenolone reveals a previously unknown paracrine/autocrine loop protecting the brain from CB1 receptor overactivation that could open an unforeseen approach for the treatment of cannabis intoxication and addiction.
Strong suppression of shot noise in a feedback-controlled single-electron transistor
NASA Astrophysics Data System (ADS)
Wagner, Timo; Strasberg, Philipp; Bayer, Johannes C.; Rugeramigabo, Eddy P.; Brandes, Tobias; Haug, Rolf J.
2017-03-01
Feedback control of quantum mechanical systems is rapidly attracting attention not only due to fundamental questions about quantum measurements, but also because of its novel applications in many fields in physics. Quantum control has been studied intensively in quantum optics but progress has recently been made in the control of solid-state qubits as well. In quantum transport only a few active and passive feedback experiments have been realized on the level of single electrons, although theoretical proposals exist. Here we demonstrate the suppression of shot noise in a single-electron transistor using an exclusively electronic closed-loop feedback to monitor and adjust the counting statistics. With increasing feedback response we observe a stronger suppression and faster freezing of charge current fluctuations. Our technique is analogous to the generation of squeezed light with in-loop photodetection as used in quantum optics. Sub-Poisson single-electron sources will pave the way for high-precision measurements in quantum transport similar to optical or optomechanical equivalents.
A cognitive neuroprosthetic that uses cortical stimulation for somatosensory feedback.
Klaes, Christian; Shi, Ying; Kellis, Spencer; Minxha, Juri; Revechkis, Boris; Andersen, Richard A
2014-10-01
Present day cortical brain-machine interfaces (BMIs) have made impressive advances using decoded brain signals to control extracorporeal devices. Although BMIs are used in a closed-loop fashion, sensory feedback typically is visual only. However medical case studies have shown that the loss of somesthesis in a limb greatly reduces the agility of the limb even when visual feedback is available. To overcome this limitation, this study tested a closed-loop BMI that utilizes intracortical microstimulation to provide 'tactile' sensation to a non-human primate. Using stimulation electrodes in Brodmann area 1 of somatosensory cortex (BA1) and recording electrodes in the anterior intraparietal area, the parietal reach region and dorsal area 5 (area 5d), it was found that this form of feedback can be used in BMI tasks. Providing somatosensory feedback has the poyential to greatly improve the performance of cognitive neuroprostheses especially for fine control and object manipulation. Adding stimulation to a BMI system could therefore improve the quality of life for severely paralyzed patients.
Li, Wei; Fan, Kexing; Qian, Weizhu; Hou, Sheng; Wang, Hao; Dai, Jianxin; Wei, Huafeng; Guo, Yajun
2014-01-01
Although HER2-targeting antibody trastuzumab confers a substantial benefit for patients with HER2-overexpressing breast and gastric cancer, overcoming trastuzumab resistance remains a large unmet need. In this study, we revealed a STAT3-centered positive feedback loop that mediates the resistance of trastuzumab. Mechanistically, chronic exposure of trastuzumab causes the upregulation of fibronection (FN), EGF and IL-6 in parental trastuzumab-sensitive breast and gastric cells and convergently leads to STAT3 hyperactivation. Activated STAT3 enhances the expression of FN, EGF and IL-6, thus constituting a positive feedback loop which amplifies and maintains the STAT3 signal; furthermore, hyperactivated STAT3 signal promotes the expression of MUC1 and MUC4, consequently mediating trastuzumab resistance via maintenance of persistent HER2 activation and masking of trastuzumab binding to HER2 respectively. Genetic or pharmacological inhibition of STAT3 disrupted STAT3-dependent positive feedback loop and recovered the trastuzumab sensitivity partially due to increased apoptosis induction. Combined trastuzumab with STAT3 inhibition synergistically suppressed the growth of the trastuzumab-resistant tumor xenografts in vivo. Taken together, our results suggest that feedback activation of STAT3 constitutes a key node mediating trastuzumab resistance. Combinatorial targeting on both HER2 and STAT3 may enhance the efficacy of trastuzumab or other HER2-targeting agents in HER2-positive breast and gastric cancer. PMID:25327561
Li, Guangchao; Zhao, Likun; Li, Wei; Fan, Kexing; Qian, Weizhu; Hou, Sheng; Wang, Hao; Dai, Jianxin; Wei, Huafeng; Guo, Yajun
2014-09-30
Although HER2-targeting antibody trastuzumab confers a substantial benefit for patients with HER2-overexpressing breast and gastric cancer, overcoming trastuzumab resistance remains a large unmet need. In this study, we revealed a STAT3-centered positive feedback loop that mediates the resistance of trastuzumab. Mechanistically, chronic exposure of trastuzumab causes the upregulation of fibronection (FN), EGF and IL-6 in parental trastuzumab-sensitive breast and gastric cells and convergently leads to STAT3 hyperactivation. Activated STAT3 enhances the expression of FN, EGF and IL-6, thus constituting a positive feedback loop which amplifies and maintains the STAT3 signal; furthermore, hyperactivated STAT3 signal promotes the expression of MUC1 and MUC4, consequently mediating trastuzumab resistance via maintenance of persistent HER2 activation and masking of trastuzumab binding to HER2 respectively. Genetic or pharmacological inhibition of STAT3 disrupted STAT3-dependent positive feedback loop and recovered the trastuzumab sensitivity partially due to increased apoptosis induction. Combined trastuzumab with STAT3 inhibition synergistically suppressed the growth of the trastuzumab-resistant tumor xenografts in vivo. Taken together, our results suggest that feedback activation of STAT3 constitutes a key node mediating trastuzumab resistance. Combinatorial targeting on both HER2 and STAT3 may enhance the efficacy of trastuzumab or other HER2-targeting agents in HER2-positive breast and gastric cancer.
The Dishevelled-binding protein CXXC5 negatively regulates cutaneous wound healing
Lee, Soung-Hoon; Kim, Mi-Yeon; Kim, Hyun-Yi; Lee, Young-Mi; Kim, Heesu; Nam, Kyoung Ae; Roh, Mi Ryung; Min, Do Sik; Chung, Kee Yang
2015-01-01
Wnt/β-catenin signaling plays important roles in cutaneous wound healing and dermal fibrosis. However, its regulatory mechanism has not been fully elucidated, and a commercially available wound-healing agent targeting this pathway is desirable but currently unavailable. We found that CXXC-type zinc finger protein 5 (CXXC5) serves as a negative feedback regulator of the Wnt/β-catenin pathway by interacting with the Dishevelled (Dvl) protein. In humans, CXXC5 protein levels were reduced in epidermal keratinocytes and dermal fibroblasts of acute wounds. A differential regulation of β-catenin, α-smooth muscle actin (α-SMA), and collagen I by overexpression and silencing of CXXC5 in vitro indicated a critical role for this factor in myofibroblast differentiation and collagen production. In addition, CXXC5−/− mice exhibited accelerated cutaneous wound healing, as well as enhanced keratin 14 and collagen synthesis. Protein transduction domain (PTD)–Dvl-binding motif (DBM), a competitor peptide blocking CXXC5-Dvl interactions, disrupted this negative feedback loop and activated β-catenin and collagen production in vitro. Co-treatment of skin wounds with PTD-DBM and valproic acid (VPA), a glycogen synthase kinase 3β (GSK3β) inhibitor which activates the Wnt/β-catenin pathway, synergistically accelerated cutaneous wound healing in mice. Together, these data suggest that CXXC5 would represent a potential target for future therapies aimed at improving wound healing. PMID:26056233
Yang, Tao; Li, Shisheng; Liu, Jiajia; Yin, Danhui; Yang, Xinming; Tang, Qinglai
2018-05-01
Laryngeal cancer is one of the most common head and neck malignant tumors and is commonly resistant to X-ray-based radiotherapy. NF-κB interacting lncRNA (NKILA) has been reported to serve as a tumor suppressor in several cancers through combining with NF-κB: IκB complex thereby inhibiting NF-κB activation. Herein, we demonstrated a low NKILA expression in laryngeal cancer and its correlation with shorter overall survival in patients with laryngeal cancer. NKILA serves as a tumor suppressor in laryngeal cancer by suppressing laryngeal cancer cell viability and migration, whereas promoting cell apoptosis; NKILA knockdown reverses the cytotoxicity of X-ray radiation on laryngeal cancer cells through combining with NF-κB: IκB complex to inhibit IκB phosphorylation, inhibit p65 nuclear translocation, and finally inhibit NF-κB activation. NF-κB binds to the promoter region of NKILA to activate its transcriptional activity, upregulated NKILA then inhibits IκB phosphorylation and NF-κB activation, thus forming a negative feedback loop to sensitize laryngeal cancer cell to X-ray radiation. In conclusion, NKILA can serve as a promising agent of enhancing the cytotoxicity of X-ray radiation on laryngeal cancer and addressing the radioresistance of laryngeal cancer. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
Casein kinase 1α–dependent feedback loop controls autophagy in RAS-driven cancers
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
The FANTASTIC FOUR proteins influence shoot meristem size in Arabidopsis thaliana.
