Antagonistic autoregulation speeds up a homogeneous response in Escherichia coli.

PubMed

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.

An expanding universe of circadian networks in higher plants.

PubMed

Pruneda-Paz, Jose L; Kay, Steve A

2010-05-01

Extensive circadian clock networks regulate almost every biological process in plants. Clock-controlled physiological responses are coupled with daily oscillations in environmental conditions resulting in enhanced fitness and growth vigor. Identification of core clock components and their associated molecular interactions has established the basic network architecture of plant clocks, which consists of multiple interlocked feedback loops. A hierarchical structure of transcriptional feedback overlaid with regulated protein turnover sets the pace of the clock and ultimately drives all clock-controlled processes. Although originally described as linear entities, increasing evidence suggests that many signaling pathways can act as both inputs and outputs within the overall network. Future studies will determine the molecular mechanisms involved in these complex regulatory loops. 2010 Elsevier Ltd. All rights reserved.

Direct binding of arsenic trioxide to AMPK and generation of inhibitory effects on acute myeloid leukemia precursors

PubMed Central

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

A regulatory network to segregate the identity of neuronal subtypes.

PubMed

Lee, Seunghee; Lee, Bora; Joshi, Kaumudi; Pfaff, Samuel L; Lee, Jae W; Lee, Soo-Kyung

2008-06-01

Spinal motor neurons (MNs) and V2 interneurons (V2-INs) are specified by two related LIM-complexes, MN-hexamer and V2-tetramer, respectively. Here we show how multiple parallel and complementary feedback loops are integrated to assign these two cell fates accurately. While MN-hexamer response elements (REs) are specific to MN-hexamer, V2-tetramer-REs can bind both LIM-complexes. In embryonic MNs, however, two factors cooperatively suppress the aberrant activation of V2-tetramer-REs. First, LMO4 blocks V2-tetramer assembly. Second, MN-hexamer induces a repressor, Hb9, which binds V2-tetramer-REs and suppresses their activation. V2-INs use a similar approach; V2-tetramer induces a repressor, Chx10, which binds MN-hexamer-REs and blocks their activation. Thus, our study uncovers a regulatory network to segregate related cell fates, which involves reciprocal feedforward gene regulatory loops.

Functional Association between Regulatory RNAs and the Annexins

PubMed Central

Monastyrskaya, Katia

2018-01-01

Cells respond to pathophysiological states by activation of stress-induced signalling. Regulatory non-coding microRNAs (miRNAs) often form stable feed-forward loops which ensure prolongation of the signal, contributing to sustained activation. Members of the annexin protein family act as sensors for Ca2+, pH, and lipid second messengers, and regulate various signalling pathways. Recently, annexins were reported to participate in feedback loops, suppressing miRNA synthesis and attenuating stress-induced dysregulation of gene expression. They can directly or indirectly associate with RNAs, and are transferred between the cells in exosomes and shed microvesicles. The ability of annexins to recruit other proteins and miRNAs into exosomes implicates them in control of cell–cell interactions, affecting the adaptive responses and remodelling processes during disease. The studies summarized in this Review point to an emerging role of annexins in influencing the synthesis, localisation, and transfer of regulatory RNAs. PMID:29462943

Modeling and control of non-square MIMO system using relay feedback.

PubMed

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.

Regulation during Cooperative and Collaborative Learning: A Theory-Based Review of Terms and Concepts

ERIC Educational Resources Information Center

Schoor, Cornelia; Narciss, Susanne; Körndle, Hermann

2015-01-01

This article reviews the terms and concepts that have been used for describing regulation of learning during cooperative and collaborative learning and suggests differentiating them on the basis of which parts of a regulatory feedback loop model are being shared. During cooperative and collaborative learning, not only self-regulation but also the…

A feed-back regulatory loop between glycerol-3-phosphate and lipid transfer proteins DIR1 and AZI1 mediates azelaic acid-induced systemic immunity

USDA-ARS?s Scientific Manuscript database

Systemic acquired resistance (SAR), a highly desirable form of plant defense, provides broad-spectrum immunity against diverse pathogens. The recent identification of seemingly unrelated chemical inducers of SAR warrants an investigation of their mutual interrelationships. We show that SAR induced b...

Positive and negative feedback regulatory loops of thiol-oxidative stress response mediated by an unstable isoform of sigmaR in actinomycetes.

PubMed

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.

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.

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.

Cross-cohort analysis identifies a TEAD4 ↔ MYCN positive-feedback loop as the core regulatory element of high-risk neuroblastoma. | Office of Cancer Genomics

Cancer.gov

High-risk neuroblastomas show a paucity of recurrent somatic mutations at diagnosis. As a result, the molecular basis for this aggressive phenotype remains elusive. Recent progress in regulatory network analysis helped us elucidate disease-driving mechanisms downstream of genomic alterations, including recurrent chromosomal alterations. Our analysis identified three molecular subtypes of high-risk neuroblastomas, consistent with chromosomal alterations, and identified subtype-specific master regulator (MR) proteins that were conserved across independent cohorts.

Toll-like receptors and intestinal defence: molecular basis and therapeutic implications.

PubMed

Cario, Elke

2003-07-07

Toll-like receptors (TLRs) play a principle role in distinct pathogen recognition and in the initiation of innate immune responses of the intestinal mucosa. Activated innate immunity interconnects downstream with adaptive immunity in complex feedback regulatory loops. Intestinal disease might result from inappropriate activation of the mucosal immune system driven by TLRs in response to normal luminal flora.

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

PubMed

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

2013-04-25

Systemic acquired resistance (SAR), a highly desirable form of plant defense, provides broad-spectrum immunity against diverse pathogens. The recent identification of seemingly unrelated chemical inducers of SAR warrants an investigation of their mutual interrelationships. We show that SAR induced by the dicarboxylic acid azelaic acid (AA) requires the phosphorylated sugar derivative glycerol-3-phosphate (G3P). Pathogen inoculation induced the release of free unsaturated fatty acids (FAs) and thereby triggered AA accumulation, because these FAs serve as precursors for AA. AA accumulation in turn increased the levels of G3P, which is required for AA-conferred SAR. The lipid transfer proteins DIR1 and AZI1, both of which are required for G3P- and AA-induced SAR, were essential for G3P accumulation. Conversely, reduced G3P resulted in decreased AZI1 and DIR1 transcription. Our results demonstrate that an intricate feedback regulatory loop among G3P, DIR1, and AZI1 regulates SAR and that AA functions upstream of G3P in this pathway. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

A Role for Timely Nuclear Translocation of Clock Repressor Proteins in Setting Circadian Clock Speed

PubMed Central

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

GARP: a key receptor controlling FOXP3 in human regulatory T cells.

PubMed

Probst-Kepper, M; Geffers, R; Kröger, A; Viegas, N; Erck, C; Hecht, H-J; Lünsdorf, H; Roubin, R; Moharregh-Khiabani, D; Wagner, K; Ocklenburg, F; Jeron, A; Garritsen, H; Arstila, T P; Kekäläinen, E; Balling, R; Hauser, H; Buer, J; Weiss, S

2009-09-01

Recent evidence suggests that regulatory pathways might control sustained high levels of FOXP3 in regulatory CD4(+)CD25(hi) T (T(reg)) cells. Based on transcriptional profiling of ex vivo activated T(reg) and helper CD4(+)CD25(-) T (T(h)) cells we have identified GARP (glycoprotein-A repetitions predominant), LGALS3 (lectin, galactoside-binding, soluble, 3) and LGMN (legumain) as novel genes implicated in human T(reg) cell function, which are induced upon T-cell receptor stimulation. Retroviral overexpression of GARP in antigen-specific T(h) cells leads to an efficient and stable re-programming of an effector T cell towards a regulatory T cell, which involves up-regulation of FOXP3, LGALS3, LGMN and other T(reg)-associated markers. In contrast, overexpression of LGALS3 and LGMN enhance FOXP3 and GARP expression, but only partially induced a regulatory phenotype. Lentiviral down-regulation of GARP in T(reg) cells significantly impaired the suppressor function and was associated with down-regulation of FOXP3. Moreover, down-regulation of FOXP3 resulted in similar phenotypic changes and down-regulation of GARP. This provides compelling evidence for a GARP-FOXP3 positive feedback loop and provides a rational molecular basis for the known difference between natural and transforming growth factor-beta induced T(reg) cells as we show here that the latter do not up-regulate GARP. In summary, we have identified GARP as a key receptor controlling FOXP3 in T(reg) cells following T-cell activation in a positive feedback loop assisted by LGALS3 and LGMN, which represents a promising new system for the therapeutic manipulation of T cells in human disease.

Periodic, Quasi-periodic and Chaotic Dynamics in Simple Gene Elements with Time Delays

PubMed Central

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.

Form and function in gene regulatory networks: the structure of network motifs determines fundamental properties of their dynamical state space.

PubMed

Ahnert, S E; Fink, T M A

2016-07-01

Network motifs have been studied extensively over the past decade, and certain motifs, such as the feed-forward loop, play an important role in regulatory networks. Recent studies have used Boolean network motifs to explore the link between form and function in gene regulatory networks and have found that the structure of a motif does not strongly determine its function, if this is defined in terms of the gene expression patterns the motif can produce. Here, we offer a different, higher-level definition of the 'function' of a motif, in terms of two fundamental properties of its dynamical state space as a Boolean network. One is the basin entropy, which is a complexity measure of the dynamics of Boolean networks. The other is the diversity of cyclic attractor lengths that a given motif can produce. Using these two measures, we examine all 104 topologically distinct three-node motifs and show that the structural properties of a motif, such as the presence of feedback loops and feed-forward loops, predict fundamental characteristics of its dynamical state space, which in turn determine aspects of its functional versatility. We also show that these higher-level properties have a direct bearing on real regulatory networks, as both basin entropy and cycle length diversity show a close correspondence with the prevalence, in neural and genetic regulatory networks, of the 13 connected motifs without self-interactions that have been studied extensively in the literature. © 2016 The Authors.

MYC association with cancer risk and a new model of MYC-mediated repression.

PubMed

Cole, Michael D

2014-07-01

MYC is one of the most frequently mutated and overexpressed genes in human cancer but the regulation of MYC expression and the ability of MYC protein to repress cellular genes (including itself) have remained mysterious. Recent genome-wide association studies show that many genetic polymorphisms associated with disease risk map to distal regulatory elements that regulate the MYC promoter through large chromatin loops. Cancer risk-associated single-nucleotide polymorphisms (SNPs) contain more potent enhancer activity, promoting higher MYC levels and a greater risk of disease. The MYC promoter is also subject to complex regulatory circuits and limits its own expression by a feedback loop. A model for MYC autoregulation is discussed which involves a signaling pathway between the PTEN (phosphatase and tensin homolog) tumor suppressor and repressive histone modifications laid down by the EZH2 methyltransferase. Copyright © 2014 Cold Spring Harbor Laboratory Press; all rights reserved.

Transcription factor trapping by RNA in gene regulatory elements.

PubMed

Sigova, Alla A; Abraham, Brian J; Ji, Xiong; Molinie, Benoit; Hannett, Nancy M; Guo, Yang Eric; Jangi, Mohini; Giallourakis, Cosmas C; Sharp, Phillip A; Young, Richard A

2015-11-20

Transcription factors (TFs) bind specific sequences in promoter-proximal and -distal DNA elements to regulate gene transcription. RNA is transcribed from both of these DNA elements, and some DNA binding TFs bind RNA. Hence, RNA transcribed from regulatory elements may contribute to stable TF occupancy at these sites. We show that the ubiquitously expressed TF Yin-Yang 1 (YY1) binds to both gene regulatory elements and their associated RNA species across the entire genome. Reduced transcription of regulatory elements diminishes YY1 occupancy, whereas artificial tethering of RNA enhances YY1 occupancy at these elements. We propose that RNA makes a modest but important contribution to the maintenance of certain TFs at gene regulatory elements and suggest that transcription of regulatory elements produces a positive-feedback loop that contributes to the stability of gene expression programs. Copyright © 2015, American Association for the Advancement of Science.

FOXP3: required but not sufficient. the role of GARP (LRRC32) as a safeguard of the regulatory phenotype.

PubMed

Probst-Kepper, M; Balling, R; Buer, J

2010-08-01

FOXP3 is essential for the development and function of regulatory CD4(+)CD25(hi) T (T(reg)) cells. However, recent evidence suggests that FOXP3 alone is not sufficient to completely explain the regulatory phenotype of these key players in autoimmunity and inflammation: after being activated, conventional human CD4(+) T cells transiently up-regulate FOXP3 without acquiring a regulatory function. Researchers have recently found that glycoprotein A repetitions predominant (GARP, or LRRC32) is a T(reg)-specific receptor that binds latent TGF-beta and dominantly controls FOXP3 and the regulatory phenotype via a positive feedback loop. This finding provides a missing link in our molecular understanding of FOXP3 in T(reg) cells. This viewpoint focuses on GARP as safeguard of FOXP3 and the regulatory phenotype.

20-Hydroxyecdysone (20E) Primary Response Gene E75 Isoforms Mediate Steroidogenesis Autoregulation and Regulate Developmental Timing in Bombyx*

PubMed Central

Li, Kang; Tian, Ling; Guo, Zhongjian; Guo, Sanyou; Zhang, Jianzhen; Gu, Shi-Hong; Palli, Subba R.; Cao, Yang; Li, Sheng

2016-01-01

The temporal control mechanisms that precisely control animal development remain largely elusive. The timing of major developmental transitions in insects, including molting and metamorphosis, is coordinated by the steroid hormone 20-hydroxyecdysone (20E). 20E involves feedback loops to maintain pulses of ecdysteroid biosynthesis leading to its upsurge, whereas the underpinning molecular mechanisms are not well understood. Using the silkworm Bombyx mori as a model, we demonstrated that E75, the 20E primary response gene, mediates a regulatory loop between ecdysteroid biosynthesis and 20E signaling. E75 isoforms A and C directly bind to retinoic acid receptor-related response elements in Halloween gene promoter regions to induce gene expression thus promoting ecdysteroid biosynthesis and developmental transition, whereas isoform B antagonizes the transcriptional activity of isoform A/C through physical interaction. As the expression of E75 isoforms is differentially induced by 20E, the E75-mediated regulatory loop represents a fine autoregulation of steroidogenesis, which contributes to the precise control of developmental timing. PMID:27365399

Molecular genetic analysis of circadian timekeeping in Drosophila

PubMed Central

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Che, Qi; Liu, Bin-Ya; Wang, Fang-Yuan

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

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.

Requirements for efficient cell-type proportioning: regulatory timescales, stochasticity and lateral inhibition

NASA Astrophysics Data System (ADS)

Pfeuty, B.; Kaneko, K.

2016-04-01

The proper functioning of multicellular organisms requires the robust establishment of precise proportions between distinct cell types. This developmental differentiation process typically involves intracellular regulatory and stochastic mechanisms to generate cell-fate diversity as well as intercellular signaling mechanisms to coordinate cell-fate decisions at tissue level. We thus surmise that key insights about the developmental regulation of cell-type proportion can be captured by the modeling study of clustering dynamics in population of inhibitory-coupled noisy bistable systems. This general class of dynamical system is shown to exhibit a very stable two-cluster state, but also metastability, collective oscillations or noise-induced state hopping, which can prevent from timely and reliably reaching a robust and well-proportioned clustered state. To circumvent these obstacles or to avoid fine-tuning, we highlight a general strategy based on dual-time positive feedback loops, such as mediated through transcriptional versus epigenetic mechanisms, which improves proportion regulation by coordinating early and flexible lineage priming with late and firm commitment. This result sheds new light on the respective and cooperative roles of multiple regulatory feedback, stochasticity and lateral inhibition in developmental dynamics.

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.

Asymmetric dual-loop feedback to suppress spurious tones and reduce timing jitter in self-mode-locked quantum-dash lasers emitting at 155 μm

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.

P53-miR-191-SOX4 regulatory loop affects apoptosis in breast cancer.

PubMed

Sharma, Shivani; Nagpal, Neha; Ghosh, Prahlad C; Kulshreshtha, Ritu

2017-08-01

miRNAs have emerged as key participants of p53 signaling pathways because they regulate or are regulated by p53. Here, we provide the first study demonstrating direct regulation of an oncogenic miRNA, miR-191-5p, by p53 and existence of a regulatory feedback loop. Using a combination of qRT-PCR, promoter-luciferase, and chromatin-immunoprecipitation assays, we show that p53 brings about down-regulation of miR-191-5p in breast cancer. miR-191-5p overexpression brought about inhibition of apoptosis in breast cancer cell lines (MCF7 and ZR-75) as demonstrated by reduction in annexin-V stained cells and caspase 3/7 activity, whereas miR-191-5p down-regulation showed the opposite. We further unveiled that SOX4 was a direct target of miR-191-5p. SOX4 overexpression was shown to increase p53 protein levels in MCF7 cells. miR-191-5p overexpression brought about down-regulation of SOX4 and thus p53 levels, suggesting the existence of a regulatory feedback loop. Breast cancer treatment by doxorubicin, an anti-cancer drug, involves induction of apoptosis by p53; we thus wanted to check whether miR-191-5p affects doxorubicin sensitivity. Interestingly, Anti-miR-191 treatment significantly decreased the IC50 of the doxorubicin drug and thus sensitized breast cancer cells to doxorubicin treatment by promoting apoptosis. Overall, this work highlights the importance of the p53-miR-191- SOX4 axis in the regulation of apoptosis and drug resistance in breast cancer and offers a preclinical proof-of-concept for use of an Anti-miR-191 and doxorubicin combination as a rational approach to pursue for better breast cancer treatment. © 2017 Sharma et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

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.

CK1/Doubletime activity delays transcription activation in the circadian clock

PubMed Central

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

PubMed Central

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

Structure of GlnK1 with bound effectors indicates regulatory mechanism for ammonia uptake.

PubMed

Yildiz, Ozkan; Kalthoff, Christoph; Raunser, Stefan; Kühlbrandt, Werner

2007-01-24

A binary complex of the ammonia channel Amt1 from Methanococcus jannaschii and its cognate P(II) signalling protein GlnK1 has been produced and characterized. Complex formation is prevented specifically by the effector molecules Mg-ATP and 2-ketoglutarate. Single-particle electron microscopy of the complex shows that GlnK1 binds on the cytoplasmic side of Amt1. Three high-resolution X-ray structures of GlnK1 indicate that the functionally important T-loop has an extended, flexible conformation in the absence of Mg-ATP, but assumes a compact, tightly folded conformation upon Mg-ATP binding, which in turn creates a 2-ketoglutarate-binding site. We propose a regulatory mechanism by which nitrogen uptake is controlled by the binding of both effector molecules to GlnK1. At normal effector levels, a 2-ketoglutarate molecule binding at the apex of the compact T-loop would prevent complex formation, ensuring uninhibited ammonia uptake. At low levels of Mg-ATP, the extended loops would seal the ammonia channels in the complex. Binding of both effector molecules to P(II) signalling proteins may thus represent an effective feedback mechanism for regulating ammonium uptake through the membrane.

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

PubMed

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

2009-04-01

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

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

PubMed Central

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

Dependable control systems with Internet of Things.

PubMed

Tran, Tri; Ha, Q P

2015-11-01

This paper presents an Internet of Things (IoT)-enabled dependable control system (DepCS) for continuous processes. In a DepCS, an actuator and a transmitter form a regulatory control loop. Each processor inside such actuator and transmitter is designed as a computational platform implementing the feedback control algorithm. The connections between actuators and transmitters via IoT create a reliable backbone for a DepCS. The centralized input-output marshaling system is not required in DepCSs. A state feedback control synthesis method for DepCS applying the self-recovery constraint is presented in the second part of the paper. Copyright © 2015 ISA. Published by Elsevier Ltd. All rights reserved.

TNFα-senescence initiates a STAT-dependent positive feedback loop, leading to a sustained interferon signature, DNA damage, and cytokine secretion

PubMed Central

Kandhaya-Pillai, Renuka; Miro-Mur, Francesc; Alijotas-Reig, Jaume; Tchkonia, Tamara; Kirkland, James L.; Schwartz, Simo

2017-01-01

Cellular senescence is a cell fate program that entails essentially irreversible proliferative arrest in response to damage signals. Tumor necrosis factor-alpha (TNFα), an important pro-inflammatory cytokine secreted by some types of senescent cells, can induce senescence in mouse and human cells. However, downstream signaling pathways linking TNFα-related inflammation to senescence are not fully characterized. Using human umbilical vein endothelial cells (HUVECs) as a model, we show that TNFα induces permanent growth arrest and increases p21CIP1, p16INK4A, and SA-β-gal, accompanied by persistent DNA damage and ROS production. By gene expression profiling, we identified the crucial involvement of inflammatory and JAK/STAT pathways in TNFα-mediated senescence. We found that TNFα activates a STAT-dependent autocrine loop that sustains cytokine secretion and an interferon signature to lock cells into senescence. Furthermore, we show STAT1/3 activation is necessary for cytokine and ROS production during TNFα-induced senescence. However, inhibition of STAT1/3 did not rescue cells from proliferative arrest, but rather suppressed cell cycle regulatory genes and altered TNFα-induced senescence. Our findings suggest a positive feedback mechanism via the STAT pathway that sustains cytokine production and reveal a reciprocal regulatory role of JAK/STAT in TNFα-mediated senescence. PMID:29176033

The FANTASTIC FOUR proteins influence shoot meristem size in Arabidopsis thaliana.

PubMed

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.

Dynamical Consequences of Bandpass Feedback Loops in a Bacterial Phosphorelay

PubMed Central

Sen, Shaunak; Garcia-Ojalvo, Jordi; Elowitz, Michael B.

2011-01-01

Under conditions of nutrient limitation, Bacillus subtilis cells terminally differentiate into a dormant spore state. Progression to sporulation is controlled by a genetic circuit consisting of a phosphorelay embedded in multiple transcriptional feedback loops, which is used to activate the master regulator Spo0A by phosphorylation. These transcriptional regulatory interactions are “bandpass”-like, in the sense that activation occurs within a limited band of Spo0A∼P concentrations. Additionally, recent results show that the phosphorelay activation occurs in pulses, in a cell-cycle dependent fashion. However, the impact of these pulsed bandpass interactions on the circuit dynamics preceding sporulation remains unclear. In order to address this question, we measured key features of the bandpass interactions at the single-cell level and analyzed them in the context of a simple mathematical model. The model predicted the emergence of a delayed phase shift between the pulsing activity of the different sporulation genes, as well as the existence of a stable state, with elevated Spo0A activity but no sporulation, embedded within the dynamical structure of the system. To test the model, we used time-lapse fluorescence microscopy to measure dynamics of single cells initiating sporulation. We observed the delayed phase shift emerging during the progression to sporulation, while a re-engineering of the sporulation circuit revealed behavior resembling the predicted additional state. These results show that periodically-driven bandpass feedback loops can give rise to complex dynamics in the progression towards sporulation. PMID:21980382

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

PubMed

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.

Functional architecture and global properties of the Corynebacterium glutamicum regulatory network: Novel insights from a dataset with a high genomic coverage.

PubMed

Freyre-González, Julio A; Tauch, Andreas

2017-09-10

Corynebacterium glutamicum is a Gram-positive, anaerobic, rod-shaped soil bacterium able to grow on a diversity of carbon sources like sugars and organic acids. It is a biotechnological relevant organism because of its highly efficient ability to biosynthesize amino acids, such as l-glutamic acid and l-lysine. Here, we reconstructed the most complete C. glutamicum regulatory network to date and comprehensively analyzed its global organizational properties, systems-level features and functional architecture. Our analyses show the tremendous power of Abasy Atlas to study the functional organization of regulatory networks. We created two models of the C. glutamicum regulatory network: all-evidences (containing both weak and strong supported interactions, genomic coverage=73%) and strongly-supported (only accounting for strongly supported evidences, genomic coverage=71%). Using state-of-the-art methodologies, we prove that power-law behaviors truly govern the connectivity and clustering coefficient distributions. We found a non-previously reported circuit motif that we named complex feed-forward motif. We highlighted the importance of feedback loops for the functional architecture, beyond whether they are statistically over-represented or not in the network. We show that the previously reported top-down approach is inadequate to infer the hierarchy governing a regulatory network because feedback bridges different hierarchical layers, and the top-down approach disregards the presence of intermodular genes shaping the integration layer. Our findings all together further support a diamond-shaped, three-layered hierarchy exhibiting some feedback between processing and coordination layers, which is shaped by four classes of systems-level elements: global regulators, locally autonomous modules, basal machinery and intermodular genes. Copyright © 2016 Elsevier B.V. All rights reserved.

IFN-γ signaling maintains skin pigmentation homeostasis through regulation of melanosome maturation

PubMed Central

Natarajan, Vivek T.; Ganju, Parul; Singh, Archana; Vijayan, Vinaya; Kirty, Kritika; Yadav, Shalini; Puntambekar, Shraddha; Bajaj, Sonali; Dani, Prachi P.; Kar, Hemanta K.; Gadgil, Chetan J.; Natarajan, Krishnamurthy; Rani, Rajni; Gokhale, Rajesh S.

2014-01-01

Cellular homeostasis is an outcome of complex interacting processes with nonlinear feedbacks that can span distinct spatial and temporal dimensions. Skin tanning is one such dynamic response that maintains genome integrity of epidermal cells. Although pathways underlying hyperpigmentation cascade are recognized, negative feedback regulatory loops that can dampen the activated melanogenesis process are not completely understood. In this study, we delineate a regulatory role of IFN-γ in skin pigmentation biology. We show that IFN-γ signaling impedes maturation of the key organelle melanosome by concerted regulation of several pigmentation genes. Withdrawal of IFN-γ signal spontaneously restores normal cellular programming. This effect in melanocytes is mediated by IFN regulatory factor-1 and is not dependent on the central regulator microphthalmia-associated transcription factor. Chronic IFN-γ signaling shows a clear hypopigmentation phenotype in both mouse and human skin. Interestingly, IFN-γ KO mice display a delayed recovery response to restore basal state of epidermal pigmentation after UV-induced tanning. Together, our studies delineate a new spatiotemporal role of the IFN-γ signaling network in skin pigmentation homeostasis, which could have implications in various cutaneous depigmentary and malignant disorders. PMID:24474804

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

DOEpatents

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.

How short RNAs impact the human ribonuclease Dicer activity: putative regulatory feedback-loops and other RNA-mediated mechanisms controlling microRNA processing.

PubMed

Koralewska, Natalia; Hoffmann, Weronika; Pokornowska, Maria; Milewski, Marek; Lipinska, Andrea; Bienkowska-Szewczyk, Krystyna; Figlerowicz, Marek; Kurzynska-Kokorniak, Anna

2016-01-01

Ribonuclease Dicer plays a pivotal role in RNA interference pathways by processing long double-stranded RNAs and single-stranded hairpin RNA precursors into small interfering RNAs (siRNAs) and microRNAs (miRNAs), respectively. While details of Dicer regulation by a variety of proteins are being elucidated, less is known about non-protein factors, e.g. RNA molecules, that may influence this enzyme's activity. Therefore, we decided to investigate the question of whether the RNA molecules can function not only as Dicer substrates but also as its regulators. Our previous in vitro studies indicated that the activity of human Dicer can be influenced by short RNA molecules that either bind to Dicer or interact with its substrates, or both. Those studies were carried out with commercial Dicer preparations. Nevertheless, such preparations are usually not homogeneous enough to carry out more detailed RNA-binding studies. Therefore, we have established our own system for the production of human Dicer in insect cells. In this manuscript, we characterize the RNA-binding and RNA-cleavage properties of the obtained preparation. We demonstrate that Dicer can efficiently bind single-stranded RNAs that are longer than ~20-nucleotides. Consequently, we revisit possible scenarios of Dicer regulation by single-stranded RNA species ranging from ~10- to ~60-nucleotides, in the context of their binding to this enzyme. Finally, we show that siRNA/miRNA-sized RNAs may affect miRNA production either by binding to Dicer or by participating in regulatory feedback-loops. Altogether, our studies suggest a broad regulatory role of short RNAs in Dicer functioning.

Refined molecular hinge between allosteric and catalytic domain determines allosteric regulation and stability of fungal chorismate mutase

PubMed Central

Helmstaedt, Kerstin; Heinrich, Gabriele; Lipscomb, William N.; Braus, Gerhard H.

2002-01-01

The yeast chorismate mutase is regulated by tyrosine as feedback inhibitor and tryptophan as crosspathway activator. The monomer consists of a catalytic and a regulatory domain covalently linked by the loop L220s (212–226), which functions as a molecular hinge. Two monomers form the active dimeric enzyme stabilized by hydrophobic interactions in the vicinity of loop L220s. The role of loop L220s and its environment for enzyme regulation, dimerization, and stability was analyzed. Substitution of yeast loop L220s in place of the homologous loop from the corresponding and similarly regulated Aspergillus enzyme (and the reverse substitution) changed tyrosine inhibition to activation. Yeast loop L220s substituted into the Aspergillus enzyme resulted in a tryptophan-inhibitable enzyme. Monomeric yeast chorismate mutases could be generated by substituting two hydrophobic residues in and near the hinge region. The resulting Thr-212→Asp–Phe-28→Asp enzyme was as stable as wild type, but lost allosteric regulation and showed reduced catalytic activity. These results underline the crucial role of this molecular hinge for inhibition, activation, quaternary structure, and stability of yeast chorismate mutase. PMID:11997452

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.

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.

On the Minimization of Fluctuations in the Response Times of Autoregulatory Gene Networks

PubMed Central

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

The magnetosphere as system

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.

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…

Isodeoxyelephantopin induces protective autophagy in lung cancer cells via Nrf2-p62-keap1 feedback loop

PubMed Central

Wang, Yang; Zhang, Jing; Huang, Zhi-Hao; Huang, Xiao-Hui; Zheng, Wei-Bin; Yin, Xing-Feng; Li, Yao-Lan; Li, Bin; He, Qing-Yu

2017-01-01

Isodeoxyelephantopin (ESI), isolated from Elephantopus scaber L. has been reported to exert anticancer effects. In this study, we aimed to investigate whether and how cancer cells exert protective responses against ESI treatment. Confocal fluorescence microscopy showed that ESI significantly induced autophagy flux in the lung cancer cells expressing mCherry-EGFP-LC3 reporter. Treatment of the cells with ESI increased the expression levels of the autophagy markers including LC3-II, ATG3 and Beclin1 in a dose-dependent manner. Pretreatment with autophagy inhibitor 3-methyladenine (3-MA) not only attenuated the effects of ESI on autophagy, but also enhanced the effects of ESI on cell viability and apoptosis. Mechanistically, the SILAC quantitative proteomics coupled with bioinformatics analysis revealed that the ESI-regulated proteins were mainly involved in Nrf2-mediated oxidative stress response. We found that ESI induced the nuclear translocation of Nrf2 for activating the downstream target genes including HO-1 and p62 (SQSTM1). More importantly, ESI-induced p62 could competitively bind with Keap1, and releases Nrf2 to activate downstream target gene p62 as a positive feedback loop, therefore promoting autophagy. Furthermore, knockdown of Nrf2 or p62 could abrogate the ESI-induced autophagy and significantly enhanced the anticancer effect of ESI. Taken together, we demonstrated that ESI can sustain cell survival by activating protective autophagy through Nrf2-p62-keap1 feedback loop, whereas targeting this regulatory axis combined with ESI treatment may be a promising strategy for anticancer therapy. PMID:28617433

Isodeoxyelephantopin induces protective autophagy in lung cancer cells via Nrf2-p62-keap1 feedback loop.

PubMed

Wang, Yang; Zhang, Jing; Huang, Zhi-Hao; Huang, Xiao-Hui; Zheng, Wei-Bin; Yin, Xing-Feng; Li, Yao-Lan; Li, Bin; He, Qing-Yu

2017-06-15

Isodeoxyelephantopin (ESI), isolated from Elephantopus scaber L. has been reported to exert anticancer effects. In this study, we aimed to investigate whether and how cancer cells exert protective responses against ESI treatment. Confocal fluorescence microscopy showed that ESI significantly induced autophagy flux in the lung cancer cells expressing mCherry-EGFP-LC3 reporter. Treatment of the cells with ESI increased the expression levels of the autophagy markers including LC3-II, ATG3 and Beclin1 in a dose-dependent manner. Pretreatment with autophagy inhibitor 3-methyladenine (3-MA) not only attenuated the effects of ESI on autophagy, but also enhanced the effects of ESI on cell viability and apoptosis. Mechanistically, the SILAC quantitative proteomics coupled with bioinformatics analysis revealed that the ESI-regulated proteins were mainly involved in Nrf2-mediated oxidative stress response. We found that ESI induced the nuclear translocation of Nrf2 for activating the downstream target genes including HO-1 and p62 (SQSTM1). More importantly, ESI-induced p62 could competitively bind with Keap1, and releases Nrf2 to activate downstream target gene p62 as a positive feedback loop, therefore promoting autophagy. Furthermore, knockdown of Nrf2 or p62 could abrogate the ESI-induced autophagy and significantly enhanced the anticancer effect of ESI. Taken together, we demonstrated that ESI can sustain cell survival by activating protective autophagy through Nrf2-p62-keap1 feedback loop, whereas targeting this regulatory axis combined with ESI treatment may be a promising strategy for anticancer therapy.

