WorldWideScience

Sample records for feedback loops involving

  1. Feedback Loop Gains and Feedback Behavior (1996)

    DEFF Research Database (Denmark)

    Kampmann, Christian Erik

    2012-01-01

    Linking feedback loops and system behavior is part of the foundation of system dynamics, yet the lack of formal tools has so far prevented a systematic application of the concept, except for very simple systems. Having such tools at their disposal would be a great help to analysts in understanding...... large, complicated simulation models. The paper applies tools from graph theory formally linking individual feedback loop strengths to the system eigenvalues. The significance of a link or a loop gain and an eigenvalue can be expressed in the eigenvalue elasticity, i.e., the relative change...... of an eigenvalue resulting from a relative change in the gain. The elasticities of individual links and loops may be found through simple matrix operations on the linearized system. Even though the number of feedback loops can grow rapidly with system size, reaching astronomical proportions even for modest systems...

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

    Energy Technology Data Exchange (ETDEWEB)

    Che, Qi; Liu, Bin-Ya; Wang, Fang-Yuan; He, Yin-Yan; Lu, Wen; Liao, Yun [Department of Obstetrics and Gynecology, Shanghai First People’s Hospital Affiliated to Shanghai Jiao Tong University, Shanghai (China); Gu, Wei, E-mail: krisgu70@163.com [Department of Obstetrics and Gynecology, International Peace Maternity and Child Health Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai (China); Wan, Xiao-Ping, E-mail: wanxp@sjtu.edu.cn [Department of Obstetrics and Gynecology, Shanghai First Maternity and Infant Hospital Affiliated to Tong Ji University, Shanghai (China)

    2014-03-28

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

  3. Regulation of β-catenin nuclear dynamics by GSK-3β involves a LEF-1 positive feedback loop.

    Science.gov (United States)

    Jamieson, Cara; Sharma, Manisha; Henderson, Beric R

    2011-08-01

    Nuclear localization of β-catenin is integral to its role in Wnt signaling and cancer. Cellular stimulation by Wnt or lithium chloride (LiCl) inactivates glycogen synthase kinase-3β (GSK-3β), causing nuclear accumulation of β-catenin and transactivation of genes that transform cells. β-catenin is a shuttling protein; however, the mechanism by which GSK-3β regulates β-catenin nuclear dynamics is poorly understood. Here, fluorescence recovery after photobleaching assays were used to measure the β-catenin-green fluorescent protein dynamics in NIH 3T3 cells before and after GSK-3β inhibition. We show for the first time that LiCl and Wnt3a cause a specific increase in β-catenin nuclear retention in live cells and in fixed cells after detergent extraction. Moreover, LiCl reduced the rate of nuclear export but did not affect import, hence biasing β-catenin transport toward the nucleus. Interestingly, the S45A mutation, which blocks β-catenin phosphorylation by GSK-3β, did not alter nuclear retention or transport, implying that GSK-3β acts through an independent regulator. We compared five nuclear binding partners and identified LEF-1 as the key mediator of Wnt3a and LiCl-induced nuclear retention of β-catenin. Thus, Wnt stimulation triggered a LEF-1 positive feedback loop to enhance the nuclear chromatin-retained pool of β-catenin by 100-300%. These findings shed new light on regulation of β-catenin nuclear dynamics.

  4. UWB communication receiver feedback loop

    Science.gov (United States)

    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.

  5. Positive feedback promotes oscillations in negative feedback loops.

    Directory of Open Access Journals (Sweden)

    Bharath Ananthasubramaniam

    Full Text Available A simple three-component negative feedback loop is a recurring motif in biochemical oscillators. This motif oscillates as it has the three necessary ingredients for oscillations: a three-step delay, negative feedback, and nonlinearity in the loop. However, to oscillate, this motif under the common Goodwin formulation requires a high degree of cooperativity (a measure of nonlinearity in the feedback that is biologically "unlikely." Moreover, this recurring negative feedback motif is commonly observed augmented by positive feedback interactions. Here we show that these positive feedback interactions promote oscillation at lower degrees of cooperativity, and we can thus unify several common kinetic mechanisms that facilitate oscillations, such as self-activation and Michaelis-Menten degradation. The positive feedback loops are most beneficial when acting on the shortest lived component, where they function by balancing the lifetimes of the different components. The benefits of multiple positive feedback interactions are cumulative for a majority of situations considered, when benefits are measured by the reduction in the cooperativity required to oscillate. These positive feedback motifs also allow oscillations with longer periods than that determined by the lifetimes of the components alone. We can therefore conjecture that these positive feedback loops have evolved to facilitate oscillations at lower, kinetically achievable, degrees of cooperativity. Finally, we discuss the implications of our conclusions on the mammalian molecular clock, a system modeled extensively based on the three-component negative feedback loop.

  6. A Mutant of Hepatitis B Virus X Protein (HBxΔ127 Promotes Cell Growth through A Positive Feedback Loop Involving 5-Lipoxygenase and Fatty Acid Synthase

    Directory of Open Access Journals (Sweden)

    Qi Wang

    2010-02-01

    Full Text Available Hepatocellular carcinoma (HCC is one of the most common malignant tumors worldwide. Hepatitis B virus X protein (HBx contributes to the development of HCC, whereas HBx with COOH-terminal deletion is a frequent event in the HCC tissues. Previously, we identified a natural mutant of HBx-truncated 27 amino acids at the COOH-terminal (termed HBxΔ127, which strongly enhanced cell growth. In the present study, we focused on investigating the mechanism. Accordingly, fatty acid synthase (FAS plays a crucial role in cancer cell survival and proliferation; thus, we examined the signaling pathways involving FAS. Our data showed that HBxΔ127 strongly increased the transcriptional activities of FAS in human hepatoma HepG2 and H7402 cells. Moreover, we found that 5-lipoxygenase (5-LOX was responsible for the up-regulation of FAS by using MK886 (an inhibitor of 5-LOX and 5-LOX small interfering RNA. We observed that HBxΔ127 could upregulate 5-LOX through phosphorylated extracellular signal-regulated protein kinases 1/2 and thus resulted in the increase of released leukotriene B4 (LTB4, a metabolite of 5-LOX by ELISA. The additional LTB4 could upregulate the expression of FAS in the cells as well. Interestingly, we found that FAS was able to upregulate the expression of 5-LOX in a feedback manner by using cerulenin (an inhibitor of FAS. Collectively, HBxΔ127 promotes cell growth through a positive feedback loop involving 5-LOX and FAS, in which released LTB4 is involved in the up-regulation of FAS. Thus, our finding provides a new insight into the mechanism involving the promotion of cell growth mediated by HBxΔ127.

  7. Finding the positive feedback loops underlying multi-stationarity

    DEFF Research Database (Denmark)

    Feliu, Elisenda; Wiuf, Carsten

    2015-01-01

    BACKGROUND: Bistability is ubiquitous in biological systems. For example, bistability is found in many reaction networks that involve the control and execution of important biological functions, such as signaling processes. Positive feedback loops, composed of species and reactions, are necessary...... for bistability, and generally for multi-stationarity, to occur. These loops are therefore often used to illustrate and pinpoint the parts of a multi-stationary network that are relevant ('responsible') for the observed multi-stationarity. However positive feedback loops are generally abundant in reaction...... networks but not all of them are important for understanding the network's dynamics. RESULTS: We present an automated procedure to determine the relevant positive feedback loops of a multi-stationary reaction network. The procedure only reports the loops that are relevant for multi-stationarity (that is...

  8. Finding the positive feedback loops underlying multi-stationarity

    DEFF Research Database (Denmark)

    Feliu, Elisenda; Wiuf, Carsten

    2015-01-01

    BACKGROUND: Bistability is ubiquitous in biological systems. For example, bistability is found in many reaction networks that involve the control and execution of important biological functions, such as signaling processes. Positive feedback loops, composed of species and reactions, are necessary...... for bistability, and generally for multi-stationarity, to occur. These loops are therefore often used to illustrate and pinpoint the parts of a multi-stationary network that are relevant ('responsible') for the observed multi-stationarity. However positive feedback loops are generally abundant in reaction...... networks but not all of them are important for understanding the network's dynamics. RESULTS: We present an automated procedure to determine the relevant positive feedback loops of a multi-stationary reaction network. The procedure only reports the loops that are relevant for multi-stationarity (that is...

  9. Pleckstrin homology domain-containing protein PHLDB3 supports cancer growth via a negative feedback loop involving p53

    Science.gov (United States)

    Chao, Tengfei; Zhou, Xiang; Cao, Bo; Liao, Peng; Liu, Hongbing; Chen, Yun; Park, Hee-Won; Zeng, Shelya X.; Lu, Hua

    2016-01-01

    The tumour suppressor p53 transactivates the expression of its target genes to exert its functions. Here, we identify a pleckstrin homology domain-containing protein (PHLDB3)-encoding gene as a p53 target. PHLDB3 overexpression increases proliferation and restrains apoptosis of wild-type p53-harboring cancer cells by reducing p53 protein levels. PHLDB3 binds to MDM2 (mouse double minute 2 homolog) and facilitates MDM2-mediated ubiquitination and degradation of p53. Knockdown of PHLDB3 more efficiently inhibits the growth of mouse xenograft tumours derived from human colon cancer HCT116 cells that contain wild type p53 compared with p53-deficient HCT116 cells, and also sensitizes tumour cells to doxorubicin and 5-Fluorouracil. Analysis of cancer genomic databases reveals that PHLDB3 is amplified and/or highly expressed in numerous human cancers. Altogether, these results demonstrate that PHLDB3 promotes tumour growth by inactivating p53 in a negative feedback fashion and suggest PHLDB3 as a potential therapeutic target in various human cancers. PMID:28008906

  10. Cutting the Loops of Depression: a System Dynamics Representation of the Feedback Mechanisms Involved in Depression Development

    NARCIS (Netherlands)

    Herrera, D.; Bleijenbergh, I.L.

    2016-01-01

    Depression is a complex illness that involves the instability of biological and psychological structures in an individual. These disturbances make a depressed person to be affected in the personal relationships within his social circles and to be unable to fulfill normal daily activities as expected

  11. Activation of PI3K/AKT and MAPK pathway through a PDGFRβ-dependent feedback loop is involved in rapamycin resistance in hepatocellular carcinoma.

    Directory of Open Access Journals (Sweden)

    Quan-Lin Li

    Full Text Available 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.

  12. Designing Self-Organized Contextualized Feedback Loops

    NARCIS (Netherlands)

    Kalz, Marco

    2013-01-01

    Kalz, M. (2013). Designing Self-Organized Contextualized Feedback Loops. In D. Whitelock, W. Warburton, G. Wills, & L. Gilbert (Eds.), International Conference on Computer Assisted Assessment (CAA 2013). July, 9-10, 2013, University of Southampton, Southampton, UK. http://caaconference.com.

  13. An adaptive phase alignment algorithm for cartesian feedback loops

    Science.gov (United States)

    Gimeno-Martin, A.; Pardo-Martin, J.; Ortega-Gonzalez, F.

    2010-01-01

    An adaptive algorithm to correct phase misalignments in Cartesian feedback linearization loops for power amplifiers has been presented. It yields an error smaller than 0.035 rad between forward and feedback loop signals once convergence is reached. Because this algorithm enables a feedback system to process forward and feedback samples belonging to almost the same algorithm iteration, it is suitable to improve the performance not only of power amplifiers but also any other digital feedback system for communications systems and circuits such as all digital phase locked loops. Synchronizing forward and feedback paths of Cartesian feedback loops takes a small period of time after the system starts up. The phase alignment algorithm needs to converge before the feedback Cartesian loop can start its ideal behavior. However, once the steady state is reached, both paths can be considered synchronized, and the Cartesian feedback loop will only depend on the loop parameters (open-loop gain, loop bandwidth, etc.). It means that the linearization process will also depend only on these parameters since the misalignment effect disappears. Therefore, this algorithm relieves the power amplifier linearizer circuit design of any task required for solving phase misalignment effects inherent to Cartesian feedback systems. Furthermore, when a feedback Cartesian loop has to be designed, the designer can consider that forward and feedback paths are synchronized, since the phase alignment algorithm will do this task. This will reduce the simulation complexity. Then, all efforts are applied to determining the suitable loop parameters that will make the linearization process more efficient.

  14. A novel positive feedback loop involving FASN/p-ERK1/2/5-LOX/LTB4/FASN sustains high growth of breast cancer cells

    Institute of Scientific and Technical Information of China (English)

    Nan HU; Yu LI; Yu ZHAO; Qi WANG; Jia-cong YOU; Xiao-dong ZHANG; Li-hong YE

    2011-01-01

    Aim: To investigate the endogenous signaling pathways associated with high proliferation potential of breast cancer cells.Methods: Breast cancer cell lines LM-MCF-7 and MCF-7 with high and low proliferation capability were used. The promoter activity of fatty acid synthase (FASN) was examined using luciferase reporter gene assay. The expression level of FASN mRNA was measured using RT-PCR and real time PCR, respectively. The level of leukotriene B4 (LTB4) was determined with ELISA. The expression levels of 5-lipoxygenase (5-LOX) was analyzed using RT-PCR and Western blot, respectively. 5-Bromo-20-deoxyuridine (BrdU) incorporation assay was used to study the proliferation of LM-MCF-7 and MCF-7 cells.Results: The promoter activity of FASN was significantly higher in LM-MCF-7 cells than MCF-7 cells. Treatment of LM-MCF-7 cells with ERK1/2 inhibitor PD98059 (30-50 μmol/L) or LOX inhibitor NDGA (25 μmol/L) abolished the activation of FASN. Moreover, treatment of LM-MCF-7 cells with the specific 5-LOX inhibitor MK-886 (20-40 μmol/L) or 5-LOX siRNA (50-100 nmol/L) decreased the promoter activity of FASN. The level of LTB4, the final metabolite produced by 5-LOX, was significantly higher in LM-MCF-7 cells than MCF-7 cells.Administration of exogenous LTB4 (1-10 nmol/L) was able to stimulate the promoter activity of FASN in MCF-7 cells. Treatment of LMMCF-7 cells with the FASN inhibitor cerulenin (10 μmol/L) reduced all the levels of p-ERK1/2, 5-LOX, and LTB4. Treatment of LM-MCF-7cells with cerulenin, PD98059, or MK-886 abolished the proliferation. Administration of exogenous LTB4 (10 nmol/L) significantly increased BrdU incorporation in MCF-7cells.Conclusion: These results suggest a novel positive feedback loop involving FASN/p-ERK1/2/5-LOX/LTB4/FASN contributes to the sustaining growth of breast cancer LM-MCF-7 cells.