Wahl, Vanessa; Brand, Luise H; Guo, Ya-Long; Schmid, Markus
2010-12-22
Throughout their lives plants produce new organs from groups of pluripotent cells called meristems, located at the tips of the shoot and the root. The size of the shoot meristem is tightly controlled by a feedback loop, which involves the homeodomain transcription factor WUSCHEL (WUS) and the CLAVATA (CLV) proteins. This regulatory circuit is further fine-tuned by morphogenic signals such as hormones and sugars. Here we show that a family of four plant-specific proteins, encoded by the FANTASTIC FOUR (FAF) genes, has the potential to regulate shoot meristem size in Arabidopsis thaliana. FAF2 and FAF4 are expressed in the centre of the shoot meristem, overlapping with the site of WUS expression. Consistent with a regulatory interaction between the FAF gene family and WUS, our experiments indicate that the FAFs can repress WUS, which ultimately leads to an arrest of meristem activity in FAF overexpressing lines. The finding that meristematic expression of FAF2 and FAF4 is under negative control by CLV3 further supports the hypothesis that the FAFs are modulators of the genetic circuit that regulates the meristem. This study reports the initial characterization of the Arabidopsis thaliana FAF gene family. Our data indicate that the FAF genes form a plant specific gene family, the members of which have the potential to regulate the size of the shoot meristem by modulating the CLV3-WUS feedback loop.
Carbon Climate Feedbacks and Climate Sensitivity (Invited)
NASA Astrophysics Data System (ADS)
Fung, I.
2009-12-01
The Charney report (22 pages including bibliography and appendices) was written when atmospheric CO2 was 334 ppmv (1979). It estimates a climate sensitivity of 3 +/- 1.5C for a doubling of CO2, and points out the warming delay due to the slow penetration of heat into intermediate depths in the oceans and the decreasing capacity of the oceans to serve a CO2 sink. “We may not be given a warning until the CO2 loading is such that an appreciable climate change is inevitable. The equilibrium warming will eventually occur; it will merely have been postponed.” CO2 exceeded 385 ppmv in 2008, and the warning signs are now abundantly evident. One of the “slow” feedbacks not included in the Charney Report involves the interaction between the land carbon cycle and climate change. The carbon cycle on land is coupled to the water and energy cycles. This paper reviews positive and negative carbon-climate feedbacks associated with changes in the function and distribution of land ecosystems. These feedbacks, once in gear, will magnify climate sensitivity and accelerate global warming.
Huffmeijer, Renske; Alink, Lenneke R A; Tops, Mattie; Grewen, Karen M; Light, Kathleen C; Bakermans-Kranenburg, Marian J; van Ijzendoorn, Marinus H
2013-03-01
This is the first experimental study on the effect of oxytocin administration on the neural processing of facial stimuli conducted with female participants that uses event-related potentials (ERPs). Using a double-blind, placebo-controlled within-subjects design, we studied the effects of 16 IU of intranasal oxytocin on ERPs to pictures combining performance feedback with emotional facial expressions in 48 female undergraduate students. Participants also reported on the amount of love withdrawal they experienced from their mothers. Vertex positive potential (VPP) and late positive potential (LPP) amplitudes were more positive after oxytocin compared to placebo administration. This suggests that oxytocin increased attention to the feedback stimuli (LPP) and enhanced the processing of emotional faces (VPP). Oxytocin heightened processing of the happy and disgusted faces primarily for those reporting less love withdrawal. Significant associations with LPP amplitude suggest that more maternal love withdrawal relates to the allocation of attention toward the motivationally relevant combination of negative feedback with a disgusted face. Copyright © 2012 Elsevier Inc. All rights reserved.
Stereoscopic distance perception
NASA Technical Reports Server (NTRS)
Foley, John M.
1989-01-01
Limited cue, open-loop tasks in which a human observer indicates distances or relations among distances are discussed. By open-loop tasks, it is meant tasks in which the observer gets no feedback as to the accuracy of the responses. What happens when cues are added and when the loop is closed are considered. The implications of this research for the effectiveness of visual displays is discussed. Errors in visual distance tasks do not necessarily mean that the percept is in error. The error could arise in transformations that intervene between the percept and the response. It is argued that the percept is in error. It is also argued that there exist post-perceptual transformations that may contribute to the error or be modified by feedback to correct for the error.
A novel feedforward compensation canceling input filter-regulator interaction
NASA Technical Reports Server (NTRS)
Kelkar, S. S.; Lee, F. C.
1983-01-01
The interaction between the input and the control loop of switching regulators often results in deterimental effects, such as loop instability, degradation of transient response, and audiosusceptibility, etc. The concept of pole-zero cancelation is employed to mitigate some of these detrimental effects and is implemented using a novel feedforward loop, in addition to existing feedback loops of a buck regulator. Experimental results are presented which show excellent correlation with theory.
Reflection and Double Loop Learning: The Case of HS2
ERIC Educational Resources Information Center
Synnott, Michael
2013-01-01
This paper focuses on the potential role of reflection and double loop learning in policy analysis and shared community learning. The discussion is illustrated by the case of HS2, a proposed high-speed railway project in England. It is noted that the foundation of social learning models is a rejection of traditional reliance on technologies or…
The Learning-Paradigm Campus: From Single- to Double-Loop Learning
ERIC Educational Resources Information Center
Tagg, John
2010-01-01
Since the 1980s, advocates for change in higher education have called for double-loop learning. One of the main criticisms of the evaluation of colleges and universities was that they measured inputs rather than the outputs. Higher education now needs to apply the lessons of learning and change to campus leadership and organization.
Chen, Yi-Ching; Lin, Linda L; Lin, Yen-Ting; Hu, Chia-Ling; Hwang, Ing-Shiou
2017-01-01
Error amplification (EA) feedback is a promising approach to advance visuomotor skill. As error detection and visuomotor processing at short time scales decline with age, this study examined whether older adults could benefit from EA feedback that included higher-frequency information to guide a force-tracking task. Fourteen young and 14 older adults performed low-level static isometric force-tracking with visual guidance of typical visual feedback and EA feedback containing augmented high-frequency errors. Stabilogram diffusion analysis was used to characterize force fluctuation dynamics. Also, the discharge behaviors of motor units and pooled motor unit coherence were assessed following the decomposition of multi-channel surface electromyography (EMG). EA produced different behavioral and neurophysiological impacts on young and older adults. Older adults exhibited inferior task accuracy with EA feedback than with typical visual feedback, but not young adults. Although stabilogram diffusion analysis revealed that EA led to a significant decrease in critical time points for both groups, EA potentiated the critical point of force fluctuations [Formula: see text], short-term effective diffusion coefficients (Ds), and short-term exponent scaling only for the older adults. Moreover, in older adults, EA added to the size of discharge variability of motor units and discharge regularity of cumulative discharge rate, but suppressed the pooled motor unit coherence in the 13-35 Hz band. Virtual EA alters the strategic balance between open-loop and closed-loop controls for force-tracking. Contrary to expectations, the prevailing use of closed-loop control with EA that contained high-frequency error information enhanced the motor unit discharge variability and undermined the force steadiness in the older group, concerning declines in physiological complexity in the neurobehavioral system and the common drive to the motoneuronal pool against force destabilization.