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.

The FANTASTIC FOUR proteins influence shoot meristem size in Arabidopsis thaliana

PubMed Central

2010-01-01

Background 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. Results 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. Conclusion 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. PMID:21176196

Servo control booster system for minimizing following error

DOEpatents

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…

Computational Model of a Positive BDNF Feedback Loop in Hippocampal Neurons Following Inhibitory Avoidance Training

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…

A linear quadratic Gaussian with loop transfer recovery proximity operations autopilot for spacecraft. M.S. Thesis - MIT

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.

miR-137 forms a regulatory loop with nuclear receptor TLX and LSD1 in neural stem cells

PubMed Central

Sun, GuoQiang; Ye, Peng; Murai, Kiyohito; Lang, Ming-Fei; Li, Shengxiu; Zhang, Heying; Li, Wendong; Fu, Chelsea; Yin, Jason; Wang, Allen; Ma, Xiaoxiao; Shi, Yanhong

2012-01-01

miR-137 is a brain-enriched microRNA. Its role in neural development remains unknown. Here we show that miR-137 plays an essential role in controlling embryonic neural stem cell fate determination. miR-137 negatively regulates cell proliferation and accelerates neural differentiation of embryonic neural stem cells. In addition, we show that histone demethylase LSD1, a transcriptional co-repressor of nuclear receptor TLX, is a downstream target of miR-137. In utero electroporation of miR-137 in embryonic mouse brains led to premature differentiation and outward migration of the transfected cells. Introducing a LSD1 expression vector lacking the miR-137 recognition site rescued miR-137-induced precocious differentiation. Furthermore, we demonstrate that TLX, an essential regulator of neural stem cell self-renewal, represses the expression of miR-137 by recruiting LSD1 to the genomic regions of miR-137. Thus, miR-137 forms a feedback regulatory loop with TLX and LSD1 to control the dynamics between neural stem cell proliferation and differentiation during neural development. PMID:22068596

Autoregulatory mechanisms controlling the Microprocessor.

PubMed

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.

Multivariable control of the Space Shuttle Remote Manipulator System using linearization by state feedback. M.S. Thesis

NASA Technical Reports Server (NTRS)

Gettman, Chang-Ching LO

1993-01-01

This thesis develops and demonstrates an approach to nonlinear control system design using linearization by state feedback. The design provides improved transient response behavior allowing faster maneuvering of payloads by the SRMS. Modeling uncertainty is accounted for by using a second feedback loop designed around the feedback linearized dynamics. A classical feedback loop is developed to provide the easy implementation required for the relatively small on board computers. Feedback linearization also allows the use of higher bandwidth model based compensation in the outer loop, since it helps maintain stability in the presence of the nonlinearities typically neglected in model based designs.

Causal structure of oscillations in gene regulatory networks: Boolean analysis of ordinary differential equation attractors.

PubMed

Sun, Mengyang; Cheng, Xianrui; Socolar, Joshua E S

2013-06-01

A common approach to the modeling of gene regulatory networks is to represent activating or repressing interactions using ordinary differential equations for target gene concentrations that include Hill function dependences on regulator gene concentrations. An alternative formulation represents the same interactions using Boolean logic with time delays associated with each network link. We consider the attractors that emerge from the two types of models in the case of a simple but nontrivial network: a figure-8 network with one positive and one negative feedback loop. We show that the different modeling approaches give rise to the same qualitative set of attractors with the exception of a possible fixed point in the ordinary differential equation model in which concentrations sit at intermediate values. The properties of the attractors are most easily understood from the Boolean perspective, suggesting that time-delay Boolean modeling is a useful tool for understanding the logic of regulatory networks.

Perspectives on Regulatory T Cell Therapies

PubMed Central

Probst-Kepper, Michael; Kröger, Andrea; Garritsen, Henk S.P.; Buer, Jan

2009-01-01

Summary Adoptive transfer in animal models clearly indicate an essential role of CD4+ CD25+ FOXP3+ regulatory T (Treg) cells in prevention and treatment of autoimmune and graft-versus-host disease. Thus, Treg cell therapies and development of drugs that specifically enhance Treg cell function and development represent promising tools to establish dominant tolerance. So far, lack of specific markers to differentiate human Treg cells from activated CD4+ CD25+ effector T cells, which also express FOXP3 at different levels, hampered such an approach. Recent identification of the orphan receptor glycoprotein-A repetitions predominant (GARP or LRRC32) as Treg cell-specific key molecule that dominantly controls FOXP3 via a positive feedback loop opens up new perspectives for molecular and cellular therapies. This brief review focuses on the role of GARP as a safeguard of a complex regulatory network of human Treg cells and its implications for regulatory T cell therapies in autoimmunity and graft-versus-host disease. PMID:21076548

Perspectives on Regulatory T Cell Therapies.

PubMed

Probst-Kepper, Michael; Kröger, Andrea; Garritsen, Henk S P; Buer, Jan

2009-01-01

Adoptive transfer in animal models clearly indicate an essential role of CD4+ CD25+ FOXP3+ regulatory T (T(reg)) cells in prevention and treatment of autoimmune and graft-versus-host disease. Thus, T(reg) cell therapies and development of drugs that specifically enhance T(reg) cell function and development represent promising tools to establish dominant tolerance. So far, lack of specific markers to differentiate human T(reg) cells from activated CD4+ CD25+ effector T cells, which also express FOXP3 at different levels, hampered such an approach. Recent identification of the orphan receptor glycoprotein-A repetitions predominant (GARP or LRRC32) as T(reg) cell-specific key molecule that dominantly controls FOXP3 via a positive feedback loop opens up new perspectives for molecular and cellular therapies. This brief review focuses on the role of GARP as a safeguard of a complex regulatory network of human T(reg) cells and its implications for regulatory T cell therapies in autoimmunity and graft-versus-host disease.

Coordination of the Arc Regulatory System and Pheromone-Mediated Positive Feedback in Controlling the Vibrio fischeri lux Operon

PubMed Central

Septer, Alecia N.; Stabb, Eric V.

2012-01-01

Bacterial pheromone signaling is often governed both by environmentally responsive regulators and by positive feedback. This regulatory combination has the potential to coordinate a group response among distinct subpopulations that perceive key environmental stimuli differently. We have explored the interplay between an environmentally responsive regulator and pheromone-mediated positive feedback in intercellular signaling by Vibrio fischeri ES114, a bioluminescent bacterium that colonizes the squid Euprymna scolopes. Bioluminescence in ES114 is controlled in part by N-(3-oxohexanoyl)-L-homoserine lactone (3OC6), a pheromone produced by LuxI that together with LuxR activates transcription of the luxICDABEG operon, initiating a positive feedback loop and inducing luminescence. The lux operon is also regulated by environmentally responsive regulators, including the redox-responsive ArcA/ArcB system, which directly represses lux in culture. Here we show that inactivating arcA leads to increased 3OC6 accumulation to initiate positive feedback. In the absence of positive feedback, arcA-mediated control of luminescence was only ∼2-fold, but luxI-dependent positive feedback contributed more than 100 fold to the net induction of luminescence in the arcA mutant. Consistent with this overriding importance of positive feedback, 3OC6 produced by the arcA mutant induced luminescence in nearby wild-type cells, overcoming their ArcA repression of lux. Similarly, we found that artificially inducing ArcA could effectively repress luminescence before, but not after, positive feedback was initiated. Finally, we show that 3OC6 produced by a subpopulation of symbiotic cells can induce luminescence in other cells co-colonizing the host. Our results suggest that even transient loss of ArcA-mediated regulation in a sub-population of cells can induce luminescence in a wider community. Moreover, they indicate that 3OC6 can communicate information about both cell density and the state of ArcA/ArcB. PMID:23152924

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.

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.

A theory of circular organization and negative feedback: defining life in a cybernetic context.

PubMed

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.

Monitoring substrate enables real-time regulation of a protein localization pathway.

PubMed

Ito, Koreaki; Mori, Hiroyuki; Chiba, Shinobu

2018-06-01

Protein localization machinery supports cell survival and physiology, suggesting the potential importance of its expression regulation. Here, we summarize a remarkable scheme of regulation, which allows real-time feedback regulation of the machinery expression. A class of regulatory nascent polypeptides, called monitoring substrates, undergoes force-sensitive translation arrest. The resulting ribosome stalling on the mRNA then affects mRNA folding to expose the ribosome-binding site of the downstream target gene and upregulate its translation. The target gene encodes a component of the localization machinery, whose physical action against the monitoring substrate leads to arrest cancellation. Thus, this scheme of feedback loop allows the cell to adjust the amount of the machinery to correlate inversely with the effectiveness of the process at a given moment. The system appears to have emerged late in evolution, in which a narrow range of organisms selected a distinct monitoring substrate-machinery combination. Currently, regulatory systems of SecM-SecA, VemP-SecDF2 and MifM-YidC2 are known to occur in different bacterial species.

Circuitry, systems and methods for detecting magnetic fields

DOEpatents

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.

Functions of Vγ4 T Cells and Dendritic Epidermal T Cells on Skin Wound Healing

PubMed Central

Li, Yashu; Wu, Jun; Luo, Gaoxing; He, Weifeng

2018-01-01

Wound healing is a complex and dynamic process that progresses through the distinct phases of hemostasis, inflammation, proliferation, and remodeling. Both inflammation and re-epithelialization, in which skin γδ T cells are heavily involved, are required for efficient skin wound healing. Dendritic epidermal T cells (DETCs), which reside in murine epidermis, are activated to secrete epidermal cell growth factors, such as IGF-1 and KGF-1/2, to promote re-epithelialization after skin injury. Epidermal IL-15 is not only required for DETC homeostasis in the intact epidermis but it also facilitates the activation and IGF-1 production of DETC after skin injury. Further, the epidermal expression of IL-15 and IGF-1 constitutes a feedback regulatory loop to promote wound repair. Dermis-resident Vγ4 T cells infiltrate into the epidermis at the wound edges through the CCR6-CCL20 pathway after skin injury and provide a major source of IL-17A, which enhances the production of IL-1β and IL-23 in the epidermis to form a positive feedback loop for the initiation and amplification of local inflammation at the early stages of wound healing. IL-1β and IL-23 suppress the production of IGF-1 by DETCs and, therefore, impede wound healing. A functional loop may exist among Vγ4 T cells, epidermal cells, and DETCs to regulate wound repair.

Autonomous feedback loop of RUNX1-p53-CBFB in acute myeloid leukemia cells.

PubMed

Morita, Ken; Noura, Mina; Tokushige, Chieko; Maeda, Shintaro; Kiyose, Hiroki; Kashiwazaki, Gengo; Taniguchi, Junichi; Bando, Toshikazu; Yoshida, Kenichi; Ozaki, Toshifumi; Matsuo, Hidemasa; Ogawa, Seishi; Liu, Pu Paul; Nakahata, Tatsutoshi; Sugiyama, Hiroshi; Adachi, Souichi; Kamikubo, Yasuhiko

2017-11-30

Although runt-related transcription factor 1 (RUNX1) and its associating core binding factor-β (CBFB) play pivotal roles in leukemogenesis, and inhibition of RUNX1 has now been widely recognized as a novel strategy for anti-leukemic therapies, it has been elusive how leukemic cells could acquire the serious resistance against RUNX1-inhibition therapies and also whether CBFB could participate in this process. Here, we show evidence that p53 (TP53) and CBFB are sequentially up-regulated in response to RUNX1 depletion, and their mutual interaction causes the physiological resistance against chemotherapy for acute myeloid leukemia (AML) cells. Mechanistically, p53 induced by RUNX1 gene silencing directly binds to CBFB promoter and stimulates its transcription as well as its translation, which in turn acts as a platform for the stabilization of RUNX1, thereby creating a compensative RUNX1-p53-CBFB feedback loop. Indeed, AML cells derived from relapsed cases exhibited higher CBFB expression levels compared to those from primary AML cells at diagnosis, and these CBFB expressions were positively correlated to those of p53. Our present results underscore the importance of RUNX1-p53-CBFB regulatory loop in the development and/or maintenance of AML cells, which could be targeted at any sides of this triangle in strategizing anti-leukemia therapies.

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.

Dynamics and control of the ERK signaling pathway: Sensitivity, bistability, and oscillations.

PubMed

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.

Explicit knowledge about the availability of visual feedback affects grasping with the left but not the right hand.

PubMed

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.

Watch what you type: the role of visual feedback from the screen and hands in skilled typewriting.

PubMed

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.

Modularized TGFbeta-Smad Signaling Pathway

NASA Technical Reports Server (NTRS)

Li, Yongfeng; Wang, M.; Carra, C.; Cucinotta, F. A.

2011-01-01

The Transforming Growth Factor beta (TGFbeta) signaling pathway is a prominent regulatory signaling pathway controlling various important cellular processes. It can be induced by several factors, including ionizing radiation. It is regulated by Smads in a negative feedback loop through promoting increases in the regulatory Smads in the cell nucleus, and subsequent expression of inhibitory Smad, Smad7 to form a ubiquitin ligase with Smurf targeting active TGF receptors for degradation. In this work, we proposed a mathematical model to study the radiation-induced Smad-regulated TGF signaling pathway. By modularization, we are able to analyze each module (subsystem) and recover the nonlinear dynamics of the entire network system. Meanwhile the excitability, a common feature observed in the biological systems, along the TGF signaling pathway is discussed by mathematical analysis and numerical simulation.

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.

Experimental validation of a predicted feedback loop in the multi-oscillator clock of Arabidopsis thaliana

PubMed Central

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

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

NASA Technical Reports Server (NTRS)

Broussard, J. R.; Halyo, N.

1984-01-01

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

MiR-125a TNF receptor-associated factor 6 to inhibit osteoclastogenesis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guo, Li-Juan; Liao, Lan; Yang, Li

MicroRNAs (miRNAs) play important roles in osteoclastogenesis and bone resorption. In the present study, we found that miR-125a was dramatically down-regulated during macrophage colony stimulating factor (M-CSF) and receptor activator of nuclear factor-κB ligand (RANKL) induced osteoclastogenesis of circulating CD14+ peripheral blood mononuclear cells (PBMCs). Overexpression of miR-125a in CD14+ PBMCs inhibited osteoclastogenesis, while inhibition of miR-125a promoted osteoclastogenesis. TNF receptor-associated factor 6 (TRAF6), a transduction factor for RANKL/RANK/NFATc1 signal, was confirmed to be a target of miR-125a. EMSA and ChIP assays confirmed that NFATc1 bound to the promoter of the miR-125a. Overexpression of NFATc1 inhibited miR-125a transcription, and blockmore » of NFATc1 expression attenuated RANKL-regulated miR-125a transcription. Here, we reported that miR-125a played a biological function in osteoclastogenesis through a novel TRAF6/ NFATc1/miR-125a regulatory feedback loop. It suggests that regulation of miR-125a expression may be a potential strategy for ameliorating metabolic disease. - Highlights: • MiR-125a was significantly down-regulated in osteoclastogenesis of CD14+ PBMCs. • MiR-125a inhibited osteoclast differentiation by targeting TRAF6. • NFATc1 inhibited miR-125a transciption by binding to the promoter of miR-125a. • TRAF6/NFATc1 and miR-125a form a regulatory feedback loop in osteoclastogenesis.« less

Complexity in built environment, health, and destination walking: a neighborhood-scale analysis.

PubMed

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.

Adaptive Sliding Mode Control of Dynamic Systems Using Double Loop Recurrent Neural Network Structure.

PubMed

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.

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

NASA Astrophysics Data System (ADS)

Ishikawa, Kaoru; Nakamura, Taro; Osumi, Hisashi

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

Switching of the positive feedback for RAS activation by a concerted function of SOS membrane association domains.

PubMed

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.

miR-137 forms a regulatory loop with nuclear receptor TLX and LSD1 in neural stem cells.

PubMed

Sun, GuoQiang; Ye, Peng; Murai, Kiyohito; Lang, Ming-Fei; Li, Shengxiu; Zhang, Heying; Li, Wendong; Fu, Chelsea; Yin, Jason; Wang, Allen; Ma, Xiaoxiao; Shi, Yanhong

2011-11-08

miR-137 is a brain-enriched microRNA. Its role in neural development remains unknown. Here we show that miR-137 has an essential role in controlling embryonic neural stem cell fate determination. miR-137 negatively regulates cell proliferation and accelerates neural differentiation of embryonic neural stem cells. In addition, we show that the histone lysine-specific demethylase 1 (LSD1), a transcriptional co-repressor of nuclear receptor TLX, is a downstream target of miR-137. In utero electroporation of miR-137 in embryonic mouse brains led to premature differentiation and outward migration of the transfected cells. Introducing a LSD1 expression vector lacking the miR-137 recognition site rescued miR-137-induced precocious differentiation. Furthermore, we demonstrate that TLX, an essential regulator of neural stem cell self-renewal, represses the expression of miR-137 by recruiting LSD1 to the genomic regions of miR-137. Thus, miR-137 forms a feedback regulatory loop with TLX and LSD1 to control the dynamics between neural stem cell proliferation and differentiation during neural development.

Optimal management of nutrient reserves in microorganisms under time-varying environmental conditions.

PubMed

Nev, Olga A; Nev, Oleg A; van den Berg, Hugo A

2017-09-21

Intracellular reserves are a conspicuous feature of many bacteria; such internal stores are often present in the form of inclusions in which polymeric storage compounds are accumulated. Such reserves tend to increase in times of plenty and be used up in times of scarcity. Mathematical models that describe the dynamical nature of reserve build-up and use are known as "cell quota," "dynamic energy/nutrient budget," or "variable-internal-stores" models. Here we present a stoichiometrically consistent macro-chemical model that accounts for variable stores as well as adaptive allocation of building blocks to various types of catalytic machinery. The model posits feedback loops linking expression of assimilatory machinery to reserve density. The precise form of the "regulatory law" at the heart of such a loop expresses how the cell manages internal stores. We demonstrate how this "regulatory law" can be recovered from experimental data using several empirical data sets. We find that stores should be expected to be negligibly small in stable growth-sustaining environments, but prominent in environments characterised by marked fluctuations on time scales commensurate with the inherent dynamic time scale of the organismal system. Copyright © 2017 Elsevier Ltd. All rights reserved.

Autoregulatory mechanisms controlling the microprocessor.

PubMed

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.

Feedback control methods for drug dosage optimisation. Concepts, classification and clinical application.

PubMed

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.

Simulating closed- and open-loop voluntary movement: a nonlinear control-systems approach.

PubMed

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.

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…

Exploring information transmission in gene networks using stochastic simulation and machine learning

NASA Astrophysics Data System (ADS)

Park, Kyemyung; Prüstel, Thorsten; Lu, Yong; Narayanan, Manikandan; Martins, Andrew; Tsang, John

How gene regulatory networks operate robustly despite environmental fluctuations and biochemical noise is a fundamental question in biology. Mathematically the stochastic dynamics of a gene regulatory network can be modeled using chemical master equation (CME), but nonlinearity and other challenges render analytical solutions of CMEs difficult to attain. While approaches of approximation and stochastic simulation have been devised for simple models, obtaining a more global picture of a system's behaviors in high-dimensional parameter space without simplifying the system substantially remains a major challenge. Here we present a new framework for understanding and predicting the behaviors of gene regulatory networks in the context of information transmission among genes. Our approach uses stochastic simulation of the network followed by machine learning of the mapping between model parameters and network phenotypes such as information transmission behavior. We also devised ways to visualize high-dimensional phase spaces in intuitive and informative manners. We applied our approach to several gene regulatory circuit motifs, including both feedback and feedforward loops, to reveal underexplored aspects of their operational behaviors. This work is supported by the Intramural Program of NIAID/NIH.

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.

Plug-in module acceleration feedback control for fast steering mirror-based beam stabilization systems

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.

Real-time control of hind limb functional electrical stimulation using feedback from dorsal root ganglia recordings

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.

Real-time control of hind limb functional electrical stimulation using feedback from dorsal root ganglia recordings

PubMed Central

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

Modularized Smad-regulated TGFβ signaling pathway.

PubMed

Li, Yongfeng; Wang, Minli; Carra, Claudio; Cucinotta, Francis A

2012-12-01

The transforming Growth Factor β (TGFβ) signaling pathway is a prominent regulatory signaling pathway controlling various important cellular processes. TGFβ signaling can be induced by several factors including ionizing radiation. The pathway is regulated in a negative feedback loop through promoting the nuclear import of the regulatory Smads and a subsequent expression of inhibitory Smad7, that forms ubiquitin ligase with Smurf2, targeting active TGFβ receptors for degradation. In this work, we proposed a mathematical model to study the Smad-regulated TGFβ signaling pathway. By modularization, we are able to analyze mathematically each component subsystem and recover the nonlinear dynamics of the entire network system. Meanwhile the excitability, a common feature observed in the biological systems, in the TGFβ signaling pathway is discussed and supported as well by numerical simulation, indicating the robustness of the model. Published by Elsevier Inc.

Switching of the positive feedback for RAS activation by a concerted function of SOS membrane association domains

PubMed Central

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…

Interrogation of inhibitor of nuclear factor κB α/nuclear factor κB (IκBα/NF-κB) negative feedback loop dynamics: from single cells to live animals in vivo.

PubMed

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.

Feedback Synthesizes Neural Codes for Motion.

PubMed

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.

Contemplating the plasmalemmal control center model

NASA Technical Reports Server (NTRS)

Pickard, B. G.

1994-01-01

An abundant epidermal mechanosensory calcium-selective ion channel appears able not only to detect mechanical stimuli such as those that initiate gravitropism but also to detect thermal, electrical, and various chemical stimuli. Because it responds to multimodal input with a second messenger output, this channel system seems likely to be an integrator that can engage in feedbacks with many other systems of the cell--and feedback is the hallmark of regulation. In general, the mechanical tension required for channel activation is likely transmitted from the relatively rigid cell wall to the plasma membrane system via linkage or adhesion sites that display antigenicities recognized by antibodies to animal beta-1 integrin, vitronectin, and fibronectin and which have mechanical connections to the cytoskeleton. Thus, functionally, leverage exerted against any given adhesion site will tend to control channels within a surrounding domain. Reactions initiated by passage of calcium ions through the channels could presumably be more effectively regulated if channels within the domains were somewhat clustered and if appropriate receptors, kinases, porters, pumps, and some key cytoskeletal anchoring sites were in turn clustered about them. Accumulating evidence suggests not only that activity of clusters of channels may contribute to control of cytoskeletal architecture and of regulatory protein function within their domain, but also that both a variety of regulatory proteins and components of the cortical cytoskeleton may contribute to control of channel activity. The emerging capabilities of electronic optical microscopy are well suited for resolving the spatial distributions of many of these cytoskeletal and regulatory molecules in living cells, and for following some of their behaviors as channels are stimulated to open and cytosolic calcium builds in their vicinity. Such microscopy, coupled with biochemical and physiological probing, should help to establish the nature of the feedback loops putatively controlled by the linkage sites and their channel domains.

Systems-Level Feedbacks of NRF2 Controlling Autophagy upon Oxidative Stress Response

PubMed Central

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

Open-loop-feedback control of serum drug concentrations: pharmacokinetic approaches to drug therapy.

PubMed

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

DOEpatents

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.

Functional Conservation of the Glide/Gcm Regulatory Network Controlling Glia, Hemocyte, and Tendon Cell Differentiation in Drosophila

PubMed Central

Cattenoz, Pierre B.; Popkova, Anna; Southall, Tony D.; Aiello, Giuseppe; Brand, Andrea H.; Giangrande, Angela

2016-01-01

High-throughput screens allow us to understand how transcription factors trigger developmental processes, including cell specification. A major challenge is identification of their binding sites because feedback loops and homeostatic interactions may mask the direct impact of those factors in transcriptome analyses. Moreover, this approach dissects the downstream signaling cascades and facilitates identification of conserved transcriptional programs. Here we show the results and the validation of a DNA adenine methyltransferase identification (DamID) genome-wide screen that identifies the direct targets of Glide/Gcm, a potent transcription factor that controls glia, hemocyte, and tendon cell differentiation in Drosophila. The screen identifies many genes that had not been previously associated with Glide/Gcm and highlights three major signaling pathways interacting with Glide/Gcm: Notch, Hedgehog, and JAK/STAT, which all involve feedback loops. Furthermore, the screen identifies effector molecules that are necessary for cell-cell interactions during late developmental processes and/or in ontogeny. Typically, immunoglobulin (Ig) domain–containing proteins control cell adhesion and axonal navigation. This shows that early and transiently expressed fate determinants not only control other transcription factors that, in turn, implement a specific developmental program but also directly affect late developmental events and cell function. Finally, while the mammalian genome contains two orthologous Gcm genes, their function has been demonstrated in vertebrate-specific tissues, placenta, and parathyroid glands, begging questions on the evolutionary conservation of the Gcm cascade in higher organisms. Here we provide the first evidence for the conservation of Gcm direct targets in humans. In sum, this work uncovers novel aspects of cell specification and sets the basis for further understanding of the role of conserved Gcm gene regulatory cascades. PMID:26567182

Molecular mechanisms of OLIG2 transcription factor in brain cancer

PubMed Central

Lian, Nathan; Kesari, Santosh

2016-01-01

Oligodendrocyte lineage transcription factor 2 (OLIG2) plays a pivotal role in glioma development. Here we conducted a comprehensive study of the critical gene regulatory networks involving OLIG2. These include the networks responsible for OLIG2 expression, its translocation to nucleus, cell cycle, epigenetic regulation, and Rho-pathway interactions. We described positive feedback loops including OLIG2: loops of epigenetic regulation and loops involving receptor tyrosine kinases. These loops may be responsible for the prolonged oncogenic activity of OLIG2. The proposed schemes for epigenetic regulation of the gene networks involving OLIG2 are confirmed by patient survival (Kaplan–Meier) curves based on the cancer genome atlas (TCGA) datasets. Finally, we elucidate the Coherent-Gene Modules (CGMs) networks—framework of OLIG2 involvement in cancer. We showed that genes interacting with OLIG2 formed eight CGMs having a set of intermodular connections. We showed also that among the genes involved in these modules the most connected hub is EGFR, then, on lower level, HSP90 and CALM1, followed by three lower levels including epigenetic genes KDM1A and NCOR1. The genes on the six upper levels of the hierarchy are involved in interconnections of all eight CGMs and organize functionally defined gene-signaling subnetworks having specific functions. For example, CGM1 is involved in epigenetic control. CGM2 is significantly related to cell proliferation and differentiation. CGM3 includes a number of interconnected helix–loop–helix transcription factors (bHLH) including OLIG2. Many of these TFs are partially controlled by OLIG2. The CGM4 is involved in PDGF-related: angiogenesis, tumor cell proliferation and differentiation. These analyses provide testable hypotheses and approaches to inhibit OLIG2 pathway and relevant feed-forward and feedback loops to be interrogated. This broad approach can be applied to other TFs. PMID:27447975

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

PubMed Central

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

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

PubMed

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

PubMed Central

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

2016-01-01

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

Ethanol and liver: Recent insights into the mechanisms of ethanol-induced fatty liver

PubMed Central

Liu, Jinyao

2014-01-01

Alcoholic fatty liver disease (AFLD), a potentially pathologic condition, can progress to steatohepatitis, fibrosis, and cirrhosis, leading to an increased probability of hepatic failure and death. Alcohol induces fatty liver by increasing the ratio of reduced form of nicotinamide adenine dinucleotide to oxidized form of nicotinamide adenine dinucleotide in hepatocytes; increasing hepatic sterol regulatory element-binding protein (SREBP)-1, plasminogen activator inhibitor (PAI)-1, and early growth response-1 activity; and decreasing hepatic peroxisome proliferator-activated receptor-α activity. Alcohol activates the innate immune system and induces an imbalance of the immune response, which is followed by activated Kupffer cell-derived tumor necrosis factor (TNF)-α overproduction, which is in turn responsible for the changes in the hepatic SREBP-1 and PAI-1 activity. Alcohol abuse promotes the migration of bone marrow-derived cells (BMDCs) to the liver and then reprograms TNF-α expression from BMDCs. Chronic alcohol intake triggers the sympathetic hyperactivity-activated hepatic stellate cell (HSC) feedback loop that in turn activates the HSCs, resulting in HSC-derived TNF-α overproduction. Carvedilol may block this feedback loop by suppressing sympathetic activity, which attenuates the progression of AFLD. Clinical studies evaluating combination therapy of carvedilol with a TNF-α inhibitor to treat patients with AFLD are warranted to prevent the development of alcoholic liver disease. PMID:25356030

The influence of visual feedback from the recent past on the programming of grip aperture is grasp-specific, shared between hands, and mediated by sensorimotor memory not task set.

PubMed

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.

Digital phase-lock loop

NASA Technical Reports Server (NTRS)

Thomas, Jr., Jess B. (Inventor)

1991-01-01

An improved digital phase lock loop incorporates several distinctive features that attain better performance at high loop gain and better phase accuracy. These features include: phase feedback to a number-controlled oscillator in addition to phase rate; analytical tracking of phase (both integer and fractional cycles); an amplitude-insensitive phase extractor; a more accurate method for extracting measured phase; a method for changing loop gain during a track without loss of lock; and a method for avoiding loss of sampled data during computation delay, while maintaining excellent tracking performance. The advantages of using phase and phase-rate feedback are demonstrated by comparing performance with that of rate-only feedback. Extraction of phase by the method of modeling provides accurate phase measurements even when the number-controlled oscillator phase is discontinuously updated.

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

PubMed

Hao, Lijie; Yang, Zhuoqin; Bi, Yuanhong

2016-04-01

The cyclic AMP (cAMP)-response element-binding protein (CREB) family of transcription factors is crucial in regulating gene expression required for long-term memory (LTM) formation. Upon exposure of sensory neurons to the neurotransmitter serotonin (5-HT), CREB1 is activated via activation of the protein kinase A (PKA) intracellular signaling pathways, and CREB2 as a transcriptional repressor is relieved possibly via phosphorylation of CREB2 by mitogen-activated protein kinase (MAPK). Song et al. [18] proposed a minimal model with only interlinked positive and negative feedback loops of transcriptional regulation by the activator CREB1 and the repressor CREB2. Without considering feedbacks between the CREB proteins, Pettigrew et al. [8] developed a computational model characterizing complex dynamics of biochemical pathways downstream of 5-HT receptors. In this work, to describe more simply the biochemical pathways and gene regulation underlying 5-HT-induced LTM, we add the important extracellular sensitizing stimulus 5-HT as well as the product Ap-uch into the Song's minimal model. We also strive to examine dynamical properties of the gene regulatory network under the changing concentration of the stimulus, [5-HT], cooperating with the varying positive feedback strength in inducing a high state of CREB1 for the establishment of long-term memory. Different dynamics including monostability, bistability and multistability due to coexistence of stable steady states and oscillations is investigated by means of codimension-2 bifurcation analysis. At the different positive feedback strengths, comparative analysis of deterministic and stochastic dynamics reveals that codimension-1 bifurcation with respect to [5-HT] as the parameter can predict diverse stochastic behaviors resulted from the finite number of molecules, and the number of CREB1 molecules more and more preferentially resides near the high steady state with increasing [5-HT], which contributes to long-term memory formation. Copyright © 2016 Elsevier Inc. All rights reserved.

Masters change, slaves remain.

PubMed

Graham, Patricia; Penn, Jill K M; Schedl, Paul

2003-01-01

Sex determination offers an opportunity to address many classic questions of developmental biology. In addition, because sex determination evolves rapidly, it offers an opportunity to investigate the evolution of genetic hierarchies. Sex determination in Drosophila melanogaster is controlled by the master regulatory gene, Sex lethal (Sxl). DmSxl controls the alternative splicing of a downstream gene, transformer (tra), which acts with tra2 to control alternative splicing of doublesex (dsx). DmSxl also controls its own splicing, creating an autoregulatory feedback loop that ensures expression of Sxl in females, but not males. A recent paper has shown that in the dipteran Ceratitis capitata later (downstream) steps in the regulatory hierarchy are conserved, while earlier (upstream) steps are not. Cctra is regulated by alternative splicing and apparently controls the alternative splicing of Ccdsx. However, Cctra is not regulated by CcSxl. Instead it appears to autoregulate in a manner similar to the autoregulation seen with DmSxl. Copyright 2002 Wiley Periodicals, Inc.