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

    Science.gov (United States)

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

    2015-12-07

    Controlling cell division and differentiation in meristems is essential for proper plant growth. Two bHLH heterodimers consisting of LONESOME HIGHWAY (LHW) and TARGET OF MONOPTEROS 5 (TMO5)/TMO5-LIKE1 (T5L1) regulate periclinal cell division in vascular cells in the root apical meristem (RAM). In this study, we further investigated the functions of LHW-T5L1, finding that in addition to controlling cell division, this complex regulates xylem differentiation in the RAM via a novel negative regulatory system. LHW-T5L1 upregulated the thermospermine synthase gene ACAULIS5 (ACL5), as well as SUPPRESSOR OF ACAULIS5 LIKE3 (SACL3), which encodes a bHLH protein, in the RAM. The SACL3 promoter sequence contains a conserved upstream open reading frame (uORF), which blocked translation of the main SACL3 ORF in the absence of thermospermine. Thermospermine eliminated the negative effect of uORF and enhanced SACL3 production. Further genetic and molecular biological analyses indicated that ACL5 and SACL3 suppress the function of LHW-T5L1 through a protein-protein interaction between LHW and SACL3. Finally, we showed that a negative feedback loop consisting of LHW-T5L1, ACL5, SACL3, and LHW-SACL3 contributes to maintain RAM size and proper root growth. These findings suggest that a negative feedback loop regulates the LHW-T5L1 output level to coordinate cell division and differentiation in a cell-autonomous manner. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Identification of a feedback loop involving beta-glucosidase 2 and its product sphingosine sheds light on the molecular mechanisms in Gaucher disease.

    Science.gov (United States)

    Schonauer, Sophie; Körschen, Heinz G; Penno, Anke; Rennhack, Andreas; Breiden, Bernadette; Sandhoff, Konrad; Gutbrod, Katharina; Dörmann, Peter; Raju, Diana N; Haberkant, Per; Gerl, Mathias J; Brügger, Britta; Zigdon, Hila; Vardi, Ayelet; Futerman, Anthony H; Thiele, Christoph; Wachten, Dagmar

    2017-03-03

    The lysosomal acid beta-glucosidase GBA1 and the non-lysosomal beta-glucosidase GBA2 degrade glucosylceramide (GlcCer) to glucose and ceramide in different cellular compartments. Loss of GBA2 activity and the resulting accumulation of GlcCer results in male infertility, whereas mutations in the GBA1 gene and loss of GBA1 activity cause the lipid-storage disorder Gaucher disease. However, the role of GBA2 in Gaucher disease pathology and its relationship to GBA1 is not well understood. Here, we report a GBA1-dependent down-regulation of GBA2 activity in patients with Gaucher disease. Using an experimental approach combining cell biology, biochemistry, and mass spectrometry, we show that sphingosine, the cytotoxic metabolite accumulating in Gaucher cells through the action of GBA2, directly binds to GBA2 and inhibits its activity. We propose a negative feed-back loop, in which sphingosine inhibits GBA2 activity in Gaucher cells, preventing further sphingosine accumulation and, thereby, cytotoxicity. Our findings add a new chapter to the understanding of the complex molecular mechanism underlying Gaucher disease and the regulation of beta-glucosidase activity in general.

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

    Science.gov (United States)

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

    2011-01-01

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

  18. Let-7b/c enhance the stability of a tissue-specific mRNA during mammalian organogenesis as part of a feedback loop involving KSRP.

    Science.gov (United States)

    Repetto, Emanuela; Briata, Paola; Kuziner, Nathalie; Harfe, Brian D; McManus, Michael T; Gherzi, Roberto; Rosenfeld, Michael G; Trabucchi, Michele

    2012-01-01

    Gene silencing mediated by either microRNAs (miRNAs) or Adenylate/uridylate-rich elements Mediated mRNA Degradation (AMD) is a powerful way to post-transcriptionally modulate gene expression. We and others have reported that the RNA-binding protein KSRP favors the biogenesis of select miRNAs (including let-7 family) and activates AMD promoting the decay of inherently labile mRNAs. Different layers of interplay between miRNA- and AMD-mediated gene silencing have been proposed in cultured cells, but the relationship between the two pathways in living organisms is still elusive. We conditionally deleted Dicer in mouse pituitary from embryonic day (E) 9.5 through Cre-mediated recombination. In situ hybridization, immunohistochemistry, and quantitative reverse transcriptase-PCR revealed that Dicer is essential for pituitary morphogenesis and correct expression of hormones. Strikingly, αGSU (alpha glycoprotein subunit, common to three pituitary hormones) was absent in Dicer-deleted pituitaries. αGSU mRNA is unstable and its half-life increases during pituitary development. A transcriptome-wide analysis of microdissected E12.5 pituitaries revealed a significant increment of KSRP expression in conditional Dicer-deleted mice. We found that KSRP directly binds to αGSU mRNA, promoting its rapid decay; and, during pituitary development, αGSU expression displays an inverse temporal relationship to KSRP. Further, let-7b/c downregulated KSRP expression, promoting the degradation of its mRNA by directly binding to the 3'UTR. Therefore, we propose a model in which let-7b/c and KSRP operate within a negative feedback loop. Starting from E12.5, KSRP induces the maturation of let-7b/c that, in turn, post-transcriptionally downregulates the expression of KSRP itself. This event leads to stabilization of αGSU mRNA, which ultimately enhances the steady-state expression levels. We have identified a post-transcriptional regulatory network active during mouse pituitary development in

  19. Let-7b/c enhance the stability of a tissue-specific mRNA during mammalian organogenesis as part of a feedback loop involving KSRP.

    Directory of Open Access Journals (Sweden)

    Emanuela Repetto

    Full Text Available Gene silencing mediated by either microRNAs (miRNAs or Adenylate/uridylate-rich elements Mediated mRNA Degradation (AMD is a powerful way to post-transcriptionally modulate gene expression. We and others have reported that the RNA-binding protein KSRP favors the biogenesis of select miRNAs (including let-7 family and activates AMD promoting the decay of inherently labile mRNAs. Different layers of interplay between miRNA- and AMD-mediated gene silencing have been proposed in cultured cells, but the relationship between the two pathways in living organisms is still elusive. We conditionally deleted Dicer in mouse pituitary from embryonic day (E 9.5 through Cre-mediated recombination. In situ hybridization, immunohistochemistry, and quantitative reverse transcriptase-PCR revealed that Dicer is essential for pituitary morphogenesis and correct expression of hormones. Strikingly, αGSU (alpha glycoprotein subunit, common to three pituitary hormones was absent in Dicer-deleted pituitaries. αGSU mRNA is unstable and its half-life increases during pituitary development. A transcriptome-wide analysis of microdissected E12.5 pituitaries revealed a significant increment of KSRP expression in conditional Dicer-deleted mice. We found that KSRP directly binds to αGSU mRNA, promoting its rapid decay; and, during pituitary development, αGSU expression displays an inverse temporal relationship to KSRP. Further, let-7b/c downregulated KSRP expression, promoting the degradation of its mRNA by directly binding to the 3'UTR. Therefore, we propose a model in which let-7b/c and KSRP operate within a negative feedback loop. Starting from E12.5, KSRP induces the maturation of let-7b/c that, in turn, post-transcriptionally downregulates the expression of KSRP itself. This event leads to stabilization of αGSU mRNA, which ultimately enhances the steady-state expression levels. We have identified a post-transcriptional regulatory network active during mouse pituitary

  20. Control of breathing by interacting pontine and pulmonary feedback loops

    Directory of Open Access Journals (Sweden)

    Yaroslav I Molkov

    2013-02-01

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

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

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

    2002-12-01

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

  3. Reciprocal Feedback: Closing the Loop on Postactivity Surveys.

    Science.gov (United States)

    Watson, Richard A

    2015-01-01

    Those who conduct feedback surveys, which follow almost every CME presentation and medical-school lecture, would do well to offer participants' reciprocal feedback. That is, the course director should provide each survey respondent, on request, a brief summary of the comments received from this survey and the extent to which the recommendations will lead to objective improvements in the future. Surveyors who provide respondents with reciprocal feedback can expect heightened credibility, more reliable feedback in the future, and an added incentive to effect significant change for the better. Feedback has not circled all the way back until we have provided a succinct summary of results to those who have offered us their comments and suggestions. Let us close the loop; let reciprocal feedback become the last word in CME surveys.

  4. The double-loop feedback for active learning with understanding

    DEFF Research Database (Denmark)

    Christensen, Hans Peter

    2004-01-01

    Learning is an active process, and in engineering education authentic projects is often used to activate the students and promote learning. However, it is not all activity that leads to deep learning; and in a rapid changing society deep understanding is necessary for life-long learning. Empirical...... findings at DTU question the direct link between high activity and a deep approach to learning. Active learning is important to obtain engineering competencies, but active learning requires more than activity. Feedback and reflection is crucial to the learning process, since new knowledge is built...... on the student’s existing understanding. A model for an active learning process with a double-loop feedback is suggested - the first loop gives the student experience through experimentation, the second conceptual understanding through reflection. Students often miss the second loop, so it is important...

  5. The double-loop feedback for active learning with understanding

    DEFF Research Database (Denmark)

    Christensen, Hans Peter

    2004-01-01

    on the student’s existing understanding. A model for an active learning process with a double-loop feedback is suggested - the first loop gives the student experience through experimentation, the second conceptual understanding through reflection. Students often miss the second loop, so it is important......Learning is an active process, and in engineering education authentic projects is often used to activate the students and promote learning. However, it is not all activity that leads to deep learning; and in a rapid changing society deep understanding is necessary for life-long learning. Empirical...... findings at DTU question the direct link between high activity and a deep approach to learning. Active learning is important to obtain engineering competencies, but active learning requires more than activity. Feedback and reflection is crucial to the learning process, since new knowledge is built...

  6. Feedback Control Systems Loop Shaping Design with Practical Considerations

    Science.gov (United States)

    Kopsakis, George

    2007-01-01

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

  7. No evidence for an elephant-termite feedback loop in Sand Forest, South Africa

    NARCIS (Netherlands)

    Lagendijk, D. D G; Davies, A. B.; Eggleton, P.; Slotow, R.

    2016-01-01

    Termites and mammalian herbivores might derive mutual benefit from each other through positive feedback loops, but empirical evidence is lacking. One suggested positive feedback loop is between termites and elephant, both ecosystem engineers. Termites, as decomposer organisms, contribute to nutrient

  8. Towards a robust phase locked loop tune feedback system

    CERN Document Server

    Jones, R; Luo, Y

    2005-01-01

    Attempts to introduce a reliable tune feedback loop at RHIC (BNL) [1] have been thwarted by two main problems, namely transition crossing and betatron coupling. The problem of transition crossing is a dynamic range problem, resulting from the increase in the revolution content of the observed signal as the bunch length becomes short and from the fast orbit changes that occur during transition. The dynamic range issue is being addressed by the development of a baseband tune measurement system [2] as part of the US LHC Accelerator Research Program (US-LARP). This paper will focus on the second problem, showing how a phase locked loop (PLL) tune measurement system can be used to continuously measure global betatron coupling, and in so doing allow for robust tune measurement and feedback in the presence of coupling.

  9. System and method of designing models in a feedback loop

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    Science.gov (United States)

    Tiwari, Abhinav; Igoshin, Oleg A

    2012-10-01

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

  11. Dynamical consequences of bandpass feedback loops in a bacterial phosphorelay.

    Directory of Open Access Journals (Sweden)

    Shaunak Sen

    Full Text Available 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.

  12. A closed-loop analysis of the tubuloglomerular feedback mechanism

    DEFF Research Database (Denmark)

    Holstein-Rathlou, N H

    1991-01-01

    The tubuloglomerular feedback (TGF) mechanism is of importance in the regulation of glomerular filtration rate (GFR). A second mechanism of potential importance is the change in proximal pressure caused by a change, for example, in the rate of proximal fluid reabsorption. The quantitative...... nl/min in steps of 5 nl/min. The open-loop gain (OLG) was 3.1 (range 1.5-9.9, n = 13) at the unperturbed tubular flow rate, and decreased as the tubular flow rate was either increased or decreased. The proximal pressure increased by 0.21 +/- 0.03 mmHg per unit increase in late proximal flow rate (nl...... contributions of these two mechanisms to the regulation of GFR and the late proximal flow rate are not known. To determine the regulatory efficiency of these two mechanisms, the late proximal flow rate was perturbed by microperfusion with artificial tubular fluid in halothane-anesthetized Sprague-Dawley rats...

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

    Science.gov (United States)

    Sherblom, Stephen A.

    2015-01-01

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

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

    Science.gov (United States)

    Sherblom, Stephen A.

    2015-01-01

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

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

    Science.gov (United States)

    Vijayan, V; Panda, Rames C

    2012-07-01

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

  16. A Feedback Loop between Inflammation and Zn Uptake.

    Directory of Open Access Journals (Sweden)

    Paola Bonaventura

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

  17. A Feedback Loop between Inflammation and Zn Uptake.

    Science.gov (United States)

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

    2016-01-01

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

  18. Immune signal transduction in leishmaniasis from natural to artificial systems: role of feedback loop insertion.

    Science.gov (United States)

    Mol, Milsee; Patole, Milind S; Singh, Shailza

    2014-01-01

    Modulated immune signal (CD14-TLR and TNF) in leishmaniasis can be linked to EGFR pathway involved in wound healing, through crosstalk points. This signaling network can be further linked to a synthetic gene circuit acting as a positive feedback loop to elicit a synchronized intercellular communication among the immune cells which may contribute to a better understanding of signaling dynamics in leishmaniasis. Network reconstruction with positive feedback loop, simulation (ODE 15s solver) and sensitivity analysis of CD14-TLR, TNF and EGFR was done in SimBiology (MATLAB 7.11.1). Cytoscape and adjacency matrix were used to calculate network topology. PCA was extracted by using sensitivity coefficient in MATLAB. Model reduction was done using time, flux and sensitivity score. Network has five crosstalk points: NIK, IκB-NFκB and MKK (4/7, 3/6, 1/2) which show high flux and sensitivity. PI3K in EGFR pathway shows high flux and sensitivity. PCA score was high for cytoplasmic ERK1/2, PI3K, Atk, STAT1/3 and nuclear JNK. Of the 125 parameters, 20% are crucial as deduced by model reduction. EGFR can be linked to CD14-TLR and TNF through the MAPK crosstalk points. These pathways may be controlled through Ras and Raf that lie upstream of signaling components ERK ½ (c) and JNK (n) that have a high PCA score via a synthetic gene circuit for activating cell-cell communication to elicit an inflammatory response. Also a disease resolving effect may be achieved through PI3K in the EGFR pathway. The reconstructed signaling network can be linked to a gene circuit with a positive feedback loop, for cell-cell communication resulting in synchronized response in the immune cell population, for disease resolving effect in leishmaniasis. © 2013 Elsevier B.V. All rights reserved.

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

    CERN Document Server

    Teytelman, Dmitry

    2005-01-01

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

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

    Science.gov (United States)

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

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

  1. All-Optical WDM Buffer System Realized by NOLM and Feedback Loop Structure

    Institute of Scientific and Technical Information of China (English)

    Seungwoo Yi; Kyeong-Mo Yoon; Yong-Gi Lee; Jinseob Eom

    2003-01-01

    We propose an all-optical WDM buffer for optical packet switching system, which consists of NOLM and feedback loop. The proposed structure provides more than 40 turn buffering and nice output of buffered data when selected by control signal.

  2. Poisoned Feedback: The Impact of Malicious Users in Closed-Loop Multiuser MIMO Systems

    CERN Document Server

    Mukherjee, Amitav

    2010-01-01

    Accurate channel state information (CSI) at the transmitter is critical for maximizing spectral efficiency on the downlink of multi-antenna networks. In this work we analyze a novel form of physical layer attacks on such closed-loop wireless networks. Specifically, this paper considers the impact of deliberately inaccurate feedback by malicious users in a multiuser multicast system. Numerical results demonstrate the significant degradation in performance of closed-loop transmission schemes due to intentional feedback of false CSI by adversarial users.