Chen, Yi-Ching; Lin, Linda L.; Lin, Yen-Ting; Hu, Chia-Ling; Hwang, Ing-Shiou
2017-01-01
Error amplification (EA) feedback is a promising approach to advance visuomotor skill. As error detection and visuomotor processing at short time scales decline with age, this study examined whether older adults could benefit from EA feedback that included higher-frequency information to guide a force-tracking task. Fourteen young and 14 older adults performed low-level static isometric force-tracking with visual guidance of typical visual feedback and EA feedback containing augmented high-frequency errors. Stabilogram diffusion analysis was used to characterize force fluctuation dynamics. Also, the discharge behaviors of motor units and pooled motor unit coherence were assessed following the decomposition of multi-channel surface electromyography (EMG). EA produced different behavioral and neurophysiological impacts on young and older adults. Older adults exhibited inferior task accuracy with EA feedback than with typical visual feedback, but not young adults. Although stabilogram diffusion analysis revealed that EA led to a significant decrease in critical time points for both groups, EA potentiated the critical point of force fluctuations <ΔFc2>, short-term effective diffusion coefficients (Ds), and short-term exponent scaling only for the older adults. Moreover, in older adults, EA added to the size of discharge variability of motor units and discharge regularity of cumulative discharge rate, but suppressed the pooled motor unit coherence in the 13–35 Hz band. Virtual EA alters the strategic balance between open-loop and closed-loop controls for force-tracking. Contrary to expectations, the prevailing use of closed-loop control with EA that contained high-frequency error information enhanced the motor unit discharge variability and undermined the force steadiness in the older group, concerning declines in physiological complexity in the neurobehavioral system and the common drive to the motoneuronal pool against force destabilization. PMID:29167637
Ligerot, Yasmine; de Saint Germain, Alexandre; Troadec, Christelle; Citerne, Sylvie; Pillot, Jean-Paul; Prigge, Michael; Aubert, Grégoire; Bendahmane, Abdelhafid; Estelle, Mark; Debellé, Frédéric
2017-01-01
Strigolactones (SLs) are well known for their role in repressing shoot branching. In pea, increased transcript levels of SL biosynthesis genes are observed in stems of highly branched SL deficient (ramosus1 (rms1) and rms5) and SL response (rms3 and rms4) mutants indicative of negative feedback control. In contrast, the highly branched rms2 mutant has reduced transcript levels of SL biosynthesis genes. Grafting studies and hormone quantification led to a model where RMS2 mediates a shoot-to-root feedback signal that regulates both SL biosynthesis gene transcript levels and xylem sap levels of cytokinin exported from roots. Here we cloned RMS2 using synteny with Medicago truncatula and demonstrated that it encodes a putative auxin receptor of the AFB4/5 clade. Phenotypes similar to rms2 were found in Arabidopsis afb4/5 mutants, including increased shoot branching, low expression of SL biosynthesis genes and high auxin levels in stems. Moreover, afb4/5 and rms2 display a specific resistance to the herbicide picloram. Yeast-two-hybrid experiments supported the hypothesis that the RMS2 protein functions as an auxin receptor. SL root feeding using hydroponics repressed auxin levels in stems and down-regulated transcript levels of auxin biosynthesis genes within one hour. This auxin down-regulation was also observed in plants treated with the polar auxin transport inhibitor NPA. Together these data suggest a homeostatic feedback loop in which auxin up-regulates SL synthesis in an RMS2-dependent manner and SL down-regulates auxin synthesis in an RMS3 and RMS4-dependent manner. PMID:29220348
Ligerot, Yasmine; de Saint Germain, Alexandre; Waldie, Tanya; Troadec, Christelle; Citerne, Sylvie; Kadakia, Nikita; Pillot, Jean-Paul; Prigge, Michael; Aubert, Grégoire; Bendahmane, Abdelhafid; Leyser, Ottoline; Estelle, Mark; Debellé, Frédéric; Rameau, Catherine
2017-12-01
Strigolactones (SLs) are well known for their role in repressing shoot branching. In pea, increased transcript levels of SL biosynthesis genes are observed in stems of highly branched SL deficient (ramosus1 (rms1) and rms5) and SL response (rms3 and rms4) mutants indicative of negative feedback control. In contrast, the highly branched rms2 mutant has reduced transcript levels of SL biosynthesis genes. Grafting studies and hormone quantification led to a model where RMS2 mediates a shoot-to-root feedback signal that regulates both SL biosynthesis gene transcript levels and xylem sap levels of cytokinin exported from roots. Here we cloned RMS2 using synteny with Medicago truncatula and demonstrated that it encodes a putative auxin receptor of the AFB4/5 clade. Phenotypes similar to rms2 were found in Arabidopsis afb4/5 mutants, including increased shoot branching, low expression of SL biosynthesis genes and high auxin levels in stems. Moreover, afb4/5 and rms2 display a specific resistance to the herbicide picloram. Yeast-two-hybrid experiments supported the hypothesis that the RMS2 protein functions as an auxin receptor. SL root feeding using hydroponics repressed auxin levels in stems and down-regulated transcript levels of auxin biosynthesis genes within one hour. This auxin down-regulation was also observed in plants treated with the polar auxin transport inhibitor NPA. Together these data suggest a homeostatic feedback loop in which auxin up-regulates SL synthesis in an RMS2-dependent manner and SL down-regulates auxin synthesis in an RMS3 and RMS4-dependent manner.
Haji, Mohsin; Hou, Lianping; Kelly, Anthony E; Akbar, Jehan; Marsh, John H; Arnold, John M; Ironside, Charles N
2012-01-30
Optical self seeding feedback techniques can be used to improve the noise characteristics of passively mode-locked laser diodes. External cavities such as fiber optic cables can increase the memory of the phase and subsequently improve the timing jitter. In this work, an improved optical feedback architecture is proposed using an optical fiber loop delay as a cavity extension of the mode-locked laser. We investigate the effect of the noise reduction as a function of the loop length and feedback power. The well known composite cavity technique is also implemented for suppressing supermode noise artifacts presented due to harmonic mode locking effects. Using this method, we achieve a record low radio frequency linewidth of 192 Hz for any high frequency (>1 GHz) passively mode-locked laser to date (to the best of the authors' knowledge), making it promising for the development of high frequency optoelectronic oscillators.
A cognitive neuroprosthetic that uses cortical stimulation for somatosensory feedback
Klaes, Christian; Shi, Ying; Kellis, Spencer; Minxha, Juri; Revechkis, Boris; Andersen, Richard A.
2015-01-01
Present day cortical brain machine interfaces (BMI) have made impressive advances using decoded brain signals to control extracorporeal devices. Although BMIs are used in a closed-loop fashion, sensory feedback typically is visual only. However medical case studies have shown that the loss of somesthesis in a limb greatly reduces the agility of the limb even when visual feedback is available (for review see Robles-De-La-Torre, 2006). To overcome this limitation, this study tested a closed-loop BMI that utilizes intracortical microstimulation (ICMS) to provide ‘tactile’ sensation to a non-human primate (NHP). Using stimulation electrodes in Brodmann area 1 of somatosensory cortex (BA1) and recording electrodes in the anterior intraparietal area (AIP), the parietal reach region (PRR) and dorsal area 5 (area 5d), it was found that this form of feedback can be used in BMI tasks. PMID:25242377
Simple way to calculate a UV-finite one-loop quantum energy in the Randall-Sundrum model
NASA Astrophysics Data System (ADS)
Altshuler, Boris L.
2017-04-01
The surprising simplicity of Barvinsky-Nesterov or equivalently Gelfand-Yaglom methods of calculation of quantum determinants permits us to obtain compact expressions for a UV-finite difference of one-loop quantum energies for two arbitrary values of the parameter of the double-trace asymptotic boundary conditions. This result generalizes the Gubser and Mitra calculation for the particular case of difference of "regular" and "irregular" one-loop energies in the one-brane Randall-Sundrum model. The approach developed in the paper also allows us to get "in one line" the one-loop quantum energies in the two-brane Randall-Sundrum model. The relationship between "one-loop" expressions corresponding to the mixed Robin and to double-trace asymptotic boundary conditions is traced.
Potentiated processing of negative feedback in depression is attenuated by anhedonia
Mueller, E. M.; Pechtel, P.; Cohen, A.L.; Douglas, S.R.; Pizzagalli, D.A.
2014-01-01
Background Although cognitive theories of depression have postulated enhanced processing of negatively valenced information, previous EEG studies have shown both increased and reduced sensitivity for negative performance feedback in MDD. To reconcile these paradoxical findings, it has been speculated that sensitivity for negative feedback is potentiated in moderate MDD but reduced in highly anhedonic subjects. The goal of this study was to test this hypothesis by analyzing the feedback-related negativity (FRN), frontomedial theta power (FMT), and source-localized anterior midcingulate cortex (aMCC) activity after negative feedback. Methods Fourteen unmedicated participants with MDD and 15 control participants performed a reinforcement learning task while 128-channel EEG was recorded. FRN, FMT and LORETA source-localized aMCC activity after negative and positive feedback were compared between groups. Results The MDD group showed higher FRN amplitudes and aMCC activation to negative feedback than controls. Moreover, aMCC activation to negative feedback was inversely related to self-reported anhedonia. In contrast, self-reported anxiety correlated with feedback-evoked frontomedial theta (FMT) within the depression group. Conclusions The present findings suggest that, among depressed and anxious individuals, enhanced processing of negative feedback occurs relatively early in the information processing stream. These results extend prior work and indicate that although moderate depression is associated with elevated sensitivity for negative feedback, high levels of anhedonia may attenuate this effect. PMID:25620272
Feedback Interactions of Polymerized Actin with the Cell Membrane: Waves, Pulses, and Oscillations
NASA Astrophysics Data System (ADS)
Carlsson, Anders
Polymerized filaments of the protein actin have crucial functions in cell migration, and in bending the cell membrane to drive endocytosis or the formation of protrusions. The nucleation and polymerization of actin filaments are controlled by upstream agents in the cell membrane, including nucleation-promoting factors (NPFs) that activate the Arp2/3 complex to form new branches on pre-existing filaments. But polymerized actin (F-actin) also feeds back on the assembly of NPFs. We explore the effects of the resulting feedback loop of F-actin and NPFs on two phenomena: actin pulses that drive endocytosis in yeast, and actin waves traveling along the membrane of several cell types. In our model of endocytosis in yeast, the actin network is grown explicitly in three dimensions, exerts a negative feedback interaction on localized patch of NPFs in the membrane, and bends the membrane by exerting a distribution of forces. This model explains observed actin and NPF pulse dynamics, and the effects of several interventions including i) NPF mutations, ii) inhibition of actin polymerization, and iii) deletion of a protein that allows F-actin to bend the cell membrane. The model predicts that mutation of the active region of an NPF will enhance the accumulation of that NPF, and we confirm this prediction by quantitative fluorescence microscopy. For actin waves, we treat a similar model, with NPFs distributed over a larger region of the cell membrane. This model naturally generates actin waves, and predicts a transition from wave behavior to spatially localized oscillations when NPFs are confined to a small region. We also predict a transition from waves to static polarization as the negative-feedback coupling between F-actin and the NPFs is reduced. Supported by NIGMS Grant R01 GM107667.