Information-reduced Carrier Synchronization of Iterative Decoded BPSK and QPSK using Soft Decision (Extrinsic) Feedback

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.

Increasing Signal Specificity of the TOL Network of Pseudomonas putida mt-2 by Rewiring the Connectivity of the Master Regulator XylR

PubMed Central

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

An Integrated Loop Model of Corrective Feedback and Oral English Learning: A Case of International Students in the United States

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'…

[Study of negative feedback between wild-type BRAF or RAFV600E and Mps1 in melanoma].

PubMed

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.

Design of multivariable feedback control systems via spectral assignment using reduced-order models and reduced-order observers

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

PubMed Central

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

2014-01-01

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

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.

Design of multivariable feedback control systems via spectral assignment using reduced-order models and reduced-order observers

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.

PubMed

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.

Positive feedback between RNA-binding protein HuD and transcription factor SATB1 promotes neurogenesis.

PubMed

Wang, Feifei; Tidei, Joseph J; Polich, Eric D; Gao, Yu; Zhao, Huashan; Perrone-Bizzozero, Nora I; Guo, Weixiang; Zhao, Xinyu

2015-09-08

The mammalian embryonic lethal abnormal vision (ELAV)-like protein HuD is a neuronal RNA-binding protein implicated in neuronal development, plasticity, and diseases. Although HuD has long been associated with neuronal development, the functions of HuD in neural stem cell differentiation and the underlying mechanisms have gone largely unexplored. Here we show that HuD promotes neuronal differentiation of neural stem/progenitor cells (NSCs) in the adult subventricular zone by stabilizing the mRNA of special adenine-thymine (AT)-rich DNA-binding protein 1 (SATB1), a critical transcriptional regulator in neurodevelopment. We find that SATB1 deficiency impairs the neuronal differentiation of NSCs, whereas SATB1 overexpression rescues the neuronal differentiation phenotypes resulting from HuD deficiency. Interestingly, we also discover that SATB1 is a transcriptional activator of HuD during NSC neuronal differentiation. In addition, we demonstrate that NeuroD1, a neuronal master regulator, is a direct downstream target of SATB1. Therefore, HuD and SATB1 form a positive regulatory loop that enhances NeuroD1 transcription and subsequent neuronal differentiation. Our results here reveal a novel positive feedback network between an RNA-binding protein and a transcription factor that plays critical regulatory roles in neurogenesis.

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...

A theory of how active behavior stabilises neural activity: Neural gain modulation by closed-loop environmental feedback

PubMed Central

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

A theory of how active behavior stabilises neural activity: Neural gain modulation by closed-loop environmental feedback.

PubMed

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.

Auto-Regulatory RNA Editing Fine-Tunes mRNA Re-Coding and Complex Behaviour in Drosophila

PubMed Central

Savva, Yiannis A.; Jepson, James E.C; Sahin, Asli; Sugden, Arthur U.; Dorsky, Jacquelyn S.; Alpert, Lauren; Lawrence, Charles; Reenan, Robert A.

2014-01-01

Auto-regulatory feedback loops are a common molecular strategy used to optimize protein function. In Drosophila many mRNAs involved in neuro-transmission are re-coded at the RNA level by the RNA editing enzyme dADAR, leading to the incorporation of amino acids that are not directly encoded by the genome. dADAR also re-codes its own transcript, but the consequences of this auto-regulation in vivo are unclear. Here we show that hard-wiring or abolishing endogenous dADAR auto-regulation dramatically remodels the landscape of re-coding events in a site-specific manner. These molecular phenotypes correlate with altered localization of dADAR within the nuclear compartment. Furthermore, auto-editing exhibits sexually dimorphic patterns of spatial regulation and can be modified by abiotic environmental factors. Finally, we demonstrate that modifying dAdar auto-editing affects adaptive complex behaviors. Our results reveal the in vivo relevance of auto-regulatory control over post-transcriptional mRNA re-coding events in fine-tuning brain function and organismal behavior. PMID:22531175

Dose response relationship in anti-stress gene regulatory networks.

PubMed

Zhang, Qiang; Andersen, Melvin E

2007-03-02

To maintain a stable intracellular environment, cells utilize complex and specialized defense systems against a variety of external perturbations, such as electrophilic stress, heat shock, and hypoxia, etc. Irrespective of the type of stress, many adaptive mechanisms contributing to cellular homeostasis appear to operate through gene regulatory networks that are organized into negative feedback loops. In general, the degree of deviation of the controlled variables, such as electrophiles, misfolded proteins, and O2, is first detected by specialized sensor molecules, then the signal is transduced to specific transcription factors. Transcription factors can regulate the expression of a suite of anti-stress genes, many of which encode enzymes functioning to counteract the perturbed variables. The objective of this study was to explore, using control theory and computational approaches, the theoretical basis that underlies the steady-state dose response relationship between cellular stressors and intracellular biochemical species (controlled variables, transcription factors, and gene products) in these gene regulatory networks. Our work indicated that the shape of dose response curves (linear, superlinear, or sublinear) depends on changes in the specific values of local response coefficients (gains) distributed in the feedback loop. Multimerization of anti-stress enzymes and transcription factors into homodimers, homotrimers, or even higher-order multimers, play a significant role in maintaining robust homeostasis. Moreover, our simulation noted that dose response curves for the controlled variables can transition sequentially through four distinct phases as stressor level increases: initial superlinear with lesser control, superlinear more highly controlled, linear uncontrolled, and sublinear catastrophic. Each phase relies on specific gain-changing events that come into play as stressor level increases. The low-dose region is intrinsically nonlinear, and depending on the level of local gains, presence of gain-changing events, and degree of feedforward gene activation, this region can appear as superlinear, sublinear, or even J-shaped. The general dose response transition proposed here was further examined in a complex anti-electrophilic stress pathway, which involves multiple genes, enzymes, and metabolic reactions. This work would help biologists and especially toxicologists to better assess and predict the cellular impact brought about by biological stressors.

Quantitative implementation of the endogenous molecular-cellular network hypothesis in hepatocellular carcinoma.

PubMed

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.

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

PubMed Central

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

Smart Braid Feedback for the Closed-Loop Control of Soft Robotic Systems.

PubMed

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.

Construction of regulatory networks using expression time-series data of a genotyped population.

PubMed

Yeung, Ka Yee; Dombek, Kenneth M; Lo, Kenneth; Mittler, John E; Zhu, Jun; Schadt, Eric E; Bumgarner, Roger E; Raftery, Adrian E

2011-11-29

The inference of regulatory and biochemical networks from large-scale genomics data is a basic problem in molecular biology. The goal is to generate testable hypotheses of gene-to-gene influences and subsequently to design bench experiments to confirm these network predictions. Coexpression of genes in large-scale gene-expression data implies coregulation and potential gene-gene interactions, but provide little information about the direction of influences. Here, we use both time-series data and genetics data to infer directionality of edges in regulatory networks: time-series data contain information about the chronological order of regulatory events and genetics data allow us to map DNA variations to variations at the RNA level. We generate microarray data measuring time-dependent gene-expression levels in 95 genotyped yeast segregants subjected to a drug perturbation. We develop a Bayesian model averaging regression algorithm that incorporates external information from diverse data types to infer regulatory networks from the time-series and genetics data. Our algorithm is capable of generating feedback loops. We show that our inferred network recovers existing and novel regulatory relationships. Following network construction, we generate independent microarray data on selected deletion mutants to prospectively test network predictions. We demonstrate the potential of our network to discover de novo transcription-factor binding sites. Applying our construction method to previously published data demonstrates that our method is competitive with leading network construction algorithms in the literature.

Dynamics of nonlinear feedback control.

PubMed

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.

Integrated optical sensor

DOEpatents

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.

Integrated optical sensor

DOEpatents

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.

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

PubMed Central

Brainard, Michael S.; Jin, Dezhe Z.

2015-01-01

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

Study on real-time force feedback for a master-slave interventional surgical robotic system.

PubMed

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

Short- and Long-Term Learning of Feedforward Control of a Myoelectric Prosthesis with Sensory Feedback by Amputees.

PubMed

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.

DTIC Science & Technology

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

REVIEW ARTICLE: Oscillations and temporal signalling in cells

NASA Astrophysics Data System (ADS)

Tiana, G.; Krishna, S.; Pigolotti, S.; Jensen, M. H.; Sneppen, K.

2007-06-01

The development of new techniques to quantitatively measure gene expression in cells has shed light on a number of systems that display oscillations in protein concentration. Here we review the different mechanisms which can produce oscillations in gene expression or protein concentration using a framework of simple mathematical models. We focus on three eukaryotic genetic regulatory networks which show 'ultradian' oscillations, with a time period of the order of hours, and involve, respectively, proteins important for development (Hes1), apoptosis (p53) and immune response (NF-κB). We argue that underlying all three is a common design consisting of a negative feedback loop with time delay which is responsible for the oscillatory behaviour.

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.

Programmed cell death 4 protein (Pdcd4) and homeodomain-interacting protein kinase 2 (Hipk2) antagonistically control translation of Hipk2 mRNA.

PubMed

Ohnheiser, Johanna; Ferlemann, Eva; Haas, Astrid; Müller, Jan P; Werwein, Eugen; Fehler, Olesja; Biyanee, Abhiruchi; Klempnauer, Karl-Heinz

2015-07-01

The tumor suppressor protein programmed cell death 4 (Pdcd4) is a highly conserved RNA-binding protein that inhibits the translation of specific mRNAs. Here, we have identified the homeobox-interacting protein kinase-2 (Hipk2) mRNA as a novel translational target of Pdcd4. Unlike most other protein kinases Hipk2 is constitutively active after being synthesized by the ribosome and its expression and activity are thought to be mainly controlled by modulation of the half-life of the kinase. Our work provides the first evidence that Hipk2 expression is also controlled on the level of translation. We show that Hipk2 stimulates the translation of its own mRNA and that Pdcd4 suppresses the translation of Hipk2 mRNA by interfering with this auto-regulatory feedback mechanism. We also show that the translation of the related kinase Hipk1 is controlled by a similar feedback loop and that Hipk2 also stimulates the translation of Hipk1 mRNA. Taken together, our work describes a novel mechanism of translational suppression by Pdcd4 and shows for the first time that Hipk2 controls its own synthesis by an auto-regulatory feedback mechanism. Furthermore, the effect of Hipk2 on the translation of Hipk1 RNA suggests that Hipk2 and Pdcd4 can act in similar manner to control the translation of other mRNAs. Copyright © 2015 Elsevier B.V. All rights reserved.

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.

PubMed

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.

Self-reinforcing feedback loop in financial markets with coupling of market impact and momentum traders

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.

Deciphering the Principles of Bacterial Nitrogen Dietary Preferences: a Strategy for Nutrient Containment.

PubMed

Wang, Jilong; Yan, Dalai; Dixon, Ray; Wang, Yi-Ping

2016-07-19

A fundamental question in microbial physiology concerns why organisms prefer certain nutrients to others. For example, among different nitrogen sources, ammonium is the preferred nitrogen source, supporting fast growth, whereas alternative nitrogen sources, such as certain amino acids, are considered to be poor nitrogen sources, supporting much slower exponential growth. However, the physiological/regulatory logic behind such nitrogen dietary choices remains elusive. In this study, by engineering Escherichia coli, we switched the dietary preferences toward amino acids, with growth rates equivalent to that of the wild-type strain grown on ammonia. However, when the engineered strain was cultured together with wild-type E. coli, this growth advantage was diminished as a consequence of ammonium leakage from the transport-and-catabolism (TC)-enhanced (TCE) cells, which are preferentially utilized by wild-type bacteria. Our results reveal that the nitrogen regulatory (Ntr) system fine tunes the expression of amino acid transport and catabolism components to match the flux through the ammonia assimilation pathway such that essential nutrients are retained, but, as a consequence, the fast growth rate on amino acids is sacrificed. Bacteria exhibit different growth rates under various nutrient conditions. These environmentally related behaviors reflect the coordination between metabolism and the underlying regulatory networks. In the present study, we investigated the intertwined nitrogen metabolic and nitrogen regulatory systems to understand the growth differences between rich and poor nitrogen sources. Although maximal growth rate is considered to be evolutionarily advantageous for bacteria (as remarked by François Jacob, who said that the "dream" of every cell is to become two cells), we showed that negative-feedback loops in the regulatory system inhibit growth rates on amino acids. We demonstrated that in the absence of regulatory feedback, amino acids are capable of supporting fast growth rates, but this results in ammonia leaking out from cells as "waste," benefiting the growth of competitors. These findings provide important insights into the regulatory logic that controls metabolic flux and ensures nutrient containment but consequently sacrifices growth rate. Copyright © 2016 Wang et al.

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.

An investigation into closed-loop treatment of neurological disorders based on sensing mitochondrial dysfunction.

PubMed

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.

PubMed

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

2015-03-01

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

Canopy1, a positive feedback regulator of FGF signaling, controls progenitor cell clustering during Kupffer's vesicle organogenesis

PubMed Central

Matsui, Takaaki; Thitamadee, Siripong; Murata, Tomoko; Kakinuma, Hisaya; Nabetani, Takuji; Hirabayashi, Yoshio; Hirate, Yoshikazu; Okamoto, Hitoshi; Bessho, Yasumasa

2011-01-01

The assembly of progenitor cells is a crucial step for organ formation during vertebrate development. Kupffer's vesicle (KV), a key organ required for the left–right asymmetric body plan in zebrafish, is generated from a cluster of ∼20 dorsal forerunner cells (DFCs). Although several genes are known to be involved in KV formation, how DFC clustering is regulated and how cluster formation then contributes to KV formation remain unclear. Here we show that positive feedback regulation of FGF signaling by Canopy1 (Cnpy1) controls DFC clustering. Cnpy1 positively regulates FGF signals within DFCs, which in turn promote Cadherin1-mediated cell adhesion between adjacent DFCs to sustain cell cluster formation. When this FGF positive feedback loop is disrupted, the DFC cluster fails to form, eventually leading to KV malformation and defects in the establishment of laterality. Our results therefore uncover both a previously unidentified role of FGF signaling during vertebrate organogenesis and a regulatory mechanism underlying cell cluster formation, which is an indispensable step for formation of a functional KV and establishment of the left–right asymmetric body plan. PMID:21628557

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

PubMed Central

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

A vicious loop of fatty acid-binding protein 4 and DNA methyltransferase 1 promotes acute myeloid leukemia and acts as a therapeutic target

PubMed Central

Yan, F; Shen, N; Pang, JX; Zhao, N; Zhang, YW; Bode, AM; Al-Kali, A; Litzow, MR; Li, B; Liu, SJ

2017-01-01

Aberrant DNA methylation mediated by deregulation of DNA methyltransferases (DNMT) is a key hallmark of acute myeloid leukemia (AML), yet efforts to target DNMT deregulation for drug development have lagged. We previously demonstrated that upregulation of fatty acid-binding protein 4 (FABP4) promotes AML aggressiveness through enhanced DNMT1-dependent DNA methylation. Here we demonstrate that FABP4 upregulation in AML cells occurs through vascular endothelial growth factor (VEGF) signaling, thus elucidating a crucial FABP4-DNMT1 regulatory feedback loop in AML biology. We show that FABP4 dysfunction by its selective inhibitor BMS309403 leads to downregulation of DNMT1, decrease of global DNA methylation and re-expression of p15INK4B tumor suppressor gene by promoter DNA hypomethylation in vitro, ex vivo and in vivo. Functionally, BMS309403 suppresses cell colony formation, induces cell differentiation, and, importantly, impairs leukemic disease progression in mouse models of leukemia. Our findings highlight AML-promoting properties of the FABP4-DNMT1 vicious loop, and identify an attractive class of therapeutic agents with a high potential for clinical use in AML patients. The results will also assist in establishing the FABP4-DNMT1 loop as a target for therapeutic discovery to enhance the index of current epigenetic therapies. PMID:28993705

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.

Mitogen-Inducible Gene-6 Mediates Feedback Inhibition from Mutated BRAF towards the Epidermal Growth Factor Receptor and Thereby Limits Malignant Transformation

PubMed Central

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

Network-Based Methods for Identifying Key Active Proteins in the Extracellular Electron Transfer Process in Shewanella oneidensis MR-1.

PubMed

Ding, Dewu; Sun, Xiao

2018-01-16

Shewanella oneidensis MR-1 can transfer electrons from the intracellular environment to the extracellular space of the cells to reduce the extracellular insoluble electron acceptors (Extracellular Electron Transfer, EET). Benefiting from this EET capability, Shewanella has been widely used in different areas, such as energy production, wastewater treatment, and bioremediation. Genome-wide proteomics data was used to determine the active proteins involved in activating the EET process. We identified 1012 proteins with decreased expression and 811 proteins with increased expression when the EET process changed from inactivation to activation. We then networked these proteins to construct the active protein networks, and identified the top 20 key active proteins by network centralization analysis, including metabolism- and energy-related proteins, signal and transcriptional regulatory proteins, translation-related proteins, and the EET-related proteins. We also constructed the integrated protein interaction and transcriptional regulatory networks for the active proteins, then found three exclusive active network motifs involved in activating the EET process-Bi-feedforward Loop, Regulatory Cascade with a Feedback, and Feedback with a Protein-Protein Interaction (PPI)-and identified the active proteins involved in these motifs. Both enrichment analysis and comparative analysis to the whole-genome data implicated the multiheme c -type cytochromes and multiple signal processing proteins involved in the process. Furthermore, the interactions of these motif-guided active proteins and the involved functional modules were discussed. Collectively, by using network-based methods, this work reported a proteome-wide search for the key active proteins that potentially activate the EET process.

Generation of oscillating gene regulatory network motifs

NASA Astrophysics Data System (ADS)

van Dorp, M.; Lannoo, B.; Carlon, E.

2013-07-01

Using an improved version of an evolutionary algorithm originally proposed by François and Hakim [Proc. Natl. Acad. Sci. USAPNASA60027-842410.1073/pnas.0304532101 101, 580 (2004)], we generated small gene regulatory networks in which the concentration of a target protein oscillates in time. These networks may serve as candidates for oscillatory modules to be found in larger regulatory networks and protein interaction networks. The algorithm was run for 105 times to produce a large set of oscillating modules, which were systematically classified and analyzed. The robustness of the oscillations against variations of the kinetic rates was also determined, to filter out the least robust cases. Furthermore, we show that the set of evolved networks can serve as a database of models whose behavior can be compared to experimentally observed oscillations. The algorithm found three smallest (core) oscillators in which nonlinearities and number of components are minimal. Two of those are two-gene modules: the mixed feedback loop, already discussed in the literature, and an autorepressed gene coupled with a heterodimer. The third one is a single gene module which is competitively regulated by a monomer and a dimer. The evolutionary algorithm also generated larger oscillating networks, which are in part extensions of the three core modules and in part genuinely new modules. The latter includes oscillators which do not rely on feedback induced by transcription factors, but are purely of post-transcriptional type. Analysis of post-transcriptional mechanisms of oscillation may provide useful information for circadian clock research, as recent experiments showed that circadian rhythms are maintained even in the absence of transcription.

Pulsatile desynchronizing delayed feedback for closed-loop deep brain stimulation

PubMed Central

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.

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)

Multivariate assessment of the central-cardiorespiratory network structure in neuropathological disease.

PubMed

Schulz, Steffen; Haueisen, Jens; Bär, Karl-Juergen; Voss, Andreas

2018-06-22

The new interdisciplinary field of network physiology is getting more and more into the focus of interest in medicine. The autonomic nervous system (ANS) dysfunction is well described in schizophrenia (SZO). However, the linear and nonlinear coupling between the ANS and central nervous system (CNS) is only partly addressed until now. This coupling can be assumed as a feedback-feedforward network, reacting with flexible and adaptive responses to internal and external factors. Approach: For the first time, in this study, we investigated linear and nonlinear short-term central-cardiorespiratory couplings of 17 patients suffering from paranoid schizophrenia (SZO) in comparison to 17 age-gender matched healthy subjects (CON) analyzing heart rate (HR), respiration (RESP) and the power of frontal EEG activity (PEEG). The objective is to determine how the different regulatory aspects of the CNS-ANS compose the central-cardiorespiratory network (CCRN). To quantify these couplings within the CCRN the normalized short time partial directed coherence (NSTPDC) and the new multivariate high-resolution joint symbolic dynamics (mHRJSD) were applied. Main results: We found that the CCRN in SZO is characterized as a bidirectional one, with stronger central driving mechanisms (PEEG→HR) towards HR regulation than vice versa, and with stronger respiratory influence (RESP→PEEG) on central activity than vice versa. This suggests that the central-cardiorespiratory process (closed-loop) is mainly focusing on adapting the HR via the sinoatrial node than focusing on respiratory regulation. On the other side, the feedback-loop from ANS to CNS is strongly dominated via respiratory activity. Significance: We could demonstrate a considerably significantly different central-cardiorespiratory network structure in schizophrenia with strong central influence on the cardiac system and a strong respiratory influence on the central nervous system. Moreover, this study provides a more in-depth understanding of the interplay of the central and autonomic regulatory network in healthy subjects and schizophrenic patients. . © 2018 Institute of Physics and Engineering in Medicine.

A feedback loop comprising PRMT7 and miR-24-2 interplays with Oct4, Nanog, Klf4 and c-Myc to regulate stemness

PubMed Central

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

A feedback loop comprising PRMT7 and miR-24-2 interplays with Oct4, Nanog, Klf4 and c-Myc to regulate stemness.

PubMed

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.

Coordination of meristem and boundary functions by transcription factors in the SHOOT MERISTEMLESS regulatory network.

PubMed

Scofield, Simon; Murison, Alexander; Jones, Angharad; Fozard, John; Aida, Mitsuhiro; Band, Leah R; Bennett, Malcolm; Murray, James A H

2018-04-30

The Arabidopsis homeodomain transcription factor SHOOT MERISTEMLESS (STM) is crucial for shoot apical meristem (SAM) function, yet the components and structure of the STM gene regulatory network (GRN) are largely unknown. Here, we show that transcriptional regulators are overrepresented among STM-regulated genes and, using these as GRN components in Bayesian network analysis, we infer STM GRN associations and reveal regulatory relationships between STM and factors involved in multiple aspects of SAM function. These include hormone regulation, TCP-mediated control of cell differentiation, AIL/PLT-mediated regulation of pluripotency and phyllotaxis, and specification of meristem-organ boundary zones via CUC1. We demonstrate a direct positive transcriptional feedback loop between STM and CUC1, despite their distinct expression patterns in the meristem and organ boundary, respectively. Our further finding that STM activates expression of the CUC1-targeting microRNA miR164c combined with mathematical modelling provides a potential solution for this apparent contradiction, demonstrating that these proposed regulatory interactions coupled with STM mobility could be sufficient to provide a mechanism for CUC1 localisation at the meristem-organ boundary. Our findings highlight the central role for the STM GRN in coordinating SAM functions. © 2018. Published by The Company of Biologists Ltd.

Log amplifier with pole-zero compensation

DOEpatents

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.

PubMed

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.

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.

Vertebrate limb development: moving from classical morphogen gradients to an integrated 4-dimensional patterning system.

PubMed

Bénazet, Jean-Denis; Zeller, Rolf

2009-10-01

A wealth of classical embryological manipulation experiments taking mainly advantage of the chicken limb buds identified the apical ectodermal ridge (AER) and the zone of polarizing activity (ZPA) as the respective ectodermal and mesenchymal key signaling centers coordinating proximodistal (PD) and anteroposterior (AP) limb axis development. These experiments inspired Wolpert's French flag model, which is a classic among morphogen gradient models. Subsequent molecular and genetic analysis in the mouse identified retinoic acid as proximal signal, and fibroblast growth factors (FGFs) and sonic hedgehog (SHH) as the essential instructive signals produced by AER and ZPA, respectively. Recent studies provide good evidence that progenitors are specified early with respect to their PD and AP fates and that morpho-regulatory signaling is also required for subsequent proliferative expansion of the specified progenitor pools. The determination of particular fates seems to occur rather late and depends on additional signals such as bone morphogenetic proteins (BMPs), which indicates that cells integrate signaling inputs over time and space. The coordinate regulation of PD and AP axis patterning is controlled by an epithelial-mesenchymal feedback signaling system, in which transcriptional regulation of the BMP antagonist Gremlin1 integrates inputs from the BMP, SHH, and FGF pathways. Vertebrate limb-bud development is controlled by a 4-dimensional (4D) patterning system integrating positive and negative regulatory feedback loops, rather than thresholds set by morphogen gradients.

Comparison of the Performance of Modal Control Schemes for an Adaptive Optics System and Analysis of the Effect of Actuator Limitations

DTIC Science & Technology

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

The p53–Mdm2 feedback loop protects against DNA damage by inhibiting p53 activity but is dispensable for p53 stability, development, and longevity

PubMed Central

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

Stabilization and control of the carrier-envelope phase of high-power femtosecond laser pulses using the direct locking technique.

PubMed

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.

PubMed

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.

Cofilin-1 in the podocyte: a molecular switch for actin dynamics.

PubMed

Berger, Katja; Moeller, Marcus J

2011-03-01

Studies by Garg et al. and Ashworth et al. investigated the functional relevance of a key regulatory protein, cofilin-1, for podocyte actin dynamics (Ashworth et al. in PLos One 5:e12626, 2010; Garg et al. in J Biol Chem 285:22676-22688, 2010). Using different model organisms (zebrafish or transgenic mice), both groups observed a collapse of the glomerular filtration barrier upon inactivation of cofilin-1. In elegant biochemical studies, Garg et al. established that cofilin-1 activity is regulated by nephrin, which is part of the slit diaphragm complex. Two feedback loops stabilize cofilin-1 in the phosphorylated versus dephosphorylated state. The novel findings render cofilin-1 activity as potential diagnostic marker for pathological changes in the podocyte cytoarchitecture.

S-Glutathionylation of Keap1: a new role for glutathione S-transferase pi in neuronal protection.

PubMed

Carvalho, Andreia Neves; Marques, Carla; Guedes, Rita C; Castro-Caldas, Margarida; Rodrigues, Elsa; van Horssen, Jack; Gama, Maria João

2016-05-01

Oxidative stress is a key pathological feature of Parkinson's disease (PD). Glutathione S-transferase pi (GSTP) is a neuroprotective antioxidant enzyme regulated at the transcriptional level by the antioxidant master regulator nuclear factor-erythroid 2-related factor 2 (Nrf2). Here, we show for the first time that upon MPTP-induced oxidative stress, GSTP potentiates S-glutathionylation of Kelch-like ECH-associated protein 1 (Keap1), an endogenous repressor of Nrf2, in vivo. S-glutathionylation of Keap1 leads to Nrf2 activation and subsequently increases expression of GSTP. This positive feedback regulatory loop represents a novel mechanism by which GSTP elicits antioxidant protection in the brain. © 2016 Federation of European Biochemical Societies.

Inflammation as a Driver of Clonal Evolution in Myeloproliferative Neoplasm

DTIC Science & Technology

2017-10-01

ligation due to a defect in the negative regulatory feedback loop which normally serves to dampen TNF production . We have localized this defect to a...excessive inflammatory cytokine production in MPN. 15. SUBJECT TERMS Myeloproliferative neoplasm, JAK2V617F, IL-10, TNF, inflammation 16. SECURITY...4 4. Impact…………………………...……………………………………9 5. Changes/Problems...….………………………………………………11 6. Products …………………………………….……….….…………….12 7

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.

System 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.

Development of closed-loop neural interface technology in a rat model: combining motor cortex operant conditioning with visual cortex microstimulation.

PubMed

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.

An Iterative Information-Reduced Quadriphase-Shift-Keyed Carrier Synchronization Scheme Using Decision Feedback for Low Signal-to-Noise Ratio Applications

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.

PREDICT: Privacy and Security Enhancing Dynamic Information Monitoring

DTIC Science & Technology

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.

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

PubMed

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

2014-07-01

During adaptation to environments, bacteria employ two-component signal transduction systems, which contain histidine kinases and response regulators, to sense and respond to exogenous and cellular stimuli in an accurate spatio-temporal manner. Although the protein phosphorylation process between histidine kinase and response regulator has been well documented, the molecular mechanism fine-tuning phosphorylation levels of response regulators is comparatively less studied. Here we combined genetic and biochemical approaches to reveal that a hybrid histidine kinase, SreS, is involved in the SreK-SreR phosphotransfer process to control salt stress response in the bacterium Xanthomonas campestris. The N-terminal receiver domain of SreS acts as a phosphate sink by competing with the response regulator SreR to accept the phosphoryl group from the latter's cognate histidine kinase SreK. This regulatory process is critical for bacterial survival because the dephosphorylated SreR protein participates in activating one of the tandem promoters (P2) at the 5' end of the sreK-sreR-sreS-hppK operon, and then modulates a transcriptional surge of the stress-responsive gene hppK, which is required for folic acid synthesis. Therefore, our study dissects the biochemical process of a positive feedback loop in which a 'three-component' signalling system fine-tunes expression kinetics of downstream genes. © 2013 Society for Applied Microbiology and John Wiley & Sons Ltd.

Resilience of honeybee colonies via common stomach: A model of self-regulation of foraging

PubMed Central

Schmickl, Thomas

2017-01-01

We propose a new regulation mechanism based on the idea of the “common stomach” to explain several aspects of the resilience and homeostatic regulation of honeybee colonies. This mechanism exploits shared pools of substances (pollen, nectar, workers, brood) that modulate recruitment, abandonment and allocation patterns at the colony-level and enable bees to perform several survival strategies to cope with difficult circumstances: Lack of proteins leads to reduced feeding of young brood, to early capping of old brood and to regaining of already spent proteins through brood cannibalism. We modeled this system by linear interaction terms and mass-action law. To test the predictive power of the model of this regulatory mechanism we compared our model predictions to experimental data of several studies. These comparisons show that the proposed regulation mechanism can explain a variety of colony level behaviors. Detailed analysis of the model revealed that these mechanisms could explain the resilience, stability and self-regulation observed in honeybee colonies. We found that manipulation of material flow and applying sudden perturbations to colony stocks are quickly compensated by a resulting counter-acting shift in task selection. Selective analysis of feedback loops allowed us to discriminate the importance of different feedback loops in self-regulation of honeybee colonies. We stress that a network of simple proximate mechanisms can explain significant colony-level abilities that can also be seen as ultimate reasoning of the evolutionary trajectory of honeybees. PMID:29161278

Dynamic processes in regulation and some implications for biofeedback and biobehavioral interventions.

PubMed

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.

Fast flux locked loop

DOEpatents

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

2002-09-10

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

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.

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

PubMed Central

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

Closed-Loop Hybrid Gaze Brain-Machine Interface Based Robotic Arm Control with Augmented Reality Feedback

PubMed Central

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

Prox1 and fibroblast growth factor receptors form a novel regulatory loop controlling lens fiber differentiation and gene expression

PubMed Central

Audette, Dylan S.; Anand, Deepti; So, Tammy; Rubenstein, Troy B.; Lachke, Salil A.; Lovicu, Frank J.; Duncan, Melinda K.

2016-01-01

Lens epithelial cells differentiate into lens fibers (LFs) in response to a fibroblast growth factor (FGF) gradient. This cell fate decision requires the transcription factor Prox1, which has been hypothesized to promote cell cycle exit in differentiating LF cells. However, we find that conditional deletion of Prox1 from mouse lenses results in a failure in LF differentiation despite maintenance of normal cell cycle exit. Instead, RNA-seq demonstrated that Prox1 functions as a global regulator of LF cell gene expression. Intriguingly, Prox1 also controls the expression of fibroblast growth factor receptors (FGFRs) and can bind to their promoters, correlating with decreased downstream signaling through MAPK and AKT in Prox1 mutant lenses. Further, culturing rat lens explants in FGF increased their expression of Prox1, and this was attenuated by the addition of inhibitors of MAPK. Together, these results describe a novel feedback loop required for lens differentiation and morphogenesis, whereby Prox1 and FGFR signaling interact to mediate LF differentiation in response to FGF. PMID:26657765

Prox1 and fibroblast growth factor receptors form a novel regulatory loop controlling lens fiber differentiation and gene expression.