  3. Time Optimal Synchronization Procedure and Associated Feedback Loops

    CERN Document Server

    Angoletta, Maria Elena; CERN. Geneva. ATS Department

    2016-01-01

    A procedure to increase the speed of currently used synchronization loops in a synchrotron by an order of magnitude is presented. Beams dynamics constraint imposes an upper limit on excursions in stable phase angle, and the procedure presented exploits this limit to arrive in the synchronized state from an arbitrary initial state in the fastest possible way. Detailed corrector design for beam phase loop, differential frequency loop and final synchronization loop is also presented. Finally, an overview of the synchronization methods currently deployed in some other CERN’s machines is provided, together with a brief comparison with the newly proposed time-optimal algorithm.

  4. Stress-specific response of the p53-Mdm2 feedback loop

    Directory of Open Access Journals (Sweden)

    Jensen Mogens H

    2010-07-01

    Full Text Available Abstract Background The p53 signalling pathway has hundreds of inputs and outputs. It can trigger cellular senescence, cell-cycle arrest and apoptosis in response to diverse stress conditions, including DNA damage, hypoxia and nutrient deprivation. Signals from all these inputs are channeled through a single node, the transcription factor p53. Yet, the pathway is flexible enough to produce different downstream gene expression patterns in response to different stresses. Results We construct a mathematical model of the negative feedback loop involving p53 and its inhibitor, Mdm2, at the core of this pathway, and use it to examine the effect of different stresses that trigger p53. In response to DNA damage, hypoxia, etc., the model exhibits a wide variety of specific output behaviour - steady states with low or high levels of p53 and Mdm2, as well as spiky oscillations with low or high average p53 levels. Conclusions We show that even a simple negative feedback loop is capable of exhibiting the kind of flexible stress-specific response observed in the p53 system. Further, our model provides a framework for predicting the differences in p53 response to different stresses and single nucleotide polymorphisms.

  5. Robot impedance control and passivity analysis with inner torque and velocity feedback loops

    Institute of Scientific and Technical Information of China (English)

    Michele FOCCHI; Gustavo A MEDRANO-CERDA; Thiago BOAVENTURA; Marco FRIGERIO; Claudio SEMINI; Jonas BUCHLI; Darwin G CALDWELL

    2016-01-01

    Impedance control is a well-established technique to control interaction forces in robotics. However, real implementations of impedance control with an inner loop may suffer from several limitations. In particular, the viable range of stable stiffness and damping values can be strongly affected by the bandwidth of the inner control loops (e.g., a torque loop) as well as by the filtering and sampling frequency. This paper provides an extensive analysis on how these aspects influence the stability region of impedance parameters as well as the passivity of the system. This will be supported by both simulations and experimental data. Moreover, a methodology for designing joint impedance controllers based on an inner torque loop and a positive velocity feedback loop will be presented. The goal of the velocity feedback is to increase (given the constraints to preserve stability) the bandwidth of the torque loop without the need of a complex controller.

  6. OncomiR addiction is generated by a miR-155 feedback loop in Theileria-transformed leukocytes.

    Science.gov (United States)

    Marsolier, Justine; Pineau, Sandra; Medjkane, Souhila; Perichon, Martine; Yin, Qinyan; Flemington, Erik; Weitzman, Matthew D; Weitzman, Jonathan B

    2013-01-01

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

  7. Identification of feedback loops embedded in cellular circuits by investigating non-causal impulse response components.

    Science.gov (United States)

    Dong, Chao-Yi; Yoon, Tae-Woong; Bates, Declan G; Cho, Kwang-Hyun

    2010-02-01

    Feedback circuits are crucial dynamic motifs which occur in many biomolecular regulatory networks. They play a pivotal role in the regulation and control of many important cellular processes such as gene transcription, signal transduction, and metabolism. In this study, we develop a novel computationally efficient method to identify feedback loops embedded in intracellular networks, which uses only time-series experimental data and requires no knowledge of the network structure. In the proposed approach, a non-parametric system identification technique, as well as a spectral factor analysis, is applied to derive a graphical criterion based on non-causal components of the system's impulse response. The appearance of non-causal components in the impulse response sequences arising from stochastic output perturbations is shown to imply the presence of underlying feedback connections within a linear network. In order to extend the approach to nonlinear networks, we linearize the intracellular networks about an equilibrium point, and then choose the magnitude of the output perturbations sufficiently small so that the resulting time-series responses remain close to the chosen equilibrium point. In this way, the impulse response sequences of the linearized system can be used to determine the presence or absence of feedback loops in the corresponding nonlinear network. The proposed method utilizes the time profile data from intracellular perturbation experiments and only requires the perturbability of output nodes. Most importantly, the method does not require any a priori knowledge of the system structure. For these reasons, the proposed approach is very well suited to identifying feedback loops in large-scale biomolecular networks. The effectiveness of the proposed method is illustrated via two examples: a synthetic network model with a negative feedback loop and a nonlinear caspase function model of apoptosis with a positive feedback loop.

  8. A negative feedback loop mediated by STAT3 limits human Th17 responses.

    Science.gov (United States)

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

    2014-08-01

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

  9. Charge-driven feedback loop in the resonance fluorescence of a single quantum dot

    Science.gov (United States)

    Merkel, B.; Kurzmann, A.; Schulze, J.-H.; Strittmatter, A.; Geller, M.; Lorke, A.

    2017-03-01

    We demonstrate a feedback loop that manifests itself in a strong hysteresis and bistability of the exciton resonance fluorescence signal. Field ionization of photogenerated quantum dot excitons leads to the formation of a charged interface layer that drags the emission line along over a frequency range of more than 30 GHz . These measurements are well described by a rate equation model. With a time-resolved resonance fluorescence measurement we determined the buildup times for the hole gas in the orders of milliseconds. This internal charge-driven feedback loop could be used to reduce the spectral wandering in the emission spectra of single self-assembled quantum dots.

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

    Science.gov (United States)

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

    2010-11-01

    The investigation of the structure and dynamics of signal transduction systems through data-based mathematical models in ordinary differential equations or other paradigms has proven to be a successful approach in recent times. Extending this concept, we here analysed the use of kinetic models based on power-law terms with non-integer kinetic orders in the validation of hypotheses concerning regulatory structures in signalling systems. We integrated pre-existent biological knowledge, hypotheses and experimental quantitative data into a power-law model to validate the existence of certain regulatory loops in the Ras/Raf-1/MEK/ERK pathway, a MAPK pathway involved in the transduction of mitogenic and differentiation signals. Towards this end, samples of a human mammary epithelial cell line (MCF-10A) were used to obtain time-series data, characterising the behaviour of the system after epidermal growth factor stimulation in different scenarios of expression for the critical players of the system regarding the investigated loops (e.g., the inhibitory protein RKIP). The mathematical model was calibrated using a computational procedure that included: analysis of structural identifiability, global ranking of parameters to detect the most sensitivity ones towards the experimental setup, model calibration using global optimization methods to find the parameter values that better fit the data, and practical identifiability analysis to estimate the confidence in the estimated values for the parameters. The obtained model was used to perform computational simulations concerning the role of the investigated regulatory loops in the time response of the signalling pathway. Our findings suggest that the special regularity in the structure of the power-law terms make them suitable for a data-based validation of regulatory loops in signalling pathways. The model-based analysis performed identified RKIP as an actual inhibitor of the activation of the ERK pathway, but also suggested

  11. The oncoprotein HBXIP modulates the feedback loop of MDM2/p53 to enhance the growth of breast cancer.

    Science.gov (United States)

    Li, Hang; Liu, Qian; Wang, Zhen; Fang, Runping; Shen, Yu; Cai, Xiaoli; Gao, Yuen; Li, Yinghui; Zhang, Xiaodong; Ye, Lihong

    2015-09-11

    MDM2 and p53 form a negative feedback loop, in which p53 as a transcription factor positively regulates MDM2 and MDM2 negatively regulates tumor suppressor p53 through promoting its degradation. However, the mechanism of the feedback loop is poorly understood in cancers. We had reported previously that the oncoprotein hepatitis B X-interacting protein (HBXIP) is a key oncoprotein in the development of cancer. Thus, we supposed that HBXIP might be involved in the event. Here, we observed that the expression levels of HBXIP were positively correlated to those of MDM2 in clinical breast cancer tissues. Interestingly, HBXIP was able to up-regulate MDM2 at the levels of mRNA and protein in MCF-7 breast cancer cells. Mechanically, HBXIP increased the promoter activities of MDM2 through directly binding to p53 in the P2 promoter of MDM2. Strikingly, we identified that the acetyltransferase p300 was recruited by HBXIP to p53 in the promoter of MDM2. Moreover, we validated that HBXIP enhanced the p53 degradation mediated by MDM2. Functionally, the knockdown of HBXIP or/and p300 inhibited the proliferation of breast cancer cells in vitro, and the depletion of MDM2 or overexpression of p53 significantly blocked the HBXIP-promoted growth of breast cancer in vitro and in vivo. Thus, we concluded that highly expressed HBXIP accelerates the MDM2-mediated degradation of p53 in breast cancer through modulating the feedback loop of MDM2/p53, resulting in the fast growth of breast cancer cells. Our findings provide new insights into the mechanism of the acceleration of the MDM2/p53 feedback loop in the development of cancer.

  12. Analysis of feedback loops and robustness in network evolution based on Boolean models

    Directory of Open Access Journals (Sweden)

    Cho Kwang-Hyun

    2007-11-01

    Full Text Available Abstract Background Many biological networks such as protein-protein interaction networks, signaling networks, and metabolic networks have topological characteristics of a scale-free degree distribution. Preferential attachment has been considered as the most plausible evolutionary growth model to explain this topological property. Although various studies have been undertaken to investigate the structural characteristics of a network obtained using this growth model, its dynamical characteristics have received relatively less attention. Results In this paper, we focus on the robustness of a network that is acquired during its evolutionary process. Through simulations using Boolean network models, we found that preferential attachment increases the number of coupled feedback loops in the course of network evolution. Whereas, if networks evolve to have more coupled feedback loops rather than following preferential attachment, the resulting networks are more robust than those obtained through preferential attachment, although both of them have similar degree distributions. Conclusion The presented analysis demonstrates that coupled feedback loops may play an important role in network evolution to acquire robustness. The result also provides a hint as to why various biological networks have evolved to contain a number of coupled feedback loops.

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

    Science.gov (United States)

    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…

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

    Directory of Open Access Journals (Sweden)

    Saunders Ian

    2011-10-01

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

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

    Science.gov (United States)

    Ito, Sosuke; Sagawa, Takahiro

    2015-06-23

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

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

    Science.gov (United States)

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

    2016-03-16

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

  17. Micro-RNA Feedback Loops Modulating the Calcineurin/NFAT Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Shichina Kannambath

    2016-05-01

    Full Text Available Nuclear factor of activated T cells (NFAT is a family of transcription factors important for innate and adaptive immune responses. NFAT activation is tightly regulated through the calcineurin/NFAT signaling pathway. There is increasing evidence on non-coding RNAs such as miRNAs playing a crucial role in regulating transcription factors and signaling pathways. However, not much is known about microRNAs (miRNAs targeting the calcineurin/NFAT signaling pathway involved in immune response in human. In this study, a comprehensive pathway level analysis has been carried out to identify miRNAs regulating the calcineurin/NFAT signaling pathway. Firstly, by incorporating experimental data and computational predictions, 191 unique miRNAs were identified to be targeting the calcineurin/NFAT signaling pathway in humans. Secondly, combining miRNA expression data from activated T cells and computational predictions, 32 miRNAs were observed to be induced by NFAT transcription factors. Finally, 11 miRNAs were identified to be involved in a feedback loop to modulate the calcineurin/NFAT signaling pathway activity. This data demonstrate the potential role of miRNAs as regulators of the calcineurin/NFAT signaling pathway. The present study thus emphasizes the importance of pathway level analysis to identify miRNAs and understands their role in modulating signaling pathways and transcription factor activity.

  18. The oncoprotein p28GANK establishes a positive feedback loop in β-catenin signaling

    Institute of Scientific and Technical Information of China (English)

    Li-wei Dong; Guang-zhen Yang; Yu-fei Pan; Yao Chen; Ye-xiong Tan; Rong-yang Dai; Yi-bin Ren; Jing Fu; Hong-yang Wang

    2011-01-01

    p28GANK (also known as PSMD10 or gankyrin) is a novel oncoprotein that is highly expressed in hepatocellular carcinoma (HCC). Through its interaction with various proteins, p28GANK mediates the degradation of the tumor suppressor proteins Rb and p53. Although p53 was reported to downregulate β-catenin, whether p28GANK is involved in the regulation of β-catenin remains uncertain. Here we report that both growth factors and Ras upregulate p28GANK expression through the activation of the phosphoinosttide 3-kinase-AKT pathway. Upregulation of p28GANK expression subsequently enhanced the transcription activity of β-catenin. This effect was observed in p53-deficient cells, suggesting a p53-independent mechanism for the p28GANK-mediated activation of β-catenin, p28GANK overexpression also reduced E-cadherin protein levels, leading to increased release of free β-catenin into the cytoplasm from the cadherin-bound pool. Interestingly, exogenous expression of p28GANK resulted in elevated expression of the endogenous protein. We also observed that both β-catenin and c-Myc were transcriptional activators of p28GANK, and a correlation between p28GANK overexpression and c-Myc, cyclin D1 and β-catenin activation in primary human HCC. Together, these results suggest that p28GANK expression is regulated by a positive feedback loop involving β-catenin, which may play a critical role in tumorigenesis and the progression of HCC.

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

    Science.gov (United States)

    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.