NASA Astrophysics Data System (ADS)
Mehta, Sohan S.; Ganta, Lakshmi K.; Chauhan, Vikrant; Wu, Yixu; Singh, Sunil; Ann, Chia; Subramany, Lokesh; Higgins, Craig; Erenturk, Burcin; Srivastava, Ravi; Singh, Paramjit; Koh, Hui Peng; Cho, David
2015-03-01
Immersion based 20nm technology node and below becoming very challenging to chip designers, process and integration due to multiple patterning to integrate one design layer . Negative tone development (NTD) processes have been well accepted by industry experts for enabling technologies 20 nm and below. 193i double patterning is the technology solution for pitch down to 80 nm. This imposes tight control in critical dimension(CD) variation in double patterning where design patterns are decomposed in two different masks such as in litho-etch-litho etch (LELE). CD bimodality has been widely studied in LELE double patterning. A portion of CD tolerance budget is significantly consumed by variations in CD in double patterning. The objective of this work is to study the process variation challenges and resolution in the Negative Tone Develop Process for 20 nm and Below Technology Node. This paper describes the effect of dose slope on CD variation in negative tone develop LELE process. This effect becomes even more challenging with standalone NTD developer process due to q-time driven CD variation. We studied impact of different stacks with combination of binary and attenuated phase shift mask and estimated dose slope contribution individually from stack and mask type. Mask 3D simulation was carried out to understand theoretical aspect. In order to meet the minimum insulator requirement for the worst case on wafer the overlay and critical dimension uniformity (CDU) budget margins have slimmed. Besides the litho process and tool control using enhanced metrology feedback, the variation control has other dependencies too. Color balancing between the two masks in LELE is helpful in countering effects such as iso-dense bias, and pattern shifting. Dummy insertion and the improved decomposition techniques [2] using multiple lower priority constraints can help to a great extent. Innovative color aware routing techniques [3] can also help with achieving more uniform density and color balanced layouts.
Control systems for platform landings cushioned by air bags
NASA Astrophysics Data System (ADS)
Ross, Edward W.
1987-07-01
This report presents an exploratory mathematical study of control systems for airdrop platform landings cushioned by airbags. The basic theory of airbags is reviewed and solutions to special cases are noted. A computer program is presented, which calculates the time-dependence of the principal variables during a landing under the action of various control systems. Two existing control systems of open-loop type are compared with a conceptual feedback (closed-loop) system for a fairly typical set of landing conditions. The feedback controller is shown to have performance much superior to the other systems. The feedback system undergoes an interesting oscillation not present in the other systems, the source of which is investigated. Recommendations for future work are included.
Jiang, Xingxing; Cheng, Mengfan; Luo, Fengguang; Deng, Lei; Fu, Songnian; Ke, Changjian; Zhang, Minming; Tang, Ming; Shum, Ping; Liu, Deming
2016-12-12
A novel electro-optic chaos source is proposed on the basis of the reverse-time chaos theory and an analog-digital hybrid feedback loop. The analog output of the system can be determined by the numeric states of shift registers, which makes the system robust and easy to control. The dynamical properties as well as the complexity dependence on the feedback parameters are investigated in detail. The correlation characteristics of the system are also studied. Two improving strategies which were established in digital field and analog field are proposed to conceal the time-delay signature. The proposed scheme has the potential to be used in radar and optical secure communication systems.
Compliance and control characteristics of an additive manufactured-flexure stage
DOE Office of Scientific and Technical Information (OSTI.GOV)
Lee, ChaBum; Tarbutton, Joshua A.
2015-04-15
This paper presents a compliance and positioning control characteristics of additive manufactured-nanopositioning system consisted of the flexure mechanism and voice coil motor (VCM). The double compound notch type flexure stage was designed to utilize the elastic deformation of two symmetrical four-bar mechanisms to provide a millimeter-level working range. Additive manufacturing (AM) process, stereolithography, was used to fabricate the flexure stage. The AM stage was inspected by using 3D X-ray computerized tomography scanner: air-voids and shape irregularity. The compliance, open-loop resonance peak, and damping ratio of the AM stage were measured 0.317 mm/N, 80 Hz, and 0.19, respectively. The AM stagemore » was proportional-integral-derivative positioning feedback-controlled and the capacitive type sensor was used to measure the displacement. As a result, the AM flexure mechanism was successfully 25 nm positioning controlled within 500 μm range. The resonance peak was found approximately at 280 Hz in closed-loop. This research showed that the AM flexure mechanism and the VCM can provide millimeter range with high precision and can be a good alternative to an expensive metal-based flexure mechanism and piezoelectric transducer.« less
Identity Change in Newly Married Couples: Effects of Positive and Negative Feedback
ERIC Educational Resources Information Center
Cast, Alicia D.; Cantwell, Allison M.
2007-01-01
Previous research has examined individuals' relative preference for consistent and enhancing feedback by examining reactions to negative and positive feedback. Recent research shows that, in general, individuals prefer feedback that is consistent with self-views, even if feedback is negative. It is unclear, however, whether negative and positive…
Opto-electronic oscillators having optical resonators
NASA Technical Reports Server (NTRS)
Yao, Xiaotian Steve (Inventor); Maleki, Lutfollah (Inventor); Ilchenko, Vladimir (Inventor)
2003-01-01
Systems and techniques of incorporating an optical resonator in an optical part of a feedback loop in opto-electronic oscillators. This optical resonator provides a sufficiently long energy storage time and hence to produce an oscillation of a narrow linewidth and low phase noise. Certain mode matching conditions are required. For example, the mode spacing of the optical resonator is equal to one mode spacing, or a multiplicity of the mode spacing, of an opto-electronic feedback loop that receives a modulated optical signal and to produce an electrical oscillating signal.
Entry flight control system downmoding evaluation
NASA Technical Reports Server (NTRS)
Barnes, H. A.
1978-01-01
A method to desensitize the entry flight control system to structural vibration feedback which might induce an oscillatory instability is described. Trends in vehicle response and handling characteristics as a function of gain combinations in the FCS forward and rate feedback loops were described as observed in a man-in-the-loop simulation. Among the flight conditions considered are the effects of downmoding with APU failures, off-nominal trajectory conditions, sensed angle of attack errors, the impact on RCS fuel consumption, performance in the presence of aero variations, recovery from large FCS upsets, and default gains.
Adaptive antenna arrays for satellite communication
NASA Technical Reports Server (NTRS)
Gupta, Inder J.
1989-01-01
The feasibility of using adaptive antenna arrays to provide interference protection in satellite communications was studied. The feedback loops as well as the sample matric inversion (SMI) algorithm for weight control were studied. Appropriate modifications in the two were made to achieve the required interference suppression. An experimental system was built to test the modified feedback loops and the modified SMI algorithm. The performance of the experimental system was evaluated using bench generated signals and signals received from TVRO geosynchronous satellites. A summary of results is given. Some suggestions for future work are also presented.
Feedback Valence Affects Auditory Perceptual Learning Independently of Feedback Probability
Amitay, Sygal; Moore, David R.; Molloy, Katharine; Halliday, Lorna F.
2015-01-01
Previous studies have suggested that negative feedback is more effective in driving learning than positive feedback. We investigated the effect on learning of providing varying amounts of negative and positive feedback while listeners attempted to discriminate between three identical tones; an impossible task that nevertheless produces robust learning. Four feedback conditions were compared during training: 90% positive feedback or 10% negative feedback informed the participants that they were doing equally well, while 10% positive or 90% negative feedback informed them they were doing equally badly. In all conditions the feedback was random in relation to the listeners’ responses (because the task was to discriminate three identical tones), yet both the valence (negative vs. positive) and the probability of feedback (10% vs. 90%) affected learning. Feedback that informed listeners they were doing badly resulted in better post-training performance than feedback that informed them they were doing well, independent of valence. In addition, positive feedback during training resulted in better post-training performance than negative feedback, but only positive feedback indicating listeners were doing badly on the task resulted in learning. As we have previously speculated, feedback that better reflected the difficulty of the task was more effective in driving learning than feedback that suggested performance was better than it should have been given perceived task difficulty. But contrary to expectations, positive feedback was more effective than negative feedback in driving learning. Feedback thus had two separable effects on learning: feedback valence affected motivation on a subjectively difficult task, and learning occurred only when feedback probability reflected the subjective difficulty. To optimize learning, training programs need to take into consideration both feedback valence and probability. PMID:25946173
Enhanced negative feedback responses in remitted depression.
Santesso, Diane L; Steele, Katherine T; Bogdan, Ryan; Holmes, Avram J; Deveney, Christen M; Meites, Tiffany M; Pizzagalli, Diego A
2008-07-02
Major depressive disorder (MDD) is characterized by hypersensitivity to negative feedback that might involve frontocingulate dysfunction. MDD patients exhibit enhanced electrophysiological responses to negative internal (errors) and external (feedback) cues. Whether this dysfunction extends to remitted depressed (RD) individuals with a history of MDD is currently unknown. To address this issue, we examined the feedback-related negativity in RD and control participants using a probabilistic punishment learning task. Despite equivalent behavioral performance, RD participants showed larger feedback-related negativities to negative feedback relative to controls; group differences remained after accounting for residual anxiety and depressive symptoms. The present findings suggest that abnormal responses to negative feedback extend to samples at increased risk for depressive episodes in the absence of current symptoms.
Closing the Loop on Student Feedback: The Case of Australian and Scottish Universities
ERIC Educational Resources Information Center
Shah, Mahsood; Cheng, Ming; Fitzgerald, Robert
2017-01-01
Universities have a long history of collecting student feedback using surveys and other mechanisms. The last decade has witnessed a significant shift in how student feedback is systematically collected, analysed, reported, and used by governments and institutions. This shift is due to a number of factors, including changes in government policy…
A Case Study of Representing Signal Transduction in Liver Cells as a Feedback Control Problem
ERIC Educational Resources Information Center
Singh, Abhay; Jayaraman, Arul; Hahn, Juergen
2007-01-01
Cell signaling pathways often contain feedback loops where proteins are produced that regulate signaling. While feedback regulatory mechanisms are commonly found in signaling pathways, there is no example available in the literature that is simple enough to be presented in an undergraduate control class. This paper presents a simulation study of…
NASA Astrophysics Data System (ADS)
Zhang, Kemei; Zhao, Cong-Ran; Xie, Xue-Jun
2015-12-01
This paper considers the problem of output feedback stabilisation for stochastic high-order feedforward nonlinear systems with time-varying delay. By using the homogeneous domination theory and solving several troublesome obstacles in the design and analysis, an output feedback controller is constructed to drive the closed-loop system globally asymptotically stable in probability.