PubMed

Audette, Dylan S; Anand, Deepti; So, Tammy; Rubenstein, Troy B; Lachke, Salil A; Lovicu, Frank J; Duncan, Melinda K

2016-01-15

Lens epithelial cells differentiate into lens fibers (LFs) in response to a fibroblast growth factor (FGF) gradient. This cell fate decision requires the transcription factor Prox1, which has been hypothesized to promote cell cycle exit in differentiating LF cells. However, we find that conditional deletion of Prox1 from mouse lenses results in a failure in LF differentiation despite maintenance of normal cell cycle exit. Instead, RNA-seq demonstrated that Prox1 functions as a global regulator of LF cell gene expression. Intriguingly, Prox1 also controls the expression of fibroblast growth factor receptors (FGFRs) and can bind to their promoters, correlating with decreased downstream signaling through MAPK and AKT in Prox1 mutant lenses. Further, culturing rat lens explants in FGF increased their expression of Prox1, and this was attenuated by the addition of inhibitors of MAPK. Together, these results describe a novel feedback loop required for lens differentiation and morphogenesis, whereby Prox1 and FGFR signaling interact to mediate LF differentiation in response to FGF. © 2016. Published by The Company of Biologists Ltd.

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%.

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.

PubMed

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

DOEpatents

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

DTIC Science & Technology

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.

PubMed

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

2015-07-01

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

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.

Uncovering the spatially distant feedback loops of global trade: A network and input-output approach.

PubMed

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.

Autopilot for frequency-modulation atomic force microscopy.

PubMed

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.

In-Silico Identification Of Micro-Loops In Myelodysplastic Syndromes

NASA Astrophysics Data System (ADS)

Beck, Dominik; Brandl, Miriam; Pham, Tuan D.; Chang, Chung-Che; Zhou, Xiaobo

2011-06-01

Micro-loops are regulatory network motifs that leverage transcriptional and posttranscriptional control to effectively regulate the transcriptome. In this paper a regulatory network for Myelodysplastic Syndromes (MDSs) was constructed from the literature and publicly available data sources. The network was filtered using data from deep-sequencing of small RNAs, exon and microarrays. Motif discovery showed that micro-loops might exist in MDS. We further used the identified micro-loops and performed basic network analysis to identify the known disease gene RUNX1/AML, as well as miRNA family hsa-mir-181. This suggested that the concept of micro-loops can be applied to enhance disease gene identification and biomarker discovery.

Biodiversity maintenance in food webs with regulatory environmental feedbacks.

PubMed

Bagdassarian, Carey K; Dunham, Amy E; Brown, Christopher G; Rauscher, Daniel

2007-04-21

Although the food web is one of the most fundamental and oldest concepts in ecology, elucidating the strategies and structures by which natural communities of species persist remains a challenge to empirical and theoretical ecologists. We show that simple regulatory feedbacks between autotrophs and their environment when embedded within complex and realistic food-web models enhance biodiversity. The food webs are generated through the niche-model algorithm and coupled with predator-prey dynamics, with and without environmental feedbacks at the autotroph level. With high probability and especially at lower, more realistic connectance levels, regulatory environmental feedbacks result in fewer species extinctions, that is, in increased species persistence. These same feedback couplings, however, also sensitize food webs to environmental stresses leading to abrupt collapses in biodiversity with increased forcing. Feedback interactions between species and their material environments anchor food-web persistence, adding another dimension to biodiversity conservation. We suggest that the regulatory features of two natural systems, deep-sea tubeworms with their microbial consortia and a soil ecosystem manifesting adaptive homeostatic changes, can be embedded within niche-model food-web dynamics.

Synthetic in vitro transcriptional oscillators

PubMed Central

Kim, Jongmin; Winfree, Erik

2011-01-01

The construction of synthetic biochemical circuits from simple components illuminates how complex behaviors can arise in chemistry and builds a foundation for future biological technologies. A simplified analog of genetic regulatory networks, in vitro transcriptional circuits, provides a modular platform for the systematic construction of arbitrary circuits and requires only two essential enzymes, bacteriophage T7 RNA polymerase and Escherichia coli ribonuclease H, to produce and degrade RNA signals. In this study, we design and experimentally demonstrate three transcriptional oscillators in vitro. First, a negative feedback oscillator comprising two switches, regulated by excitatory and inhibitory RNA signals, showed up to five complete cycles. To demonstrate modularity and to explore the design space further, a positive-feedback loop was added that modulates and extends the oscillatory regime. Finally, a three-switch ring oscillator was constructed and analyzed. Mathematical modeling guided the design process, identified experimental conditions likely to yield oscillations, and explained the system's robust response to interference by short degradation products. Synthetic transcriptional oscillators could prove valuable for systematic exploration of biochemical circuit design principles and for controlling nanoscale devices and orchestrating processes within artificial cells. PMID:21283141

Multistability in the lactose utilization network of Escherichia coli

NASA Astrophysics Data System (ADS)

Ozbudak, Ertugrul M.; Thattai, Mukund; Lim, Han N.; Shraiman, Boris I.; van Oudenaarden, Alexander

2004-02-01

Multistability, the capacity to achieve multiple internal states in response to a single set of external inputs, is the defining characteristic of a switch. Biological switches are essential for the determination of cell fate in multicellular organisms, the regulation of cell-cycle oscillations during mitosis and the maintenance of epigenetic traits in microbes. The multistability of several natural and synthetic systems has been attributed to positive feedback loops in their regulatory networks. However, feedback alone does not guarantee multistability. The phase diagram of a multistable system, a concise description of internal states as key parameters are varied, reveals the conditions required to produce a functional switch. Here we present the phase diagram of the bistable lactose utilization network of Escherichia coli. We use this phase diagram, coupled with a mathematical model of the network, to quantitatively investigate processes such as sugar uptake and transcriptional regulation in vivo. We then show how the hysteretic response of the wild-type system can be converted to an ultrasensitive graded response. The phase diagram thus serves as a sensitive probe of molecular interactions and as a powerful tool for rational network design.

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).

Control of a flexible link by shaping the closed loop frequency response function through optimised feedback filters

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.

Developmental gene regulatory network architecture across 500 million years of echinoderm evolution

NASA Technical Reports Server (NTRS)

Hinman, Veronica F.; Nguyen, Albert T.; Cameron, R. Andrew; Davidson, Eric H.

2003-01-01

Evolutionary change in morphological features must depend on architectural reorganization of developmental gene regulatory networks (GRNs), just as true conservation of morphological features must imply retention of ancestral developmental GRN features. Key elements of the provisional GRN for embryonic endomesoderm development in the sea urchin are here compared with those operating in embryos of a distantly related echinoderm, a starfish. These animals diverged from their common ancestor 520-480 million years ago. Their endomesodermal fate maps are similar, except that sea urchins generate a skeletogenic cell lineage that produces a prominent skeleton lacking entirely in starfish larvae. A relevant set of regulatory genes was isolated from the starfish Asterina miniata, their expression patterns determined, and effects on the other genes of perturbing the expression of each were demonstrated. A three-gene feedback loop that is a fundamental feature of the sea urchin GRN for endoderm specification is found in almost identical form in the starfish: a detailed element of GRN architecture has been retained since the Cambrian Period in both echinoderm lineages. The significance of this retention is highlighted by the observation of numerous specific differences in the GRN connections as well. A regulatory gene used to drive skeletogenesis in the sea urchin is used entirely differently in the starfish, where it responds to endomesodermal inputs that do not affect it in the sea urchin embryo. Evolutionary changes in the GRNs since divergence are limited sharply to certain cis-regulatory elements, whereas others have persisted unaltered.

Dynamic Processes in Regulation and Some Implications for Biofeedback and Biobehavioral Interventions

PubMed Central

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)

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

A Conserved Network of Transcriptional Activators and Repressors Regulates Anthocyanin Pigmentation in Eudicots[C][W][OPEN

PubMed Central

Albert, Nick W.; Davies, Kevin M.; Lewis, David H.; Zhang, Huaibi; Montefiori, Mirco; Brendolise, Cyril; Boase, Murray R.; Ngo, Hanh; Jameson, Paula E.; Schwinn, Kathy E.

2014-01-01

Plants require sophisticated regulatory mechanisms to ensure the degree of anthocyanin pigmentation is appropriate to myriad developmental and environmental signals. Central to this process are the activity of MYB-bHLH-WD repeat (MBW) complexes that regulate the transcription of anthocyanin genes. In this study, the gene regulatory network that regulates anthocyanin synthesis in petunia (Petunia hybrida) has been characterized. Genetic and molecular evidence show that the R2R3-MYB, MYB27, is an anthocyanin repressor that functions as part of the MBW complex and represses transcription through its C-terminal EAR motif. MYB27 targets both the anthocyanin pathway genes and basic-helix-loop-helix (bHLH) ANTHOCYANIN1 (AN1), itself an essential component of the MBW activation complex for pigmentation. Other features of the regulatory network identified include inhibition of AN1 activity by the competitive R3-MYB repressor MYBx and the activation of AN1, MYB27, and MYBx by the MBW activation complex, providing for both reinforcement and feedback regulation. We also demonstrate the intercellular movement of the WDR protein (AN11) and R3-repressor (MYBx), which may facilitate anthocyanin pigment pattern formation. The fundamental features of this regulatory network in the Asterid model of petunia are similar to those in the Rosid model of Arabidopsis thaliana and are thus likely to be widespread in the Eudicots. PMID:24642943

A Novel YY1-miR-1 Regulatory Circuit in Skeletal Myogenesis Revealed by Genome-Wide Prediction of YY1-miRNA Network

PubMed Central

Lu, Leina; Zhou, Liang; Chen, Eric Z.; Sun, Kun; Jiang, Peiyong; Wang, Lijun; Su, Xiaoxi; Sun, Hao; Wang, Huating

2012-01-01

microRNAs (miRNAs) are non-coding RNAs that regulate gene expression post-transcriptionally, and mounting evidence supports the prevalence and functional significance of their interplay with transcription factors (TFs). Here we describe the identification of a regulatory circuit between muscle miRNAs (miR-1, miR-133 and miR-206) and Yin Yang 1 (YY1), an epigenetic repressor of skeletal myogenesis in mouse. Genome-wide identification of potential down-stream targets of YY1 by combining computational prediction with expression profiling data reveals a large number of putative miRNA targets of YY1 during skeletal myoblasts differentiation into myotubes with muscle miRs ranking on top of the list. The subsequent experimental results demonstrate that YY1 indeed represses muscle miRs expression in myoblasts and the repression is mediated through multiple enhancers and recruitment of Polycomb complex to several YY1 binding sites. YY1 regulating miR-1 is functionally important for both C2C12 myogenic differentiation and injury-induced muscle regeneration. Furthermore, we demonstrate that miR-1 in turn targets YY1, thus forming a negative feedback loop. Together, these results identify a novel regulatory circuit required for skeletal myogenesis and reinforce the idea that regulatory circuitries involving miRNAs and TFs are prevalent mechanisms. PMID:22319554

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

PubMed Central

2008-01-01

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

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.

Diurnal suppression of EGFR signalling by glucocorticoids and implications for tumour progression and treatment.

PubMed

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.

Dual-range linearized transimpedance amplifier system

DOEpatents

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).

A mixed incoherent feed-forward loop contributes to the regulation of bacterial photosynthesis genes.

PubMed

Mank, Nils N; Berghoff, Bork A; Klug, Gabriele

2013-03-01

Living cells use a variety of regulatory network motifs for accurate gene expression in response to changes in their environment or during differentiation processes. In Rhodobacter sphaeroides, a complex regulatory network controls expression of photosynthesis genes to guarantee optimal energy supply on one hand and to avoid photooxidative stress on the other hand. Recently, we identified a mixed incoherent feed-forward loop comprising the transcription factor PrrA, the sRNA PcrZ and photosynthesis target genes as part of this regulatory network. This point-of-view provides a comparison to other described feed-forward loops and discusses the physiological relevance of PcrZ in more detail.

A mixed incoherent feed-forward loop contributes to the regulation of bacterial photosynthesis genes

PubMed Central

Mank, Nils N.; Berghoff, Bork A.; Klug, Gabriele

2013-01-01

Living cells use a variety of regulatory network motifs for accurate gene expression in response to changes in their environment or during differentiation processes. In Rhodobacter sphaeroides, a complex regulatory network controls expression of photosynthesis genes to guarantee optimal energy supply on one hand and to avoid photooxidative stress on the other hand. Recently, we identified a mixed incoherent feed-forward loop comprising the transcription factor PrrA, the sRNA PcrZ and photosynthesis target genes as part of this regulatory network. This point-of-view provides a comparison to other described feed-forward loops and discusses the physiological relevance of PcrZ in more detail. PMID:23392242

Regulating prefrontal cortex activation: an emerging role for the 5-HT₂A serotonin receptor in the modulation of emotion-based actions?

PubMed

Aznar, Susana; Klein, Anders B

2013-12-01

The prefrontal cortex (PFC) is involved in mediating important higher-order cognitive processes such as decision making, prompting thereby our actions. At the same time, PFC activation is strongly influenced by emotional reactions through its functional interaction with the amygdala and the striatal circuitry, areas involved in emotion and reward processing. The PFC, however, is able to modulate amygdala reactivity via a feedback loop to this area. A role for serotonin in adjusting for this circuitry of cognitive regulation of emotion has long been suggested based primarily on the positive pharmacological effect of elevating serotonin levels in anxiety regulation. Recent animal and human functional magnetic resonance studies have pointed to a specific involvement of the 5-hydroxytryptamine (5-HT)2A serotonin receptor in the PFC feedback regulatory projection onto the amygdala. This receptor is highly expressed in the prefrontal cortex areas, playing an important role in modulating cortical activity and neural oscillations (brain waves). This makes it an interesting potential pharmacological target for the treatment of neuropsychiatric modes characterized by lack of inhibitory control of emotion-based actions, such as addiction and other impulse-related behaviors. In this review, we give an overview of the 5-HT2A receptor distribution (neuronal, intracellular, and anatomical) along with its functional and physiological effect on PFC activation, and how that relates to more recent findings of a regulatory effect of the PFC on the emotional control of our actions.

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

DTIC Science & Technology

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

Homeostatic Immunity and the Microbiota.

PubMed

Belkaid, Yasmine; Harrison, Oliver J

2017-04-18

The microbiota plays a fundamental role in the induction, education, and function of the host immune system. In return, the host immune system has evolved multiple means by which to maintain its symbiotic relationship with the microbiota. The maintenance of this dialogue allows the induction of protective responses to pathogens and the utilization of regulatory pathways involved in the sustained tolerance to innocuous antigens. The ability of microbes to set the immunological tone of tissues, both locally and systemically, requires tonic sensing of microbes and complex feedback loops between innate and adaptive components of the immune system. Here we review the dominant cellular mediators of these interactions and discuss emerging themes associated with our current understanding of the homeostatic immunological dialogue between the host and its microbiota. Published by Elsevier Inc.

Effects of the Global Regulator CsrA on the BarA/UvrY Two-Component Signaling System

PubMed Central

Camacho, Martha I.; Alvarez, Adrian F.; Gonzalez Chavez, Ricardo; Romeo, Tony; Merino, Enrique

2014-01-01

The hybrid sensor kinase BarA and its cognate response regulator UvrY, members of the two-component signal transduction family, activate transcription of CsrB and CsrC noncoding RNAs. These two small RNAs act by sequestering the RNA binding protein CsrA, which posttranscriptionally regulates translation and/or stability of its target mRNAs. Here, we provide evidence that CsrA positively affects, although indirectly, uvrY expression, at both the transcriptional and translational levels. We also demonstrate that CsrA is required for properly switching BarA from its phosphatase to its kinase activity. Thus, the existence of a feedback loop mechanism that involves the Csr and BarA/UvrY global regulatory systems is exposed. PMID:25535275

Homeostatic immunity and the microbiota

PubMed Central

Belkaid, Yasmine; Harrison, Oliver J.

2017-01-01

The microbiota plays a fundamental role in the induction, education and function of the host immune system. In return, the host immune system has evolved multiple means by which to maintain its symbiotic relationship with the microbiota. The maintenance of this dialogue allows the induction of protective responses to pathogens and the utilization of regulatory pathways involved in the sustained tolerance to innocuous antigens. The ability of microbes to set the immunological tone of tissues, both locally and systemically, requires tonic sensing of microbes and complex feedback loops between innate and adaptive components of the immune system. In this review, we will highlight the dominant cellular mediators of these interactions and discuss emerging themes associated with our current understanding of the homeostatic immunological dialogue between the host and its microbiota. PMID:28423337

Evaluating the strength of the land$-$atmosphere moisture feedback in Earth system models using satellite observations

DOE PAGES

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

Closed Loop Vibrational Control: Theory and Applications

DTIC Science & Technology

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

Direct laser additive fabrication system with image feedback control

DOEpatents

Griffith, Michelle L.; Hofmeister, William H.; Knorovsky, Gerald A.; MacCallum, Danny O.; Schlienger, M. Eric; Smugeresky, John E.

2002-01-01

A closed-loop, feedback-controlled direct laser fabrication system is disclosed. The feedback refers to the actual growth conditions obtained by real-time analysis of thermal radiation images. The resulting system can fabricate components with severalfold improvement in dimensional tolerances and surface finish.

Different designs of kinase-phosphatase interactions and phosphatase sequestration shapes the robustness and signal flow in the MAPK cascade

PubMed Central

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

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.

The CK2 Kinase Stabilizes CLOCK and Represses Its Activity in the Drosophila Circadian Oscillator

PubMed Central

Szabó, Áron; Papin, Christian; Zorn, Daniela; Ponien, Prishila; Weber, Frank; Raabe, Thomas; Rouyer, François

2013-01-01

Phosphorylation is a pivotal regulatory mechanism for protein stability and activity in circadian clocks regardless of their evolutionary origin. It determines the speed and strength of molecular oscillations by acting on transcriptional activators and their repressors, which form negative feedback loops. In Drosophila, the CK2 kinase phosphorylates and destabilizes the PERIOD (PER) and TIMELESS (TIM) proteins, which inhibit CLOCK (CLK) transcriptional activity. Here we show that CK2 also targets the CLK activator directly. Downregulating the activity of the catalytic α subunit of CK2 induces CLK degradation, even in the absence of PER and TIM. Unexpectedly, the regulatory β subunit of the CK2 holoenzyme is not required for the regulation of CLK stability. In addition, downregulation of CK2α activity decreases CLK phosphorylation and increases per and tim transcription. These results indicate that CK2 inhibits CLK degradation while reducing its activity. Since the CK1 kinase promotes CLK degradation, we suggest that CLK stability and transcriptional activity result from counteracting effects of CK1 and CK2. PMID:24013921

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.

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.

Global properties in an experimental realization of time-delayed feedback control with an unstable control loop.

PubMed

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.

VRILLE Controls PDF Neuropeptide Accumulation and Arborization Rhythms in Small Ventrolateral Neurons to Drive Rhythmic Behavior in Drosophila.

PubMed

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.

Experimental test of an eco-evolutionary dynamic feedback loop between evolution and population density in the green peach aphid.

PubMed

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.

PubMed

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.

Establishing a Framework for the Ad/Abaxial Regulatory Network of Arabidopsis: Ascertaining Targets of Class III HOMEODOMAIN LEUCINE ZIPPER and KANADI Regulation[W

PubMed Central

Reinhart, Brenda J.; Liu, Tie; Newell, Nicole R.; Magnani, Enrico; Huang, Tengbo; Kerstetter, Randall; Michaels, Scott; Barton, M. Kathryn

2013-01-01

The broadly conserved Class III HOMEODOMAIN LEUCINE ZIPPER (HD-ZIPIII) and KANADI transcription factors have opposing and transformational effects on polarity and growth in all tissues and stages of the plant's life. To obtain a comprehensive understanding of how these factors work, we have identified transcripts that change in response to induced HD-ZIPIII or KANADI function. Additional criteria used to identify high-confidence targets among this set were presence of an adjacent HD-ZIPIII binding site, expression enriched within a subdomain of the shoot apical meristem, mutant phenotype showing defect in polar leaf and/or meristem development, physical interaction between target gene product and HD-ZIPIII protein, opposite regulation by HD-ZIPIII and KANADI, and evolutionary conservation of the regulator–target relationship. We find that HD-ZIPIII and KANADI regulate tissue-specific transcription factors involved in subsidiary developmental decisions, nearly all major hormone pathways, and new actors (such as INDETERMINATE DOMAIN4) in the ad/abaxial regulatory network. Multiple feedback loops regulating HD-ZIPIII and KANADI are identified, as are mechanisms through which HD-ZIPIII and KANADI oppose each other. This work lays the foundation needed to understand the components, structure, and workings of the ad/abaxial regulatory network directing basic plant growth and development. PMID:24076978

The regulatory function of self-esteem: testing the epistemic and acceptance signaling systems.

PubMed

Stinson, Danu Anthony; Logel, Christine; Holmes, John G; Wood, Joanne V; Forest, Amanda L; Gaucher, Danielle; Fitzsimons, Grainné M; Kath, Jennifer

2010-12-01

The authors draw on sociometer theory (e.g., Leary, 2004) and self-verification theory (e.g., Swann, 1997) to propose an expanded model of the regulatory function of self-esteem. The model suggests that people not only possess an acceptance signaling system that indicates whether relational value is high or low but also possess an epistemic signaling system that indicates whether social feedback is consistent or inconsistent with chronic perceived relational value (i.e., global self-esteem). One correlational study and 5 experiments, with diverse operationalizations of social feedback, demonstrated that the epistemic signaling system responds to self-esteem consistent or inconsistent relational-value feedback with increases or deceases in epistemic certainty. Moreover, Studies 3-6 demonstrated that the acceptance and epistemic signaling systems respond uniquely to social feedback. Finally, Studies 5 and 6 provide evidence that the epistemic signaling system is part of a broader self-regulatory system: Self-esteem inconsistent feedback caused cognitive efforts to decrease the discrepancy between self-views and feedback and caused depleted self-regulatory capacity on a subsequent self-control task. PsycINFO Database Record (c) 2010 APA, all rights reserved.

Tracheophytes Contain Conserved Orthologs of a Basic Helix-Loop-Helix Transcription Factor That Modulate ROOT HAIR SPECIFIC Genes[OPEN

PubMed Central

Cho, Hyun-Min

2017-01-01

ROOT HAIR SPECIFIC (RHS) genes, which contain the root hair-specific cis-element (RHE) in their regulatory regions, function in root hair morphogenesis. Here, we demonstrate that an Arabidopsis thaliana basic helix-loop-helix transcription factor, ROOT HAIR DEFECTVE SIX-LIKE4 (RSL4), directly binds to the RHE in vitro and in vivo, upregulates RHS genes, and stimulates root hair formation in Arabidopsis. Orthologs of RSL4 from a eudicot (poplar [Populus trichocarpa]), a monocot (rice [Oryza sativa]), and a lycophyte (Selaginella moellendorffii) each restored root hair growth in the Arabidopsis rsl4 mutant. In addition, the rice and S. moellendorffii RSL4 orthologs bound to the RHE in in vitro and in vivo assays. The RSL4 orthologous genes contain RHEs in their promoter regions, and RSL4 was able to bind to its own RHEs in vivo and amplify its own expression. This process likely provides a positive feedback loop for sustainable root hair growth. When RSL4 and its orthologs were expressed in cells in non-root-hair positions, they induced ectopic root hair growth, indicating that these genes are sufficient to specify root hair formation. Our results suggest that RSL4 mediates root hair formation by regulating RHS genes and that this mechanism is conserved throughout the tracheophyte (vascular plant) lineage. PMID:28087829

The NRF2-related interactome and regulome contain multifunctional proteins and fine-tuned autoregulatory loops.

PubMed

Papp, Diána; Lenti, Katalin; Módos, Dezső; Fazekas, Dávid; Dúl, Zoltán; Türei, Dénes; Földvári-Nagy, László; Nussinov, Ruth; Csermely, Péter; Korcsmáros, Tamás

2012-06-21

NRF2 is a well-known, master transcription factor (TF) of oxidative and xenobiotic stress responses. Recent studies uncovered an even wider regulatory role of NRF2 influencing carcinogenesis, inflammation and neurodegeneration. Prompted by these advances here we present a systems-level resource for NRF2 interactome and regulome that includes 289 protein-protein, 7469 TF-DNA and 85 miRNA interactions. As systems-level examples of NRF2-related signaling we identified regulatory loops of NRF2 interacting proteins (e.g., JNK1 and CBP) and a fine-tuned regulatory system, where 35 TFs regulated by NRF2 influence 63 miRNAs that down-regulate NRF2. The presented network and the uncovered regulatory loops may facilitate the development of efficient, NRF2-based therapeutic agents. Copyright © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

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

PubMed Central

Zhao, Huiwu; Kalota, Anna; Jin, Shenghao

2009-01-01

The c-myb proto-oncogene encodes an obligate hematopoietic cell transcription factor important for lineage commitment, proliferation, and differentiation. Given its critical functions, c-Myb regulatory factors are of great interest but remain incompletely defined. Herein we show that c-Myb expression is subject to posttranscriptional regulation by microRNA (miRNA)–15a. Using a luciferase reporter assay, we found that miR-15a directly binds the 3′-UTR of c-myb mRNA. By transfecting K562 myeloid leukemia cells with a miR-15a mimic, functionality of binding was shown. The mimic decreased c-Myb expression, and blocked the cells in the G1 phase of cell cycle. Exogenous expression of c-myb mRNA lacking the 3′-UTR partially rescued the miR-15a induced cell-cycle block. Of interest, the miR-15a promoter contained several potential c-Myb protein binding sites. Occupancy of one canonical c-Myb binding site was demonstrated by chromatin immunoprecipitation analysis and shown to be required for miR-15a expression in K562 cells. Finally, in studies using normal human CD34+ cells, we showed that c-Myb and miR-15a expression were inversely correlated in cells undergoing erythroid differentiation, and that overexpression of miR-15a blocked both erythroid and myeloid colony formation in vitro. In aggregate, these findings suggest the presence of a c-Myb–miR-15a autoregulatory feedback loop of potential importance in human hematopoiesis. PMID:18818396

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

PubMed

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

2015-05-28

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

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

PubMed Central

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

2015-01-01

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

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

PubMed Central

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

2013-01-01

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

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

PubMed Central

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

2012-01-01

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

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.

Specific interaction between hnRNP H and HPV16 L1 proteins: Implications for late gene auto-regulation enabling rapid viral capsid protein production

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zheng, Zi-Zheng; Sun, Yuan-Yuan; Zhao, Min

2013-01-18

Highlights: ► The RNA-binding hnRNP H regulates late viral gene expression. ► hnRNP H activity was inhibited by a late viral protein. ► Specific interaction between HPV L1 and hnRNP H was demonstrated. ► Co-localization of HPV L1 and hnRNP H inside cells was observed. ► Viral capsid protein production, enabling rapid capsid assembly, was implicated. -- Abstract: Heterogeneous nuclear ribonucleoproteins (hnRNPs), including hnRNP H, are RNA-binding proteins that function as splicing factors and are involved in downstream gene regulation. hnRNP H, which binds to G triplet regions in RNA, has been shown to play an important role in regulatingmore » the staged expression of late proteins in viral systems. Here, we report that the specific association between hnRNP H and a late viral capsid protein, human papillomavirus (HPV) L1 protein, leads to the suppressed function of hnRNP H in the presence of the L1 protein. The direct interaction between the L1 protein and hnRNP H was demonstrated by complex formation in solution and intracellularly using a variety of biochemical and immunochemical methods, including peptide mapping, specific co-immunoprecipitation and confocal fluorescence microscopy. These results support a working hypothesis that a late viral protein HPV16 L1, which is down regulated by hnRNP H early in the viral life cycle may provide an auto-regulatory positive feedback loop that allows the rapid production of HPV capsid proteins through suppression of the function of hnRNP H at the late stage of the viral life cycle. In this positive feedback loop, the late viral gene products that were down regulated earlier themselves disable their suppressors, and this feedback mechanism could facilitate the rapid production of capsid proteins, allowing staged and efficient viral capsid assembly.« less

Positive and negative feedback loops in nutrient phytoplankton interactions related to climate dynamics factors in a shallow temperate estuary (Vistula Lagoon, southern Baltic)

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.

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…

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.

ONE SHAKE GATE FORMER

DOEpatents

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.

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 and robust control of quantum systems.

PubMed

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.

PubMed

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.

An open-closed-loop iterative learning control approach for nonlinear switched systems with application to freeway traffic control

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.

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.

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

PubMed Central

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

Closed-loop control of grasping with a myoelectric hand prosthesis: which are the relevant feedback variables for force control?

PubMed

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.

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.

PubMed

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.

Short and long sympathetic-sensory feedback loops in white fat

PubMed Central

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

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.

Identification of optimal feedback control rules from micro-quadrotor and insect flight trajectories.

PubMed

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.

PubMed

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

2012-06-01

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

Complete analog control of the carrier-envelope-phase of a high-power laser amplifier.

PubMed

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.

Conceptual model of sedimentation in the Sacramento-San Joaquin River Delta

USGS Publications Warehouse

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.

Predictive genomics: a cancer hallmark network framework for predicting tumor clinical phenotypes using genome sequencing data.

PubMed

Wang, Edwin; Zaman, Naif; Mcgee, Shauna; Milanese, Jean-Sébastien; Masoudi-Nejad, Ali; O'Connor-McCourt, Maureen

2015-02-01

Tumor genome sequencing leads to documenting thousands of DNA mutations and other genomic alterations. At present, these data cannot be analyzed adequately to aid in the understanding of tumorigenesis and its evolution. Moreover, we have little insight into how to use these data to predict clinical phenotypes and tumor progression to better design patient treatment. To meet these challenges, we discuss a cancer hallmark network framework for modeling genome sequencing data to predict cancer clonal evolution and associated clinical phenotypes. The framework includes: (1) cancer hallmarks that can be represented by a few molecular/signaling networks. 'Network operational signatures' which represent gene regulatory logics/strengths enable to quantify state transitions and measures of hallmark traits. Thus, sets of genomic alterations which are associated with network operational signatures could be linked to the state/measure of hallmark traits. The network operational signature transforms genotypic data (i.e., genomic alterations) to regulatory phenotypic profiles (i.e., regulatory logics/strengths), to cellular phenotypic profiles (i.e., hallmark traits) which lead to clinical phenotypic profiles (i.e., a collection of hallmark traits). Furthermore, the framework considers regulatory logics of the hallmark networks under tumor evolutionary dynamics and therefore also includes: (2) a self-promoting positive feedback loop that is dominated by a genomic instability network and a cell survival/proliferation network is the main driver of tumor clonal evolution. Surrounding tumor stroma and its host immune systems shape the evolutionary paths; (3) cell motility initiating metastasis is a byproduct of the above self-promoting loop activity during tumorigenesis; (4) an emerging hallmark network which triggers genome duplication dominates a feed-forward loop which in turn could act as a rate-limiting step for tumor formation; (5) mutations and other genomic alterations have specific patterns and tissue-specificity, which are driven by aging and other cancer-inducing agents. This framework represents the logics of complex cancer biology as a myriad of phenotypic complexities governed by a limited set of underlying organizing principles. It therefore adds to our understanding of tumor evolution and tumorigenesis, and moreover, potential usefulness of predicting tumors' evolutionary paths and clinical phenotypes. Strategies of using this framework in conjunction with genome sequencing data in an attempt to predict personalized drug targets, drug resistance, and metastasis for cancer patients, as well as cancer risks for healthy individuals are discussed. Accurate prediction of cancer clonal evolution and clinical phenotypes will have substantial impact on timely diagnosis, personalized treatment and personalized prevention of cancer. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

Origin of bistability underlying mammalian cell cycle entry

PubMed Central

Yao, Guang; Tan, Cheemeng; West, Mike; Nevins, Joseph R; You, Lingchong

2011-01-01

Precise control of cell proliferation is fundamental to tissue homeostasis and differentiation. Mammalian cells commit to proliferation at the restriction point (R-point). It has long been recognized that the R-point is tightly regulated by the Rb–E2F signaling pathway. Our recent work has further demonstrated that this regulation is mediated by a bistable switch mechanism. Nevertheless, the essential regulatory features in the Rb–E2F pathway that create this switching property have not been defined. Here we analyzed a library of gene circuits comprising all possible link combinations in a simplified Rb–E2F network. We identified a minimal circuit that is able to generate robust, resettable bistability. This minimal circuit contains a feed-forward loop coupled with a mutual-inhibition feedback loop, which forms an AND-gate control of the E2F activation. Underscoring its importance, experimental disruption of this circuit abolishes maintenance of the activated E2F state, supporting its importance for the bistability of the Rb–E2F system. Our findings suggested basic design principles for the robust control of the bistable cell cycle entry at the R-point. PMID:21525871

Pluripotency gene network dynamics: System views from parametric analysis.