  20. Closed-loop response properties of a visual interneuron involved in fly optomotor control

    Directory of Open Access Journals (Sweden)

    Naveed eEjaz

    2013-03-01

    Full Text Available Due to methodological limitations neural function is mostly studied under open-loop conditions. Normally, however, nervous systems operate in closed-loop where sensory input is processed to generate behavioural outputs, which again change the sensory input. Here, we investigate the closed-loop responses of an identified visual interneuron, the blowfly H1-cell, that is part of a neural circuit involved in optomotor flight and gaze control. Those behaviours may be triggered by attitude changes during flight in turbulent air. The fly analyses the resulting retinal image shifts and performs compensatory body and head rotations to regain its default attitude. We developed a fly-robot interface to study H1-cell responses in a 1 degree-of-freedom image stabilization task. Image shifts, induced by externally forced rotations, modulate the cell’s spike rate that controls counter rotations of a mobile robot to minimize relative motion between the robot and its visual surroundings. A feedback controller closed the loop between neural activity and the rotation of the robot. Under these conditions we found the following H1-cell response properties: (i the peak spike rate decreases when the mean image velocity is increased, (ii the relationship between spike rate and image velocity depends on the standard deviation of the image velocities suggesting adaptive scaling of the cell’s signalling range, and (iii the cell’s gain decreases linearly with increasing image accelerations.Our results reveal a remarkable qualitative similarity between the response dynamics of the H1-cell under closed-loop conditions with those obtained in previous open-loop experiments. Finally, we show that the adaptive scaling of the H1-cell’s responses, while maximizing information on image velocity, decreases the cell’s sensitivity to image accelerations. Understanding such trade-offs in biological vision systems may advance the design of smart vision sensors for autonomous

  1. Closed-loop response properties of a visual interneuron involved in fly optomotor control.

    Science.gov (United States)

    Ejaz, Naveed; Krapp, Holger G; Tanaka, Reiko J

    2013-01-01

    Due to methodological limitations neural function is mostly studied under open-loop conditions. Normally, however, nervous systems operate in closed-loop where sensory input is processed to generate behavioral outputs, which again change the sensory input. Here, we investigate the closed-loop responses of an identified visual interneuron, the blowfly H1-cell, that is part of a neural circuit involved in optomotor flight and gaze control. Those behaviors may be triggered by attitude changes during flight in turbulent air. The fly analyses the resulting retinal image shifts and performs compensatory body and head rotations to regain its default attitude. We developed a fly robot interface to study H1-cell responses in a 1 degree-of-freedom image stabilization task. Image shifts, induced by externally forced rotations, modulate the cell's spike rate that controls counter rotations of a mobile robot to minimize relative motion between the robot and its visual surroundings. A feedback controller closed the loop between neural activity and the rotation of the robot. Under these conditions we found the following H1-cell response properties: (i) the peak spike rate decreases when the mean image velocity is increased, (ii) the relationship between spike rate and image velocity depends on the standard deviation of the image velocities suggesting adaptive scaling of the cell's signaling range, and (iii) the cell's gain decreases linearly with increasing image accelerations. Our results reveal a remarkable qualitative similarity between the response dynamics of the H1-cell under closed-loop conditions with those obtained in previous open-loop experiments. Finally, we show that the adaptive scaling of the H1-cell's responses, while maximizing information on image velocity, decreases the cell's sensitivity to image accelerations. Understanding such trade-offs in biological vision systems may advance the design of smart vision sensors for autonomous robots.

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

    Science.gov (United States)

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

    2012-01-01

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

  3. Self-injection-locked magnetron as an active ring resonator side coupled to a waveguide with a delayed feedback loop

    CERN Document Server

    Bliokh, Y P; Felsteiner, J

    2011-01-01

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

  4. Negative feedback loops leading to nitrate homeostasis and oscillatory nitrate assimilation in plants and fungi.

    OpenAIRE

    Huang, Yongshun

    2011-01-01

    Nitrate is an important nutrient for plants and fungi. For plants it has been shown that cytosolic nitrate levels are under homeostatic control. Here we describe two networks that can obtain robust, i.e. perturbation independent, homeostatic behavior in cytosolic nitrate concentration. One of the networks, a member in the family of outflow controllers, is based on a negative feedback loop containing a nitrate-induced activation of a controller molecule which removes nitrate. In plants this co...

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

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

    2012-12-01

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

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

    Science.gov (United States)

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

    2011-01-01

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

  8. REVEILLE8 and PSEUDO-REPONSE REGULATOR5 form a negative feedback loop within the Arabidopsis circadian clock.

    Directory of Open Access Journals (Sweden)

    Reetika Rawat

    2011-03-01

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

  9. A Platform for Closing the Open Data Feedback Loop Based on Web2.0 Functionality

    Directory of Open Access Journals (Sweden)

    Charalampos Alexopoulos

    2014-11-01

    Full Text Available One essential element of open data ecosystems concerns their development through feedback loops, discussions and dynamic supplier and user interactions. These user-centric features communicate the users’ needs to the open data community as well to the public sector bodies responsible for data publication. Addressing these needs by the corresponding public sector bodies or even by utilising the power of the community as ENGAGE supports will actually accelerate innovation. However, these elements appear barely to be part of existing open data practices. We conducted a survey which showed that most professional open data users did not know at least one open data infrastructure that enabled five specific types of discussion and feedback mechanisms. The survey showed that much can still be done to improve feedback and discussion on open data infrastructures. In this paper we discuss an open data platform which has started to contribute to filling this gap and present a usage scenario explaining the sequence of the underlined functionality. The discussed ENGAGE open data infrastructure combines functionalities to close the feedback loop and to return information to public authorities for better open data use and publication as well as establishing communication channels between stakeholders. This may effectively lead to the stimulation and facilitation of value generation from open data, as such functionality position the user at the centre of the open data publication process.

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

    Energy Technology Data Exchange (ETDEWEB)

    Dunlop, Mary; Keasling, Jay; Mukhopadhyay, Aindrila

    2011-07-14

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

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

    Science.gov (United States)

    Wang, Junwei; Zhou, Tianshou

    2010-06-01

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

  12. Equilibrium models of coronal loops that involve curvature and buoyancy

    CERN Document Server

    Hindman, Bradley W

    2013-01-01

    We construct magnetostatic models of coronal loops in which the thermodynamics of the loop is fully consistent with the shape and geometry of the loop. This is achieved by treating the loop as a thin, compact, magnetic fibril that is a small departure from a force-free state. The density along the loop is related to the loop's curvature by requiring that the Lorentz force arising from this deviation is balanced by buoyancy. This equilibrium, coupled with hydrostatic balance and the ideal gas law, then connects the temperature of the loop with the curvature of the loop without resorting to a detailed treatment of heating and cooling. We present two example solutions: one with a spatially invariant magnetic Bond number (the dimensionless ratio of buoyancy to Lorentz forces) and the other with a constant radius of curvature of the loop's axis. We find that the density and temperature profiles are quite sensitive to curvature variations along the loop, even for loops with similar aspect ratios.

  13. Equilibrium Models of Coronal Loops That Involve Curvature and Buoyancy

    Science.gov (United States)

    Hindman, Bradley W.; Jain, Rekha

    2013-12-01

    We construct magnetostatic models of coronal loops in which the thermodynamics of the loop is fully consistent with the shape and geometry of the loop. This is achieved by treating the loop as a thin, compact, magnetic fibril that is a small departure from a force-free state. The density along the loop is related to the loop's curvature by requiring that the Lorentz force arising from this deviation is balanced by buoyancy. This equilibrium, coupled with hydrostatic balance and the ideal gas law, then connects the temperature of the loop with the curvature of the loop without resorting to a detailed treatment of heating and cooling. We present two example solutions: one with a spatially invariant magnetic Bond number (the dimensionless ratio of buoyancy to Lorentz forces) and the other with a constant radius of the curvature of the loop's axis. We find that the density and temperature profiles are quite sensitive to curvature variations along the loop, even for loops with similar aspect ratios.

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

    Science.gov (United States)

    Shi, X; Zhan, X; Wu, J

    2015-11-30

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

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

    Science.gov (United States)

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

    2016-09-01

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

  16. A feedback loop between dynamin and actin recruitment during clathrin-mediated endocytosis.

    Directory of Open Access Journals (Sweden)

    Marcus J Taylor

    Full Text Available 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.

  17. Impact of time delays on oscillatory dynamics of interlinked positive and negative feedback loops

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    Banerjee, Subhasis; Bose, Indrani

    2008-12-01

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

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

    Science.gov (United States)

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

    2002-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Richard Moore

    2015-12-01

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

  1. Designing Dialogic E-Learning in Pharmacy Professionalism Using Calibrated Feedback Loops (CFLs

    Directory of Open Access Journals (Sweden)

    Sue Roff

    2013-09-01

    Full Text Available The feedback analytics of online software including Articulate and Bristol Online Surveys can be used to facilitate dialogic learning in a community of practice such as Pharmacy and, thereby, promote reflective learning by the creation of formative calibrated feedback loops. Based on work with medical, dental, nursing, osteopathic, and social work students, trainees, and registrants, the paper shows how an online learning community can be created along the continuum from undergraduate to registrant to develop authentic dialogic e-learning around standards of Professionalism. The Dundee PolyProfessionalism inventories and Situational Judgement Scenarios (SJSs can be customised for Pharmacy Professionalism learning to support evidence-based curriculum design along benchmarked learning curves and to profile Professionalism learning in individuals and cohorts.

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

    Science.gov (United States)

    Joo, Jaewook

    2010-03-01

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

  3. A Positive Feedback Loop between Akt and mTORC2 via SIN1 Phosphorylation

    OpenAIRE

    Guang Yang; Danielle S. Murashige; Sean J. Humphrey; David E. James

    2015-01-01

    The mechanistic target of rapamycin complex 2 (mTORC2) regulates cell survival and cytoskeletal organization by phosphorylating its AGC kinase substrates; however, little is known about the regulation of mTORC2 itself. It was previously reported that Akt phosphorylates the mTORC2 subunit SIN1 at T86, activating mTORC2 through a positive feedback loop, though another study reported that S6K phosphorylates SIN1 at the same site, inhibiting mTORC2 activity. We performed extensive analysis of SIN...

  4. Quantitative assessment of the p53-Mdm2 feedback loop using protein lysate microarrays.

    Science.gov (United States)

    Ramalingam, Sundhar; Honkanen, Peter; Young, Lynn; Shimura, Tsutomu; Austin, John; Steeg, Patricia S; Nishizuka, Satoshi

    2007-07-01

    Mathematical simulations of the p53-Mdm2 feedback loop suggest that both proteins will exhibit impulsive expression characteristics in response to high cellular stress levels. However, little quantitative experimental evaluation has been done, particularly of the phosphorylated forms. To evaluate the mathematical models experimentally, we used lysate microarrays from an isogenic pair of gamma-ray-irradiated cell lysates from HCT116 (p53(+/+) and p53(-/-)). Both p53 and Mdm2 proteins showed expected pulses in the wild type, whereas no pulses were seen in the knockout. Based on experimental observations, we determined model parameters and generated an in silico "knockout," reflecting the experimental data, including phosphorylated proteins.

  5. Controlling Unknown Saddle Type Steady States of Dynamical Systems with Latency in the Feedback Loop

    DEFF Research Database (Denmark)

    Tamasevicius, Arunas; Bumeliene, Skaidra; Tamaseviciute, Elena

    2009-01-01

    We suggest an adaptive control technique for stabilizing saddle type unstable steady states of dynamical systems. The controller is composed of an unstable and a stable high-pass filters operating in parallel. The mathematical model is considered analytically and numerically. The conjoint...... controller is sufficiently robust to time latencies in the feedback loop. In addition, it is not sensitive to the damping parameters of the system and is relatively fast. Experiments have been performed using a simplified version of the electronic Young-Silva circuit imitating behavior of the Duffing...

  6. The regulation of the p53/MDM2 feedback loop by microRNAs

    OpenAIRE

    2015-01-01

    Tumor suppressor p53 and its signaling pathway play a central role in tumor prevention. The E3 ubiquitin ligase MDM2, which is a direct p53 transcriptional target and also the most critical negative regulator of p53, forms an autoregulatory negative feedback loop with p53 in the cell to tightly regulate the levels and activity of p53. MicroRNAs (miRNAs) are endogenously expressed small non-coding RNAs that play a critical role in the post-translational regulation of gene expression. Recent st...

  7. DESIGN OF MULTIPLE-LOOP FEEDBACK HIGH-ORDER CURRENT-MODE FILTER BASED ON FTFNS

    Institute of Scientific and Technical Information of China (English)

    Xi Yanhui; Peng Liangyu

    2009-01-01

    A general multiple-loop feedback approach for realization of Four-Terminal Floating Nullor C (FTFN-RC) filter is presented.The proposed filter is constructed by multi-output FTFNs,capacitors and resistors.It can simultaneously realize slow-pass,band-pass(if order is even number),and high-pass filter responses.With RC elements grounded and requiring no component matching constraints,it is fully integrated conveniently.Simulations are performed for the fourth-order Butterworth filter to verify the validity of the circuit.

  8. Pulse oximeter improvement with an ADC-DAC feedback loop and a radial reflectance sensor.

    Science.gov (United States)

    Thompson, David; Wareing, Austin; Day, Dwight; Warren, Steve

    2006-01-01

    Pulse oximeter circuitry must meet several design constraints, including the ability to separate a small pulsatile signal component from a large signal baseline. This paper describes pulse oximeter design changes that produced order-of-magnitude improvements in signal quality. The primary changes were (a) the replacement of an analog sample-and-hold-based differentiator circuit with an ADC-DAC feedback loop and (b) the replacement of a side-by-side reflectance sensor design with a radial sensor arrangement that maximizes the pulsatile-to-baseline signal ratio.

  9. Synthetic feedback loop model for increasing microbial biofuel production using a biosensor

    Directory of Open Access Journals (Sweden)

    Mary eHarrison

    2012-10-01

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

  10. Stability of an ion beam in synchrotrons with digital filters in the feedback loop of a transverse damper

    Science.gov (United States)

    Zhabitsky, V. M.

    2010-12-01

    The stability of an ion beam in synchrotrons with digital filters in the feedback loop of a transverse damper is treated. A transverse feedback system (TFS) is required in synchrotrons to stabilize the high intensity ion beams against transverse instabilities and to damp the beam injection errors. The TFS damper kicker (DK) corrects the transverse momentum of a bunch in proportion to its displacement from the closed orbit at the location of the beam position monitor (BPM). The digital signal processing unit in the feedback loop between BPM and DK ensures a condition to achieve optimal damping. Damping rates of the feedback systems with digital filters are analysed in comparison with those in an ideal feedback system.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

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

    2016-01-01

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

  13. Resilience of Urban Smart Grids Involving Multiple Control Loops

    DEFF Research Database (Denmark)

    Madsen, Jacob Theilgaard; Pillai, Jayakrishnan Radhakrishna; Schwefel, Hans-Peter

    2016-01-01

    Intelligent control of energy distribution grids is implemented via a hierarchy of control loops with different input values and different control targets, which also work on different time-scales. This control is enabled by a bi-directional communication flow, which can be interrupted due to ICT...... attacks. It is therefore necessary to analyze and understand the emergent behavior resulting from the interplay of the different control loops and how this behavior may change under different communication scenarios. The simulation scenario considered in this paper is a medium and low voltage grid...... in island mode with a limited grid buffer capacity subjected to ICT attacks. First the interplay of four different control loops that all react to time-varying prices is analyzed. A co-simulation framework is applied to specifically investigate the sensitivity of the emergent grid behavior to extreme...

  14. Positive Feedback Loop of Autocrine BDNF from Microglia Causes Prolonged Microglia Activation

    Directory of Open Access Journals (Sweden)

    Xin Zhang

    2014-08-01

    Full Text Available Background/Aims: Microglia, which represent the immune cells of the central nervous system (CNS, have long been a subject of study in CNS disease research. Substantial evidence indicates that microglial activation functions as a strong neuro-inflammatory response in neuropathic pain, promoting the release of pro-inflammatory cytokines, such as tumor necrosis factor (TNF-α. In addition, activated microglia release brain-derived neurotrophic factor (BDNF, which acts as a powerful cytokine. In this study, we performed a series of in vitro experiments to examine whether a positive autocrine feedback loop existed between microglia-derived BDNF and subsequent microglial activation as well as the mechanisms underlying this positive feedback loop. Methods: Because ATP is a classic inducer of microglial activation, firstly, we examined ATP-activated microglia in the present study. Secondly, we used TrkB/Fc, the BDNF sequester, to eliminate the effects of endogenous BDNF. ATP-stimulated microglia without BDNF was examined. Finally, we used exogenous BDNF to further determine whether BDNF could directly activate BV2 microglia. In all experiments, to quantify BV2 microglia activation, the protein levels of CD11b, a microglial activation marker, were measured by western blot. A Transwell migration assay was used to examine microglial migration. To assess the synthesis and release of proinflammatory cytokines, western blot was used to measure BDNF synthesis, and ELISA was used to quantify TNF-α release. Results: In our present research, we have observed that ATP dramatically activates microglia, enhancing microglial migration, increasing the synthesis of BDNF and up-regulating the release of TNF-α. Microglial activation is inhibited following the sequestration of endogenous BDNF, resulting in impaired microglial migration and decreased TNF-α release. Furthermore, exogenous BDNF can also activate microglia to subsequently enhance migration and increase TNF

  15. Resilience of Urban Smart Grids Involving Multiple Control Loops

    DEFF Research Database (Denmark)

    Madsen, Jacob Theilgaard; Pillai, Jayakrishnan Radhakrishna; Schwefel, Hans-Peter

    2016-01-01

    Intelligent control of energy distribution grids is implemented via a hierarchy of control loops with different input values and different control targets, which also work on different time-scales. This control is enabled by a bi-directional communication flow, which can be interrupted due to ICT...