Computer automation for feedback system design
NASA Technical Reports Server (NTRS)
1975-01-01
Mathematical techniques and explanations of various steps used by an automated computer program to design feedback systems are summarized. Special attention was given to refining the automatic evaluation suboptimal loop transmission and the translation of time to frequency domain specifications.
Periodic motion planning and control for underactuated mechanical systems
NASA Astrophysics Data System (ADS)
Wang, Zeguo; Freidovich, Leonid B.; Zhang, Honghua
2018-06-01
We consider the problem of periodic motion planning and of designing stabilising feedback control laws for such motions in underactuated mechanical systems. A novel periodic motion planning method is proposed. Each state is parametrised by a truncated Fourier series. Then we use numerical optimisation to search for the parameters of the trigonometric polynomial exploiting the measure of discrepancy in satisfying the passive dynamics equations as a performance index. Thus an almost feasible periodic motion is found. Then a linear controller is designed and stability analysis is given to verify that solutions of the closed-loop system stay inside a tube around the planned approximately feasible periodic trajectory. Experimental results for a double rotary pendulum are shown, while numerical simulations are given for models of a spacecraft with liquid sloshing and of a chain of mass spring system.
Closed-Loop and Robust Control of Quantum Systems
Wang, Lin-Cheng
2013-01-01
For most practical quantum control systems, it is important and difficult to attain robustness and reliability due to unavoidable uncertainties in the system dynamics or models. Three kinds of typical approaches (e.g., closed-loop learning control, feedback control, and robust control) have been proved to be effective to solve these problems. This work presents a self-contained survey on the closed-loop and robust control of quantum systems, as well as a brief introduction to a selection of basic theories and methods in this research area, to provide interested readers with a general idea for further studies. In the area of closed-loop learning control of quantum systems, we survey and introduce such learning control methods as gradient-based methods, genetic algorithms (GA), and reinforcement learning (RL) methods from a unified point of view of exploring the quantum control landscapes. For the feedback control approach, the paper surveys three control strategies including Lyapunov control, measurement-based control, and coherent-feedback control. Then such topics in the field of quantum robust control as H ∞ control, sliding mode control, quantum risk-sensitive control, and quantum ensemble control are reviewed. The paper concludes with a perspective of future research directions that are likely to attract more attention. PMID:23997680
Parity-time–symmetric optoelectronic oscillator
2018-01-01
An optoelectronic oscillator (OEO) is a hybrid microwave and photonic system incorporating an amplified positive feedback loop to enable microwave oscillation to generate a high-frequency and low–phase noise microwave signal. The low phase noise is ensured by the high Q factor of the feedback loop enabled by the use of a long and low-loss optical fiber. However, an OEO with a long fiber loop would have a small free spectral range, leading to a large number of closely spaced oscillation modes. To ensure single-mode oscillation, an ultranarrowband optical filter must be used, but such an optical filter is hard to implement and the stability is poor. Here, we use a novel concept to achieve single-mode oscillation without using an ultranarrowband optical filter. The single-mode operation is achieved based on parity-time (PT) symmetry by using two identical feedback loops, with one having a gain and the other having a loss of the same magnitude. The operation is analyzed theoretically and verified by an experiment. Stable single-mode oscillation at an ultralow phase noise is achieved without the use of an ultranarrowband optical filter. The use of PT symmetry in an OEO overcomes the long-existing mode-selection challenge that would greatly simplify the implementation of OEOs for ultralow–phase noise microwave generation. PMID:29888325
Schwaiberger, David; Pickerodt, Philipp A; Pomprapa, Anake; Tjarks, Onno; Kork, Felix; Boemke, Willehad; Francis, Roland C E; Leonhardt, Steffen; Lachmann, Burkhard
2018-06-01
Adherence to low tidal volume (V T ) ventilation and selected positive end-expiratory pressures are low during mechanical ventilation for treatment of the acute respiratory distress syndrome. Using a pig model of severe lung injury, we tested the feasibility and physiological responses to a novel fully closed-loop mechanical ventilation algorithm based on the "open lung" concept. Lung injury was induced by surfactant washout in pigs (n = 8). Animals were ventilated following the principles of the "open lung approach" (OLA) using a fully closed-loop physiological feedback algorithm for mechanical ventilation. Standard gas exchange, respiratory- and hemodynamic parameters were measured. Electrical impedance tomography was used to quantify regional ventilation distribution during mechanical ventilation. Automatized mechanical ventilation provided strict adherence to low V T -ventilation for 6 h in severely lung injured pigs. Using the "open lung" approach, tidal volume delivery required low lung distending pressures, increased recruitment and ventilation of dorsal lung regions and improved arterial blood oxygenation. Physiological feedback closed-loop mechanical ventilation according to the principles of the open lung concept is feasible and provides low tidal volume ventilation without human intervention. Of importance, the "open lung approach"-ventilation improved gas exchange and reduced lung driving pressures by opening atelectasis and shifting of ventilation to dorsal lung regions.
Electronic Maxwell demon in the coherent strong-coupling regime
NASA Astrophysics Data System (ADS)
Schaller, Gernot; Cerrillo, Javier; Engelhardt, Georg; Strasberg, Philipp
2018-05-01
We consider an external feedback control loop implementing the action of a Maxwell demon. Applying control actions that are conditioned on measurement outcomes, the demon may transport electrons against a bias voltage and thereby effectively converts information into electric power. While the underlying model—a feedback-controlled quantum dot that is coupled to two electronic leads—is well explored in the limit of small tunnel couplings, we can address the strong-coupling regime with a fermionic reaction-coordinate mapping. This exact mapping transforms the setup into a serial triple quantum dot coupled to two leads. We find that a continuous projective measurement of the central dot occupation would lead to a complete suppression of electronic transport due to the quantum Zeno effect. In contrast, by using a microscopic detector model we can implement a weak measurement, which allows for closure of the control loop without transport blockade. Then, in the weak-coupling regime, the energy flows associated with the feedback loop are negligible, and dominantly the information gained in the measurement induces a bound for the generated electric power. In the strong coupling limit, the protocol may require more energy for operating the control loop than electric power produced, such that the whole device is no longer information dominated and can thus not be interpreted as a Maxwell demon.
Macuga, Kristen L; Frey, Scott H
2014-05-15
Damage to the superior and/or inferior parietal lobules (SPL, IPL) (Sirigu et al., 1996) or cerebellum (Grealy and Lee, 2011) can selectively disrupt motor imagery, motivating the hypothesis that these regions participate in predictive (i.e., feedforward) control. If so, then the SPL, IPL, and cerebellum should show greater activity as the demands on feedforward control increase from visually-guided execution (closed-loop) to execution without visual feedback (open-loop) to motor imagery. Using fMRI and a Fitts' reciprocal aiming task with tools directed at targets in far space, we found that the SPL and cerebellum exhibited greater activity during closed-loop control. Conversely, open-loop and imagery conditions were associated with increased activity within the IPL and prefrontal areas. These results are consistent with a superior-to-inferior gradient in the representation of feedback-to-feedforward control within the posterior parietal cortex. Additionally, the anterior SPL displayed greater activity when aiming movements were performed with a stick vs. laser pointer. This may suggest that it is involved in the remapping of far into near (reachable) space (Maravita and Iriki, 2004), or in distalization of the end-effector from hand to stick (Arbib et al., 2009). Copyright © 2014 Elsevier Inc. All rights reserved.
Magnetic field homogeneity of a conical coaxial coil pair.
Salazar, F J; Nieves, F J; Bayón, A; Gascón, F
2017-09-01
An analytical study of the magnetic field created by a double-conical conducting sheet is presented. The analysis is based on the expansion of the magnetic field in terms of Legendre polynomials. It is demonstrated analytically that the angle of the conical surface that produces a nearly homogeneous magnetic field coincides with that of a pair of loops that fulfills the Helmholtz condition. From the results obtained, we propose an electric circuit formed by pairs of isolated conducting loops tightly wound around a pair of conical surfaces, calculating numerically the magnetic field produced by this system and its heterogeneity. An experimental setup of the proposed circuit was constructed and its magnetic field was measured. The results were compared with those obtained by numerical calculation, finding a good agreement. The numerical results demonstrate a significant improvement in homogeneity in the field of the proposed pair of conical coils compared with that achieved with a simple pair of Helmholtz loops or with a double solenoid. Moreover, a new design of a double pair of conical coils based on Braunbek's four loops is also proposed to achieve greater homogeneity. Regarding homogeneity, the rating of the analyzed configurations from best to worst is as follows: (1) double pair of conical coils, (2) pair of conical coils, (3) Braunbek's four loops, (4) Helmholtz pair, and (5) solenoid pair.
Magnetic field homogeneity of a conical coaxial coil pair
NASA Astrophysics Data System (ADS)
Salazar, F. J.; Nieves, F. J.; Bayón, A.; Gascón, F.