PubMed

Akberdin, Ilya R; Omelyanchuk, Nadezda A; Fadeev, Stanislav I; Leskova, Natalya E; Oschepkova, Evgeniya A; Kazantsev, Fedor V; Matushkin, Yury G; Afonnikov, Dmitry A; Kolchanov, Nikolay A

2018-01-01

Multiple experimental data demonstrated that the core gene network orchestrating self-renewal and differentiation of mouse embryonic stem cells involves activity of Oct4, Sox2 and Nanog genes by means of a number of positive feedback loops among them. However, recent studies indicated that the architecture of the core gene network should also incorporate negative Nanog autoregulation and might not include positive feedbacks from Nanog to Oct4 and Sox2. Thorough parametric analysis of the mathematical model based on this revisited core regulatory circuit identified that there are substantial changes in model dynamics occurred depending on the strength of Oct4 and Sox2 activation and molecular complexity of Nanog autorepression. The analysis showed the existence of four dynamical domains with different numbers of stable and unstable steady states. We hypothesize that these domains can constitute the checkpoints in a developmental progression from naïve to primed pluripotency and vice versa. During this transition, parametric conditions exist, which generate an oscillatory behavior of the system explaining heterogeneity in expression of pluripotent and differentiation factors in serum ESC cultures. Eventually, simulations showed that addition of positive feedbacks from Nanog to Oct4 and Sox2 leads mainly to increase of the parametric space for the naïve ESC state, in which pluripotency factors are strongly expressed while differentiation ones are repressed.

Asymptotic Eigenstructures

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.

Validation of snow characteristics and snow albedo feedback in the Canadian Regional Climate Model simulations over North America

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.

Disturbed P53-MDM2 Feedback Loop Contributes to Thoracic Aortic Dissection Formation and May be a Result of TRIM25 Overexpression.

PubMed

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.

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

PubMed

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

2002-01-01

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

A novel P53/POMC/Gαs/SASH1 autoregulatory feedback loop activates mutated SASH1 to cause pathologic hyperpigmentation.

PubMed

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.

Activation of PI3K/AKT and MAPK Pathway through a PDGFRβ-Dependent Feedback Loop Is Involved in Rapamycin Resistance in Hepatocellular Carcinoma

PubMed Central

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

Discriminating tastes

PubMed Central

Storz, Gisela

2011-01-01

Hfq-binding small RNAs (sRNAs) are critical regulators that form limited base-pairing interactions with target mRNAs in bacteria. These sRNAs have been linked to diverse environmental responses, yet little is known how Hfq-binding sRNAs participate in the regulatory networks associated with each response. We recently described how the Hfq-binding sRNA Spot 42 in Escherichia coli contributes to catabolite repression, a regulatory phenomenon that allows bacteria to consume some carbon sources over others. Spot 42 base pairs with numerous mRNAs encoding enzymes in central and secondary metabolism, redox balancing, and the uptake and consumption of non-preferred carbon sources. Many of the corresponding genes are transcriptionally activated by the Spot 42-repressor CRP, forming a regulatory circuit called a multi-output feedforward loop. We found that this loop influences both the steady-state levels and dynamics of gene regulation. In this article, we discuss how the CRP-Spot 42 feedforward loop is integrated into encompassing networks and how this loop may benefit enteric bacteria facing uncertain and changing nutrient conditions. PMID:21788732

Invariant TAD Boundaries Constrain Cell-Type-Specific Looping Interactions between Promoters and Distal Elements around the CFTR Locus

PubMed Central

Smith, Emily M.; Lajoie, Bryan R.; Jain, Gaurav; Dekker, Job

2016-01-01

Three-dimensional genome structure plays an important role in gene regulation. Globally, chromosomes are organized into active and inactive compartments while, at the gene level, looping interactions connect promoters to regulatory elements. Topologically associating domains (TADs), typically several hundred kilobases in size, form an intermediate level of organization. Major questions include how TADs are formed and how they are related to looping interactions between genes and regulatory elements. Here we performed a focused 5C analysis of a 2.8 Mb chromosome 7 region surrounding CFTR in a panel of cell types. We find that the same TAD boundaries are present in all cell types, indicating that TADs represent a universal chromosome architecture. Furthermore, we find that these TAD boundaries are present irrespective of the expression and looping of genes located between them. In contrast, looping interactions between promoters and regulatory elements are cell-type specific and occur mostly within TADs. This is exemplified by the CFTR promoter that in different cell types interacts with distinct sets of distal cell-type-specific regulatory elements that are all located within the same TAD. Finally, we find that long-range associations between loci located in different TADs are also detected, but these display much lower interaction frequencies than looping interactions within TADs. Interestingly, interactions between TADs are also highly cell-type-specific and often involve loci clustered around TAD boundaries. These data point to key roles of invariant TAD boundaries in constraining as well as mediating cell-type-specific long-range interactions and gene regulation. PMID:26748519

The R2R3-MYB–Like Regulatory Factor EOBI, Acting Downstream of EOBII, Regulates Scent Production by Activating ODO1 and Structural Scent-Related Genes in Petunia[C][W

PubMed Central

Spitzer-Rimon, Ben; Farhi, Moran; Albo, Boaz; Cna’ani, Alon; Ben Zvi, Michal Moyal; Masci, Tania; Edelbaum, Orit; Yu, Yixun; Shklarman, Elena; Ovadis, Marianna; Vainstein, Alexander

2012-01-01

Flower scent is a highly dynamic trait, under developmental, spatial, and diurnal regulation. The mechanism governing scent production is only beginning to be unraveled. In petunia (Petunia hybrida), EMISSION OF BENZENOIDS II (EOBII) controls transcription of both the shikimate pathway-regulating MYB factor ODORANT1 (ODO1) and phenylpropanoid scent-related structural genes. A promoter-activation screen identified an R2R3-MYB–like regulatory factor of phenylpropanoid volatile biosynthesis acting downstream of EOBII, designated EOBI. EOBI silencing led to downregulation of ODO1 and numerous structural scent-related genes from both the shikimate and phenylpropanoid pathways. The ability of EOBI to directly activate ODO1, as revealed by electrophoretic mobility shift assay and yeast one-hybrid analysis, place EOBI upstream of ODO1 in regulating substrate availability for volatile biosynthesis. Interestingly, ODO1-silenced transgenic petunia flowers accumulated higher EOBI transcript levels than controls, suggesting a complex feedback loop between these regulatory factors. The accumulation pattern of EOBI transcript relative to EOBII and ODO1, and the effect of up/downregulation of EOBII on transcript levels of EOBI and ODO1, further support these factors' hierarchical relationships. The dependence of scent production on EOBI expression and its direct interaction with both regulatory and structural genes provide evidence for EOBI’s wide-ranging involvement in the production of floral volatiles. PMID:23275577

The R2R3-MYB-like regulatory factor EOBI, acting downstream of EOBII, regulates scent production by activating ODO1 and structural scent-related genes in petunia.

PubMed

Spitzer-Rimon, Ben; Farhi, Moran; Albo, Boaz; Cna'ani, Alon; Ben Zvi, Michal Moyal; Masci, Tania; Edelbaum, Orit; Yu, Yixun; Shklarman, Elena; Ovadis, Marianna; Vainstein, Alexander

2012-12-01

Flower scent is a highly dynamic trait, under developmental, spatial, and diurnal regulation. The mechanism governing scent production is only beginning to be unraveled. In petunia (Petunia hybrida), EMISSION OF BENZENOIDS II (EOBII) controls transcription of both the shikimate pathway-regulating MYB factor ODORANT1 (ODO1) and phenylpropanoid scent-related structural genes. A promoter-activation screen identified an R2R3-MYB-like regulatory factor of phenylpropanoid volatile biosynthesis acting downstream of EOBII, designated EOBI. EOBI silencing led to downregulation of ODO1 and numerous structural scent-related genes from both the shikimate and phenylpropanoid pathways. The ability of EOBI to directly activate ODO1, as revealed by electrophoretic mobility shift assay and yeast one-hybrid analysis, place EOBI upstream of ODO1 in regulating substrate availability for volatile biosynthesis. Interestingly, ODO1-silenced transgenic petunia flowers accumulated higher EOBI transcript levels than controls, suggesting a complex feedback loop between these regulatory factors. The accumulation pattern of EOBI transcript relative to EOBII and ODO1, and the effect of up/downregulation of EOBII on transcript levels of EOBI and ODO1, further support these factors' hierarchical relationships. The dependence of scent production on EOBI expression and its direct interaction with both regulatory and structural genes provide evidence for EOBI's wide-ranging involvement in the production of floral volatiles.

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.

PubMed

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.

Feedback activation of STAT3 mediates trastuzumab resistance via upregulation of MUC1 and MUC4 expression

PubMed Central

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

Feedback activation of STAT3 mediates trastuzumab resistance via upregulation of MUC1 and MUC4 expression.

PubMed

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.

MicroRNAs and cancer: a meeting summary of the eponymous Keystone Conference.

PubMed

Godshalk, Sirie E; Melnik-Martinez, Katya V; Pasquinelli, Amy E; Slack, Frank J

2010-02-16

This report summarizes the information presented at the 2009 Keystone Conference on MicroRNAs and Cancer, held in Keystone, Colorado, USA, June 10th to 15th 2009. Soon after microRNAs (miRNAs) emerged as an abundant new class of non-coding RNAs (ncRNAs), evidence started to mount supporting important roles for these regulatory RNAs in human health and disease. Mis-regulation of specific miRNA pathways has been linked to diverse cancers. The recent Keystone meeting highlighted progress in understanding the role of miRNAs in normal development and oncogenesis. Recurring themes included the complexities associated with miRNA biogenesis, target recognition, elucidation of genetic networks where miRNAs play pivotal roles often within feedback loops, and the promise of small RNAs as diagnostics and therapeutics in combating cancer.

Systemic signaling during plant defense.

PubMed

Kachroo, Aardra; Robin, Guillaume P

2013-08-01

Systemic acquired resistance (SAR) is a type of pathogen-induced broad-spectrum resistance in plants. During SAR, primary infection-induced rapid generation and transportation of mobile signal(s) 'prepare' the rest of the plant for subsequent infections. Several, seemingly unrelated, mobile chemical inducers of SAR have been identified, at least two of which function in a feed-back regulatory loop with a lipid transfer-like protein. Signal(s) perception in the systemic tissues relies on the presence of an intact cuticle, the waxy layer covering all aerial parts of the plant. SAR results in chromatin modifications, which prime systemic tissues for enhanced and rapid signaling derived from salicylic acid, which along with its signaling components is key for SAR induction. This review summarizes recent findings related to SAR signal generation, movement, and perception. Copyright © 2013 Elsevier Ltd. 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.

Analytical study of robustness of a negative feedback oscillator by multiparameter sensitivity

PubMed Central

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

Variations in Static Force Control and Motor Unit Behavior with Error Amplification Feedback in the Elderly.

PubMed

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.

Variations in Static Force Control and Motor Unit Behavior with Error Amplification Feedback in the Elderly

PubMed Central

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

High frequency optoelectronic oscillators based on the optical feedback of semiconductor mode-locked laser diodes.

PubMed

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

PubMed Central

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

The mechanosensory calcium-selective ion channel: key component of a plasmalemmal control centre?

NASA Technical Reports Server (NTRS)

Pickard, B. G.; Ding, J. P.

1993-01-01

Mechanosensory calcium-selective ion channels probably serve to detect not only mechanical stress but also electrical, thermal, and diverse chemical stimuli. Because all stimuli result in a common output, most notably a shift in second messenger calcium concentration, the channels are presumed to serve as signal integrators. Further, insofar as second messenger calcium in turn gives rise to mechanical, electrical, and diverse chemical changes, the channels are postulated to initiate regulatory feedbacks. It is proposed that the channels and the feedback loops play a wide range of roles in regulating normal plant function, as well as in mediating disturbance of normal function by environmental stressors and various pathogens. In developing evidence for the physiological performance of the channel, a model for a cluster of regulatory plasmalemmal proteins and cytoskeletal elements grouped around a set of wall-to-membrane and transmembrane linkers has proved useful. An illustration of how the model might operate is presented. It is founded on the demonstration that several xenobiotics interfere both with normal channel behaviour and with gravitropic reception. Accordingly, the first part of the illustration deals with how the channels and the control system within which they putatively operate might initiate gravitropism. Assuming that gravitropism is an asymmetric expression of growth, the activities of the channels and the plasmalemmal control system are extrapolated to account for regulation of both rate and allometry of cell expansion. Finally, it is discussed how light, hormones, redox agents and herbicides could in principle affect growth via the putative plasmalemmal control cluster or centre.

Actin cytoskeleton of chemotactic amoebae operates close to the onset of oscillations

PubMed Central

Westendorf, Christian; Negrete, Jose; Bae, Albert J.; Sandmann, Rabea; Bodenschatz, Eberhard; Beta, Carsten

2013-01-01

The rapid reorganization of the actin cytoskeleton in response to external stimuli is an essential property of many motile eukaryotic cells. Here, we report evidence that the actin machinery of chemotactic Dictyostelium cells operates close to an oscillatory instability. When averaging the actin response of many cells to a short pulse of the chemoattractant cAMP, we observed a transient accumulation of cortical actin reminiscent of a damped oscillation. At the single-cell level, however, the response dynamics ranged from short, strongly damped responses to slowly decaying, weakly damped oscillations. Furthermore, in a small subpopulation, we observed self-sustained oscillations in the cortical F-actin concentration. To substantiate that an oscillatory mechanism governs the actin dynamics in these cells, we systematically exposed a large number of cells to periodic pulse trains of different frequencies. Our results indicate a resonance peak at a stimulation period of around 20 s. We propose a delayed feedback model that explains our experimental findings based on a time-delay in the regulatory network of the actin system. To test the model, we performed stimulation experiments with cells that express GFP-tagged fusion proteins of Coronin and actin-interacting protein 1, as well as knockout mutants that lack Coronin and actin-interacting protein 1. These actin-binding proteins enhance the disassembly of actin filaments and thus allow us to estimate the delay time in the regulatory feedback loop. Based on this independent estimate, our model predicts an intrinsic period of 20 s, which agrees with the resonance observed in our periodic stimulation experiments. PMID:23431176

Systems-level feedback regulation of cell cycle transitions in Ostreococcus tauri.

PubMed

Kapuy, Orsolya; Vinod, P K; Bánhegyi, Gábor; Novák, Béla

2018-05-01

Ostreococcus tauri is the smallest free-living unicellular organism with one copy of each core cell cycle genes in its genome. There is a growing interest in this green algae due to its evolutionary origin. Since O. tauri is diverged early in the green lineage, relatively close to the ancestral eukaryotic cell, it might hold a key phylogenetic position in the eukaryotic tree of life. In this study, we focus on the regulatory network of its cell division cycle. We propose a mathematical modelling framework to integrate the existing knowledge of cell cycle network of O. tauri. We observe that feedback loop regulation of both G1/S and G2/M transitions in O. tauri is conserved, which can make the transition bistable. This is essential to make the transition irreversible as shown in other eukaryotic organisms. By performing sequence analysis, we also predict the presence of the Greatwall/PP2A pathway in the cell cycle of O. tauri. Since O. tauri cell cycle machinery is conserved, the exploration of the dynamical characteristic of the cell division cycle will help in further understanding the regulation of cell cycle in higher eukaryotes. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

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.

Electro-optic chaotic system based on the reverse-time chaos theory and a nonlinear hybrid feedback loop.

PubMed

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.

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.

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…

Global output feedback stabilisation of stochastic high-order feedforward nonlinear systems with time-delay

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.

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.

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.

CUL4B impedes stress-induced cellular senescence by dampening a p53-reactive oxygen species positive feedback loop.

PubMed

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.

Closed-Loop and Robust Control of Quantum Systems

PubMed Central

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

PubMed Central

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

Closed-loop mechanical ventilation for lung injury: a novel physiological-feedback mode following the principles of the open lung concept.

PubMed

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.

Differential contributions of the superior and inferior parietal cortex to feedback versus feedforward control of tools.

PubMed

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.

Network efficient power control for wireless communication systems.

PubMed

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

PubMed Central

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.

Closed-loop control of renal perfusion pressure in physiological experiments.

PubMed

Campos-Delgado, D U; Bonilla, I; Rodríguez-Martínez, M; Sánchez-Briones, M E; Ruiz-Hernández, E

2013-07-01

This paper presents the design, experimental modeling, and control of a pump-driven renal perfusion pressure (RPP)-regulatory system to implement precise and relatively fast RPP regulation in rats. The mechatronic system is a simple, low-cost, and reliable device to automate the RPP regulation process based on flow-mediated occlusion. Hence, the regulated signal is the RPP measured in the left femoral artery of the rat, and the manipulated variable is the voltage applied to a dc motor that controls the occlusion of the aorta. The control system is implemented in a PC through the LabView software, and a data acquisition board NI USB-6210. A simple first-order linear system is proposed to approximate the dynamics in the experiment. The parameters of the model are chosen to minimize the error between the predicted and experimental output averaged from eight input/output datasets at different RPP operating conditions. A closed-loop servocontrol system based on a pole-placement PD controller plus dead-zone compensation was proposed for this purpose. First, the feedback structure was validated in simulation by considering parameter uncertainty, and constant and time-varying references. Several experimental tests were also conducted to validate in real time the closed-loop performance for stepwise and fast switching references, and the results show the effectiveness of the proposed automatic system to regulate the RPP in the rat, in a precise, accurate (mean error less than 2 mmHg) and relatively fast mode (10-15 s of response time).

Epigenetic and Posttranslational Modifications in Light Signal Transduction and the Circadian Clock in Neurospora crassa

PubMed Central

Proietto, Marco; Bianchi, Michele Maria; Ballario, Paola; Brenna, Andrea

2015-01-01

Blue light, a key abiotic signal, regulates a wide variety of physiological processes in many organisms. One of these phenomena is the circadian rhythm presents in organisms sensitive to the phase-setting effects of blue light and under control of the daily alternation of light and dark. Circadian clocks consist of autoregulatory alternating negative and positive feedback loops intimately connected with the cellular metabolism and biochemical processes. Neurospora crassa provides an excellent model for studying the molecular mechanisms involved in these phenomena. The White Collar Complex (WCC), a blue-light receptor and transcription factor of the circadian oscillator, and Frequency (FRQ), the circadian clock pacemaker, are at the core of the Neurospora circadian system. The eukaryotic circadian clock relies on transcriptional/translational feedback loops: some proteins rhythmically repress their own synthesis by inhibiting the activity of their transcriptional factors, generating self-sustained oscillations over a period of about 24 h. One of the basic mechanisms that perpetuate self-sustained oscillations is post translation modification (PTM). The acronym PTM generically indicates the addition of acetyl, methyl, sumoyl, or phosphoric groups to various types of proteins. The protein can be regulatory or enzymatic or a component of the chromatin. PTMs influence protein stability, interaction, localization, activity, and chromatin packaging. Chromatin modification and PTMs have been implicated in regulating circadian clock function in Neurospora. Research into the epigenetic control of transcription factors such as WCC has yielded new insights into the temporal modulation of light-dependent gene transcription. Here we report on epigenetic and protein PTMs in the regulation of the Neurospora crassa circadian clock. We also present a model that illustrates the molecular mechanisms at the basis of the blue light control of the circadian clock. PMID:26198228

Third-Kind Encounters in Biomedicine: Immunology Meets Mathematics and Informatics to Become Quantitative and Predictive.

PubMed

Eberhardt, Martin; Lai, Xin; Tomar, Namrata; Gupta, Shailendra; Schmeck, Bernd; Steinkasserer, Alexander; Schuler, Gerold; Vera, Julio

2016-01-01

The understanding of the immune response is right now at the center of biomedical research. There are growing expectations that immune-based interventions will in the midterm provide new, personalized, and targeted therapeutic options for many severe and highly prevalent diseases, from aggressive cancers to infectious and autoimmune diseases. To this end, immunology should surpass its current descriptive and phenomenological nature, and become quantitative, and thereby predictive.Immunology is an ideal field for deploying the tools, methodologies, and philosophy of systems biology, an approach that combines quantitative experimental data, computational biology, and mathematical modeling. This is because, from an organism-wide perspective, the immunity is a biological system of systems, a paradigmatic instance of a multi-scale system. At the molecular scale, the critical phenotypic responses of immune cells are governed by large biochemical networks, enriched in nested regulatory motifs such as feedback and feedforward loops. This network complexity confers them the ability of highly nonlinear behavior, including remarkable examples of homeostasis, ultra-sensitivity, hysteresis, and bistability. Moving from the cellular level, different immune cell populations communicate with each other by direct physical contact or receiving and secreting signaling molecules such as cytokines. Moreover, the interaction of the immune system with its potential targets (e.g., pathogens or tumor cells) is far from simple, as it involves a number of attack and counterattack mechanisms that ultimately constitute a tightly regulated multi-feedback loop system. From a more practical perspective, this leads to the consequence that today's immunologists are facing an ever-increasing challenge of integrating massive quantities from multi-platforms.In this chapter, we support the idea that the analysis of the immune system demands the use of systems-level approaches to ensure the success in the search for more effective and personalized immune-based therapies.

Comprehensive Logic Based Analyses of Toll-Like Receptor 4 Signal Transduction Pathway

PubMed Central

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

Invariant TAD Boundaries Constrain Cell-Type-Specific Looping Interactions between Promoters and Distal Elements around the CFTR Locus.

PubMed

Smith, Emily M; Lajoie, Bryan R; Jain, Gaurav; Dekker, Job

2016-01-07

Three-dimensional genome structure plays an important role in gene regulation. Globally, chromosomes are organized into active and inactive compartments while, at the gene level, looping interactions connect promoters to regulatory elements. Topologically associating domains (TADs), typically several hundred kilobases in size, form an intermediate level of organization. Major questions include how TADs are formed and how they are related to looping interactions between genes and regulatory elements. Here we performed a focused 5C analysis of a 2.8 Mb chromosome 7 region surrounding CFTR in a panel of cell types. We find that the same TAD boundaries are present in all cell types, indicating that TADs represent a universal chromosome architecture. Furthermore, we find that these TAD boundaries are present irrespective of the expression and looping of genes located between them. In contrast, looping interactions between promoters and regulatory elements are cell-type specific and occur mostly within TADs. This is exemplified by the CFTR promoter that in different cell types interacts with distinct sets of distal cell-type-specific regulatory elements that are all located within the same TAD. Finally, we find that long-range associations between loci located in different TADs are also detected, but these display much lower interaction frequencies than looping interactions within TADs. Interestingly, interactions between TADs are also highly cell-type-specific and often involve loci clustered around TAD boundaries. These data point to key roles of invariant TAD boundaries in constraining as well as mediating cell-type-specific long-range interactions and gene regulation. Copyright © 2016 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

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

PubMed Central

Morgans, Aimee S.

2016-01-01

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

Steady state statistical correlations predict bistability in reaction motifs.

PubMed

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.

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.

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

PubMed Central

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

2014-01-01

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

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.

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.

Dual Nature of Translational Control by Regulatory BC RNAs ▿

PubMed Central

Eom, Taesun; Berardi, Valerio; Zhong, Jun; Risuleo, Gianfranco; Tiedge, Henri

2011-01-01

In higher eukaryotes, increasing evidence suggests, gene expression is to a large degree controlled by RNA. Regulatory RNAs have been implicated in the management of neuronal function and plasticity in mammalian brains. However, much of the molecular-mechanistic framework that enables neuronal regulatory RNAs to control gene expression remains poorly understood. Here, we establish molecular mechanisms that underlie the regulatory capacity of neuronal BC RNAs in the translational control of gene expression. We report that regulatory BC RNAs employ a two-pronged approach in translational control. One of two distinct repression mechanisms is mediated by C-loop motifs in BC RNA 3′ stem-loop domains. These C-loops bind to eIF4B and prevent the factor's interaction with 18S rRNA of the small ribosomal subunit. In the second mechanism, the central A-rich domains of BC RNAs target eIF4A, specifically inhibiting its RNA helicase activity. Thus, BC RNAs repress translation initiation in a bimodal mechanistic approach. As BC RNA functionality has evolved independently in rodent and primate lineages, our data suggest that BC RNA translational control was necessitated and implemented during mammalian phylogenetic development of complex neural systems. PMID:21930783

The Tumor Suppressor Cdkn3 Is Required for Maintaining the Proper Number of Centrosomes by Regulating the Centrosomal Stability of Mps1.

PubMed

Srinivas, Vinayaka; Kitagawa, Mayumi; Wong, Jasmine; Liao, Pei-Ju; Lee, Sang Hyun

2015-11-24

Supernumerary centrosomes promote the assembly of abnormal spindles in many human cancers. The observation that modest changes in the centrosomal levels of Mps1 kinase can cause centrosome overduplication in human cells suggests the existence of a regulatory system that may tightly control its centrosomal stability. Here, we show that Cdkn3, a Cdk-associated phosphatase, prevents Mps1-mediated centrosome overduplication. We identify Cdkn3 as a direct binding partner of Mps1. The interaction between Mps1 and Cdkn3 is required for Mps1 to recruit Cdkn3 to centrosomes. Subsequently, Mps1-bound Cdkn3 forms a regulatory system that controls the centrosomal levels of Mps1 through proteasome-mediated degradation and thereby prevents Mps1-mediated centrosome overduplication. Conversely, knockdown of Cdkn3 stabilizes Mps1 at centrosomes, which promotes centrosome overduplication. We suggest that Mps1 and Cdkn3 form a self-regulated feedback loop at centrosomes to tightly control the centrosomal levels of Mps1, which prevents centrosome overduplication in human cells. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Cutting Edge: Differential Regulation of PTEN by TCR, Akt, and FoxO1 Controls CD4+ T Cell Fate Decisions.

PubMed

Hawse, William F; Sheehan, Robert P; Miskov-Zivanov, Natasa; Menk, Ashley V; Kane, Lawrence P; Faeder, James R; Morel, Penelope A

2015-05-15

Signaling via the Akt/mammalian target of rapamycin pathway influences CD4(+) T cell differentiation; low levels favor regulatory T cell induction and high levels favor Th induction. Although the lipid phosphatase phosphatase and tensin homolog (PTEN) suppresses Akt activity, the control of PTEN activity is poorly studied in T cells. In this study, we identify multiple mechanisms that regulate PTEN expression. During Th induction, PTEN function is suppressed via lower mRNA levels, lower protein levels, and an increase in C-terminal phosphorylation. Conversely, during regulatory T cell induction, PTEN function is maintained through the stabilization of PTEN mRNA transcription and sustained protein levels. We demonstrate that differential Akt/mammalian target of rapamycin signaling regulates PTEN transcription via the FoxO1 transcription factor. A mathematical model that includes multiple modes of PTEN regulation recapitulates our experimental findings and demonstrates how several feedback loops determine differentiation outcomes. Collectively, this work provides novel mechanistic insights into how differential regulation of PTEN controls alternate CD4(+) T cell fate outcomes. Copyright © 2015 by The American Association of Immunologists, Inc.

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

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.

A low noise and ultra-narrow bandwidth frequency-locked loop based on the beat method.

PubMed

Gao, Wei; Sui, Jianping; Chen, Zhiyong; Yu, Fang; Sheng, Rongwu

2011-06-01

A novel frequency-locked loop (FLL) based on the beat method is proposed in this paper. Compared with other frequency feedback loops, this FLL is a digital loop with simple structure and very low noise. As shown in the experimental results, this FLL can be used to reduce close-in phase noise on atomic frequency standards, through which a composite frequency standard with ultra-low phase noise and low cost can be easily realized.

Efficient dynamic coherence transfer relying on offset locking using optical phase-locked loop

NASA Astrophysics Data System (ADS)

Xie, Weilin; Dong, Yi; Bretenaker, Fabien; Shi, Hongxiao; Zhou, Qian; Xia, Zongyang; Qin, Jie; Zhang, Lin; Lin, Xi; Hu, Weisheng

2018-01-01

We design and experimentally demonstrate a highly efficient coherence transfer based on composite optical phaselocked loop comprising multiple feedback servo loops. The heterodyne offset-locking is achieved by conducting an acousto-optic frequency shifter in combination with the current tuning and the temperature controlling of the semiconductor laser. The adaptation of the composite optical phase-locked loop enables the tight coherence transfer from a frequency comb to a semiconductor laser in a fully dynamic manner.

A tutorial on the LQG/LTR method. [Linear Quadratic Gaussian/Loop Transfer Recovery

NASA Technical Reports Server (NTRS)

Athans, M.

1986-01-01

In this paper the so-called Linear-Quadratic-Gaussian method with Loop-Transfer-Recovery is surveyed. The objective is to provide a pragmatic exposition, with special emphasis on the step-by-step characteristics for designing multivariable feedback control systems.

Diagonal dominance for the multivariable Nyquist array using function minimization

NASA Technical Reports Server (NTRS)

Leininger, G. G.

1977-01-01

A new technique for the design of multivariable control systems using the multivariable Nyquist array method was developed. A conjugate direction function minimization algorithm is utilized to achieve a diagonal dominant condition over the extended frequency range of the control system. The minimization is performed on the ratio of the moduli of the off-diagonal terms to the moduli of the diagonal terms of either the inverse or direct open loop transfer function matrix. Several new feedback design concepts were also developed, including: (1) dominance control parameters for each control loop; (2) compensator normalization to evaluate open loop conditions for alternative design configurations; and (3) an interaction index to determine the degree and type of system interaction when all feedback loops are closed simultaneously. This new design capability was implemented on an IBM 360/75 in a batch mode but can be easily adapted to an interactive computer facility. The method was applied to the Pratt and Whitney F100 turbofan engine.

A closed-loop photon beam control study for the Advanced Light Source

DOE Office of Scientific and Technical Information (OSTI.GOV)

Portmann, G.; Bengtsson, J.

1993-05-01

The third generation Advanced Light Source (ALS) will produce extremely bright photon beams using undulators and wigglers. In order to position the photon beams accurate to the micron level, a closed-loop feedback system is being developed. Using photon position monitors and dipole corrector magnets, a closed-loop system can automatically compensate for modeling uncertainties and exogenous disturbances. The following paper will present a dynamics model for the perturbations of the closed orbit of the electron beam in the ALS storage ring including the vacuum chamber magnetic field penetration effects. Using this reference model, two closed-loop feedback algorithms will be compared --more » a classical PI controller and a two degree-of-freedom approach. The two degree-of-freedom method provides superior disturbance rejection while maintaining the desired performance goals. Both methods will address the need to gain schedule the controller due to the time varying dynamics introduced by changing field strengths when scanning the insertion devices.« less

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

PubMed

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

2016-05-01

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

A dual-loop model of the human controller

NASA Technical Reports Server (NTRS)

Hess, R. A.

1977-01-01

A representative model of the human controller in single-axis compensatory tracking tasks that exhibits an internal feedback loop which is not evident in single-loop models now in common use is presented. This hypothetical inner-loop involves a neuromuscular command signal derived from the time rate of change of controlled element output which is due to control activity. It is not contended that the single-loop human controller models now in use are incorrect, but that they contain an implicit but important internal loop closure, which, if explicitly considered, can account for a good deal of the adaptive nature of the human controller in a systematic manner.

Emotional metacontrol of attention: Top-down modulation of sensorimotor processes in a robotic visual search task.

PubMed

Belkaid, Marwen; Cuperlier, Nicolas; Gaussier, Philippe

2017-01-01

Emotions play a significant role in internal regulatory processes. In this paper, we advocate four key ideas. First, novelty detection can be grounded in the sensorimotor experience and allow higher order appraisal. Second, cognitive processes, such as those involved in self-assessment, influence emotional states by eliciting affects like boredom and frustration. Third, emotional processes such as those triggered by self-assessment influence attentional processes. Last, close emotion-cognition interactions implement an efficient feedback loop for the purpose of top-down behavior regulation. The latter is what we call 'Emotional Metacontrol'. We introduce a model based on artificial neural networks. This architecture is used to control a robotic system in a visual search task. The emotional metacontrol intervenes to bias the robot visual attention during active object recognition. Through a behavioral and statistical analysis, we show that this mechanism increases the robot performance and fosters the exploratory behavior to avoid deadlocks.