  16. Adaptive correction of human-eye aberrations in a subjective feedback loop.

    Science.gov (United States)

    Vdovin, G; Loktev, M; Simonov, A; Kijko, V; Volkov, S

    2005-04-01

    An adaptive optical system with a subjective feedback loop is used to improve the visual acuity and to determine the aberrations of the human eye. Corrections of as many as 12 low-order aberration modes were made, based on the perceived sharpness of the test object observed through the adaptive optical system. The acuity of vision was improved by adjustment of the weights of the orthogonal modes produced by a deformable mirror. Objective measurements of the correcting aspherical figures, obtained in independent subjective correction cycles for one person, demonstrated good repeatability. Participants in the study with strong ocular aberrations reported moderate to significant improvement of their visual acuity, estimated with the U.S. Air Force 1951 acuity chart.

  17. Messenger RNA Fluctuations and Regulatory RNAs Shape the Dynamics of Negative Feedback Loop

    CERN Document Server

    Martínez, María Rodríguez; Tlusty, Tsvi; Pilpel, Yitzhak; Furman, Itay; 10.1103/PhysRevE.81.031924

    2010-01-01

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

  18. The Double Feedback Loop and the Parameter Theory of Text Genres

    DEFF Research Database (Denmark)

    Bundgaard, Peer; Østergaard, Svend

    2014-01-01

    parameter theory of genres which is presented in Section 3. Here we consider genres as governed by parameters external to them and intrinsic to the situations they are dynamically related to. Genres should thus be understood not simply in terms of inherent textual or formal traits, but also relative......[This article has a double scope. First, we consider the dynamics inherent in the emergence of genres. Our view is that genres emerge relative to two sets of constraints, which we aim to capture in our double feedback loop model for the dynamics of genres. On the one hand, (text) genres, or text...... to a certain set of situational parameters and relative to the degree to which they are governed by them.]...

  19. PML, YAP, and p73 are components of a proapoptotic autoregulatory feedback loop.

    Science.gov (United States)

    Lapi, Eleonora; Di Agostino, Silvia; Donzelli, Sara; Gal, Hilah; Domany, Eytan; Rechavi, Gideon; Pandolfi, Pier Paolo; Givol, David; Strano, Sabrina; Lu, Xin; Blandino, Giovanni

    2008-12-26

    p73 has been identified as a structural and functional homolog of the tumor suppressor p53. The transcriptional coactivator Yes-associated protein (YAP) has been demonstrated to interact with and to enhance p73-dependent apoptosis in response to DNA damage. Here, we show the existence of a proapoptotic autoregulatory feedback loop between p73, YAP, and the promyelocytic leukemia (PML) tumor suppressor gene. We demonstrate that PML is a direct transcriptional target of p73/YAP, and we show that PML transcriptional activation by p73/YAP is under the negative control of the proto-oncogenic Akt/PKB kinase. Importantly, we find that PML and YAP physically interact through their PVPVY and WW domains, respectively, causing PML-mediated sumoylation and stabilization of YAP. Hence, we determine a mechanistic pathway in response to DNA damage that could have relevant implications for the treatment of human cancer.

  20. Compensation of focal plane image motion perturbations with optical correlator in feedback loop

    Science.gov (United States)

    Janschek, Klaus; Tchernykh, Valerij; Dyblenko, Serguei; Flandin, Gregory; Harnisch, Bernd

    2004-11-01

    The paper presents a concept of a smart pushbroom imaging system with compensation of attitude instability effects. The compensation is performed by active opto-mechatronic stabilization of the focal plane image motion in a closed loop system with visual feedback on base of an auxiliary matrix image sensor and an onboard optical correlator. In this way the effects of the attitude instability, vibrations and micro shocks can be neutralized, the image quality improved and the requirements to satellite attitude stability reduced. To prove the feasibility and to estimate the effectiveness of the image motion stabilization, a performance model of the smart imaging system has been developed and a simulation experiment has been carried out. The description of the performance model and the results of the simulation experiment are also given.

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

    Science.gov (United States)

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

    2011-12-01

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

  2. Disturbance of the let-7/LIN28 double-negative feedback loop is associated with radio- and chemo-resistance in non-small cell lung cancer.

    Science.gov (United States)

    Yin, Jun; Zhao, Jian; Hu, Weimin; Yang, Guangping; Yu, Hui; Wang, Ruihao; Wang, Linjing; Zhang, Guoqian; Fu, Wenfan; Dai, Lu; Li, Wanzhen; Liao, Boyu; Zhang, Shuxu

    2017-01-01

    Radio- and chemo-resistance represent major obstacles in the therapy of non-small-cell lung cancer (NSCLC) and the underlying molecular mechanisms are not known. In the present study, during induction of radio- or chemo-resistance in NSCLC cells, dynamic analyses revealed that decreased expression of let-7 induced by irradiation or cisplatin resulted in increased expression of its target gene LIN28, and increased expression of LIN28 then contributed to further decreased expression of let-7 by inhibiting its maturation and biogenesis. Moreover, we showed that down-regulation of let-7 and up-regulation of LIN28 expression promoted resistance to irradiation or cisplatin by regulating the single-cell proliferative capability of NSCLC cells. Consequently, in NSCLC cells, let-7 and LIN28 can form a double-negative feedback loop through mutual inhibition, and disturbance of the let-7/LIN28 double-negative feedback loop induced by irradiation or chemotherapeutic drugs can result in radio- and chemo-resistance. In addition, low expression of let-7 and high expression of LIN28 in NSCLC patients was associated significantly with resistance to radiotherapy or chemotherapy. Therefore, our study demonstrated that disturbance of the let-7/LIN28 double-negative feedback loop is involved in the regulation of radio- and chemo-resistance, and that let-7 and LIN28 could be employed as predictive biomarkers of response to radiotherapy or chemotherapy in NSCLC patients.

  3. FRET imaging and statistical signal processing reveal positive and negative feedback loops regulating the morphology of randomly migrating HT-1080 cells.

    Science.gov (United States)

    Kunida, Katsuyuki; Matsuda, Michiyuki; Aoki, Kazuhiro

    2012-05-15

    Cell migration plays an important role in many physiological processes. Rho GTPases (Rac1, Cdc42, RhoA) and phosphatidylinositols have been extensively studied in directional cell migration. However, it remains unclear how Rho GTPases and phosphatidylinositols regulate random cell migration in space and time. We have attempted to address this issue using fluorescence resonance energy transfer (FRET) imaging and statistical signal processing. First, we acquired time-lapse images of random migration of HT-1080 fibrosarcoma cells expressing FRET biosensors of Rho GTPases and phosphatidyl inositols. We developed an image-processing algorithm to extract FRET values and velocities at the leading edge of migrating cells. Auto- and cross-correlation analysis suggested the involvement of feedback regulations among Rac1, phosphatidyl inositols and membrane protrusions. To verify the feedback regulations, we employed an acute inhibition of the signaling pathway with pharmaceutical inhibitors. The inhibition of actin polymerization decreased Rac1 activity, indicating the presence of positive feedback from actin polymerization to Rac1. Furthermore, treatment with PI3-kinase inhibitor induced an adaptation of Rac1 activity, i.e. a transient reduction of Rac1 activity followed by recovery to the basal level. In silico modeling that reproduced the adaptation predicted the existence of a negative feedback loop from Rac1 to actin polymerization. Finally, we identified MLCK as the probable controlling factor in the negative feedback. These findings quantitatively demonstrate positive and negative feedback loops that involve actin, Rac1 and MLCK, and account for the ordered patterns of membrane dynamics observed in randomly migrating cells.

  4. KAYAK-α modulates circadian transcriptional feedback loops in Drosophila pacemaker neurons.

    Science.gov (United States)

    Ling, Jinli; Dubruille, Raphaëlle; Emery, Patrick

    2012-11-21

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

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

    Science.gov (United States)

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

    2012-03-06

    Circadian clocks synchronise biological processes with the day/night cycle, using molecular mechanisms that include interlocked, transcriptional feedback loops. Recent experiments identified the evening complex (EC) as a repressor that can be essential for gene expression rhythms in plants. Integrating the EC components in this role significantly alters our mechanistic, mathematical model of the clock gene circuit. Negative autoregulation of the EC genes constitutes the clock's evening loop, replacing the hypothetical component Y. The EC explains our earlier conjecture that the morning gene Pseudo-Response Regulator 9 was repressed by an evening gene, previously identified with Timing Of CAB Expression1 (TOC1). Our computational analysis suggests that TOC1 is a repressor of the morning genes Late Elongated Hypocotyl and Circadian Clock Associated1 rather than an activator as first conceived. This removes the necessity for the unknown component X (or TOC1mod) from previous clock models. As well as matching timeseries and phase-response data, the model provides a new conceptual framework for the plant clock that includes a three-component repressilator circuit in its complex structure.

  6. Tumor-promoting function of apoptotic caspases by an amplification loop involving ROS, macrophages and JNK in Drosophila.

    Science.gov (United States)

    Pérez, Ernesto; Lindblad, Jillian L; Bergmann, Andreas

    2017-08-30

    Apoptosis and its molecular mediators, the caspases, have long been regarded as tumor suppressors and one hallmark of cancer is 'Evading Apoptosis'. However, recent work has suggested that apoptotic caspases can also promote proliferation and tumor growth under certain conditions. How caspases promote proliferation and how cells are protected from the potentially harmful action of apoptotic caspases is largely unknown. Here, we show that although caspases are activated in a well-studied neoplastic tumor model in Drosophila, oncogenic mutations of the proto-oncogene Ras (Ras(V12)) maintain tumorous cells in an 'undead'-like condition and transform caspases from tumor suppressors into tumor promotors. Instead of killing cells, caspases now promote the generation of intra- and extracellular reactive oxygen species (ROS). One function of the ROS is the recruitment and activation of macrophage-like immune cells which in turn signal back to tumorous epithelial cells to activate oncogenic JNK signaling. JNK further promotes and amplifies caspase activity, thereby constituting a feedback amplification loop. Interfering with the amplification loop strongly reduces the neoplastic behavior of these cells and significantly improves organismal survival. In conclusion, Ras(V12)-modified caspases initiate a feedback amplification loop involving tumorous epithelial cells and macrophage-like immune cells that is necessary for uncontrolled tumor growth and invasive behavior.

  7. A Diagnosis-Prognosis Feedback Loop for Improved Performance Under Uncertainties

    Science.gov (United States)

    Leser, Patrick E.; Warner, James E.

    2017-01-01

    The feed-forward relationship between diagnosis and prognosis is the foundation of both aircraft structural health management and the digital twin concept. Measurements of structural response are obtained either in-situ with mounted sensor networks or offline using more traditional techniques (e.g., nondestructive evaluation). Diagnosis algorithms process this information to detect and quantify damage and then feed this data forward to a prognostic framework. A prognosis of the structure's future operational readiness (e.g., remaining useful life or residual strength) is then made and is used to inform mission- critical decision-making. Years of research have been devoted to improving the elements of this process, but the process itself has not changed significantly. Here, a new approach is proposed in which prognosis information is not only fed forward for decision-making, but it is also fed back to the forthcoming diagnosis. In this way, diagnosis algorithms can take advantage of a priori information about the expected state of health, rather than operating in an uninformed condition. As a feasibility test, a diagnosis-prognosis feedback loop of this manner is demonstrated. The approach is applied to a numerical example in which fatigue crack growth is simulated in a simple aluminum alloy test specimen. A prognosis was derived from a set of diagnoses which provided feedback to a subsequent set of diagnoses. Improvements in accuracy and a reduction in uncertainty in the prognosis- informed diagnoses were observed when compared with an uninformed diagnostic approach.

  8. A Fully Differential Interface Circuit of Closed-loop Accelerometer with Force Feedback Linearization

    Institute of Scientific and Technical Information of China (English)

    HongLin Xu; HongNa Liu; Chong He; Liang Yin; XiaoWei Liu

    2014-01-01

    In this paper, a fifth-order fully differential interface circuit ( IC) is presented to improve the noise performance for micromechanical sigma-delta (Σ-Δ) accelerometer. A lead compensator is adopted to ensure the stability of the closed-loop high-order system. A low noise capacitance detection circuit is described with a correlated-double-sampling ( CDS) technique to decrease 1/f noise and offset of the operational amplifier. This paper also proposes a self-test technique for the interface circuit to test the harmonic distortion. An electrostatic force feedback linearization circuit is presented to reduce the harmonic distortion resulting in larger dynamic range ( DR) . The layout of the IC is implemented in a standard 0�6 μm CMOS technology and operates at a sampling frequency of 250 kHz. The interface consumes 20 mW from a 5 V supply. The post-simulation results indicate that the noise floor of the digital accelerometer is about -140 dBV/Hz1/2 at low frequency. The sensitivity is 2.5 V/g and the nonlinearity is 0�11%. The self-test function is achieved with 98�2 dB third-order harmonic distortion detection based on the electrostatic force feedback linearization.

  9. [Open loop gain of the CO2-ventilation feedback control system in chronic obstructive pulmonary disease].

    Science.gov (United States)

    Kimura, H; Kunitomo, F; Okita, S; Tojima, H; Tatsumi, K; Kuriyama, T; Hashizume, I; Honda, Y

    1989-07-01

    To evaluate the stability of the CO2-ventilation feedback system, we measured its open loop gain (G) in 12 patients with chronic obstructive pulmonary disease (COPD) and 15 control subjects. Then, we compared G to the conventional slope of the CO2-ventilation response line (S) and that of the metabolic hyperbola (SL). G was determined as the ratio of S to SL by applying external dead space of 250 and 500 ml. G, S and 1/SL in the control and the COPD were +17.1 +/- 7.2 (Mean +/- SD), 1.70 +/- 0.75 L.min-1.Torr-1 and -10.4 +/- 2.0 L-1.min.Torr, and -7.2 +/- 3.3, 0.48 +/- 0.27 L.min-1.Torr-1 and -16.1 +/- 6.4 L-1.min.Torr, respectively. G was significantly correlated with S in both groups, but that was not the case in 1/SL. The magnitude of G and S in COPD was about 42% and 28% of the control, indicating that G was maintained more stable than S. These data suggest that the decreased G in the COPD resulted from insufficient compensation of ventilatory drive, whereas 1/SL increased higher than the control. We conclude that G can be used to indicate the stability of the CO2-ventilation feedback system better than S.