2017-09-01
An analytical study of the magnetic field created by a double-conical conducting sheet is presented. The analysis is based on the expansion of the magnetic field in terms of Legendre polynomials. It is demonstrated analytically that the angle of the conical surface that produces a nearly homogeneous magnetic field coincides with that of a pair of loops that fulfills the Helmholtz condition. From the results obtained, we propose an electric circuit formed by pairs of isolated conducting loops tightly wound around a pair of conical surfaces, calculating numerically the magnetic field produced by this system and its heterogeneity. An experimental setup of the proposed circuit was constructed and its magnetic field was measured. The results were compared with those obtained by numerical calculation, finding a good agreement. The numerical results demonstrate a significant improvement in homogeneity in the field of the proposed pair of conical coils compared with that achieved with a simple pair of Helmholtz loops or with a double solenoid. Moreover, a new design of a double pair of conical coils based on Braunbek's four loops is also proposed to achieve greater homogeneity. Regarding homogeneity, the rating of the analyzed configurations from best to worst is as follows: (1) double pair of conical coils, (2) pair of conical coils, (3) Braunbek's four loops, (4) Helmholtz pair, and (5) solenoid pair.
Network efficient power control for wireless communication systems.
Campos-Delgado, Daniel U; Luna-Rivera, Jose Martin; Martinez-Sánchez, C J; Gutierrez, Carlos A; Tecpanecatl-Xihuitl, J L
2014-01-01
We introduce a two-loop power control that allows an efficient use of the overall power resources for commercial wireless networks based on cross-layer optimization. This approach maximizes the network's utility in the outer-loop as a function of the averaged signal to interference-plus-noise ratio (SINR) by considering adaptively the changes in the network characteristics. For this purpose, the concavity property of the utility function was verified with respect to the SINR, and an iterative search was proposed with guaranteed convergence. In addition, the outer-loop is in charge of selecting the detector that minimizes the overall power consumption (transmission and detection). Next the inner-loop implements a feedback power control in order to achieve the optimal SINR in the transmissions despite channel variations and roundtrip delays. In our proposal, the utility maximization process and detector selection and feedback power control are decoupled problems, and as a result, these strategies are implemented at two different time scales in the two-loop framework. Simulation results show that substantial utility gains may be achieved by improving the power management in the wireless network.
Network Efficient Power Control for Wireless Communication Systems
Campos-Delgado, Daniel U.; Luna-Rivera, Jose Martin; Martinez-Sánchez, C. J.; Gutierrez, Carlos A.; Tecpanecatl-Xihuitl, J. L.
2014-01-01
We introduce a two-loop power control that allows an efficient use of the overall power resources for commercial wireless networks based on cross-layer optimization. This approach maximizes the network's utility in the outer-loop as a function of the averaged signal to interference-plus-noise ratio (SINR) by considering adaptively the changes in the network characteristics. For this purpose, the concavity property of the utility function was verified with respect to the SINR, and an iterative search was proposed with guaranteed convergence. In addition, the outer-loop is in charge of selecting the detector that minimizes the overall power consumption (transmission and detection). Next the inner-loop implements a feedback power control in order to achieve the optimal SINR in the transmissions despite channel variations and roundtrip delays. In our proposal, the utility maximization process and detector selection and feedback power control are decoupled problems, and as a result, these strategies are implemented at two different time scales in the two-loop framework. Simulation results show that substantial utility gains may be achieved by improving the power management in the wireless network. PMID:24683350
Towards the use of Structural Loop Analysis to Study System Behaviour of Socio-Ecological Systems.
NASA Astrophysics Data System (ADS)
Abram, Joseph; Dyke, James
2016-04-01
Maintaining socio-ecological systems in desirable states is key to developing a growing economy, alleviating poverty and achieving a sustainable future. While the driving forces of an environmental system are often well known, the dynamics impacting these drivers can be hidden within a tangled structure of causal chains and feedback loops. A lack of understanding of a system's dynamic structure and its influence on a system's behaviour can cause unforeseen side-effects during model scenario testing and policy implementation. Structural Loop analysis of socio-ecological system models identifies dominant feedback structures during times of behavioural shift, allowing the user to monitor key influential drivers during model simulation. This work carries out Loop Eigenvalue Elasticity Analysis (LEEA) on three system dynamic models, exploring tipping points in lake systems undergoing eutrophication. The purpose is to explore the potential benefits and limitations of the technique in the field of socio-ecology. The LEEA technique shows promise for socio-ecological systems which undergo regime shifts or express oscillatory trends, but shows limited usefulness with large models. The results of this work highlight changes in feedback loop dominance, years prior to eutrophic tipping events in lake systems. LEEA could be used as an early warning signal to impending system changes, complementary to other known early warning signals. This approach could improve our understanding during critical times of a system's behaviour, changing how we approach model analysis and the way scenario testing and policy implementation are addressed in socio-ecological system models.
Modeling and control of non-square MIMO system using relay feedback.
Kalpana, D; Thyagarajan, T; Gokulraj, N
2015-11-01
This paper proposes a systematic approach for the modeling and control of non-square MIMO systems in time domain using relay feedback. Conventionally, modeling, selection of the control configuration and controller design of non-square MIMO systems are performed using input/output information of direct loop, while the output of undesired responses that bears valuable information on interaction among the loops are not considered. However, in this paper, the undesired response obtained from relay feedback test is also taken into consideration to extract the information about the interaction between the loops. The studies are performed on an Air Path Scheme of Turbocharged Diesel Engine (APSTDE) model, which is a typical non-square MIMO system, with input and output variables being 3 and 2 respectively. From the relay test response, the generalized analytical expressions are derived and these analytical expressions are used to estimate unknown system parameters and also to evaluate interaction measures. The interaction is analyzed by using Block Relative Gain (BRG) method. The model thus identified is later used to design appropriate controller to carry out closed loop studies. Closed loop simulation studies were performed for both servo and regulatory operations. Integral of Squared Error (ISE) performance criterion is employed to quantitatively evaluate performance of the proposed scheme. The usefulness of the proposed method is demonstrated on a lab-scale Two-Tank Cylindrical Interacting System (TTCIS), which is configured as a non-square system. Copyright © 2015 ISA. Published by Elsevier Ltd. All rights reserved.
Cao, Jianqin; Gu, Ruolei; Bi, Xuejing; Zhu, Xiangru; Wu, Haiyan
2015-01-01
Previous studies on social anxiety have demonstrated negative-expectancy bias in social contexts. In this study, we used a paradigm that employed self-relevant positive or negative social feedback, in order to test whether this negative expectancy manifests in event-related potentials (ERPs) during social evaluation among socially anxious individuals. Behavioral data revealed that individuals with social anxiety disorder (SAD) showed more negative expectancy of peer acceptance both in the experiment and in daily life than did the healthy control participants. Regarding ERP results, we found a overally larger P2 for positive social feedback and also a group main effect, such that the P2 was smaller in SAD group. SAD participants demonstrated a larger feedback-related negativity (FRN) to positive feedback than to negative feedback. In addition, SAD participants showed a more positive ΔFRN (ΔFRN = negative - positive). Furthermore, acceptance expectancy in daily life correlated negatively with ΔFRN amplitude, while the Interaction Anxiousness Scale (IAS) score correlated positively with the ΔFRN amplitude. Finally, the acceptance expectancy in daily life fully mediated the relationship between the IAS and ΔFRN. These results indicated that both groups could differentiate between positive and negative social feedback in the early stage of social feedback processing (reflected on the P2). However, the SAD group exhibited a larger FRN to positive social feedback than to negative social feedback, demonstrating their dysfunction in the late stage of social feedback processing. In our opinion, such dysfunction is due to their greater negative social feedback expectancy.
Cao, Jianqin; Gu, Ruolei; Bi, Xuejing; Zhu, Xiangru; Wu, Haiyan
2015-01-01
Previous studies on social anxiety have demonstrated negative-expectancy bias in social contexts. In this study, we used a paradigm that employed self-relevant positive or negative social feedback, in order to test whether this negative expectancy manifests in event-related potentials (ERPs) during social evaluation among socially anxious individuals. Behavioral data revealed that individuals with social anxiety disorder (SAD) showed more negative expectancy of peer acceptance both in the experiment and in daily life than did the healthy control participants. Regarding ERP results, we found a overally larger P2 for positive social feedback and also a group main effect, such that the P2 was smaller in SAD group. SAD participants demonstrated a larger feedback-related negativity (FRN) to positive feedback than to negative feedback. In addition, SAD participants showed a more positive ΔFRN (ΔFRN = negative – positive). Furthermore, acceptance expectancy in daily life correlated negatively with ΔFRN amplitude, while the Interaction Anxiousness Scale (IAS) score correlated positively with the ΔFRN amplitude. Finally, the acceptance expectancy in daily life fully mediated the relationship between the IAS and ΔFRN. These results indicated that both groups could differentiate between positive and negative social feedback in the early stage of social feedback processing (reflected on the P2). However, the SAD group exhibited a larger FRN to positive social feedback than to negative social feedback, demonstrating their dysfunction in the late stage of social feedback processing. In our opinion, such dysfunction is due to their greater negative social feedback expectancy. PMID:26635659
ERIC Educational Resources Information Center
Mano, Rita S.