Cytoplasmic destruction of p53 by the endoplasmic reticulum-resident ubiquitin ligase ‘Synoviolin'

PubMed Central

Yamasaki, Satoshi; Yagishita, Naoko; Sasaki, Takeshi; Nakazawa, Minako; Kato, Yukihiro; Yamadera, Tadayuki; Bae, Eunkyung; Toriyama, Sayumi; Ikeda, Rie; Zhang, Lei; Fujitani, Kazuko; Yoo, Eunkyung; Tsuchimochi, Kaneyuki; Ohta, Tomohiko; Araya, Natsumi; Fujita, Hidetoshi; Aratani, Satoko; Eguchi, Katsumi; Komiya, Setsuro; Maruyama, Ikuro; Higashi, Nobuyo; Sato, Mitsuru; Senoo, Haruki; Ochi, Takahiro; Yokoyama, Shigeyuki; Amano, Tetsuya; Kim, Jaeseob; Gay, Steffen; Fukamizu, Akiyoshi; Nishioka, Kusuki; Tanaka, Keiji; Nakajima, Toshihiro

2007-01-01

Synoviolin, also called HRD1, is an E3 ubiquitin ligase and is implicated in endoplasmic reticulum -associated degradation. In mammals, Synoviolin plays crucial roles in various physiological and pathological processes, including embryogenesis and the pathogenesis of arthropathy. However, little is known about the molecular mechanisms of Synoviolin in these actions. To clarify these issues, we analyzed the profile of protein expression in synoviolin-null cells. Here, we report that Synoviolin targets tumor suppressor gene p53 for ubiquitination. Synoviolin sequestrated and metabolized p53 in the cytoplasm and negatively regulated its cellular level and biological functions, including transcription, cell cycle regulation and apoptosis. Furthermore, these p53 regulatory functions of Synoviolin were irrelevant to other E3 ubiquitin ligases for p53, such as MDM2, Pirh2 and Cop1, which form autoregulatory feedback loops. Our results provide novel insights into p53 signaling mediated by Synoviolin. PMID:17170702

Cytoplasmic destruction of p53 by the endoplasmic reticulum-resident ubiquitin ligase 'Synoviolin'.

PubMed

Yamasaki, Satoshi; Yagishita, Naoko; Sasaki, Takeshi; Nakazawa, Minako; Kato, Yukihiro; Yamadera, Tadayuki; Bae, Eunkyung; Toriyama, Sayumi; Ikeda, Rie; Zhang, Lei; Fujitani, Kazuko; Yoo, Eunkyung; Tsuchimochi, Kaneyuki; Ohta, Tomohiko; Araya, Natsumi; Fujita, Hidetoshi; Aratani, Satoko; Eguchi, Katsumi; Komiya, Setsuro; Maruyama, Ikuro; Higashi, Nobuyo; Sato, Mitsuru; Senoo, Haruki; Ochi, Takahiro; Yokoyama, Shigeyuki; Amano, Tetsuya; Kim, Jaeseob; Gay, Steffen; Fukamizu, Akiyoshi; Nishioka, Kusuki; Tanaka, Keiji; Nakajima, Toshihiro

2007-01-10

Synoviolin, also called HRD1, is an E3 ubiquitin ligase and is implicated in endoplasmic reticulum -associated degradation. In mammals, Synoviolin plays crucial roles in various physiological and pathological processes, including embryogenesis and the pathogenesis of arthropathy. However, little is known about the molecular mechanisms of Synoviolin in these actions. To clarify these issues, we analyzed the profile of protein expression in synoviolin-null cells. Here, we report that Synoviolin targets tumor suppressor gene p53 for ubiquitination. Synoviolin sequestrated and metabolized p53 in the cytoplasm and negatively regulated its cellular level and biological functions, including transcription, cell cycle regulation and apoptosis. Furthermore, these p53 regulatory functions of Synoviolin were irrelevant to other E3 ubiquitin ligases for p53, such as MDM2, Pirh2 and Cop1, which form autoregulatory feedback loops. Our results provide novel insights into p53 signaling mediated by Synoviolin.

Chronobiology and circadian rhythms establish a connection to diagnosis.

PubMed

Nydegger, Urs E; Escobar, Pedro Medina; Risch, Lorenz; Risch, Martin; Stanga, Zeno

2014-12-01

Circadian rhythms are synchronized by the light/dark (L/D) cycle over the 24-h day. A suprachiasmatic nucleus in the hypothalamus governs time keeping based on melanopsin messages from the retina in the eyes and transduces regulatory signals to tissues through an array of hormonal, metabolic and neural outputs. Currently, vague impressions on circadian regulation in health and disease are replaced by scientific facts: in addition to L/D cyling, oscillation is maintained by genetic (Clock, Bmal1, Csnk1, CHRONO, Cry, Per) programs, autonomous feedback loops, including melatonin activities, aerobic glycolysis intensity and lipid signalling, among others. Such a multifaceted influential system on circadian rhythm is bound to be fragile and genomic clock acitvities can become disrupted by epigenetic modifications or such environmental factors as mistimed sleep and feeding schedules albeit leaving the centrally driven melatonin-dependent pacemakter more or less unaffected.

Flexible body stability analysis of Space Shuttle ascent flight control system by using lambda matrix solution techniques

NASA Technical Reports Server (NTRS)

Bown, R. L.; Christofferson, A.; Lardas, M.; Flanders, H.

1980-01-01

A lambda matrix solution technique is being developed to perform an open loop frequency analysis of a high order dynamic system. The procedure evaluates the right and left latent vectors corresponding to the respective latent roots. The latent vectors are used to evaluate the partial fraction expansion formulation required to compute the flexible body open loop feedback gains for the Space Shuttle Digital Ascent Flight Control System. The algorithm is in the final stages of development and will be used to insure that the feedback gains meet the design specification.

The Search for Perpetual Motion: Fatigue, Friction, and Drag in Quality Improvement.

PubMed

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.

Wide-beam sensors for controlling dual-delay systems

NASA Astrophysics Data System (ADS)

Edwards, J. B.; Twemlow, J. K.

1982-09-01

A class of dual delay feedback systems of open loop transfer function G(s) = k exp(-Xs)/l - exp(-Ws) is shown to be unstable if ratio X/W is noninteger. By means of z-transform techniques it is shown that, by using a feedback transducer that senses over a substantial distance either side of its central axis, closed-loop stability may be restored. Such transducers, termed widebeam sensors, include transmission, backscatter and natural radiation types as well as electromechanical conveyor belt weighers. Designing transducers for very narrow beams may not be desirable from the overall system viewpoint.

Air Force research in human sensory feedback for telepresence

NASA Technical Reports Server (NTRS)

Julian, Ronald G.

1993-01-01

Telepresence operations require high quality information transfer between the human master and the remotely located slave. Present Air Force research focuses on the human aspects of the information needed to complete the control/feedback loop. Work in three key areas of human sensory feedback for manipulation of objects are described. Specific projects in each key area are outlined, including research tools (hardware), planned research, and test results. Nonmanipulative feedback technologies are mentioned to complete the advanced teleoperation discussions.

Intestinal alkaline phosphatase regulates protective surface microclimate pH in rat duodenum.

PubMed

Mizumori, Misa; Ham, Maggie; Guth, Paul H; Engel, Eli; Kaunitz, Jonathan D; Akiba, Yasutada

2009-07-15

Regulation of localized extracellular pH (pH(o)) maintains normal organ function. An alkaline microclimate overlying the duodenal enterocyte brush border protects the mucosa from luminal acid. We hypothesized that intestinal alkaline phosphatase (IAP) regulates pH(o) due to pH-sensitive ATP hydrolysis as part of an ecto-purinergic pH regulatory system, comprised of cell-surface P2Y receptors and ATP-stimulated duodenal bicarbonate secretion (DBS). To test this hypothesis, we measured DBS in a perfused rat duodenal loop, examining the effect of the competitive alkaline phosphatase inhibitor glycerol phosphate (GP), the ecto-nucleoside triphosphate diphosphohydrolase inhibitor ARL67156, and exogenous nucleotides or P2 receptor agonists on DBS. Furthermore, we measured perfusate ATP concentration with a luciferin-luciferase bioassay. IAP inhibition increased DBS and luminal ATP output. Increased luminal ATP output was partially CFTR dependent, but was not due to cellular injury. Immunofluorescence localized the P2Y(1) receptor to the brush border membrane of duodenal villi. The P2Y(1) agonist 2-methylthio-ADP increased DBS, whereas the P2Y(1) antagonist MRS2179 reduced ATP- or GP-induced DBS. Acid perfusion augmented DBS and ATP release, further enhanced by the IAP inhibitor l-cysteine, and reduced by the exogenous ATPase apyrase. Furthermore, MRS2179 or the highly selective P2Y(1) antagonist MRS2500 co-perfused with acid induced epithelial injury, suggesting that IAP/ATP/P2Y signalling protects the mucosa from acid injury. Increased DBS augments IAP activity presumably by raising pH(o), increasing the rate of ATP degradation, decreasing ATP-mediated DBS, forming a negative feedback loop. The duodenal epithelial brush border IAP-P2Y-HCO(3-) surface microclimate pH regulatory system effectively protects the mucosa from acid injury.

An optimal open/closed-loop control method with application to a pre-stressed thin duralumin plate

NASA Astrophysics Data System (ADS)

Nadimpalli, Sruthi Raju

The excessive vibrations of a pre-stressed duralumin plate, suppressed by a combination of open-loop and closed-loop controls, also known as open/closed-loop control, is studied in this thesis. The two primary steps involved in this process are: Step (I) with an assumption that the closed-loop control law is proportional, obtain the optimal open-loop control by direct minimization of the performance measure consisting of energy at terminal time and a penalty on open-loop control force via calculus of variations. If the performance measure also involves a penalty on closed-loop control effort then a Fourier based method is utilized. Step (II) the energy at terminal time is minimized numerically to obtain optimal values of feedback gains. The optimal closed-loop control gains obtained are used to describe the displacement and the velocity of open-loop, closed-loop and open/closed-loop controlled duralumin plate.

Linear motor drive system for continuous-path closed-loop position control of an object

DOEpatents

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.

Velocity feedback control with a flywheel proof mass actuator

NASA Astrophysics Data System (ADS)

Kras, Aleksander; Gardonio, Paolo

2017-08-01

This paper presents four new proof mass actuators to be used in velocity feedback control systems for the control of vibrations of machines and flexible structures. A classical proof mass actuator is formed by a coil-magnet linear motor, with either the magnet or the armature-coil proof mass suspended on soft springs. This arrangement produces a net force effect at frequencies above the fundamental resonance frequency of the springs-proof mass system. Thus, it can be used to implement point velocity feedback loops, although the dynamic response and static deflection of the springs-proof mass system poses some stability and control performance limitations. The four proof mass actuators presented in this study include a flywheel element, which is used to augment the inertia effect of the suspended proof mass. The paper shows that the flywheel element modifies both the dynamic response and static deflection of the springs-proof mass system in such a way as the stability and control performance of velocity feedback loops using these actuators are significantly improved.

A multiloop generalization of the circle criterion for stability margin analysis

NASA Technical Reports Server (NTRS)

Safonov, M. G.; Athans, M.

1979-01-01

In order to provide a theoretical tool suited for characterizing the stability margins of multiloop feedback systems, multiloop input-output stability results generalizing the circle stability criterion are considered. Generalized conic sectors with 'centers' and 'radii' determined by linear dynamical operators are employed to specify the stability margins as a frequency dependent convex set of modeling errors (including nonlinearities, gain variations and phase variations) which the system must be able to tolerate in each feedback loop without instability. The resulting stability criterion gives sufficient conditions for closed loop stability in the presence of frequency dependent modeling errors, even when the modeling errors occur simultaneously in all loops. The stability conditions yield an easily interpreted scalar measure of the amount by which a multiloop system exceeds, or falls short of, its stability margin specifications.

Eigenspace techniques for active flutter suppression

NASA Technical Reports Server (NTRS)

Garrard, William L.; Liebst, Bradley S.; Farm, Jerome A.

1987-01-01

The use of eigenspace techniques for the design of an active flutter suppression system for a hypothetical research drone is discussed. One leading edge and two trailing edge aerodynamic control surfaces and four sensors (accelerometers) are available for each wing. Full state control laws are designed by selecting feedback gains which place closed loop eigenvalues and shape closed loop eigenvectors so as to stabilize wing flutter and reduce gust loads at the wing root while yielding accepatable robustness and satisfying constrains on rms control surface activity. These controllers are realized by state estimators designed using an eigenvalue placement/eigenvector shaping technique which results in recovery of the full state loop transfer characteristics. The resulting feedback compensators are shown to perform almost as well as the full state designs. They also exhibit acceptable performance in situations in which the failure of an actuator is simulated.

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.

Cardinal features of involuntary force variability can arise from the closed-loop control of viscoelastic afferented muscles

PubMed Central

Laine, Christopher M.; Valero-Cuevas, Francisco J.

2018-01-01

Involuntary force variability below 15 Hz arises from, and is influenced by, many factors including descending neural drive, proprioceptive feedback, and mechanical properties of muscles and tendons. However, their potential interactions that give rise to the well-structured spectrum of involuntary force variability are not well understood due to a lack of experimental techniques. Here, we investigated the generation, modulation, and interactions among different sources of force variability using a physiologically-grounded closed-loop simulation of an afferented muscle model. The closed-loop simulation included a musculotendon model, muscle spindle, Golgi tendon organ (GTO), and a tracking controller which enabled target-guided force tracking. We demonstrate that closed-loop control of an afferented musculotendon suffices to replicate and explain surprisingly many cardinal features of involuntary force variability. Specifically, we present 1) a potential origin of low-frequency force variability associated with co-modulation of motor unit firing rates (i.e.,‘common drive’), 2) an in-depth characterization of how proprioceptive feedback pathways suffice to generate 5-12 Hz physiological tremor, and 3) evidence that modulation of those feedback pathways (i.e., presynaptic inhibition of Ia and Ib afferents, and spindle sensitivity via fusimotor drive) influence the full spectrum of force variability. These results highlight the previously underestimated importance of closed-loop neuromechanical interactions in explaining involuntary force variability during voluntary ‘isometric’ force control. Furthermore, these results provide the basis for a unifying theory that relates spinal circuitry to various manifestations of altered involuntary force variability in fatigue, aging and neurological disease. PMID:29309405

Cardinal features of involuntary force variability can arise from the closed-loop control of viscoelastic afferented muscles.

PubMed

Nagamori, Akira; Laine, Christopher M; Valero-Cuevas, Francisco J

2018-01-01

Involuntary force variability below 15 Hz arises from, and is influenced by, many factors including descending neural drive, proprioceptive feedback, and mechanical properties of muscles and tendons. However, their potential interactions that give rise to the well-structured spectrum of involuntary force variability are not well understood due to a lack of experimental techniques. Here, we investigated the generation, modulation, and interactions among different sources of force variability using a physiologically-grounded closed-loop simulation of an afferented muscle model. The closed-loop simulation included a musculotendon model, muscle spindle, Golgi tendon organ (GTO), and a tracking controller which enabled target-guided force tracking. We demonstrate that closed-loop control of an afferented musculotendon suffices to replicate and explain surprisingly many cardinal features of involuntary force variability. Specifically, we present 1) a potential origin of low-frequency force variability associated with co-modulation of motor unit firing rates (i.e.,'common drive'), 2) an in-depth characterization of how proprioceptive feedback pathways suffice to generate 5-12 Hz physiological tremor, and 3) evidence that modulation of those feedback pathways (i.e., presynaptic inhibition of Ia and Ib afferents, and spindle sensitivity via fusimotor drive) influence the full spectrum of force variability. These results highlight the previously underestimated importance of closed-loop neuromechanical interactions in explaining involuntary force variability during voluntary 'isometric' force control. Furthermore, these results provide the basis for a unifying theory that relates spinal circuitry to various manifestations of altered involuntary force variability in fatigue, aging and neurological disease.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wichman, K.; Tsao, J.; Mayfield, M.

The regulatory application of leak before break (LBB) for operating and advanced reactors in the U.S. is described. The U.S. Nuclear Regulatory Commission (NRC) has approved the application of LBB for six piping systems in operating reactors: reactor coolant system primary loop piping, pressurizer surge, safety injection accumulator, residual heat removal, safety injection, and reactor coolant loop bypass. The LBB concept has also been applied in the design of advanced light water reactors. LBB applications, and regulatory considerations, for pressurized water reactors and advanced light water reactors are summarized in this paper. Technology development for LBB performed by the NRCmore » and the International Piping Integrity Research Group is also briefly summarized.« less

Application of system dynamics for developing financially self-sustaining management policies for water and wastewater systems.

PubMed

Rehan, R; Knight, M A; Haas, C T; Unger, A J A

2011-10-15

Recently enacted regulations in Canada and elsewhere require water utilities to be financially self-sustaining over the long-term. This implies full cost recovery for providing water and wastewater services to users. This study proposes a new approach to help water utilities plan to meet the requirements of the new regulations. A causal loop diagram is developed for a financially self-sustaining water utility which frames water and wastewater network management as a complex system with multiple interconnections and feedback loops. The novel System Dynamics approach is used to develop a demonstration model for water and wastewater network management. This is the first known application of System Dynamics to water and wastewater network management. The network simulated is that of a typical Canadian water utility that has under invested in maintenance. Model results show that with no proactive rehabilitation strategy the utility will need to substantially increase its user fees to achieve financial sustainability. This increase is further exacerbated when price elasticity of water demand is considered. When the utility pursues proactive rehabilitation, financial sustainability is achieved with lower user fees. Having demonstrated the significance of feedback loops for financial management of water and wastewater networks, the paper makes the case for a more complete utility model that considers the complexity of the system by incorporating all feedback loops. Crown Copyright © 2011. Published by Elsevier Ltd. All rights reserved.

Functional anatomy of nonvisual feedback loops during reaching: a positron emission tomography study.

PubMed

Desmurget, M; Gréa, H; Grethe, J S; Prablanc, C; Alexander, G E; Grafton, S T

2001-04-15

Reaching movements performed without vision of the moving limb are continuously monitored, during their execution, by feedback loops (designated nonvisual). In this study, we investigated the functional anatomy of these nonvisual loops using positron emission tomography (PET). Seven subjects had to "look at" (eye) or "look and point to" (eye-arm) visual targets whose location either remained stationary or changed undetectably during the ocular saccade (when vision is suppressed). Slightly changing the target location during gaze shift causes an increase in the amount of correction to be generated. Functional anatomy of nonvisual feedback loops was identified by comparing the reaching condition involving large corrections (jump) with the reaching condition involving small corrections (stationary), after subtracting the activations associated with saccadic movements and hand movement planning [(eye-arm-jumping minus eye-jumping) minus (eye-arm-stationary minus eye-stationary)]. Behavioral data confirmed that the subjects were both accurate at reaching to the stationary targets and able to update their movement smoothly and early in response to the target jump. PET difference images showed that these corrections were mediated by a restricted network involving the left posterior parietal cortex, the right anterior intermediate cerebellum, and the left primary motor cortex. These results are consistent with our knowledge of the functional properties of these areas and more generally with models emphasizing parietal-cerebellar circuits for processing a dynamic motor error signal.

78 FR 58535 - Hydropower Regulatory Efficiency Act of 2013; Supplemental Notice of Workshop

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-24

... license for hydropower development at non-powered dams and closed-loop pumped storage projects in... for licensing hydropower development at non-powered dams and closed-loop pumped storage projects... closed- loop pumped storage) affect the steps included in a two-year process? 3.9 Should there be a...

A positive feedback loop between progesterone and microsomal prostaglandin E synthase-1-mediated PGE2 promotes production of both in mouse granulosa cells.

PubMed

Tamura, Kazuhiro; Naraba, Hiroaki; Hara, Takahiko; Nakamura, Kota; Yoshie, Mikihiro; Kogo, Hiroshi; Tachikawa, Eiichi

2016-03-01

Microsomal prostaglandin E synthase-1 (mPGES-1) is primarily expressed in granulosa cells (GCs) in the preovulatory follicle. Both prostaglandin E2 (PGE2) and progesterone (P4) are implicated in various reproductive functions. Here, we demonstrate that mPges-1 may be a direct downstream target gene of the P4 receptor and P4-stimulated PGE2 secretion can stimulate P4 production in a newly generated mouse GC line (GtsT). Treatment of GtsT cells with a P4 receptor agonist, norgestrel, markedly increased mPGES-1 expression detected by RT-PCR analysis. PGE2 secretion measured by an enzyme-linked immunosorbent assay was enhanced by P4 treatment. Luciferase assays revealed that the proximal promoter region of the mPges-1 gene was responsible for the effects of P4 treatment. Conversely, PGE2 treatment stimulated P4 secretion, which coordinated with mRNA expression of steroidogenic acute regulatory protein. Taken together, P4 may regulate mPGES-1 expression to increase PGE2 secretion and in turn P4 production. An autocrine loop between P4 and PGE2 might function to maintain the increased levels of both in GCs. Copyright © 2016 Elsevier Inc. All rights reserved.

Differential ability of formononetin to stimulate proliferation of endothelial cells and breast cancer cells via a feedback loop involving MicroRNA-375, RASD1, and ERα.

PubMed

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

2018-05-02

For postmenopausal cardiovascular disease, long-term estrogen therapy may increase the risk of breast cancer. To reduce this risk, estrogen may be replaced with the phytoestrogen formononetin, but how formononetin acts on vascular endothelial cells (ECs) and breast cancer cells is unclear. Here, we show that low concentrations of formononetin induced proliferation and inhibited apoptosis more strongly in cultured human umbilical vein endothelial cells (HUVECs) than in breast cancer cells expressing estrogen receptor α (ERα) (MCF-7, BT474) or not (MDA-MB-231), and that this differential stimulation was associated with miR-375 up-regulation in HUVECs. For the first time, we demonstrate the presence of a feedback loop involving miR-375, ras dexamethasone-induced 1 (RASD1), and ERα in normal HUVECs, and we show that formononetin stimulated this feedback loop in HUVECs but not in MCF-7 or BT474 cells. In all three cell lines, formononetin increased Akt phosphorylation and Bcl-2 expression. Inhibiting miR-375 blocked these changes and increased proliferation in HUVECs, but not in MCF-7 or BT474 cells. In ovariectomized rats, formononetin increased uterine weight and caused similar changes in levels of miR-375, RASD1, ERα, and Bcl-2 in aortic ECs as in cultured HUVECs. In mice bearing MCF-7 xenografts, tumor growth was stimulated by 17β-estradiol but not by formononetin. These results suggest selective action of formononetin in ECs (proliferation stimulation and apoptosis inhibition) relative to breast cancer cells, possibly via a feedback loop involving miR-375, RASD1, and ERα. This differential effect may explain why formononetin may not increase the risk of postmenopausal breast cancer. © 2018 Wiley Periodicals, Inc.

Use of an open-loop system to increase physical activity

USDA-ARS?s Scientific Manuscript database

This study evaluated the effectiveness of an open-loop system that reinforces physical activity with TV watching to increase children’s physical activity. Non-overweight, sedentary boys and girls (8-12 y) were randomized to a group that received feedback of activity counts + reinforcement for physic...

Towards random matrix model of breaking the time-reversal invariance of elastic waves in chaotic cavities by feedback

NASA Astrophysics Data System (ADS)

Antoniuk, Oleg; Sprik, Rudolf

2010-03-01

We developed a random matrix model to describe the statistics of resonances in an acoustic cavity with broken time-reversal invariance. Time-reversal invariance braking is achieved by connecting an amplified feedback loop between two transducers on the surface of the cavity. The model is based on approach [1] that describes time- reversal properties of the cavity without a feedback loop. Statistics of eigenvalues (nearest neighbor resonance spacing distributions and spectral rigidity) has been calculated and compared to the statistics obtained from our experimental data. Experiments have been performed on aluminum block of chaotic shape confining ultrasound waves. [1] Carsten Draeger and Mathias Fink, One-channel time- reversal in chaotic cavities: Theoretical limits, Journal of Acoustical Society of America, vol. 105, Nr. 2, pp. 611-617 (1999)

A methodology for the synthesis of robust feedback systems. Ph.D. Thesis

NASA Technical Reports Server (NTRS)

Milich, David Albert

1988-01-01

A new methodology is developed for the synthesis of linear, time-variant (LTI) controllers for multivariable LTI systems. The resulting closed-loop system is nominally stable and exhibits a known level of performance. In addition, robustness of the feedback system is guaranteed, i.e., stability and performance are retained in the presence of multiple unstructured uncertainty blocks located at various points in the feedback loop. The design technique is referred to as the Causality Recovery Methodology (CRM). The CRM relies on the Youla parameterization of all stabilizing compensators to ensure nominal stability of the feedback system. A frequency-domain inequality in terms of the structured singular value mu defines the robustness specification. The optimal compensator, with respect to the mu condition, is shown to be noncausal in general. The aim of the CRM is to find a stable, causal transfer function matrix that approximates the robustness characteristics of the optimal solution. The CRM, via a series of infinite-dimensional convex programs, produces a closed-loop system whose performance robustness is at least as good as that of any initial design. The algorithm is approximated by a finite dimensional process for the purposes of implementation. Two numerical examples confirm the potential viability of the CRM concept; however, the robustness improvement comes at the expense of increased computational burden and compensator complexity.

Multiplexing Readout of TES Microcalorimeters Based on Analog Baseband Feedback

DOE Office of Scientific and Technical Information (OSTI.GOV)

Takei, Y.; Yamasaki, N.Y; Mitsuda, K.

2009-12-16

A TES microcalorimeter array is a promising spectrometer with excellent energy resolution and a moderate imaging capability. To realize a large format array in space, multiplexing the TES signals at the low tempersture stage is mandatory. We are developing frequency division multiplexing (FDM) based on baseband feedback technique. In FDM, each TES is AC-biased with a different carrier frequency. Signals from several pixels are summed and then read out by one SQUID. The maximum number of multiplexed pixels are limited by the frequency band in which the SQUID can be operated in a flux-locked loop, which is {approx}1 MHz withmore » standard flux-locked loop circuit. In the baseband feedback, the signal ({approx}10 kHz band) from the TES is once demodulated. Then a reconstructed copy of the modulated signal with an appropriate phase is fed back to the SQUID input coil to maintain an approximately constant magnetic flux. This can be implemented even for large cable delays and automatically suppresses the carrier. We developed a prototype electronics for the baseband feedback based on an analog phase sensitive detector (PSD) and a multiplier. Combined with Seiko 80-SSA SQUID amp, open-loop gain of 8 has been obtained for 10 kHz baseband signal at 5 MHz carrier frequency, with a moderate noise contribution of 27pA/{radical}(Hz) at input.« less

System properties, feedback control and effector coordination of human temperature regulation.

PubMed

Werner, Jürgen

2010-05-01

The aim of human temperature regulation is to protect body processes by establishing a relative constancy of deep body temperature (regulated variable), in spite of external and internal influences on it. This is basically achieved by a distributed multi-sensor, multi-processor, multi-effector proportional feedback control system. The paper explains why proportional control implies inherent deviations of the regulated variable from the value in the thermoneutral zone. The concept of feedback of the thermal state of the body, conveniently represented by a high-weighted core temperature (T (c)) and low-weighted peripheral temperatures (T (s)) is equivalent to the control concept of "auxiliary feedback control", using a main (regulated) variable (T (c)), supported by an auxiliary variable (T (s)). This concept implies neither regulation of T (s) nor feedforward control. Steady-states result in the closed control-loop, when the open-loop properties of the (heat transfer) process are compatible with those of the thermoregulatory processors. They are called operating points or balance points and are achieved due to the inherent property of dynamical stability of the thermoregulatory feedback loop. No set-point and no comparison of signals (e.g. actual-set value) are necessary. Metabolic heat production and sweat production, though receiving the same information about the thermal state of the body, are independent effectors with different thresholds and gains. Coordination between one of these effectors and the vasomotor effector is achieved by the fact that changes in the (heat transfer) process evoked by vasomotor control are taken into account by the metabolic/sweat processor.

Fundamental Physics and Practical Applications of Electromagnetic Local Flow Control in High Speed Flows (Rutgers)

DTIC Science & Technology

2010-02-16

field. Techniques utilizing this design use an open- loop control and no flow monitoring sensors are required. Conversely, reactive (or closed - loop ...and closed (dashed line) configuration. 38 closed configuration described above, the ambiguity in the critical limits of the transition...flow; a new vortex is then shed from the cavity leading edge, closing the feedback loop .[31] Open cavities with an L/D approximately greater than

Are Success and Failure Experiences Equally Motivational? An Investigation of Regulatory Focus and Feedback

ERIC Educational Resources Information Center

Shu, Tse-Mei; Lam, Shui-fong

2011-01-01

The present study extended regulatory focus theory (Idson & Higgins, 2000) to an educational setting and attempted to identify individuals with high motivation after both success and failure feedback. College students in Hong Kong (N = 180) participated in an experiment with a 2 promotion focus (high vs. low) x 2 prevention focus (high vs.…

Optimization of Closed Loop Eigenvalues: Maneuvering, Vibration Control, and Structure/Control Design Iteration for Flexible Spacecraft.

DTIC Science & Technology

1986-05-31

Nonlinear Feedback Control 8-16 for Spacecraft Attitude Maneuvers" 2. " Spacecraft Attitude Control Using 17-35... nonlinear state feedback control laws are developed for space- craft attitude control using the Euler parameters and conjugate angular momenta. Time... Nonlinear Feedback Control for Spacecraft Attitude Maneuvers," to appear in AIAA J. of Guidance, Control, and Dynamics, (AIAA Paper No. 83-2230-CP,

Closed-form recursive formula for an optimal tracker with terminal constraints

NASA Technical Reports Server (NTRS)

Juang, J. N.; Turner, J. D.; Chun, H. M.

1986-01-01

Feedback control laws are derived for a class of optimal finite time tracking problems with terminal constraints. Analytical solutions are obtained for the feedback gain and the closed-loop response trajectory. Such formulations are expressed in recursive forms so that a real-time computer implementation becomes feasible. An example involving the feedback slewing of a flexible spacecraft is given to illustrate the validity and usefulness of the formulations.

Brain-Computer Interfaces With Multi-Sensory Feedback for Stroke Rehabilitation: A Case Study.

PubMed

Irimia, Danut C; Cho, Woosang; Ortner, Rupert; Allison, Brendan Z; Ignat, Bogdan E; Edlinger, Guenter; Guger, Christoph

2017-11-01

Conventional therapies do not provide paralyzed patients with closed-loop sensorimotor integration for motor rehabilitation. This work presents the recoveriX system, a hardware and software platform that combines a motor imagery (MI)-based brain-computer interface (BCI), functional electrical stimulation (FES), and visual feedback technologies for a complete sensorimotor closed-loop therapy system for poststroke rehabilitation. The proposed system was tested on two chronic stroke patients in a clinical environment. The patients were instructed to imagine the movement of either the left or right hand in random order. During these two MI tasks, two types of feedback were provided: a bar extending to the left or right side of a monitor as visual feedback and passive hand opening stimulated from FES as proprioceptive feedback. Both types of feedback relied on the BCI classification result achieved using common spatial patterns and a linear discriminant analysis classifier. After 10 sessions of recoveriX training, one patient partially regained control of wrist extension in her paretic wrist and the other patient increased the range of middle finger movement by 1 cm. A controlled group study is planned with a new version of the recoveriX system, which will have several improvements. © 2017 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Identification of pilot-vehicle dynamics from simulation and flight test

NASA Technical Reports Server (NTRS)

Hess, Ronald A.

1990-01-01

The paper discusses an identification problem in which a basic feedback control structure, or pilot control strategy, is hypothesized. Identification algorithms are employed to determine the particular form of pilot equalization in each feedback loop. It was found that both frequency- and time-domain identification techniques provide useful information.

Using Control Theory to Teach Control Theory (or Any Other Course).

ERIC Educational Resources Information Center

Mansfield, George

1979-01-01

Describes an undergraduate automatic controls course in which the teaching-learning process is regarded as a closed loop feedback system. The three basic components of the system: the controller, the plant, and the learning sensors are identified as the teacher, the student, and student feedback respectively. (SMB)

78 FR 62322 - Hydropower Regulatory Efficiency Act of 2013; Notice of Rescheduled Two-Year Licensing Process...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-16

... at non-powered dams and closed-loop pumped storage projects in compliance with section 6 of the... process for licensing hydropower development at non-powered dams and closed-loop pumped storage projects...-powered dam versus closed- loop pumped storage) affect the steps included in a two-year process? 3.9...