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

    Energy Technology Data Exchange (ETDEWEB)

    Wang Junwei, E-mail: wangjunweilj@yahoo.com.c [Cisco School of Informatics, Guangdong University of Foreign Studies, Guangzhou 510006 (China); Zhou Tianshou [School of Mathematics and Computational Science, Sun Yat-Sen University, Guangzhou 510275 (China)

    2010-06-14

    Previous studies showed that a single negative feedback structure should be sufficient for robust circadian oscillations. It is thus pertinent to ask why current cellular clock models almost universally have interlocked negative feedback loop (NFL) and positive feedback loop (PFL). Here, we propose a molecular model that reflects the essential features of the Drosophila circadian clock to clarify the different roles of negative and positive feedback loops. In agreement with experimental observations, the model can simulate circadian oscillations in constant darkness, entrainment by light-dark cycles, as well as phenotypes of per{sup 01} and clk{sup Jrk} mutants. Moreover, sustained oscillations persist when the PFL is removed, implying the crucial role of NFL for rhythm generation. Through parameter sensitivity analysis, it is revealed that incorporation of PFL increases the robustness of the system to regulatory processes in PFL itself. Such reduced models can aid understanding of the design principles of circadian clocks in Drosophila and other organisms with complex transcriptional feedback structures.

  11. In vivo Microscale Measurements of Light and Photosynthesis during Coral Bleaching: Evidence for the Optical Feedback Loop?

    Science.gov (United States)

    Wangpraseurt, Daniel; Holm, Jacob B; Larkum, Anthony W D; Pernice, Mathieu; Ralph, Peter J; Suggett, David J; Kühl, Michael

    2017-01-01

    Climate change-related coral bleaching, i.e., the visible loss of zooxanthellae from the coral host, is increasing in frequency and extent and presents a major threat to coral reefs globally. Coral bleaching has been proposed to involve accelerating light stress of their microalgal endosymbionts via a positive feedback loop of photodamage, symbiont expulsion and excess in vivo light exposure. To test this hypothesis, we used light and O2 microsensors to characterize in vivo light exposure and photosynthesis of Symbiodinium during a thermal stress experiment. We created tissue areas with different densities of Symbiodinium cells in order to understand the optical properties and light microenvironment of corals during bleaching. Our results showed that in bleached Pocillopora damicornis corals, Symbiodinium light exposure was up to fivefold enhanced relative to healthy corals, and the relationship between symbiont loss and light enhancement was well-described by a power-law function. Cell-specific rates of Symbiodinium gross photosynthesis and light respiration were enhanced in bleached P. damicornis compared to healthy corals, while areal rates of net photosynthesis decreased. Symbiodinium light exposure in Favites sp. revealed the presence of low light microniches in bleached coral tissues, suggesting that light scattering in thick coral tissues can enable photoprotection of cryptic symbionts. Our study provides evidence for the acceleration of in vivo light exposure during coral bleaching but this optical feedback mechanism differs between coral hosts. Enhanced photosynthesis in relation to accelerating light exposure shows that coral microscale optics exerts a key role on coral photophysiology and the subsequent degree of radiative stress during coral bleaching.

  12. In vivo Microscale Measurements of Light and Photosynthesis during Coral Bleaching: Evidence for the Optical Feedback Loop?

    Science.gov (United States)

    Wangpraseurt, Daniel; Holm, Jacob B.; Larkum, Anthony W. D.; Pernice, Mathieu; Ralph, Peter J.; Suggett, David J.; Kühl, Michael

    2017-01-01

    Climate change-related coral bleaching, i.e., the visible loss of zooxanthellae from the coral host, is increasing in frequency and extent and presents a major threat to coral reefs globally. Coral bleaching has been proposed to involve accelerating light stress of their microalgal endosymbionts via a positive feedback loop of photodamage, symbiont expulsion and excess in vivo light exposure. To test this hypothesis, we used light and O2 microsensors to characterize in vivo light exposure and photosynthesis of Symbiodinium during a thermal stress experiment. We created tissue areas with different densities of Symbiodinium cells in order to understand the optical properties and light microenvironment of corals during bleaching. Our results showed that in bleached Pocillopora damicornis corals, Symbiodinium light exposure was up to fivefold enhanced relative to healthy corals, and the relationship between symbiont loss and light enhancement was well-described by a power-law function. Cell-specific rates of Symbiodinium gross photosynthesis and light respiration were enhanced in bleached P. damicornis compared to healthy corals, while areal rates of net photosynthesis decreased. Symbiodinium light exposure in Favites sp. revealed the presence of low light microniches in bleached coral tissues, suggesting that light scattering in thick coral tissues can enable photoprotection of cryptic symbionts. Our study provides evidence for the acceleration of in vivo light exposure during coral bleaching but this optical feedback mechanism differs between coral hosts. Enhanced photosynthesis in relation to accelerating light exposure shows that coral microscale optics exerts a key role on coral photophysiology and the subsequent degree of radiative stress during coral bleaching. PMID:28174567

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

    Science.gov (United States)

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

    2010-03-01

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

  14. A Positive Feedback Loop between Akt and mTORC2 via SIN1 Phosphorylation

    Directory of Open Access Journals (Sweden)

    Guang Yang

    2015-08-01

    Full Text Available The mechanistic target of rapamycin complex 2 (mTORC2 regulates cell survival and cytoskeletal organization by phosphorylating its AGC kinase substrates; however, little is known about the regulation of mTORC2 itself. It was previously reported that Akt phosphorylates the mTORC2 subunit SIN1 at T86, activating mTORC2 through a positive feedback loop, though another study reported that S6K phosphorylates SIN1 at the same site, inhibiting mTORC2 activity. We performed extensive analysis of SIN1 phosphorylation upon inhibition of Akt, S6K, and mTOR under diverse cellular contexts, and we found that, in all cell lines and conditions studied, Akt is the major kinase responsible for SIN1 phosphorylation. These findings refine the activation mechanism of the Akt-mTORC2 signaling branch as follows: PDK1 phosphorylates Akt at T308, increasing Akt kinase activity. Akt phosphorylates SIN1 at T86, enhancing mTORC2 kinase activity, which leads to phosphorylation of Akt S473 by mTORC2, thereby catalyzing full activation of Akt.

  15. A Positive Feedback Loop between Akt and mTORC2 via SIN1 Phosphorylation.

    Science.gov (United States)

    Yang, Guang; Murashige, Danielle S; Humphrey, Sean J; James, David E

    2015-08-11

    The mechanistic target of rapamycin complex 2 (mTORC2) regulates cell survival and cytoskeletal organization by phosphorylating its AGC kinase substrates; however, little is known about the regulation of mTORC2 itself. It was previously reported that Akt phosphorylates the mTORC2 subunit SIN1 at T86, activating mTORC2 through a positive feedback loop, though another study reported that S6K phosphorylates SIN1 at the same site, inhibiting mTORC2 activity. We performed extensive analysis of SIN1 phosphorylation upon inhibition of Akt, S6K, and mTOR under diverse cellular contexts, and we found that, in all cell lines and conditions studied, Akt is the major kinase responsible for SIN1 phosphorylation. These findings refine the activation mechanism of the Akt-mTORC2 signaling branch as follows: PDK1 phosphorylates Akt at T308, increasing Akt kinase activity. Akt phosphorylates SIN1 at T86, enhancing mTORC2 kinase activity, which leads to phosphorylation of Akt S473 by mTORC2, thereby catalyzing full activation of Akt.

  16. Supporting graduate nurse transition to practice through a quality assurance feedback loop.

    Science.gov (United States)

    Phillips, Craig; Kenny, Amanda; Esterman, Adrian

    2017-09-04

    This mixed-method study focused on new graduate nurses and their transition to practice. Transition to practice can be a time of heightened stress and anxiety, leaving many new graduates disillusioned and dissatisfied with their work. The study explored how satisfaction levels with transition may improve during their first year, using a unique approach of a continuous quality assurance feedback loop. This assurance framework is utilised in hospitality, automotive and supply chain logistics and in health, primarily to monitor patient outcomes. However, an association with graduate nurse satisfaction has not been previously reported. Graduate nurses from two health services completed a short survey questionnaire every four weeks for 12 months. De-identified aggregated data was sent to health service management, giving them an opportunity to integrate the findings with the objective of potentially increasing graduate satisfaction ratings. Quantitative findings showed no statistical significance of graduate nurse satisfaction scores between health services, however, one health service consistently outperformed the other. Qualitative findings drawn from a seminar and interviews confirmed that one health service took a more proactive stance with the monthly reports, communicating the results to ward managers. Outcomes reflected a greater commitment of support and an overall increase of satisfaction scores. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Propofol detection and quantification in human blood: the promise of feedback controlled, closed-loop anesthesia.

    Science.gov (United States)

    Kivlehan, Francine; Chaum, Edward; Lindner, Ernő

    2015-01-07

    The performance of a membrane-coated voltammetric sensor for propofol (2,6-diisopropylphenol) has been characterized in long term monitoring experiments using an automated flow analytical system (AFAS) and by analyzing human serum and whole blood samples by standard addition. It is shown that the signal of the membrane-coated electrochemical sensor for propofol is not influenced by the components of the pharmaceutical formulation of propofol (propofol injectable emulsion). The current values recorded with the electrochemical propofol sensor in buffer solutions and human serum samples spiked with propofol injectable emulsion showed excellent correlation with the peak heights recorded with an UV-Vis detector during the HPLC analysis of these samples (R(2) = 0.997 in PBS and R(2) = 0.975 in human serum). However, the determination of propofol using the electrochemical method is simpler, faster and has a better detection limit (0.08 ± 0.05 μM) than the HPLC method (0.4 ± 0.2 μM). As a first step towards feedback controlled closed-loop anesthesia, the membrane-coated electrochemical sensor has been implemented onto surface of an intravenous catheter. The response characteristics of the membrane-coated carbon fiber electrode on the catheter surface were very similar to those seen using a macroelectrode.

  18. Online Reconstruction and Calibration with Feedback Loop in the ALICE High Level Trigger

    Directory of Open Access Journals (Sweden)

    Rohr David

    2016-01-01

    at the Large Hadron Collider (LHC at CERN. The High Level Trigger (HLT is an online computing farm, which reconstructs events recorded by the ALICE detector in real-time. The most computing-intensive task is the reconstruction of the particle trajectories. The main tracking devices in ALICE are the Time Projection Chamber (TPC and the Inner Tracking System (ITS. The HLT uses a fast GPU-accelerated algorithm for the TPC tracking based on the Cellular Automaton principle and the Kalman filter. ALICE employs gaseous subdetectors which are sensitive to environmental conditions such as ambient pressure and temperature and the TPC is one of these. A precise reconstruction of particle trajectories requires the calibration of these detectors. As our first topic, we present some recent optimizations to our GPU-based TPC tracking using the new GPU models we employ for the ongoing and upcoming data taking period at LHC. We also show our new approach to fast ITS standalone tracking. As our second topic, we present improvements to the HLT for facilitating online reconstruction including a new flat data model and a new data flow chain. The calibration output is fed back to the reconstruction components of the HLT via a feedback loop. We conclude with an analysis of a first online calibration test under real conditions during the Pb-Pb run in November 2015, which was based on these new features.

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

    Science.gov (United States)

    Reed, Phil

    2016-03-01

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

  20. Online Reconstruction and Calibration with Feedback Loop in the ALICE High Level Trigger

    Science.gov (United States)

    Rohr, David; Shahoyan, Ruben; Zampolli, Chiara; Krzewicki, Mikolaj; Wiechula, Jens; Gorbunov, Sergey; Chauvin, Alex; Schweda, Kai; Lindenstruth, Volker

    2016-11-01

    ALICE (A Large Heavy Ion Experiment) is one of the four large scale experiments at the Large Hadron Collider (LHC) at CERN. The High Level Trigger (HLT) is an online computing farm, which reconstructs events recorded by the ALICE detector in real-time. The most computing-intensive task is the reconstruction of the particle trajectories. The main tracking devices in ALICE are the Time Projection Chamber (TPC) and the Inner Tracking System (ITS). The HLT uses a fast GPU-accelerated algorithm for the TPC tracking based on the Cellular Automaton principle and the Kalman filter. ALICE employs gaseous subdetectors which are sensitive to environmental conditions such as ambient pressure and temperature and the TPC is one of these. A precise reconstruction of particle trajectories requires the calibration of these detectors. As our first topic, we present some recent optimizations to our GPU-based TPC tracking using the new GPU models we employ for the ongoing and upcoming data taking period at LHC. We also show our new approach to fast ITS standalone tracking. As our second topic, we present improvements to the HLT for facilitating online reconstruction including a new flat data model and a new data flow chain. The calibration output is fed back to the reconstruction components of the HLT via a feedback loop. We conclude with an analysis of a first online calibration test under real conditions during the Pb-Pb run in November 2015, which was based on these new features.

  1. Sideband locking of a single-section semiconductor distributed-feedback laser in an optical phase-lock loop.

    Science.gov (United States)

    Satyan, Naresh; Vasilyev, Arseny; Liang, Wei; Rakuljic, George; Yariv, Amnon

    2009-11-01

    The bandwidth and performance of optical phase-lock loops (OPLLs) using single-section semiconductor lasers (SCLs) are severely limited by the nonuniform frequency modulation response of the lasers. It is demonstrated that this restriction is eliminated by the sideband locking of a single-section distributed-feedback SCL to a master laser in a heterodyne OPLL, thus enabling a delay-limited loop bandwidth. The lineshape of the phase-locked SCL output is characterized using a delayed self-heterodyne measurement.

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

    Science.gov (United States)

    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.

  3. Individualising Media Practice Education Using a Feedback Loop and Instructional Videos Within an eLearning Environment.

    Directory of Open Access Journals (Sweden)

    Trevor Harris

    2012-06-01

    Full Text Available This paper explores the development and impact of the author’s TELE (Technology Enhanced Learning Environment action research project for individualising media practice education. The latest iteration of different classroom methodologies being employed to develop high-level skills in media production, the author has combined an interactive eLearning approach with instructional videos and, crucially, an individual feedback loop in order to widen access to the curriculum and create a more efficient teaching and learning environment. The focus therefore is on student engagement and organisational efficiencies as a result of the research. It should be noted that there has been no funding attached to this work, nor are there any institutional imperatives or other stakeholder involvement in this research. This project has been undertaken by the author as an evolutionary development of the various methodologies developed, cognisant of the increased technology literacy of the student cohort. The educational benefit of bringing video instruction into the curriculum as part of the project is examined as a creative pedagogy of direct benefit to students rather than as a subliminal marketing tool that other systems are often used for. Over 16K words of written data was collected during the project, and this is analysed both quantitatively and qualitatively with reference to the initial objectives of the research

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

    Science.gov (United States)

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

    2011-05-01

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

  5. Evolution of double positive autoregulatory feedback loops in CYCLOIDEA2 clade genes is associated with the origin of floral zygomorphy.