2010-01-01
Purpose: This paper examines the critical effect of learning from past changes on employees' evaluations regarding the extent that a crisis can be controlled and prevented. It is suggested that previous changes incorporate elements of a double-loop learning process that shape managerial perceptions of crisis controllability and crisis prevention.…
N-Loop Learning: Part II--An Empirical Investigation
ERIC Educational Resources Information Center
Simonin, Bernard L.
2017-01-01
Purpose: Through a survey of firm's experiences with strategic alliances and a structural equation modeling approach, the aim of this study is to stimulate further interest in modeling and empirical research in the area of N-loop learning. Although the concepts of single-loop and double-loop learning, in particular, are well established in the…
Generation of chaotic radiation in a driven traveling wave tube amplifier with time-delayed feedback
NASA Astrophysics Data System (ADS)
Marchewka, Chad; Larsen, Paul; Bhattacharjee, Sudeep; Booske, John; Sengele, Sean; Ryskin, Nikita; Titov, Vladimir
2006-01-01
The application of chaos in communications and radar offers new and interesting possibilities. This article describes investigations on the generation of chaos in a traveling wave tube (TWT) amplifier and the experimental parameters responsible for sustaining stable chaos. Chaos is generated in a TWT amplifier when it is made to operate in a highly nonlinear regime by recirculating a fraction of the TWT output power back to the input in a delayed feedback configuration. A driver wave provides a constant external force to the system making it behave like a forced nonlinear oscillator. The effects of the feedback bandwidth, intensity, and phase are described. The study illuminates the different transitions to chaos and the effect of parameters such as the frequency and intensity of the driver wave. The detuning frequency, i.e., difference frequency between the driver wave and the natural oscillation of the system, has been identified as being an important physical parameter for controlling evolution to chaos. Among the observed routes to chaos, besides the more common period doubling, a new route called loss of frequency locking occurs when the driving frequency is adjacent to a natural oscillation mode. The feedback bandwidth controls the nonlinear dynamics of the system, particularly the number of natural oscillation modes. A computational model has been developed to simulate the experiments and reasonably good agreement is obtained between them. Experiments are described that demonstrate the feasibility of chaotic communications using two TWTs, where one is operated as a driven chaotic oscillator and the other as a time-delayed, open-loop amplifier.
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
Steady state statistical correlations predict bistability in reaction motifs.
Chakravarty, Suchana; Barik, Debashis
2017-03-28
Various cellular decision making processes are regulated by bistable switches that take graded input signals and convert them to binary all-or-none responses. Traditionally, a bistable switch generated by a positive feedback loop is characterized either by a hysteretic signal response curve with two distinct signaling thresholds or by characterizing the bimodality of the response distribution in the bistable region. To identify the intrinsic bistability of a feedback regulated network, here we propose that bistability can be determined by correlating higher order moments and cumulants (≥2) of the joint steady state distributions of two components connected in a positive feedback loop. We performed stochastic simulations of four feedback regulated models with intrinsic bistability and we show that for a bistable switch with variation of the signal dose, the steady state variance vs. covariance adopts a signatory cusp-shaped curve. Further, we find that the (n + 1)th order cross-cumulant vs. nth order cross-cumulant adopts a closed loop structure for at least n = 3. We also propose that our method is capable of identifying systems without intrinsic bistability even though the system may show bimodality in the marginal response distribution. The proposed method can be used to analyze single cell protein data measured at steady state from experiments such as flow cytometry.
Bach, Frances C; Rutten, Kirsten; Hendriks, Kristyanne; Riemers, Frank M; Cornelissen, Peter; de Bruin, Alain; Arkesteijn, Ger J; Wubbolts, Richard; Horton, William A; Penning, Louis C; Tryfonidou, Marianna A
2014-01-01
The endocrine feedback loop between vitamin D3 (1,25(OH)2D3) and parathyroid hormone (PTH) plays a central role in skeletal development. PTH-related protein (PTHrP) shares homology and its receptor (PTHR1) with PTH. The aim of this study was to investigate whether there is a functional paracrine feedback loop between 1,25(OH)2D3 and PTHrP in the growth plate, in parallel with the endocrine feedback loop between 1,25(OH)2D3 and PTH. This was investigated in ATDC5 cells treated with 10−8 M 1,25(OH)2D3 or PTHrP, Col2-pd2EGFP transgenic mice, and primary Col2-pd2EGFP growth plate chondrocytes isolated by FACS, using RT-qPCR, Western blot, PTHrP ELISA, chromatin immunoprecipitation (ChIP) assay, silencing of the 1,25(OH)2D3 receptor (VDR), immunofluorescent staining, immunohistochemistry, and histomorphometric analysis of the growth plate. The ChIP assay confirmed functional binding of the VDR to the PTHrP promoter, but not to the PTHR1 promoter. Treatment with 1,25(OH)2D3 decreased PTHrP protein production, an effect which was prevented by silencing of the VDR. Treatment with PTHrP significantly induced VDR production, but did not affect 1α- and 24-hydroxylase expression. Hypertrophic differentiation was inhibited by PTHrP and 1,25(OH)2D3 treatment. Taken together, these findings indicate that there is a functional paracrine feedback loop between 1,25(OH)2D3 and PTHrP in the growth plate. 1,25(OH)2D3 decreases PTHrP production, while PTHrP increases chondrocyte sensitivity to 1,25(OH)2D3 by increasing VDR production. In light of the role of 1,25(OH)2D3 and PTHrP in modulating chondrocyte differentiation, 1,25(OH)2D3 in addition to PTHrP could potentially be used to prevent undesirable hypertrophic chondrocyte differentiation during cartilage repair or regeneration. PMID:24777663
Rapid totally diverting loop sigmoid colostomy with noncontaminating rectal irrigation.
Sachatello, C R; Maull, K I
1977-08-01
Loop sigmoid colostomy employing a stapling device and catheter irrigation of the distal segment is less time-consuming and has lest potential for contamination than the standard double-barrel colostomy. Unlike the standard loop colostomy, it is totally diverting.
Phase-locked loop based on nanoelectromechanical resonant-body field effect transistor
NASA Astrophysics Data System (ADS)
Bartsch, S. T.; Rusu, A.; Ionescu, A. M.
2012-10-01
We demonstrate the room-temperature operation of a silicon nanoelectromechanical resonant-body field effect transistor (RB-FET) embedded into phase-locked loop (PLL). The very-high frequency resonator uses on-chip electrostatic actuation and transistor-based displacement detection. The heterodyne frequency down-conversion based on resistive FET mixing provides a loop feedback signal with high signal-to-noise ratio. We identify key parameters for PLL operation, and analyze the performance of the RB-FET at the system level. Used as resonant mass detector, the experimental frequency stability in the ppm-range translates into sub atto-gram (10-18 g) sensitivity in high vacuum. The feedback and control system are generic and may be extended to other mechanical resonators with transistor properties, such as graphene membranes and carbon nanotubes.
Dong, Shen; Corre, Béatrice; Foulon, Eliane; Dufour, Evelyne; Veillette, André; Acuto, Oreste; Michel, Frédérique
2006-01-01
Adaptor proteins positively or negatively regulate the T cell receptor for antigen (TCR) signaling cascade. We report that after TCR stimulation, the inhibitory adaptor downstream of kinase (Dok)-2 and its homologue Dok-1 are involved in a multimolecular complex including the lipid phosphatase Src homology 2 domain–containing inositol polyphosphate 5′-phosphatase (SHIP)-1 and Grb-2 which interacts with the membrane signaling scaffold linker for activation of T cells (LAT). Knockdown of LAT and SHIP-1 expression indicated that SHIP-1 favored recruitment of Dok-2 to LAT. Knockdown of Dok-2 and Dok-1 revealed their negative control on Akt and, unexpectedly, on Zap-70 activation. Our findings support the view that Dok-1 and -2 are critical elements of a LAT-dependent negative feedback loop that attenuates early TCR signal. Dok-1 and -2 may therefore exert a critical role in shaping the immune response and as gatekeepers for T cell tolerance. PMID:17043143
Design of a low parasitic inductance SiC power module with double-sided cooling
DOE Office of Scientific and Technical Information (OSTI.GOV)
Yang, Fei; Liang, Zhenxian; Wang, Fei
In this paper, a low-parasitic inductance SiC power module with double-sided cooling is designed and compared with a baseline double-sided cooled module. With the unique 3D layout utilizing vertical interconnection, the power loop inductance is effectively reduced without sacrificing the thermal performance. Both simulations and experiments are carried out to validate the design. Q3D simulation results show a power loop inductance of 1.63 nH, verified by the experiment, indicating more than 60% reduction of power loop inductance compared with the baseline module. With 0Ω external gate resistance turn-off at 600V, the voltage overshoot is less than 9% of the busmore » voltage at a load of 44.6A.« less
Feedback linearization for control of air breathing engines
NASA Technical Reports Server (NTRS)
Phillips, Stephen; Mattern, Duane
1991-01-01
The method of feedback linearization for control of the nonlinear nozzle and compressor components of an air breathing engine is presented. This method overcomes the need for a large number of scheduling variables and operating points to accurately model highly nonlinear plants. Feedback linearization also results in linear closed loop system performance simplifying subsequent control design. Feedback linearization is used for the nonlinear partial engine model and performance is verified through simulation.
PDF Signaling Is an Integral Part of the Drosophila Circadian Molecular Oscillator.