Smith predictor-based multiple periodic disturbance compensation for long dead-time processes

NASA Astrophysics Data System (ADS)

Tan, Fang; Li, Han-Xiong; Shen, Ping

2018-05-01

Many disturbance rejection methods have been proposed for processes with dead-time, while these existing methods may not work well under multiple periodic disturbances. In this paper, a multiple periodic disturbance rejection is proposed under the Smith predictor configuration for processes with long dead-time. One feedback loop is added to compensate periodic disturbance while retaining the advantage of the Smith predictor. With information of the disturbance spectrum, the added feedback loop can remove multiple periodic disturbances effectively. The robust stability can be easily maintained through the rigorous analysis. Finally, simulation examples demonstrate the effectiveness and robustness of the proposed method for processes with long dead-time.

Nonlinear cellular dynamics of keratinocytes in normal and psoriatic epidermis under action of UV radiation

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.

Motorized CPM/CAM physiotherapy device with sliding-mode Fuzzy Neural Network control loop.

PubMed

Ho, Hung-Jung; Chen, Tien-Chi

2009-11-01

Continuous passive motion (CPM) and controllable active motion (CAM) physiotherapy devices promote rehabilitation of damaged joints. This paper presents a computerized CPM/CAM system that obviates the need for mechanical resistance devices such as springs. The system is controlled by a computer which performs sliding-mode Fuzzy Neural Network (FNN) calculations online. CAM-type resistance force is generated by the active performance of an electric motor which is controlled so as to oppose the motion of the patient's leg. A force sensor under the patient's foot on the device pedal provides data for feedback in a sliding-mode FNN control loop built around the motor. Via an active impedance control feedback system, the controller drives the motor to behave similarly to a damped spring by generating and controlling the amplitude and direction of the pedal force in relation to the patient's leg. Experiments demonstrate the high sensitivity and speed of the device. The PC-based feedback nature of the control loop means that sophisticated auto-adaptable CPM/CAM custom-designed physiotherapy becomes possible. The computer base also allows extensive data recording, data analysis and network-connected remote patient monitoring.

? PID output-feedback control under event-triggered protocol

NASA Astrophysics Data System (ADS)

Zhao, Di; Wang, Zidong; Ding, Derui; Wei, Guoliang; Alsaadi, Fuad E.

2018-07-01

This paper is concerned with the ? proportional-integral-derivative (PID) output-feedback control problem for a class of linear discrete-time systems under event-triggered protocols. The controller and the actuators are connected through a communication network of limited bandwidth, and an event-triggered communication mechanism is adopted to decide when a certain control signal should be transmitted to the respective actuator. Furthermore, a novel PID output-feedback controller is designed where the accumulative sum-loop (the counterpart to the integral-loop in the continues-time setting) operates on a limited time-window with hope to mitigate the effect from the past measurement data. The main objective of the problem under consideration is to design a desired PID controller such that the closed-loop system is exponentially stable and the prescribed ? disturbance rejection attenuation level is guaranteed under event-triggered protocols. By means of the Lyapunov stability theory combined with the orthogonal decomposition, sufficient conditions are established under which the addressed PID controller design problem is recast into a linear convex optimization one that can be easily solved via available software packages. Finally, a simulation example is exploited to illustrate the usefulness and effectiveness of the established control scheme.

Evolutionary divergence of core and post-translational circadian clock genes in the pitcher-plant mosquito, Wyeomyia smithii.

PubMed

Tormey, Duncan; Colbourne, John K; Mockaitis, Keithanne; Choi, Jeong-Hyeon; Lopez, Jacqueline; Burkhart, Joshua; Bradshaw, William; Holzapfel, Christina

2015-10-06

Internal circadian (circa, about; dies, day) clocks enable organisms to maintain adaptive timing of their daily behavioral activities and physiological functions. Eukaryotic clocks consist of core transcription-translation feedback loops that generate a cycle and post-translational modifiers that maintain that cycle at about 24 h. We use the pitcher-plant mosquito, Wyeomyia smithii (subfamily Culicini, tribe Sabethini), to test whether evolutionary divergence of the circadian clock genes in this species, relative to other insects, has involved primarily genes in the core feedback loops or the post-translational modifiers. Heretofore, there is no reference transcriptome or genome sequence for any mosquito in the tribe Sabethini, which includes over 375 mainly circumtropical species. We sequenced, assembled and annotated the transcriptome of W. smithii containing nearly 95 % of conserved single-copy orthologs in animal genomes. We used the translated contigs and singletons to determine the average rates of circadian clock-gene divergence in W. smithii relative to three other mosquito genera, to Drosophila, to the butterfly, Danaus, and to the wasp, Nasonia. Over 1.08 million cDNA sequence reads were obtained consisting of 432.5 million nucleotides. Their assembly produced 25,904 contigs and 54,418 singletons of which 62 % and 28 % are annotated as protein-coding genes, respectively, sharing homology with other animal proteomes. The W. smithii transcriptome includes all nine circadian transcription-translation feedback-loop genes and all eight post-translational modifier genes we sought to identify (Fig. 1). After aligning translated W. smithii contigs and singletons from this transcriptome with other insects, we determined that there was no significant difference in the average divergence of W. smithii from the six other taxa between the core feedback-loop genes and post-translational modifiers. The characterized transcriptome is sufficiently complete and of sufficient quality to have uncovered all of the insect circadian clock genes we sought to identify (Fig. 1). Relative divergence does not differ between core feedback-loop genes and post-translational modifiers of those genes in a Sabethine species (W. smithii) that has experienced a continual northward dispersal into temperate regions of progressively longer summer day lengths as compared with six other insect taxa. An associated microarray platform derived from this work will enable the investigation of functional genomics of circadian rhythmicity, photoperiodic time measurement, and diapause along a photic and seasonal geographic gradient.

Substrate phosphorylation and feedback regulation in JFK-promoted p53 destabilization.

PubMed

Sun, Luyang; Shi, Lei; Wang, Feng; Huangyang, Peiwei; Si, Wenzhe; Yang, Jie; Yao, Zhi; Shang, Yongfeng

2011-02-11

The p53 tumor suppressor plays a central role in integrating cellular responses to various stresses. Tight regulation of p53 is thus essential for the maintenance of genome integrity and normal cell proliferation. Previously, we reported that JFK, the only Kelch domain-containing F-box protein in human, promotes ubiquitination and degradation of p53 and that unlike the other E3 ligases for p53, all of which possess an intrinsic ubiquitin ligase activity, JFK destabilizes p53 through the assembly of a Skp1-Cul1-F-box complex. Here, we report that the substrate recognition by JFK requires phosphorylation of p53 in its central core region by CSN (COP9 signalosome)-associated kinase. Significantly, inhibition of CSN-associated kinase activity or knockdown of CSN5 impairs JFK-promoted p53 degradation, enhances p53-dependent transcription, and promotes cell growth suppression, G(1) arrest, and apoptosis. Moreover, we showed that JFK is transcriptionally regulated by p53 and forms an auto-regulatory negative feedback loop with p53. These data may shed new light on the functional connection between CSN, Skp1-Cul1-F-box ubiquitin ligase, and p53 and provide a molecular mechanism for the regulation of JFK-promoted p53 degradation.

Substrate Phosphorylation and Feedback Regulation in JFK-promoted p53 Destabilization*

PubMed Central

Sun, Luyang; Shi, Lei; Wang, Feng; Huangyang, Peiwei; Si, Wenzhe; Yang, Jie; Yao, Zhi; Shang, Yongfeng

2011-01-01

The p53 tumor suppressor plays a central role in integrating cellular responses to various stresses. Tight regulation of p53 is thus essential for the maintenance of genome integrity and normal cell proliferation. Previously, we reported that JFK, the only Kelch domain-containing F-box protein in human, promotes ubiquitination and degradation of p53 and that unlike the other E3 ligases for p53, all of which possess an intrinsic ubiquitin ligase activity, JFK destabilizes p53 through the assembly of a Skp1-Cul1-F-box complex. Here, we report that the substrate recognition by JFK requires phosphorylation of p53 in its central core region by CSN (COP9 signalosome)-associated kinase. Significantly, inhibition of CSN-associated kinase activity or knockdown of CSN5 impairs JFK-promoted p53 degradation, enhances p53-dependent transcription, and promotes cell growth suppression, G1 arrest, and apoptosis. Moreover, we showed that JFK is transcriptionally regulated by p53 and forms an auto-regulatory negative feedback loop with p53. These data may shed new light on the functional connection between CSN, Skp1-Cul1-F-box ubiquitin ligase, and p53 and provide a molecular mechanism for the regulation of JFK-promoted p53 degradation. PMID:21127074

A feedback mechanism controlling SCRAMBLED receptor accumulation and cell-type pattern in Arabidopsis.

PubMed

Kwak, Su-Hwan; Schiefelbein, John

2008-12-23

Cellular pattern formation in the root epidermis of Arabidopsis occurs in a position-dependent manner, generating root-hair (H) cells contacting two underlying cortical cells and nonhair (N) cells contacting one cortical cell. SCRAMBLED (SCM), a leucine-rich repeat receptor-like kinase (LRR-RLK), mediates this process through its effect on a downstream transcription factor regulatory network. After perception of a positional cue, the SCM signaling pathway is proposed to preferentially repress WEREWOLF (WER) transcription factor expression in H cells and thereby bias the outcome of mutual lateral inhibition acting between H and N cells. However, the molecular mechanism responsible for this preferential SCM signaling is unknown. Here, we analyze the distribution of the SCM receptor and the biological effect of altering its accumulation pattern. We find that SCM expression and accumulation in the epidermal cell layer is necessary and sufficient to direct the cell-type pattern. Further, SCM preferentially accumulates in H cells, and this accumulation pattern is dependent on the downstream transcription factors. Thus, SCM participates in an autoregulatory feedback loop, enabling cells engaged in SCM signaling to maintain high levels of SCM receptor, which provides a simple mechanism for reinforcing a bias in receptor-mediated signaling to ensure robust pattern formation.

Stability estimation of autoregulated genes under Michaelis-Menten-type kinetics

NASA Astrophysics Data System (ADS)

Arani, Babak M. S.; Mahmoudi, Mahdi; Lahti, Leo; González, Javier; Wit, Ernst C.

2018-06-01

Feedback loops are typical motifs appearing in gene regulatory networks. In some well-studied model organisms, including Escherichia coli, autoregulated genes, i.e., genes that activate or repress themselves through their protein products, are the only feedback interactions. For these types of interactions, the Michaelis-Menten (MM) formulation is a suitable and widely used approach, which always leads to stable steady-state solutions representative of homeostatic regulation. However, in many other biological phenomena, such as cell differentiation, cancer progression, and catastrophes in ecosystems, one might expect to observe bistable switchlike dynamics in the case of strong positive autoregulation. To capture this complex behavior we use the generalized family of MM kinetic models. We give a full analysis regarding the stability of autoregulated genes. We show that the autoregulation mechanism has the capability to exhibit diverse cellular dynamics including hysteresis, a typical characteristic of bistable systems, as well as irreversible transitions between bistable states. We also introduce a statistical framework to estimate the kinetics parameters and probability of different stability regimes given observational data. Empirical data for the autoregulated gene SCO3217 in the SOS system in Streptomyces coelicolor are analyzed. The coupling of a statistical framework and the mathematical model can give further insight into understanding the evolutionary mechanisms toward different cell fates in various systems.

Induction of appropriate Th-cell phenotypes: cellular decision-making in heterogeneous environments.

PubMed

van den Ham, H-J; Andeweg, A C; de Boer, R J

2013-11-01

Helper T (Th)-cell differentiation is a key event in the development of the adaptive immune response. By the production of a range of cytokines, Th cells determine the type of immune response that is raised against an invading pathogen. Th cells can adopt many different phenotypes, and Th-cell phenotype decision-making is crucial in mounting effective host responses. This review discusses the different Th-cell phenotypes that have been identified and how Th cells adopt a particular phenotype. The regulation of Th-cell phenotypes has been studied extensively using mathematical models, which have explored the role of regulatory mechanisms such as autocrine cytokine signalling and cross-inhibition between self-activating transcription factors. At the single cell level, Th responses tend to be heterogeneous, but corrections can be made soon after T-cell activation. Although pathogens and the innate immune system provide signals that direct the induction of Th-cell phenotypes, these instructive mechanisms could be easily subverted by pathogens. We discuss that a model of success-driven feedback would select the most appropriate phenotype for clearing a pathogen. Given the heterogeneity in the induction phase of the Th response, such a success-driven feedback loop would allow the selection of effective Th-cell phenotypes while terminating incorrect responses. © 2013 John Wiley & Sons Ltd.

Why do some therapists not deal with outcome monitoring feedback? A feasibility study on the effect of regulatory focus and person-organization fit on attitude and outcome.

PubMed

de Jong, Kim; de Goede, Marije

2015-01-01

Despite research on its effectiveness, many therapists still have negative attitudes toward using outcome monitoring feedback. The current study aims to investigate how the perceived match between values of an individual and those of the organization (Person-Organization fit; PO fit), and motivation to prevent failure or to achieve success (regulatory focus) are related to therapists' attitude, attitude changes over time, and outcomes. Therapists (n = 20) filled out a feedback attitude questionnaire at two points in time: before the start of outcome monitoring, and after six months. In addition, they completed measures on PO fit and regulatory focus. PO fit was predictive of outcomes, when feedback was provided, but did not predict therapists' attitude. Therapists with a strong prevention focus (prevent failures), had a more positive attitude toward feedback, but achieved slower symptom reduction in their at risk cases. A strong promotion focus (achieve success) was not predictive of attitude, but did result in faster symptom reduction in at risk patients when feedback was provided. Therapists motivational approach to work and the perceived match with the organization they work for, can influence both their attitude toward outcome monitoring and their outcomes.

A PKC-MARCKS-PI3K regulatory module links Ca2+ and PIP3 signals at the leading edge of polarized macrophages.

PubMed

Ziemba, Brian P; Falke, Joseph J

2018-01-01

The leukocyte chemosensory pathway detects attractant gradients and directs cell migration to sites of inflammation, infection, tissue damage, and carcinogenesis. Previous studies have revealed that local Ca2+ and PIP3 signals at the leading edge of polarized leukocytes play central roles in positive feedback loop essential to cell polarization and chemotaxis. These prior studies showed that stimulation of the leading edge Ca2+ signal can strongly activate PI3K, thereby triggering a larger PIP3 signal, but did not elucidate the mechanistic link between Ca2+ and PIP3 signaling. A hypothesis explaining this link emerged, postulating that Ca2+-activated PKC displaces the MARCKS protein from plasma membrane PIP2, thereby releasing sequestered PIP2 to serve as the target and substrate lipid of PI3K in PIP3 production. In vitro single molecule studies of the reconstituted pathway on lipid bilayers demonstrated the feasibility of this PKC-MARCKS-PI3K regulatory module linking Ca2+ and PIP3 signals in the reconstituted system. The present study tests the model predictions in live macrophages by quantifying the effects of: (a) two pathway activators-PDGF and ATP that stimulate chemoreceptors and Ca2+ influx, respectively; and (b) three pathway inhibitors-wortmannin, EGTA, and Go6976 that inhibit PI3K, Ca2+ influx, and PKC, respectively; on (c) four leading edge activity sensors-AKT-PH-mRFP, CKAR, MARCKSp-mRFP, and leading edge area that report on PIP3 density, PKC activity, MARCKS membrane binding, and leading edge expansion/contraction, respectively. The results provide additional evidence that PKC and PI3K are both essential elements of the leading edge positive feedback loop, and strongly support the existence of a PKC-MARCKS-PI3K regulatory module linking the leading edge Ca2+ and PIP3 signals. As predicted, activators stimulate leading edge PKC activity, displacement of MARCKS from the leading edge membrane and increased leading edge PIP3 levels, while inhibitors trigger the opposite effects. Comparison of the findings for the ameboid chemotaxis of leukocytes with recently published findings for the mesenchymal chemotaxis of fibroblasts suggests that some features of the emerging leukocyte leading edge core pathway (PLC-DAG-Ca2+-PKC-MARCKS-PIP2-PI3K-PIP3) may well be shared by all chemotaxing eukaryotic cells, while other elements of the leukocyte pathway may be specialized features of these highly optimized, professional gradient-seeking cells. More broadly, the findings suggest a molecular mechanism for the strong links between phospho-MARCKS and many human cancers.

A PKC-MARCKS-PI3K regulatory module links Ca2+ and PIP3 signals at the leading edge of polarized macrophages

PubMed Central

Ziemba, Brian P.

2018-01-01

The leukocyte chemosensory pathway detects attractant gradients and directs cell migration to sites of inflammation, infection, tissue damage, and carcinogenesis. Previous studies have revealed that local Ca2+ and PIP3 signals at the leading edge of polarized leukocytes play central roles in positive feedback loop essential to cell polarization and chemotaxis. These prior studies showed that stimulation of the leading edge Ca2+ signal can strongly activate PI3K, thereby triggering a larger PIP3 signal, but did not elucidate the mechanistic link between Ca2+ and PIP3 signaling. A hypothesis explaining this link emerged, postulating that Ca2+-activated PKC displaces the MARCKS protein from plasma membrane PIP2, thereby releasing sequestered PIP2 to serve as the target and substrate lipid of PI3K in PIP3 production. In vitro single molecule studies of the reconstituted pathway on lipid bilayers demonstrated the feasibility of this PKC-MARCKS-PI3K regulatory module linking Ca2+ and PIP3 signals in the reconstituted system. The present study tests the model predictions in live macrophages by quantifying the effects of: (a) two pathway activators—PDGF and ATP that stimulate chemoreceptors and Ca2+ influx, respectively; and (b) three pathway inhibitors—wortmannin, EGTA, and Go6976 that inhibit PI3K, Ca2+ influx, and PKC, respectively; on (c) four leading edge activity sensors—AKT-PH-mRFP, CKAR, MARCKSp-mRFP, and leading edge area that report on PIP3 density, PKC activity, MARCKS membrane binding, and leading edge expansion/contraction, respectively. The results provide additional evidence that PKC and PI3K are both essential elements of the leading edge positive feedback loop, and strongly support the existence of a PKC-MARCKS-PI3K regulatory module linking the leading edge Ca2+ and PIP3 signals. As predicted, activators stimulate leading edge PKC activity, displacement of MARCKS from the leading edge membrane and increased leading edge PIP3 levels, while inhibitors trigger the opposite effects. Comparison of the findings for the ameboid chemotaxis of leukocytes with recently published findings for the mesenchymal chemotaxis of fibroblasts suggests that some features of the emerging leukocyte leading edge core pathway (PLC-DAG-Ca2+-PKC-MARCKS-PIP2-PI3K-PIP3) may well be shared by all chemotaxing eukaryotic cells, while other elements of the leukocyte pathway may be specialized features of these highly optimized, professional gradient-seeking cells. More broadly, the findings suggest a molecular mechanism for the strong links between phospho-MARCKS and many human cancers. PMID:29715315

Reliable numerical computation in an optimal output-feedback design

NASA Technical Reports Server (NTRS)

Vansteenwyk, Brett; Ly, Uy-Loi

1991-01-01

A reliable algorithm is presented for the evaluation of a quadratic performance index and its gradients with respect to the controller design parameters. The algorithm is a part of a design algorithm for optimal linear dynamic output-feedback controller that minimizes a finite-time quadratic performance index. The numerical scheme is particularly robust when it is applied to the control-law synthesis for systems with densely packed modes and where there is a high likelihood of encountering degeneracies in the closed-loop eigensystem. This approach through the use of an accurate Pade series approximation does not require the closed-loop system matrix to be diagonalizable. The algorithm was included in a control design package for optimal robust low-order controllers. Usefulness of the proposed numerical algorithm was demonstrated using numerous practical design cases where degeneracies occur frequently in the closed-loop system under an arbitrary controller design initialization and during the numerical search.

Structural Damage Detection Using Virtual Passive Controllers

NASA Technical Reports Server (NTRS)

Lew, Jiann-Shiun; Juang, Jer-Nan

2001-01-01

This paper presents novel approaches for structural damage detection which uses the virtual passive controllers attached to structures, where passive controllers are energy dissipative devices and thus guarantee the closed-loop stability. The use of the identified parameters of various closed-loop systems can solve the problem that reliable identified parameters, such as natural frequencies of the open-loop system may not provide enough information for damage detection. Only a small number of sensors are required for the proposed approaches. The identified natural frequencies, which are generally much less sensitive to noise and more reliable than the identified natural frequencies, are used for damage detection. Two damage detection techniques are presented. One technique is based on the structures with direct output feedback controllers while the other technique uses the second-order dynamic feedback controllers. A least-squares technique, which is based on the sensitivity of natural frequencies to damage variables, is used for accurately identifying the damage variables.

A functional genomics approach reveals CHE as a component of the Arabidopsis circadian clock.

PubMed

Pruneda-Paz, Jose L; Breton, Ghislain; Para, Alessia; Kay, Steve A

2009-03-13

Transcriptional feedback loops constitute the molecular circuitry of the plant circadian clock. In Arabidopsis, a core loop is established between CCA1 and TOC1. Although CCA1 directly represses TOC1, the TOC1 protein has no DNA binding domains, which suggests that it cannot directly regulate CCA1. We established a functional genomic strategy that led to the identification of CHE, a TCP transcription factor that binds specifically to the CCA1 promoter. CHE is a clock component partially redundant with LHY in the repression of CCA1. The expression of CHE is regulated by CCA1, thus adding a CCA1/CHE feedback loop to the Arabidopsis circadian network. Because CHE and TOC1 interact, and CHE binds to the CCA1 promoter, a molecular linkage between TOC1 and CCA1 gene regulation is established.

The base pairing RNA Spot 42 participates in a multi-output feedforward loop to help enact catabolite repression in Escherichia coli

PubMed Central

Beisel, Chase L.; Storz, Gisela

2011-01-01

SUMMARY Bacteria selectively consume some carbon sources over others through a regulatory mechanism termed catabolite repression. Here, we show that the base pairing RNA Spot 42 plays a broad role in catabolite repression in Escherichia coli by directly repressing genes involved in central and secondary metabolism, redox balancing, and the consumption of diverse non-preferred carbon sources. Many of the genes repressed by Spot 42 are transcriptionally activated by the global regulator CRP. Since CRP represses Spot 42, these regulators participate in a specific regulatory circuit called a multi-output feedforward loop. We found that this loop can reduce leaky expression of target genes in the presence of glucose and can maintain repression of target genes under changing nutrient conditions. Our results suggest that base pairing RNAs in feedforward loops can help shape the steady-state levels and dynamics of gene expression. PMID:21292161

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

PubMed

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

2016-08-01

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

Methionine enkephalin (MENK) improves lymphocyte subpopulations in human peripheral blood of 50 cancer patients by inhibiting regulatory T cells (Tregs)

PubMed Central

Wang, Qiushi; Gao, Xinghua; Yuan, Zhe; Wang, Zhe; Meng, Yiming; Cao, Yan; Plotnikoff, Nicolas P; Griffin, Noreen; Shan, Fengping

2014-01-01

MENK, a penta-peptide is considered as being involved in the regulatory feedback loop between the immune and neuroendocrine systems, with marked modulation of various functions of human immune cells. The aim of the present work was to investigate change of lymphocyte subpopulations in peripheral blood of 50 cancer patients before and after treatment with MENK. Peripheral blood mononuclear cells (PBMCs) of peripheral blood from 50 cancer patients were isolated by density gradient centrifugation using Ficoll-Paque solution and cultured with MENK. We measured proliferation of total nucleated cells, subpopulations of individual CD4+T cells, CD8+T cells, CD4+CD25+ regulatory T cells (Treg), natural killer cells (NK) before and after treatment with 10-12M MENK in cell culture by flow cytometry (FCM). Our results indicated that MENK showed a strong inhibiting effect on Treg cells while it stimulated marked proliferation of other lymphocyte subpopulations. All data obtained were of significance statistically. It was therefore concluded that MENK could work as a strong immune booster with great potential in restoring damaged human immune system and we could consider MENK as a drug to treat cancer patients, whose immune systems are damaged by chemotherapy or radiotherapy. Furthermore we could consider MENK as a chemotherapy additive, which would sustain immune system of cancer patients during the process of chemotherapy to get maximized efficacy with minimized side effect. PMID:25424790

Loop Heat Pipe Operation Using Heat Source Temperature for Set Point Control

NASA Technical Reports Server (NTRS)

Ku, Jentung; Paiva, Kleber; Mantelli, Marcia

2011-01-01

Loop heat pipes (LHPs) have been used for thermal control of several NASA and commercial orbiting spacecraft. The LHP operating temperature is governed by the saturation temperature of its compensation chamber (CC). Most LHPs use the CC temperature for feedback control of its operating temperature. There exists a thermal resistance between the heat source to be cooled by the LHP and the LHP's CC. Even if the CC set point temperature is controlled precisely, the heat source temperature will still vary with its heat output. For most applications, controlling the heat source temperature is of most interest. A logical question to ask is: "Can the heat source temperature be used for feedback control of the LHP operation?" A test program has been implemented to answer the above question. Objective is to investigate the LHP performance using the CC temperature and the heat source temperature for feedback control

Single link flexible beam testbed project. Thesis

NASA Technical Reports Server (NTRS)

Hughes, Declan

1992-01-01

This thesis describes the single link flexible beam testbed at the CLaMS laboratory in terms of its hardware, software, and linear model, and presents two controllers, each including a hub angle proportional-derivative (PD) feedback compensator and one augmented by a second static gain full state feedback loop, based upon a synthesized strictly positive real (SPR) output, that increases specific flexible mode pole damping ratios w.r.t the PD only case and hence reduces unwanted residual oscillation effects. Restricting full state feedback gains so as to produce a SPR open loop transfer function ensures that the associated compensator has an infinite gain margin and a phase margin of at least (-90, 90) degrees. Both experimental and simulation data are evaluated in order to compare some different observer performance when applied to the real testbed and to the linear model when uncompensated flexible modes are included.

Performance assessment of static lead-lag feedforward controllers for disturbance rejection in PID control loops.

PubMed

Yu, Zhenpeng; Wang, Jiandong

2016-09-01

This paper assesses the performance of feedforward controllers for disturbance rejection in univariate feedback plus feedforward control loops. The structures of feedback and feedforward controllers are confined to proportional-integral-derivative and static-lead-lag forms, respectively, and the effects of feedback controllers are not considered. The integral squared error (ISE) and total squared variation (TSV) are used as performance metrics. A performance index is formulated by comparing the current ISE and TSV metrics to their own lower bounds as performance benchmarks. A controller performance assessment (CPA) method is proposed to calculate the performance index from measurements. The proposed CPA method resolves two critical limitations in the existing CPA methods, in order to be consistent with industrial scenarios. Numerical and experimental examples illustrate the effectiveness of the obtained results. Copyright © 2016 ISA. Published by Elsevier Ltd. All rights reserved.

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.

Design strategies for dynamic closed-loop optogenetic neurocontrol in vivo

NASA Astrophysics Data System (ADS)

Bolus, M. F.; Willats, A. A.; Whitmire, C. J.; Rozell, C. J.; Stanley, G. B.

2018-04-01

Objective. Controlling neural activity enables the possibility of manipulating sensory perception, cognitive processes, and body movement, in addition to providing a powerful framework for functionally disentangling the neural circuits that underlie these complex phenomena. Over the last decade, optogenetic stimulation has become an increasingly important and powerful tool for understanding neural circuit function, owing to the ability to target specific cell types and bidirectionally modulate neural activity. To date, most stimulation has been provided in open-loop or in an on/off closed-loop fashion, where previously-determined stimulation is triggered by an event. Here, we describe and demonstrate a design approach for precise optogenetic control of neuronal firing rate modulation using feedback to guide stimulation continuously. Approach. Using the rodent somatosensory thalamus as an experimental testbed for realizing desired time-varying patterns of firing rate modulation, we utilized a moving average exponential filter to estimate firing rate online from single-unit spiking measured extracellularly. This estimate of instantaneous rate served as feedback for a proportional integral (PI) controller, which was designed during the experiment based on a linear-nonlinear Poisson (LNP) model of the neuronal response to light. Main results. The LNP model fit during the experiment enabled robust closed-loop control, resulting in good tracking of sinusoidal and non-sinusoidal targets, and rejection of unmeasured disturbances. Closed-loop control also enabled manipulation of trial-to-trial variability. Significance. Because neuroscientists are faced with the challenge of dissecting the functions of circuit components, the ability to maintain control of a region of interest in spite of changes in ongoing neural activity will be important for disambiguating function within networks. Closed-loop stimulation strategies are ideal for control that is robust to such changes, and the employment of continuous feedback to adjust stimulation in real-time can improve the quality of data collected using optogenetic manipulation.

Finite-time state feedback stabilisation of stochastic high-order nonlinear feedforward systems

NASA Astrophysics Data System (ADS)

Xie, Xue-Jun; Zhang, Xing-Hui; Zhang, Kemei

2016-07-01

This paper studies the finite-time state feedback stabilisation of stochastic high-order nonlinear feedforward systems. Based on the stochastic Lyapunov theorem on finite-time stability, by using the homogeneous domination method, the adding one power integrator and sign function method, constructing a ? Lyapunov function and verifying the existence and uniqueness of solution, a continuous state feedback controller is designed to guarantee the closed-loop system finite-time stable in probability.

Changes in regional and temporal patterns of activity associated with aging during the performance of a lexical set-shifting task.

PubMed

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.

Optimization of Sensing and Feedback Control for Vibration/Flutter of Rotating Disk by PZT Actuators via Air Coupled Pressure

PubMed Central

Yan, Tianhong; Xu, Xinsheng; Han, Jianqiang; Lin, Rongming; Ju, Bingfeng; Li, Qing

2011-01-01

In this paper, a feedback control mechanism and its optimization for rotating disk vibration/flutter via changes of air-coupled pressure generated using piezoelectric patch actuators are studied. A thin disk rotates in an enclosure, which is equipped with a feedback control loop consisting of a micro-sensor, a signal processor, a power amplifier, and several piezoelectric (PZT) actuator patches distributed on the cover of the enclosure. The actuator patches are mounted on the inner or the outer surfaces of the enclosure to produce necessary control force required through the airflow around the disk. The control mechanism for rotating disk flutter using enclosure surfaces bonded with sensors and piezoelectric actuators is thoroughly studied through analytical simulations. The sensor output is used to determine the amount of input to the actuator for controlling the response of the disk in a closed loop configuration. The dynamic stability of the disk-enclosure system, together with the feedback control loop, is analyzed as a complex eigenvalue problem, which is solved using Galerkin’s discretization procedure. The results show that the disk flutter can be reduced effectively with proper configurations of the control gain and the phase shift through the actuations of PZT patches. The effectiveness of different feedback control methods in altering system characteristics and system response has been investigated. The control capability, in terms of control gain, phase shift, and especially the physical configuration of actuator patches, are also evaluated by calculating the complex eigenvalues and the maximum displacement produced by the actuators. To achieve a optimal control performance, sizes, positions and shapes of PZT patches used need to be optimized and such optimization has been achieved through numerical simulations. PMID:22163788

Optimization of sensing and feedback control for vibration/flutter of rotating disk by PZT actuators via air coupled pressure.

PubMed

Yan, Tianhong; Xu, Xinsheng; Han, Jianqiang; Lin, Rongming; Ju, Bingfeng; Li, Qing

2011-01-01

In this paper, a feedback control mechanism and its optimization for rotating disk vibration/flutter via changes of air-coupled pressure generated using piezoelectric patch actuators are studied. A thin disk rotates in an enclosure, which is equipped with a feedback control loop consisting of a micro-sensor, a signal processor, a power amplifier, and several piezoelectric (PZT) actuator patches distributed on the cover of the enclosure. The actuator patches are mounted on the inner or the outer surfaces of the enclosure to produce necessary control force required through the airflow around the disk. The control mechanism for rotating disk flutter using enclosure surfaces bonded with sensors and piezoelectric actuators is thoroughly studied through analytical simulations. The sensor output is used to determine the amount of input to the actuator for controlling the response of the disk in a closed loop configuration. The dynamic stability of the disk-enclosure system, together with the feedback control loop, is analyzed as a complex eigenvalue problem, which is solved using Galerkin's discretization procedure. The results show that the disk flutter can be reduced effectively with proper configurations of the control gain and the phase shift through the actuations of PZT patches. The effectiveness of different feedback control methods in altering system characteristics and system response has been investigated. The control capability, in terms of control gain, phase shift, and especially the physical configuration of actuator patches, are also evaluated by calculating the complex eigenvalues and the maximum displacement produced by the actuators. To achieve a optimal control performance, sizes, positions and shapes of PZT patches used need to be optimized and such optimization has been achieved through numerical simulations.