    Science.gov (United States)

    Yang, Xia; Pang, Hong-Bo; Liu, Bo-Ling; Qiu, Zhi-Jing; Gao, Qiu; Wei, Lai; Dong, Yang; Wang, Yin-Zheng

    2012-05-01

    Members of the CYCLOIDEA2 (CYC2) clade of the TEOSINTE BRANCHED1, CYCLOIDEA, and PCF transcription factor genes are widely involved in controlling floral zygomorphy, a key innovation in angiosperm evolution, depending on their persistently asymmetric expression in the corresponding floral domains. However, it is unclear how this asymmetric expression is maintained throughout floral development. Selecting Primulina heterotricha as a model, we examined the expression and function of two CYC2 genes, CYC1C and CYC1D. We analyzed the role of their promoters in protein-DNA interactions and transcription activation using electrophoresis mobility shift assays, chromatin immunoprecipitation, and transient gene expression assays. We find that CYC1C and CYC1D positively autoregulate themselves and cross-regulate each other. Our results reveal a double positive autoregulatory feedback loop, evolved for a pair of CYC2 genes to maintain their expression in developing flowers. Further comparative genome analyses, together with the available expression and function data of CYC2 genes in the core eudicots, suggest that this mechanism might have led to the independent origins of floral zygomorphy, which are associated with plant-insect coevolution and the adaptive radiation of angiosperms.

  6. Quantum-enhanced metrology with the single-mode coherent states of an optical cavity inside a quantum feedback loop

    Science.gov (United States)

    Clark, Lewis A.; Stokes, Adam; Beige, Almut

    2016-08-01

    In this paper, we use the nonlinear generator of dynamics of the individual quantum trajectories of an optical cavity inside an instantaneous quantum feedback loop to measure the phase shift between two pathways of light with a precision above the standard quantum limit. The feedback laser provides a reference frame and constantly increases the dependence of the state of the resonator on the unknown phase. Since our quantum metrology scheme can be implemented with current technology and does not require highly efficient single photon detectors, it should be of practical interest until highly entangled many-photon states become more readily available.

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

    Institute of Scientific and Technical Information of China (English)

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

    2012-01-01

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

  8. Two different modes of oscillation in a gene transcription regulatory network with interlinked positive and negative feedback loops

    Science.gov (United States)

    Karmakar, Rajesh

    2016-12-01

    We study the oscillatory behavior of a gene regulatory network with interlinked positive and negative feedback loop. The frequency and amplitude are two important properties of oscillation. The studied network produces two different modes of oscillation. In one mode (mode-I), frequency of oscillation remains constant over a wide range of amplitude and in the other mode (mode-II) the amplitude of oscillation remains constant over a wide range of frequency. Our study reproduces both features of oscillations in a single gene regulatory network and shows that the negative plus positive feedback loops in gene regulatory network offer additional advantage. We identified the key parameters/variables responsible for different modes of oscillation. The network is flexible in switching between different modes by choosing appropriately the required parameters/variables.

  9. An assessment of overall open-loop "gain" of CO2-ventilation feedback control system in hypoxia.

    Science.gov (United States)

    Masuyama, H; Akiyama, S; Honda, Y

    1985-01-01

    Overall open-loop gain of the CO2-ventilation feedback control system in hypoxia (GHCO2) was determined on 8 male and one female healthy subjects. They breathed in a closed circuit, and were subjected to the progressive hypoxia test. This procedure was first conducted without dead space (DS), then with 250, 500, and finally 750 ml DS, consecutively. GHCO2 was calculated by dividing the slope of the CO2 response curve (S) by that of the metabolic hyperbola (SL). GHCO2 was considerably larger than the overall open-loop gain of the O2-ventilation feedback control system (GO2) previously obtained. This was ascribed to the facts that S was larger than the slope of the hypoxia response curve, and that the absolute value of SL in GHCO2 was smaller than that in GO2.

  10. No Longer a Teacher Monologue--Involving EFL Writing Learners in Teachers' Assessment and Feedback Processes

    Science.gov (United States)

    Huang, Shu-Chen

    2016-01-01

    This paper reports the design of learning-oriented formative assessments in an EFL writing course that involved learners in regularly responding to teacher feedback. Following major assessment and feedback frameworks developed recently, these formative assessments were explicated in three aspects: the scheduling of learning and assessment…

  11. A negative-feedback loop regulating ERK1/2 activation and mediated by RasGPR2 phosphorylation

    Energy Technology Data Exchange (ETDEWEB)

    Ren, Jinqi [Departments of Pharmacology, University of North Carolina School of Medicine, Chapel Hill, NC 27599 (United States); Cook, Aaron A.; Bergmeier, Wolfgang [Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, NC 27599 (United States); Sondek, John, E-mail: sondek@med.unc.edu [Departments of Pharmacology, University of North Carolina School of Medicine, Chapel Hill, NC 27599 (United States); Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, NC 27599 (United States); Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599 (United States)

    2016-05-20

    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–ERK 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.

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

    Science.gov (United States)

    Sundararajan, Vignesh; Gengenbacher, Nicolas; Stemmler, Marc P; Kleemann, Julia A; Brabletz, Thomas; Brabletz, Simone

    2015-09-29

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

  13. A combined modulated feedback and temperature compensation approach to improve bias drift of a closed-loop MEMS capacitive accelerometer

    Institute of Scientific and Technical Information of China (English)

    Ming-jun MA; Zhong-he JIN‡; Hui-jie ZHU

    2015-01-01

    The bias drift of a micro-electro-mechanical systems (MEMS) accelerometer suffers from the 1/f noise and the tem-perature effect. For massive applications, the bias drift urgently needs to be improved. Conventional methods often cannot ad-dress the 1/f noise and temperature effect in one architecture. In this paper, a combined approach on closed-loop architecture modification is proposed to minimize the bias drift. The modulated feedback approach is used to isolate the 1/f noise that exists in the conventional direct feedback approach. Then a common mode signal is created and added into the closed loop on the basis of modulated feedback architecture, to compensate for the temperature drift. With the combined approach, the bias instability is improved to less than 13 µg, and the drift of the Allan variance result is reduced to 17 µg at 100 s of the integration time. The temperature coefficient is reduced from 4.68 to 0.1 mg/°C. The combined approach could be useful for many other closed-loop accelerometers.

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

    Directory of Open Access Journals (Sweden)

    Der-Yen Lee

    2014-01-01

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

  15. Positive feedback loop of YB-1 interacting with Smad2 promotes liver fibrosis.

    Science.gov (United States)

    Xiong, Panpan; Zhang, Jun; Xu, Diannan; Zhu, Jie; Li, Wenshuai; Liu, Jie; Liu, Fei

    2017-03-18

    Y-box binding protein (YB-1), known as a multifunctional cellular protein in various biological processes, was recently reported to be associated with liver fibrosis. The critical role of TGF-β/Smad signaling pathway in stimulating the transcription of fibrotic genes in fibroblasts have already been identified, however, whether and how YB-1 modulated liver fibrosis via TGF-β/Smad signaling pathway remains largely unknown. In our previous study, we proved that ectopic TGF-β was associated with YB-1 expression. Herein, by combining in vitro experiments in LX2 human hepatic stellate cells and in vivo studies by building CCl4 based mice liver fibrosis model, we showed that YB-1 and p-YB-1 were upregulated in liver fibrosis tissue, and YB-1 promoted the deposition of excess extracellular matrix. Mechanistically, Smad2, a key member in TGF-β signaling pathway, acted as a transcription factor that triggered YB-1 promoter, while on the other hand, p-YB-1 stabilized Smad2 by attenuating its ubiquitination. Knockdown of Smad2 could reduce YB-1 expression, which in turn shorter the half time of Smad2. Furthermore, the serine102 residue of YB-1 both affected its binding and stabilizing activity to Smad2. These finding demonstrated that YB-1 and Smad2 played as a positive feedback loop in promoting liver fibrosis. In conclusion, TGF-β signaling pathway may influence liver fibrosis by incorporating with YB-1, indicating that YB-1 could be a potential target for therapies against liver fibrosis.

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

    Science.gov (United States)

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

    2016-06-01

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

  17. Beam Stability in Synchrotrons with Notch and All-Pass Filters in the Feedback Loop of a Transverse Damper

    CERN Document Server

    Zhabitsky, V M; Kotzian, G

    2009-01-01

    The stability of a beam in synchrotrons with digital filters in the feedback loop of a transverse damper is treated. A transverse feedback system (TFS) is required in synchrotrons to stabilize the high intensity beams against transverse instabilities and to damp the beam injection errors. The TFS damper kicker (DK) corrects the transverse momentum of a bunch in proportion to its displacement from the closed orbit at the location of the beam position monitor (BPM). The digital signal processor in the feedback loop between BPM and DK ensures the adjustment of the phase advance and the correction of the time of flight for optimum damping. Digital FIR (finite impulse response) and IIR (infinite impulse response) filters are used commonly for the signal processing. A notch filter with zeros at the revolution frequency is required to remove the closed orbit content of the signal and correct for the imperfect electric centre of the BPM. Further processing is required to adjust for the betatron phase advance between ...

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

    Energy Technology Data Exchange (ETDEWEB)

    Small, W., LLNL

    1997-02-28

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

  19. Application of non-linear discretetime feedback regulators with assignable closed-loop dynamics

    Directory of Open Access Journals (Sweden)

    Dubljević Stevan

    2003-01-01

    Full Text Available In the present work the application of a new approach is demonstrated to a discrete-time state feedback regulator synthesis with feedback linearization and pole-placement for non-linear discrete-time systems. Under the simultaneous implementation of a non-linear coordinate transformation and a non-linear state feedback law computed through the solution of a system of non-linear functional equations, both the feedback linearization and pole-placement design objectives were accomplished. The non-linear state feedback regulator synthesis method was applied to a continuous stirred tank reactor (CSTR under non-isothermal operating conditions that exhibits steady-state multiplicity. The control objective was to regulate the reactor at the middle unstable steady state by manipulating the rate of input heat in the reactor. Simulation studies were performed to evaluate the performance of the proposed non-linear state feedback regulator, as it was shown a non-linear state feedback regulator clearly outperformed a standard linear one, especially in the presence of adverse disturbance under which linear regulation at the unstable steady state was not feasible.

  20. A Proportional Integral Derivative (PID Feedback Control without a Subsidiary Speed Loop

    Directory of Open Access Journals (Sweden)

    M. Aboelhassan

    2008-01-01

    Full Text Available The aim of this investigation is to design and describe the essential features of a brushless direct-current (BLDC motor. The static and dynamical state of the BLDC-Motor is designed and calculated.Within this frame-work, it has been shown that while working with the P-controller in conjunction with the subsidiary speed loop and PD-controller (with non-zero error in a steady state without a subsidiary speed loop, there is PID-controller without a subsidiary speed loop which has zero error in a steady state. The last part of this paper is dedicated to a simulation of the circle rounds of P and PID controllers with and without a subsidiary speed loop in MATLAB–SIMULINK to decide which of these controllers is suitable, available and reliable with a BLDC-Motor and their application in cutting tool machines in general. 

  1. Professional Feedback Loop: How Can Practising Teachers’ Reflection Inform English Language Teacher Education?

    Directory of Open Access Journals (Sweden)

    Mona Evelyn Flognfeldt

    2016-04-01

    . The teacher reports were in connection with a year’s further-education course in English, which included a pedagogical development project at their own school. This study provides insights into what aspects of the subject the practising teachers defined as their main instructional challenges in the classroom and what their main learning outcomes were. The data for this article are critical reflections articulated by the teachers at the end of their projects. Based on qualitative content analysis, I identified salient language-pedagogical features and commonalities in the teachers’ conceptualisations of their role and priorities with respect to student learning. This kind of language teacher research can have important implications for the way English is taught in initial teacher education. Relevant teacher cognitions can be channelled back to student teachers to mediate their professional preparation in the teacher education programme and their future work as English teachers. The central language-pedagogical issues identified in their research can be used as analytical and reflective tools for student teachers in their preparation for the complex practicalities of the classroom. Exploring the research that practising teachers have conducted into challenges they identified can help students connect theory with practice as well as contribute to lowering the affective filter of novice teachers. This article ends with a discussion of possible forms that this professional feedback loop can take.Keywords: english language teacher education, professional development, teacher research and development, teacher learning, language pedagogy

  2. D evelopment and Testing of a Closed Loop Feedback Controlled Magnetorheological Fluid Anti-vibration Mount for Onboard Naval Applications

    Directory of Open Access Journals (Sweden)

    Reji John

    2016-06-01

    Full Text Available An intelligent semi-active anti-vibration mount using a magnetorheological (MR fluid is designed and developed for onboard applications. The mount consists of a load bearing elastomer, MR fluid chamber; MEMS based vibration sensor and a controller for closed loop feedback mechanism. The controller regulates the solenoid current in the MR fluid chamber, which in turn regulates the flow of MR fluid through the valve. Comparison of the performance of MR mount with a passive resilient rubber mount shows that the former provides 7 dB extra damping at resonance compared to the later and the isolation of MR mount starts at 10 Hz compared to 50 Hz by rubber mount. This mount can operate in real time, passive and active modes by using a closed loop feedback control mechanism. The efficacy of the mount for outdoor applications is evaluated by characterizing the mechanical, environmental, electrical and electromagnetic properties as per MIL-17185, JSS-55555 and IEC 61000 standards and found to be superior compared to passive mounts. The mount is being evaluated for onboard applications in INS Ranvijay.

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

    Energy Technology Data Exchange (ETDEWEB)

    Kido, Tatsuo; Lau, Yun-Fai Chris, E-mail: Chris.Lau@UCSF.edu

    2014-03-28

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

  4. Closed-Loop Feedback Flank Errors Correction of Topographic Modification of Helical Gears Based on Form Grinding

    Directory of Open Access Journals (Sweden)

    Huiliang Wang

    2015-01-01

    Full Text Available To increase quality, reduce heavy-duty gear noise, and avoid edge contact in manufacturing helical gears, a closed-loop feedback correction method in topographic modification tooth flank is proposed based on the gear form grinding. Equations of grinding wheel profile and grinding wheel additional radial motion are derived according to tooth segmented profile modification and longitudinal modification. Combined with gear form grinding kinematics principles, the equations of motion for each axis of five-axis computer numerical control forming grinding machine are established. Such topographical modification is achieved in gear form grinding with on-machine measurement. Based on a sensitivity analysis of polynomial coefficients of axis motion and the topographic flank errors by on-machine measuring, the corrections are determined through an optimization process that targets minimization of the tooth flank errors. A numerical example of gear grinding, including on-machine measurement and closed-loop feedback correction completing process, is presented. The validity of this flank correction method is demonstrated for tooth flank errors that are reduced. The approach is useful to precision manufacturing of spiral bevel and hypoid gears, too.

  5. Gain drift compensation with no-feedback-loop developed for the X-IFU/ATHENA readout chain

    Science.gov (United States)

    Prêle, D.; Voisin, F.; Beillimaz, C.; Chen, S.; Goldwurm, A.

    2016-07-01

    The focal plane of the X-ray Integral Field Unit (X-IFU) instrument of the Athena observatory is composed of about 4000 micro-calorimeters. These sensors, based on superconducting Transition Edge Sensors, are read out through a frequency multiplexer and a base-band feedback to linearize SQUIDs. However, the loop gain of this feedback is lower than 10 in the modulated TES signal bandwidth, which is not enough to fix the gain of the full readout chain. Calibration of the instrument is planned to be done at a time scale larger than a dozen minutes and the challenging energy resolution goal of 2.5 eV at 6 keV will probably require a gain stability larger than 10-4 over a long duration. A large part of this gain is provided by a Low-Noise Amplifier (LNA) in the Warm Front-End Electronics (WFEE). To reach such gain stability over more than a dozen minutes, this non-cooled amplifier has to cope with the temperature and supply voltage variations. Moreover, mainly for noise reasons, common large loop gain with feedback can not be used. We propose a new amplifier topology using diodes as loads of a differential amplifier to provide a fixed voltage gain, independent of the temperature and of the bias fluctuations. This amplifier is designed using a 350 nm SiGe BiCMOS technology and is part of an integrated circuit developed for the WFEE. Our simulations provide the expected gain drift and noise performances of such structure. Comparison with standard resistive loaded differential pair clearly shows the advantages of the proposed amplifier topology with a gain drift decreasing by more than an order of magnitude. Performances of this diode loaded amplifier are discussed in the context of the X-IFU requirements.