Mezan, Shaul; Feuz, Jean Daniel; Deplancke, Bart; Kadener, Sebastian
2016-10-11
Circadian clocks generate 24-hr rhythms in physiology and behavior. Despite numerous studies, it is still uncertain how circadian rhythms emerge from their molecular and neural constituents. Here, we demonstrate a tight connection between the molecular and neuronal circadian networks. Using fluorescent transcriptional reporters in a Drosophila ex vivo brain culture system, we identified a reciprocal negative regulation between the master circadian regulator CLK and expression of pdf, the main circadian neuropeptide. We show that PDF feedback is required for maintaining normal oscillation pattern in CLK-driven transcription. Interestingly, we found that CLK and neuronal firing suppresses pdf transcription, likely through a common pathway involving the transcription factors DHR38 and SR, establishing a direct link between electric activity and the circadian system. In sum, our work provides evidence for the existence of an uncharacterized CLK-PDF feedback loop that tightly wraps together the molecular oscillator with the circadian neuronal network in Drosophila. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.
Amplifiers dedicated for large area SiC photodiodes
NASA Astrophysics Data System (ADS)
Doroz, P.; Duk, M.; Korwin-Pawlowski, M. L.; Borecki, M.
2016-09-01
Large area SiC photodiodes find applications in optoelectronic sensors working at special conditions. These conditions include detection of UV radiation in harsh environment. Moreover, the mentioned sensors have to be selective and resistant to unwanted signals. For this purpose, the modulation of light at source unit and the rejection of constant current and low frequency component of signal at detector unit are used. The popular frequency used for modulation in such sensor is 1kHz. The large area photodiodes are characterized by a large capacitance and low shunt resistance that varies with polarization of the photodiode and can significantly modify the conditions of signal pre-amplification. In this paper two pre-amplifiers topology are analyzed: the transimpedance amplifier and the non-inverting voltage to voltage amplifier with negative feedback. The feedback loops of both pre-amplifiers are equipped with elements used for initial constant current and low frequency signals rejections. Both circuits are analyzed and compared using simulation and experimental approaches.
Forests and ozone: productivity, carbon storage, and feedbacks.
Wang, Bin; Shugart, Herman H; Shuman, Jacquelyn K; Lerdau, Manuel T
2016-02-22
Tropospheric ozone is a serious air-pollutant, with large impacts on plant function. This study demonstrates that tropospheric ozone, although it damages plant metabolism, does not necessarily reduce ecosystem processes such as productivity or carbon sequestration because of diversity change and compensatory processes at the community scale ameliorate negative impacts at the individual level. This study assesses the impact of ozone on forest composition and ecosystem dynamics with an individual-based gap model that includes basic physiology as well as species-specific metabolic properties. Elevated tropospheric ozone leads to no reduction of forest productivity and carbon stock and to increased isoprene emissions, which result from enhanced dominance by isoprene-emitting species (which tolerate ozone stress better than non-emitters). This study suggests that tropospheric ozone may not diminish forest carbon sequestration capacity. This study also suggests that, because of the often positive relationship between isoprene emission and ozone formation, there is a positive feedback loop between forest communities and ozone, which further aggravates ozone pollution.
Low-dimensional modelling of a transient cylinder wake using double proper orthogonal decomposition
NASA Astrophysics Data System (ADS)
Siegel, Stefan G.; Seidel, J.?Rgen; Fagley, Casey; Luchtenburg, D. M.; Cohen, Kelly; McLaughlin, Thomas
For the systematic development of feedback flow controllers, a numerical model that captures the dynamic behaviour of the flow field to be controlled is required. This poses a particular challenge for flow fields where the dynamic behaviour is nonlinear, and the governing equations cannot easily be solved in closed form. This has led to many versions of low-dimensional modelling techniques, which we extend in this work to represent better the impact of actuation on the flow. For the benchmark problem of a circular cylinder wake in the laminar regime, we introduce a novel extension to the proper orthogonal decomposition (POD) procedure that facilitates mode construction from transient data sets. We demonstrate the performance of this new decomposition by applying it to a data set from the development of the limit cycle oscillation of a circular cylinder wake simulation as well as an ensemble of transient forced simulation results. The modes obtained from this decomposition, which we refer to as the double POD (DPOD) method, correctly track the changes of the spatial modes both during the evolution of the limit cycle and when forcing is applied by transverse translation of the cylinder. The mode amplitudes, which are obtained by projecting the original data sets onto the truncated DPOD modes, can be used to construct a dynamic mathematical model of the wake that accurately predicts the wake flow dynamics within the lock-in region at low forcing amplitudes. This low-dimensional model, derived using nonlinear artificial neural network based system identification methods, is robust and accurate and can be used to simulate the dynamic behaviour of the wake flow. We demonstrate this ability not just for unforced and open-loop forced data, but also for a feedback-controlled simulation that leads to a 90% reduction in lift fluctuations. This indicates the possibility of constructing accurate dynamic low-dimensional models for feedback control by using unforced and transient forced data only.
Want More? Learn Less: Motivation Affects Adolescents Learning from Negative Feedback.
Zhuang, Yun; Feng, Wenfeng; Liao, Yu
2017-01-01
The primary goal of the present study was to investigate how positive and negative feedback may differently facilitate learning throughout development. In addition, the role of motivation as a modulating factor was examined. Participants (children, adolescents, and adults) completed two forms of the guess and application task (GAT). Feedback from the Cool-GAT task has low motivational salience because there are no consequences, while feedback from the Hot-GAT task has high motivational salience as it pertains to receiving a reward. The results indicated that negative feedback leads to a reduction in learning compared to positive feedback. The effect of negative feedback was greater in adolescent participants compared to children and adults in the Hot-GAT task, suggesting an interaction between age and motivation level on learning. Further analysis indicated that greater risk was associated with a greater reduction in learning from negative feedback and again, the reduction was greatest in adolescents. In summary, the current study supports the idea that learning from positive feedback and negative feedback differs throughout development. In a rule-based learning task, when associative learning is primarily in practice, participants learned less from negative feedback. This reduction is amplified during adolescence when task-elicited motivation is high.
Want More? Learn Less: Motivation Affects Adolescents Learning from Negative Feedback
Zhuang, Yun; Feng, Wenfeng; Liao, Yu
2017-01-01
The primary goal of the present study was to investigate how positive and negative feedback may differently facilitate learning throughout development. In addition, the role of motivation as a modulating factor was examined. Participants (children, adolescents, and adults) completed two forms of the guess and application task (GAT). Feedback from the Cool-GAT task has low motivational salience because there are no consequences, while feedback from the Hot-GAT task has high motivational salience as it pertains to receiving a reward. The results indicated that negative feedback leads to a reduction in learning compared to positive feedback. The effect of negative feedback was greater in adolescent participants compared to children and adults in the Hot-GAT task, suggesting an interaction between age and motivation level on learning. Further analysis indicated that greater risk was associated with a greater reduction in learning from negative feedback and again, the reduction was greatest in adolescents. In summary, the current study supports the idea that learning from positive feedback and negative feedback differs throughout development. In a rule-based learning task, when associative learning is primarily in practice, participants learned less from negative feedback. This reduction is amplified during adolescence when task-elicited motivation is high. PMID:28191003
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
Closed-loop Separation Control Using Oscillatory Flow Excitation
NASA Technical Reports Server (NTRS)
Allan, Brian G.; Juang, Jer-Nan; Raney, David L.; Seifert, Avi; Pack, latunia G.; Brown, Donald E.
2000-01-01
Design and implementation of a digital feedback controller for a flow control experiment was performed. The experiment was conducted in a cryogenic pressurized wind tunnel on a generic separated configuration at a chord Reynolds number of 16 million and a Mach number of 0.25. The model simulates the upper surface of a 20% thick airfoil at zero angle-of-attack. A moderate favorable pressure gradient, up to 55% of the chord, is followed by a severe adverse pressure gradient which is relaxed towards the trailing edge. The turbulent separation bubble, behind the adverse pressure gradient, is then reduced by introducing oscillatory flow excitation just upstream of the point of flow separation. The degree of reduction in the separation region can be controlled by the amplitude of the oscillatory excitation. A feedback controller was designed to track a given trajectory for the desired degree of flow reattachment and to improve the transient behavior of the flow system. Closed-loop experiments demonstrated that the feedback controller was able to track step input commands and improve the transient behavior of the open-loop response.
Optimizing the feedback control of Galvo scanners for laser manufacturing systems
NASA Astrophysics Data System (ADS)
Mirtchev, Theodore; Weeks, Robert; Minko, Sergey
2010-06-01
This paper summarizes the factors that limit the performance of moving-magnet galvo scanners driven by closed-loop digital servo amplifiers: torsional resonances, drifts, nonlinearities, feedback noise and friction. Then it describes a detailed Simulink® simulator that takes into account these factors and can be used to automatically tune the controller for best results with given galvo type and trajectory patterns. It allows for rapid testing of different control schemes, for instance combined position/velocity PID loops and displays the corresponding output in terms of torque, angular position and feedback sensor signal. The tool is configurable and can either use a dynamical state-space model of galvo's open-loop response, or can import the experimentally measured frequency domain transfer function. Next a drive signal digital pre-filtering technique is discussed. By performing a real-time Fourier analysis of the raw command signal it can be pre-warped to minimize all harmonics around the torsional resonances while boosting other non-resonant high frequencies. The optimized waveform results in much smaller overshoot and better settling time. Similar performance gain cannot be extracted from the servo controller alone.
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.