An integrated optical sensor for GMAW feedback control

DOE Office of Scientific and Technical Information (OSTI.GOV)

Taylor, P.L.; Watkins, A.D.; Larsen, E.D.

1992-08-01

The integrated optical sensor (IOS) is a multifunction feedback control sensor for arc welding, that is computer automated and independent of significant operator interaction. It is based on three major ``off-the-shelf`` components: a charged coupled device (CCD) camera, a diode laser, and a processing computer. The sensor head is compact and lightweight to avoid interference with weld head mobility, hardened to survive the harsh operating environment, and free of specialized cooling and power requirements. The sensor is positioned behind the GMAW torch and measures weld pool position and width, standoff distance, and postweld centerline cooling rate. Weld pool position andmore » width are used in a feedback loop, by the weld controller, to track the weld pool relative to the weld joint, thus allowing compensation for such phenomena as arc blow. Sensor stand off 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 infer the final metallurgical state of the weld bead and heat affected zone, thereby providing a means of controlling post weld mechanical properties.« less

An integrated optical sensor for GMAW feedback control

DOE Office of Scientific and Technical Information (OSTI.GOV)

Taylor, P.L.; Watkins, A.D.; Larsen, E.D.

1992-01-01

The integrated optical sensor (IOS) is a multifunction feedback control sensor for arc welding, that is computer automated and independent of significant operator interaction. It is based on three major off-the-shelf'' components: a charged coupled device (CCD) camera, a diode laser, and a processing computer. The sensor head is compact and lightweight to avoid interference with weld head mobility, hardened to survive the harsh operating environment, and free of specialized cooling and power requirements. The sensor is positioned behind the GMAW torch and measures weld pool position and width, standoff distance, and postweld centerline cooling rate. Weld pool position andmore » width are used in a feedback loop, by the weld controller, to track the weld pool relative to the weld joint, thus allowing compensation for such phenomena as arc blow. Sensor stand off 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 infer the final metallurgical state of the weld bead and heat affected zone, thereby providing a means of controlling post weld mechanical properties.« less

Optical frequency stabilization in infrared region using improved dual feed-back loop

NASA Astrophysics Data System (ADS)

Ružička, B.; Číp, O.; Lazar, J.

2007-03-01

Modern technologies such as DWDM (Dense Wavelength Division Multiplex) need precise stability of laser frequencies. According to this fact, requirements of new etalons of optical frequencies in the telecommunication band is rapidly growing. Lasers working in near infrared telecommunication band (1500-1600 nm) can be stabilized to 12C IIH II or 13C IIH II (acetylene) gas absorption lines. The acetylene gas absorption has been widely studied and accepted by international bodies of standardization as a primary wavelength reference in the near infrared band around 1550 nm. Our aim was to design and develop a compact fibre optics laser system generating coherent light in near-IR band with high frequency stability (at least 1.10 -8). This system should become a base for realization of a primary frequency standard for optical communications in the Czech Republic. Such an etalon will be needed for calibration of wavelengthmeters and spectral analysers for DWDM communication systems. We are co-operating with CMI (Czech Metrology Institute) on this project. We present stabilized laser system based on a single frequency DFB (Distributed Feedback) laser diode with a narrow spectral profile. The laser is pre-stabilized by means of the FM-spectroscopy on a passive resonator. Thanks to a fast feed-back loop we are able to improve spectral characteristics of the laser. The laser frequency is locked by a relatively slow second feed-back loop on an absorption line of acetylene vapour which is sealed in a cell under the optimised pressure.

Improvement of vertical stabilization on KSTAR

NASA Astrophysics Data System (ADS)

Mueller, D.; Bak, J. G.; Boyer, M. D.; Eideitis, N.; Hahn, S. H.; Humphreys, D. A.; Kim, H. S.; Jeon, Y. M.; Lanctot, M.; Walker, M. L.

2017-10-01

The successful control of strongly shaped plasmas on the Korea Superconducting Tokamak Advanced Research (KSTAR) device requires active feedback of fast motion of the plasma vertical position by the use of internal normal conducting coils (IVC). This has required new electronics to supply relative flux loop differences, for zp, and voltage loop differences, for dzp/dt, as well as a novel technique (Zfast) to use a high-pass filter, typically 1 Hz, on the error in the signal in the feedback loop. Use of Zfast avoids the potential contention encountered when the internal coil attempts to perform control of the plasma shape which should be controlled by the slower and more powerful superconducting coils. A common problem of this contention is saturation of the IVC and loss of fast vertical control. This is eliminated by proper use of the Zfast. A Ziegler-Nichols relay feedback system was used to fine tune the required feedback gains. The selection of the magnetic sensors, filter time constants, control gains and of the Zfast control strategy which allowed vertically stable operation at a plasma elongation, kappa. of up to 2.16 at li = 1.15 and Betap = 2.4 will be discussed which is beyond the design reference of KSTAR of kappa = 2.0 at li = 1.2 and Betap = 1.9. Work Supported by U.S.D.O.E. Contract No. DE-AC02-09CH11466 and DE-SC0010685 and the KSTAR project.

Multiplicity of Mathematical Modeling Strategies to Search for Molecular and Cellular Insights into Bacteria Lung Infection

PubMed Central

Cantone, Martina; Santos, Guido; Wentker, Pia; Lai, Xin; Vera, Julio

2017-01-01

Even today two bacterial lung infections, namely pneumonia and tuberculosis, are among the 10 most frequent causes of death worldwide. These infections still lack effective treatments in many developing countries and in immunocompromised populations like infants, elderly people and transplanted patients. The interaction between bacteria and the host is a complex system of interlinked intercellular and the intracellular processes, enriched in regulatory structures like positive and negative feedback loops. Severe pathological condition can emerge when the immune system of the host fails to neutralize the infection. This failure can result in systemic spreading of pathogens or overwhelming immune response followed by a systemic inflammatory response. Mathematical modeling is a promising tool to dissect the complexity underlying pathogenesis of bacterial lung infection at the molecular, cellular and tissue levels, and also at the interfaces among levels. In this article, we introduce mathematical and computational modeling frameworks that can be used for investigating molecular and cellular mechanisms underlying bacterial lung infection. Then, we compile and discuss published results on the modeling of regulatory pathways and cell populations relevant for lung infection and inflammation. Finally, we discuss how to make use of this multiplicity of modeling approaches to open new avenues in the search of the molecular and cellular mechanisms underlying bacterial infection in the lung. PMID:28912729

Multiplicity of Mathematical Modeling Strategies to Search for Molecular and Cellular Insights into Bacteria Lung Infection.

PubMed

Cantone, Martina; Santos, Guido; Wentker, Pia; Lai, Xin; Vera, Julio

2017-01-01

Even today two bacterial lung infections, namely pneumonia and tuberculosis, are among the 10 most frequent causes of death worldwide. These infections still lack effective treatments in many developing countries and in immunocompromised populations like infants, elderly people and transplanted patients. The interaction between bacteria and the host is a complex system of interlinked intercellular and the intracellular processes, enriched in regulatory structures like positive and negative feedback loops. Severe pathological condition can emerge when the immune system of the host fails to neutralize the infection. This failure can result in systemic spreading of pathogens or overwhelming immune response followed by a systemic inflammatory response. Mathematical modeling is a promising tool to dissect the complexity underlying pathogenesis of bacterial lung infection at the molecular, cellular and tissue levels, and also at the interfaces among levels. In this article, we introduce mathematical and computational modeling frameworks that can be used for investigating molecular and cellular mechanisms underlying bacterial lung infection. Then, we compile and discuss published results on the modeling of regulatory pathways and cell populations relevant for lung infection and inflammation. Finally, we discuss how to make use of this multiplicity of modeling approaches to open new avenues in the search of the molecular and cellular mechanisms underlying bacterial infection in the lung.

The MADS transcription factor XAL2/AGL14 modulates auxin transport during Arabidopsis root development by regulating PIN expression

PubMed Central

Garay-Arroyo, Adriana; Ortiz-Moreno, Enrique; de la Paz Sánchez, María; Murphy, Angus S; García-Ponce, Berenice; Marsch-Martínez, Nayelli; de Folter, Stefan; Corvera-Poiré, Adriana; Jaimes-Miranda, Fabiola; Pacheco-Escobedo, Mario A; Dubrovsky, Joseph G; Pelaz, Soraya; Álvarez-Buylla, Elena R

2013-01-01

Elucidating molecular links between cell-fate regulatory networks and dynamic patterning modules is a key for understanding development. Auxin is important for plant patterning, particularly in roots, where it establishes positional information for cell-fate decisions. PIN genes encode plasma membrane proteins that serve as auxin efflux transporters; mutations in members of this gene family exhibit smaller roots with altered root meristems and stem-cell patterning. Direct regulators of PIN transcription have remained elusive. Here, we establish that a MADS-box gene (XAANTAL2, XAL2/AGL14) controls auxin transport via PIN transcriptional regulation during Arabidopsis root development; mutations in this gene exhibit altered stem-cell patterning, root meristem size, and root growth. XAL2 is necessary for normal shootward and rootward auxin transport, as well as for maintaining normal auxin distribution within the root. Furthermore, this MADS-domain transcription factor upregulates PIN1 and PIN4 by direct binding to regulatory regions and it is required for PIN4-dependent auxin response. In turn, XAL2 expression is regulated by auxin levels thus establishing a positive feedback loop between auxin levels and PIN regulation that is likely to be important for robust root patterning. PMID:24121311

Comparison of Control Approaches in Genetic Regulatory Networks by Using Stochastic Master Equation Models, Probabilistic Boolean Network Models and Differential Equation Models and Estimated Error Analyzes

NASA Astrophysics Data System (ADS)

Caglar, Mehmet Umut; Pal, Ranadip

2011-03-01

Central dogma of molecular biology states that ``information cannot be transferred back from protein to either protein or nucleic acid''. However, this assumption is not exactly correct in most of the cases. There are a lot of feedback loops and interactions between different levels of systems. These types of interactions are hard to analyze due to the lack of cell level data and probabilistic - nonlinear nature of interactions. Several models widely used to analyze and simulate these types of nonlinear interactions. Stochastic Master Equation (SME) models give probabilistic nature of the interactions in a detailed manner, with a high calculation cost. On the other hand Probabilistic Boolean Network (PBN) models give a coarse scale picture of the stochastic processes, with a less calculation cost. Differential Equation (DE) models give the time evolution of mean values of processes in a highly cost effective way. The understanding of the relations between the predictions of these models is important to understand the reliability of the simulations of genetic regulatory networks. In this work the success of the mapping between SME, PBN and DE models is analyzed and the accuracy and affectivity of the control policies generated by using PBN and DE models is compared.

Control of Stochastic Master Equation Models of Genetic Regulatory Networks by Approximating Their Average Behavior

NASA Astrophysics Data System (ADS)

Umut Caglar, Mehmet; Pal, Ranadip

2010-10-01

The central dogma of molecular biology states that ``information cannot be transferred back from protein to either protein or nucleic acid.'' However, this assumption is not exactly correct in most of the cases. There are a lot of feedback loops and interactions between different levels of systems. These types of interactions are hard to analyze due to the lack of data in the cellular level and probabilistic nature of interactions. Probabilistic models like Stochastic Master Equation (SME) or deterministic models like differential equations (DE) can be used to analyze these types of interactions. SME models based on chemical master equation (CME) can provide detailed representation of genetic regulatory system, but their use is restricted by the large data requirements and computational costs of calculations. The differential equations models on the other hand, have low calculation costs and much more adequate to generate control procedures on the system; but they are not adequate to investigate the probabilistic nature of interactions. In this work the success of the mapping between SME and DE is analyzed, and the success of a control policy generated by DE model with respect to SME model is examined. Index Terms--- Stochastic Master Equation models, Differential Equation Models, Control Policy Design, Systems biology

Structural robustness with suboptimal responses for linear state space model

NASA Technical Reports Server (NTRS)

Keel, L. H.; Lim, Kyong B.; Juang, Jer-Nan

1989-01-01

A relationship between the closed-loop eigenvalues and the amount of perturbations in the open-loop matrix is addressed in the context of performance robustness. If the allowable perturbation ranges of elements of the open-loop matrix A and the desired tolerance of the closed-loop eigenvalues are given such that max(j) of the absolute value of Delta-lambda(j) (A+BF) should be less than some prescribed value, what is a state feedback controller F which satisfies the closed-loop eigenvalue perturbation-tolerance requirement for a class of given perturbation in A? The paper gives an algorithm to design such a controller. Numerical examples are included for illustration.

Assessing Command and Control System Vulnerabilities in Underdeveloped, Degraded and Denied Operational Environments

DTIC Science & Technology

2013-06-01

simulation of complex systems (Sterman 2000, Meadows 2008): a) Causal Loop Diagrams. A Causal Loop Diagram ( CLD ) is used to represent the feedback...structure of the dynamic system. CLDs consist of variables in the system being connected by arrows to show their causal influences and relationships. It is...distribution of orders will be included in the model. 6.4.2 Causal Loop Diagrams The CLD , as seen in Figure 5, is derived from the WDA constructs for the

CORE SATURATION BLOCKING OSCILLATOR

DOEpatents

Spinrad, R.J.

1961-10-17

A blocking oscillator which relies on core saturation regulation to control the output pulse width is described. In this arrangement an external magnetic loop is provided in which a saturable portion forms the core of a feedback transformer used with the thermionic or semi-conductor active element. A first stationary magnetic loop establishes a level of flux through the saturation portion of the loop. A second adjustable magnet moves the flux level to select a saturation point giving the desired output pulse width. (AEC)

Quantitative Feedback Technique (QFT): Bridging the Gap

DTIC Science & Technology

2003-05-01

with Eq. (2) illustrates: (a) the effect of changes of the uncertainty set P(s) upon the output of the closed -loop control system is reduced by the...Bridging the Gap root-locus technique the dominant closed -loop poles are determined for a ζ= 0.45. Table 3 presents the required value of Kx and...degree of decoupling will have been enhanced. Method 1 is then more readily applicable, with the additional benefit of reduced closed -loop BW. E.R.2

An Investigation Relating Longitudinal Pilot-Induced Oscillation Tendency Rating to Describing Function Predictions for Rate-Limited Actuators

DTIC Science & Technology

2004-03-01

2-15 2-10. Pitch Tracking Closed Loop System for Gap Criterion...................................... 2-16 2-11. Four Resulting Gap ...Level 1 Minimize Resonance Closed Loop Bode Diagram ( ) ( ) s sCommand θ θ ( ) ( ) s sCommand θ θ         BWω 2-16 Gap Criterion...System for Gap Criterion In modern fly-by-wire aircraft, feedback is an integral part of obtaining more desirable closed loop flying qualities

Turbofan engine control system design using the LQG/LTR methodology

NASA Technical Reports Server (NTRS)

Garg, Sanjay

1989-01-01

Application of the linear-quadratic-Gaussian with loop-transfer-recovery methodology to design of a control system for a simplified turbofan engine model is considered. The importance of properly scaling the plant to achieve the desired target feedback loop is emphasized. The steps involved in the application of the methodology are discussed via an example, and evaluation results are presented for a reduced-order compensator. The effect of scaling the plant on the stability robustness evaluation of the closed-loop system is studied in detail.

Turbofan engine control system design using the LQG/LTR methodology

NASA Technical Reports Server (NTRS)

Garg, Sanjay

1989-01-01

Application of the Linear-Quadratic-Gaussian with Loop-Transfer-Recovery methodology to design of a control system for a simplified turbofan engine model is considered. The importance of properly scaling the plant to achieve the desired Target-Feedback-Loop is emphasized. The steps involved in the application of the methodology are discussed via an example, and evaluation results are presented for a reduced-order compensator. The effect of scaling the plant on the stability robustness evaluation of the closed-loop system is studied in detail.

Orphanin FQ-ORL-1 regulation of reproduction and reproductive behavior in the female.

PubMed

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.

Loop Mirror Laser Neural Network with a Fast Liquid-Crystal Display

NASA Astrophysics Data System (ADS)

Mos, Evert C.; Schleipen, Jean J. H. B.; de Waardt, Huug; Khoe, Djan G. D.

1999-07-01

In our laser neural network (LNN) all-optical threshold action is obtained by application of controlled optical feedback to a laser diode. Here an extended experimental LNN is presented with as many as 32 neurons and 12 inputs. In the setup we use a fast liquid-crystal display to implement an optical matrix vector multiplier. This display, based on ferroelectric liquid-crystal material, enables us to present 125 training examples s to the LNN. To maximize the optical feedback efficiency of the setup, a loop mirror is introduced. We use a -rule learning algorithm to train the network to perform a number of functions toward the application area of telecommunication data switching.

Beyond singular values and loop shapes

NASA Technical Reports Server (NTRS)

Stein, G.

1985-01-01

The status of singular value loop-shaping as a design paradigm for multivariable feedback systems is reviewed. It shows that this paradigm is an effective design tool whenever the problem specifications are spacially round. The tool can be arbitrarily conservative, however, when they are not. This happens because singular value conditions for robust performance are not tight (necessary and sufficient) and can severely overstate actual requirements. An alternate paradign is discussed which overcomes these limitations. The alternative includes a more general problem formulation, a new matrix function mu, and tight conditions for both robust stability and robust performance. The state of the art currently permits analysis of feedback systems within this new paradigm. Synthesis remains a subject of research.

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

NASA Technical Reports Server (NTRS)

Bearden, Douglas B. (Inventor)

2007-01-01

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

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

NASA Technical Reports Server (NTRS)

Bearden, Douglas B. (Inventor)

2007-01-01

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

Silicon photonic dynamic optical channel leveler with external feedback loop.

PubMed

Doylend, J K; Jessop, P E; Knights, A P

2010-06-21

We demonstrate a dynamic optical channel leveler composed of a variable optical attenuator (VOA) integrated monolithically with a defect-mediated photodiode in a silicon photonic waveguide device. An external feedback loop mimics an analog circuit such that the photodiode directly controls the VOA to provide blind channel leveling within +/-1 dB across a 7-10 dB dynamic range for wavelengths from 1530 nm to 1570 nm. The device consumes approximately 50 mW electrical power and occupies a 6 mm x 0.1 mm footprint per channel. Dynamic leveling is accomplished without tapping optical power from the output path to the photodiode and thus the loss penalty is minimized.

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

NASA Technical Reports Server (NTRS)

1976-01-01

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

UWB communication receiver feedback loop

DOEpatents

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

2007-12-04

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

Learning the Art of Electronics

NASA Astrophysics Data System (ADS)

Hayes, Thomas C.; Horowitz, Paul

2016-03-01

1. DC circuits; 2. RC circuits; 3. Diode circuits; 4. Transistors I; 5. Transistors II; 6. Operational amplifiers I; 7. Operational amplifiers II: nice positive feedback; 8. Operational amplifiers III; 9. Operational amplifiers IV: nasty positive feedback; 10. Operational amplifiers V: PID motor control loop; 11. Voltage regulators; 12. MOSFET switches; 13. Group audio project; 14. Logic gates; 15. Logic compilers, sequential circuits, flip-flops; 16. Counters; 17. Memory: state machines; 18. Analog to digital: phase-locked loop; 19. Microcontrollers and microprocessors I: processor/controller; 20. I/O, first assembly language; 21. Bit operations; 22. Interrupt: ADC and DAC; 23. Moving pointers, serial buses; 24. Dallas Standalone Micro, SiLabs SPI RAM; 25. Toys in the attic; Appendices; Index.

Capturing complexity in work disability research: application of system dynamics modeling methodology.

PubMed

Jetha, Arif; Pransky, Glenn; Hettinger, Lawrence J

2016-01-01

Work disability (WD) is characterized by variable and occasionally undesirable outcomes. The underlying determinants of WD outcomes include patterns of dynamic relationships among health, personal, organizational and regulatory factors that have been challenging to characterize, and inadequately represented by contemporary WD models. System dynamics modeling (SDM) methodology applies a sociotechnical systems thinking lens to view WD systems as comprising a range of influential factors linked by feedback relationships. SDM can potentially overcome limitations in contemporary WD models by uncovering causal feedback relationships, and conceptualizing dynamic system behaviors. It employs a collaborative and stakeholder-based model building methodology to create a visual depiction of the system as a whole. SDM can also enable researchers to run dynamic simulations to provide evidence of anticipated or unanticipated outcomes that could result from policy and programmatic intervention. SDM may advance rehabilitation research by providing greater insights into the structure and dynamics of WD systems while helping to understand inherent complexity. Challenges related to data availability, determining validity, and the extensive time and technical skill requirements for model building may limit SDM's use in the field and should be considered. Contemporary work disability (WD) models provide limited insight into complexity associated with WD processes. System dynamics modeling (SDM) has the potential to capture complexity through a stakeholder-based approach that generates a simulation model consisting of multiple feedback loops. SDM may enable WD researchers and practitioners to understand the structure and behavior of the WD system as a whole, and inform development of improved strategies to manage straightforward and complex WD cases.

Combining Charge Couple Devices and Rate Sensors for the Feedforward Control System of a Charge Coupled Device Tracking Loop.

PubMed

Tang, Tao; Tian, Jing; Zhong, Daijun; Fu, Chengyu

2016-06-25

A rate feed forward control-based sensor fusion is proposed to improve the closed-loop performance for a charge couple device (CCD) tracking loop. The target trajectory is recovered by combining line of sight (LOS) errors from the CCD and the angular rate from a fiber-optic gyroscope (FOG). A Kalman filter based on the Singer acceleration model utilizes the reconstructive target trajectory to estimate the target velocity. Different from classical feed forward control, additive feedback loops are inevitably added to the original control loops due to the fact some closed-loop information is used. The transfer function of the Kalman filter in the frequency domain is built for analyzing the closed loop stability. The bandwidth of the Kalman filter is the major factor affecting the control stability and close-loop performance. Both simulations and experiments are provided to demonstrate the benefits of the proposed algorithm.

Adaptive Nonlinear Tracking Control of Kinematically Redundant Robot Manipulators with Sub-Task Extensions

DTIC Science & Technology

2005-01-01

C. Hughes, Spacecraft Attitude Dynamics, New York, NY: Wiley, 1994. [8] H. K. Khalil, “Adaptive Output Feedback Control of Non- linear Systems...Closed-Loop Manipulator Control Using Quaternion Feedback ”, IEEE Trans. Robotics and Automation, Vol. 4, No. 4, pp. 434-440, (1988). [23] E...full-state feedback quaternion based controller de- veloped in [5] and focuses on the design of a general sub-task controller. This sub-task controller

Frequency-Offset Cartesian Feedback Based on Polyphase Difference Amplifiers

PubMed Central

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

2010-01-01

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

Modelling and analysis of gene regulatory network using feedback control theory

NASA Astrophysics Data System (ADS)

El-Samad, H.; Khammash, M.

2010-01-01

Molecular pathways are a part of a remarkable hierarchy of regulatory networks that operate at all levels of organisation. These regulatory networks are responsible for much of the biological complexity within the cell. The dynamic character of these pathways and the prevalence of feedback regulation strategies in their operation make them amenable to systematic mathematical analysis using the same tools that have been used with success in analysing and designing engineering control systems. In this article, we aim at establishing this strong connection through various examples where the behaviour exhibited by gene networks is explained in terms of their underlying control strategies. We complement our analysis by a survey of mathematical techniques commonly used to model gene regulatory networks and analyse their dynamic behaviour.

A Simple Negative Interaction in the Positive Transcriptional Feedback of a Single Gene Is Sufficient to Produce Reliable Oscillations

PubMed Central

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

Source-drain burnout mechanism of GaAs power MESFETS: Three terminal effects

NASA Astrophysics Data System (ADS)

Takamiya, Saburo; Sonoda, Takuji; Yamanouchi, Masahide; Fujioka, Takashi; Kohno, Masaki

1997-03-01

Theoretical expressions for thermal and electrical feedback effects are derived. These limit the power capability of a power FET and lead a device to catastrophic breakdown (source-drain burnout) when the loop gain of the former reaches unity. Field emission of thermally excited electrons at the Schottky gate plays the key role in thermal feedback, while holes being impact ionized by the drain current play a similar role in the electrical feedback. Thermal feedback is dominant in a high temperature and low drain voltage area. Electrical feedback is dominant in a high drain voltage and low temperature area. In the first area, a high junction temperature is the main factor causing the thermal runaway of the device. In the second area, the electrcal feedback increases the drain current and the temperature and gives a trigger to the thermal feedback so that it reaches unity more easily. Both effects become significant in proportion to transconductance and gate bias resistance, and cause simultaneous runaway of the gate and drain currents. The expressions of the loop gains clearly indicate the safe operating conditions for a power FET. C-band 4 W (1 chip) and 16 W (4 chip) GaAs MESFETs were used as the experimental samples. With these devices the simultaneous runaway of the gate and the drain currents, apparent dependence of the three teminal breakdown voltage on the gate bias resistance in the region dominated by electrical feedback, the rapid increase of the field emitted current at the critical temperature and clear coincidence between the measured and calculated three terminal gate currents both in the thermal feedback dominant region, etc. are demonstrated. The theory explains the experimental results well.

Instrumentation to Record Evoked Potentials for Closed-Loop Control of Deep Brain Stimulation

PubMed Central

Kent, Alexander R.; Grill, Warren M.

2012-01-01

Closed-loop deep brain stimulation (DBS) systems offer promise in relieving the clinical burden of stimulus parameter selection and improving treatment outcomes. In such a system, a feedback signal is used to adjust automatically stimulation parameters and optimize the efficacy of stimulation. We explored the feasibility of recording electrically evoked compound action potentials (ECAPs) during DBS for use as a feedback control signal. A novel instrumentation system was developed to suppress the stimulus artifact and amplify the small magnitude, short latency ECAP response during DBS with clinically relevant parameters. In vitro testing demonstrated the capabilities to increase the gain by a factor of 1,000x over a conventional amplifier without saturation, reduce distortion of mock ECAP signals, and make high fidelity recordings of mock ECAPs at latencies of only 0.5 ms following DBS pulses of 50 to 100 μs duration. Subsequently, the instrumentation was used to make in vivo recordings of ECAPs during thalamic DBS in cats, without contamination by the stimulus artifact. The signal characteristics were similar across three experiments, suggesting common neural activation patterns. The ECAP recordings enabled with this novel instrumentation may provide insight into the type and spatial extent of neural elements activated during DBS, and could serve as feedback control signals for closed-loop systems. PMID:22255894

Closed loop kinesthetic feedback for postural control rehabilitation.

PubMed

Vérité, Fabien; Bachta, Wael; Morel, Guillaume

2014-01-01

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

Closed-Loop Control of Myoelectric Prostheses With Electrotactile Feedback: Influence of Stimulation Artifact and Blanking.

PubMed

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.

Valproic acid disrupts the oscillatory expression of core circadian rhythm transcription factors.

PubMed

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.

Design and hardware-in-loop implementation of collision avoidance algorithms for heavy commercial road vehicles

NASA Astrophysics Data System (ADS)

Rajaram, Vignesh; Subramanian, Shankar C.

2016-07-01

An important aspect from the perspective of operational safety of heavy road vehicles is the detection and avoidance of collisions, particularly at high speeds. The development of a collision avoidance system is the overall focus of the research presented in this paper. The collision avoidance algorithm was developed using a sliding mode controller (SMC) and compared to one developed using linear full state feedback in terms of performance and controller effort. Important dynamic characteristics such as load transfer during braking, tyre-road interaction, dynamic brake force distribution and pneumatic brake system response were considered. The effect of aerodynamic drag on the controller performance was also studied. The developed control algorithms have been implemented on a Hardware-in-Loop experimental set-up equipped with the vehicle dynamic simulation software, IPG/TruckMaker®. The evaluation has been performed for realistic traffic scenarios with different loading and road conditions. The Hardware-in-Loop experimental results showed that the SMC and full state feedback controller were able to prevent the collision. However, when the discrepancies in the form of parametric variations were included, the SMC provided better results in terms of reduced stopping distance and lower controller effort compared to the full state feedback controller.

Organization of the Indian hedgehog--parathyroid hormone-related protein system in the postnatal growth plate.

PubMed

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.

Investigation on active vibration isolation of a Stewart platform with piezoelectric actuators

NASA Astrophysics Data System (ADS)

Wang, Chaoxin; Xie, Xiling; Chen, Yanhao; Zhang, Zhiyi

2016-11-01

A Stewart platform with piezoelectric actuators is presented for micro-vibration isolation. The Jacobi matrix of the Stewart platform, which reveals the relationship between the position/pointing of the payload and the extensions of the six struts, is derived by kinematic analysis. The dynamic model of the Stewart platform is established by the FRF (frequency response function) synthesis method. In the active control loop, the direct feedback of integrated forces is combined with the FxLMS based adaptive feedback to dampen vibration of inherent modes and suppress transmission of periodic vibrations. Numerical simulations were conducted to prove vibration isolation performance of the Stewart platform under random and periodical disturbances, respectively. In the experiment, the output consistencies of the six piezoelectric actuators were measured at first and the theoretical Jacobi matrix as well as the feedback gain of each piezoelectric actuator was subsequently modified according to the measured consistencies. The direct feedback loop was adjusted to achieve sufficient active damping and the FxLMS based adaptive feedback control was adopted to suppress vibration transmission in the six struts. Experimental results have demonstrated that the Stewart platform can achieve 30 dB attenuation of periodical disturbances and 10-20 dB attenuation of random disturbances in the frequency range of 5-200 Hz.

An Augmented Lecture Feedback System to Support Learner and Teacher Communication

ERIC Educational Resources Information Center

Zarraonandia, Telmo; Aedo, Ignacio; Diaz, Paloma; Montero, Alvaro

2013-01-01

In this paper, it is advocated that the feedback loop between learners and teachers could be improved by making use of augmented reality (AR) techniques. The bidirectional communication between teacher and learners is sometimes hampered by students' fear of showing themselves up in front of their classmates. In order to overcome this problem, a…

The Social Feedback Hypothesis and Communicative Development in Autism Spectrum Disorder: A Response to Akhtar, Jaswal, Dinishak, and Stephan (2016)

PubMed Central

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

2017-01-01

We focus here on two issues raised by Akhtar, Jaswal, Dinishak, and Stephan (2016): (a) the roles of motor skill and motivation to communicate within the feedback-loop model and (b) the clinical implications of the model. We then briefly discuss two additional issues. PMID:27664191

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

ERIC Educational Resources Information Center

Powney, Janet; Hall, Stuart

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

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

ERIC Educational Resources Information Center

Keaten, James A.

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

Linking Multimodal Communication and Feedback Loops to Reinforce Plagiarism Awareness

ERIC Educational Resources Information Center

O'Donnell, Kerri

2011-01-01

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

A Model for the Epigenetic Switch Linking Inflammation to Cell Transformation: Deterministic and Stochastic Approaches

PubMed Central

Gérard, Claude; Gonze, Didier; Lemaigre, Frédéric; Novák, Béla

2014-01-01

Recently, a molecular pathway linking inflammation to cell transformation has been discovered. This molecular pathway rests on a positive inflammatory feedback loop between NF-κB, Lin28, Let-7 microRNA and IL6, which leads to an epigenetic switch allowing cell transformation. A transient activation of an inflammatory signal, mediated by the oncoprotein Src, activates NF-κB, which elicits the expression of Lin28. Lin28 decreases the expression of Let-7 microRNA, which results in higher level of IL6 than achieved directly by NF-κB. In turn, IL6 can promote NF-κB activation. Finally, IL6 also elicits the synthesis of STAT3, which is a crucial activator for cell transformation. Here, we propose a computational model to account for the dynamical behavior of this positive inflammatory feedback loop. By means of a deterministic model, we show that an irreversible bistable switch between a transformed and a non-transformed state of the cell is at the core of the dynamical behavior of the positive feedback loop linking inflammation to cell transformation. The model indicates that inhibitors (tumor suppressors) or activators (oncogenes) of this positive feedback loop regulate the occurrence of the epigenetic switch by modulating the threshold of inflammatory signal (Src) needed to promote cell transformation. Both stochastic simulations and deterministic simulations of a heterogeneous cell population suggest that random fluctuations (due to molecular noise or cell-to-cell variability) are able to trigger cell transformation. Moreover, the model predicts that oncogenes/tumor suppressors respectively decrease/increase the robustness of the non-transformed state of the cell towards random fluctuations. Finally, the model accounts for the potential effect of competing endogenous RNAs, ceRNAs, on the dynamics of the epigenetic switch. Depending on their microRNA targets, the model predicts that ceRNAs could act as oncogenes or tumor suppressors by regulating the occurrence of cell transformation. PMID:24499937