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

    Energy Technology Data Exchange (ETDEWEB)

    Darghouth, Naïm R. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Wiser, Ryan [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Barbose, Galen [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Mills, Andrew [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

    2015-01-13

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-02-15

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

  8. PERIOD-TIMELESS interval timer may require an additional feedback loop.

    Directory of Open Access Journals (Sweden)

    Robert S Kuczenski

    2007-08-01

    Full Text Available In this study we present a detailed, mechanism-based mathematical framework of Drosophila circadian rhythms. This framework facilitates a more systematic approach to understanding circadian rhythms using a comprehensive representation of the network underlying this phenomenon. The possible mechanisms underlying the cytoplasmic "interval timer" created by PERIOD-TIMELESS association are investigated, suggesting a novel positive feedback regulatory structure. Incorporation of this additional feedback into a full circadian model produced results that are consistent with previous experimental observations of wild-type protein profiles and numerous mutant phenotypes.

  9. PERIOD–TIMELESS Interval Timer May Require an Additional Feedback Loop

    Science.gov (United States)

    Kuczenski, Robert S; Hong, Kevin C; García-Ojalvo, Jordi; Lee, Kelvin H

    2007-01-01

    In this study we present a detailed, mechanism-based mathematical framework of Drosophila circadian rhythms. This framework facilitates a more systematic approach to understanding circadian rhythms using a comprehensive representation of the network underlying this phenomenon. The possible mechanisms underlying the cytoplasmic “interval timer” created by PERIOD–TIMELESS association are investigated, suggesting a novel positive feedback regulatory structure. Incorporation of this additional feedback into a full circadian model produced results that are consistent with previous experimental observations of wild-type protein profiles and numerous mutant phenotypes. PMID:17676950

  10. Numerical static state feedback laws for closed-loop singular optimal control

    NARCIS (Netherlands)

    Graaf, de S.C.; Stigter, J.D.; Straten, van G.

    2005-01-01

    Singular and non-singular control trajectories of agricultural and (bio) chemical processes may need to be recalculated from time to time for use in closed-loop optimal control, because of unforeseen changes in state values and noise. This is time consuming. As an alternative, in this paper,

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

    Science.gov (United States)

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

    1992-01-01

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

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

    Science.gov (United States)

    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…

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

    Science.gov (United States)

    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…

  14. Service user involvement in giving mental health students feedback on placement: A participatory action research study.

    Science.gov (United States)

    Speers, Janey; Lathlean, Judith

    2015-09-01

    Although the drive to engage service users in service delivery, research and education has mainstream acceptance, it is not easy to achieve meaningful involvement. The contribution that could potentially be made by users whilst accessing services is often overlooked. This study involved stakeholders (mentors, service users and a lecturer) working together to design, evaluate and refine a system enabling students to seek feedback from service users. The feedback concerned mental health students' interpersonal skills and occurred whilst on practice placement. This research aimed to explore the experiences of those concerned when nine students attempted to learn from rather than about service users. A 2-year study, encompassing five cycles of participatory action research (PAR). A small island community in the British Isles, adopting UK standards for pre-registration nurse education. Data came from interviews with service users and mentors and a series of reflective group discussions with students who volunteered to try out the feedback mechanism. The deliberations of the PAR stakeholder group informed the research cycles and added to the data, which were subject to thematic analysis. Findings indicated that service users volunteering to give feedback had unanimously positive experiences. Students' experience lay on a continuum: those with a stronger sense of self were more willing and able to ask for feedback than less confident students. Cultural adjustment to the role change needed was challenging, requiring self-awareness and courage. Over time, all students achieved deep learning and, for some, learning appeared transformative. Although contextual, the study concluded that the feedback initiative encouraged the development of more equitable relationships, in which mental health nurses respected the expertise of service users. This potentially benefits student development, recovery-orientated practice, service users and HEIs searching for meaningful ways to

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

    Science.gov (United States)

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

    2013-04-01

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

  16. Hierarchical scale dependence associated with the extension of the nonlinear feedback loop in high-dimensional Lorenz models

    Science.gov (United States)

    Shen, B. W.

    2016-12-01

    In this study, we construct a seven-dimensional Lorenz model (7DLM) to discuss the impact of an extended nonlinear feedback loop on solutions' stability and illustrate the hierarchical scale dependence of chaotic solutions. Compared to the 5DLM, the 7DLM includes two additional high wavenumber modes that are selected based on an analysis of the nonlinear temperature advection term. Fourier modes that represent temperature in the 7DLM can be categorized into three major scales as the primary (the largest scale), secondary, and tertiary (the smallest scale) modes. Further extension of the nonlinear feedback loop within the 7DLM can provide negative nonlinear feedback to stabilize solutions, thus leading to a much larger critical value for the Rayleigh parameter (rc ˜ 116.9) for the onset of chaos, as compared to an rc of 42.9 for the 5DLM as well as an rc of 24.74 for the 3DLM. The rc is determined by an analysis of ensemble Lyapunov exponents (eLEs) with a Prandtl number (σ) of 10. To examine the dependence of rc on the value of the Prandtl number, a linear stability analysis is performed by solving for the analytical solutions of the critical points and by calculating the eigenvalues of the linearized system. Within the range of (5 ≤ σ ≤ 25), the 7DLM requires a larger rc for the onset of chaos than the 5DLM. In addition to the negative nonlinear feedback illustrated and emulated by the quasi-equilibrium state solutions for high wavenumber modes, the 7DLM reveals the hierarchical scale dependence of chaotic solutions. For solutions with r = 120, the Pearson correlation coefficients (PCCs) between the primary and secondary modes (i.e., Z and Z1) and between the secondary and tertiary modes (i.e., Z1 and Z2) are 0.988 and 0.998, respectively. Here, Z, Z1, and Z2 represent the time-varying amplitudes of the primary, secondary, and tertiary modes, respectively. High PCCs indicate a strong linear relationship among the modes at various scales and a hierarchy of

  17. Dynamics simulation of the belt conveyor possessing feedback loop during starting

    Institute of Scientific and Technical Information of China (English)

    XI Ping-yuan; ZHANG Hai-tao; LIU Jun

    2005-01-01

    Synthesizing the mechanical models of the belt, the driver and the take-up device, the dynamics model was established on the longitudinal vibration of the overall belt conveyor system with finite elemental method, and S-function simulation block of asynchronous motor owing feedback function was built in Matlab/Simulink software, the simulation block indicates that motor rotation speed and its output moment vary with load and time, and the motor is a dynamic feedback system in working process. The state space block was adopted to express model of the belt. Thus it created simulation model of established dynamic model of overall belt conveyor system with Matlab/Simulink software, and simulates the course of starting by properly setting simulation parameters, and processes data for visualization.

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

    CERN Document Server

    Gaspari, M

    2015-01-01

    Supermassive black hole accretion and feedback play central role in the evolution of galaxies, groups, and clusters. I review how AGN feedback is tightly coupled with the formation of multiphase gas and the newly probed chaotic cold accretion (CCA). In a turbulent and heated atmosphere, cold clouds and kpc-scale filaments condense out of the plasma via thermal instability and rain toward the black hole. In the nucleus, the recurrent chaotic collisions between the cold clouds, filaments, and central torus promote angular momentum cancellation or mixing, boosting the accretion rate up to 100 times the Bondi rate. The rapid variability triggers powerful AGN outflows, which quench the cooling flow and star formation without destroying the cool core. The AGN heating stifles the formation of multiphase gas and accretion, the feedback subsides and the hot halo is allowed to cool again, restarting a new cycle. Ultimately, CCA creates a symbiotic link between the black hole and the whole host via a tight self-regulate...

  19. Periodic solutions of piecewise affine gene network models with non uniform decay rates: the case of a negative feedback loop.

    Science.gov (United States)

    Farcot, Etienne; Gouzé, Jean-Luc

    2009-12-01

    This paper concerns periodic solutions of a class of equations that model gene regulatory networks. Unlike the vast majority of previous studies, it is not assumed that all decay rates are identical. To handle this more general situation, we rely on monotonicity properties of these systems. Under an alternative assumption, it is shown that a classical fixed point theorem for monotone, concave operators can be applied to these systems. The required assumption is expressed in geometrical terms as an alignment condition on so-called focal points. As an application, we show the existence and uniqueness of a stable periodic orbit for negative feedback loop systems in dimension 3 or more, and of a unique stable equilibrium point in dimension 2. This extends a theorem of Snoussi, which showed the existence of these orbits only.

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

    Science.gov (United States)

    Xie, Ye-Gong; Wang, Jie; Mao, Jie-Fei; Zhang, Bin; Wang, Xin; Cao, Xu-Chen

    2016-01-01

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

  1. Feedback.

    Science.gov (United States)

    Richardson, Barbara K

    2004-12-01

    The emergency department provides a rich environment for diverse patient encounters, rapid clinical decision making, and opportunities to hone procedural skills. Well-prepared faculty can utilize this environment to teach residents and medical students and gain institutional recognition for their incomparable role and teamwork. Giving effective feedback is an essential skill for all teaching faculty. Feedback is ongoing appraisal of performance based on direct observation aimed at changing or sustaining a behavior. Tips from the literature and the author's experience are reviewed to provide formats for feedback, review of objectives, and elements of professionalism and how to deal with poorly performing students. Although the following examples pertain to medical student education, these techniques are applicable to the education of all adult learners, including residents and colleagues. Specific examples of redirection and reflection are offered, and pitfalls are reviewed. Suggestions for streamlining verbal and written feedback and obtaining feedback from others in a fast-paced environment are given. Ideas for further individual and group faculty development are presented.

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

    Science.gov (United States)

    Ghosh, Pradipto

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

  3. MicroRNA miR-308 regulates dMyc through a negative feedback loop in Drosophila

    Directory of Open Access Journals (Sweden)

    Kaveh Daneshvar

    2012-10-01

    The abundance of Myc protein must be exquisitely controlled to avoid growth abnormalities caused by too much or too little Myc. An intriguing mode of regulation exists in which Myc protein itself leads to reduction in its abundance. We show here that dMyc binds to the miR-308 locus and increases its expression. Using our gain-of-function approach, we show that an increase in miR-308 causes a destabilization of dMyc mRNA and reduced dMyc protein levels. In vivo knockdown of miR-308 confirmed the regulation of dMyc levels in embryos. This regulatory loop is crucial for maintaining appropriate dMyc levels and normal development. Perturbation of the loop, either by elevated miR-308 or elevated dMyc, caused lethality. Combining elevated levels of both, therefore restoring balance between miR-308 and dMyc levels, resulted in lower apoptotic activity and suppression of lethality. These results reveal a sensitive feedback mechanism that is crucial to prevent the pathologies caused by abnormal levels of dMyc.

  4. Nonlinear Power-Level Control of the MHTGR Only with the Feedback Loop of Helium Temperature

    Directory of Open Access Journals (Sweden)

    Zhe Dong

    2013-02-01

    Full Text Available Power-level control is a crucial technique for the safe, stable and efficient operation of modular high temperature gas-cooled nuclear reactors (MHTGRs, which have strong inherent safety features and high outlet temperatures. The current power-level controllers of the MHTGRs need measurements of both the nuclear power and the helium temperature, which cannot provide satisfactory control performance and can even induce large oscillations when the neutron sensors are in error. In order to improve the fault tolerance of the control system, it is important to develop a power-level control strategy that only requires the helium temperature. The basis for developing this kind of control law is to give a state-observer of the MHTGR a relationship that only needs the measurement of helium temperature. With this in mind, a novel nonlinear state observer which only needs the measurement of helium temperature is proposed. This observer is globally convergent if there is no disturbance, and has the L2 disturbance attenuation performance if the disturbance is nonzero. The separation principle of this observer is also proven, which denotes that this observer can recover the performance of both globally asymptotic stabilizers and L2 disturbance attenuators. Then, a new dynamic output feedback power-level control strategy is established, which is composed of this observer and the well-built static state-feedback power-level control based upon iterative dissipation assignment (IDA-PLC. Finally, numerical simulation results show the high performance and feasibility of this newly-built dynamic output feedback power-level controller.

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

    Science.gov (United States)

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

    2014-06-01

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

  6. miR-486 sustains NF-κB activity by disrupting multiple NF-κB-negative feedback loops

    Institute of Scientific and Technical Information of China (English)

    Libing Song; Chuyong Lin; Hui Gong; Chanjuan Wang; Liping Liu; Jueheng Wu; Sha Tao

    2013-01-01

    Deubiquitinases,such as CYLD,A20 and Cezanne,have emerged as important negative regulators that balance the strength and the duration of NF-κB signaling through feedback mechanisms.However,how these serial feedback loops are simultaneously disrupted in cancers,which commonly exhibit constitutively activated NF-κB,remains puzzling.Herein,we report that miR-486 directly suppresses NF-κB-negative regulators,CYLD and Cezanne,as well as multiple A20 activity regulators,including ITCH,TNIP-1,TNIP-2 and TNIP-3,resulting in promotion of ubiquitin conjugations in NF-κB signaling and sustained NF-κB activity.Furthermore,we demonstrate that upregulation of miR-486 promotes glioma aggressiveness both in vitro and in vivo through activation of NF-κB signaling pathway.Importantly,miR-486 levels in primary gliomas significantly correlate with NF-κB activation status.These findings uncover a novel mechanism for constitutive NF-κB activation in gliomas and support a functionally and clinically relevant epigenetic mechanism in cancer progression.

  7. Activation of TGF-β1-CD147 positive feedback loop in hepatic stellate cells promotes liver fibrosis.

    Science.gov (United States)

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

    2015-11-12

    Activation of hepatic stellate cells (HSCs) by transforming growth factor-β1 (TGF-β1) initiates HBV-associated fibrogenesis. The mechanism of TGF-β1 modulating HSC activation is not fully uncovered. We hypothesized a positive feedback signaling loop of TGF-β1-CD147 promoting liver fibrogenesis by activation of HSCs. Human HSC cell line LX-2 and spontaneous liver fibrosis model derived from HBV transgenic mice were used to evaluate the activation of molecules in the signaling loop. Wound healing and cell contraction assay were performed to detect the CD147-overexpressed HSC migration and contraction. The transcriptional regulation of CD147 by TGF-β1/Smad4 was determined using dual-luciferase reporter assay and chromatin immunoprecipitation. We found that a positive reciprocal regulation between TGF-β1 and CD147 mediated HSC activation. CD147 over-expression promoted HSC migration and accelerated TGF-β1-induced cell contraction. Phosphorylation of Smad2 and Smad3 in cooperation with Smad4 mediated the TGF-β1-regulated CD147 expression. Smad4 activated the transcription by direct interaction with CD147 promoter. Meanwhile, CD147 modulated the activated phenotype of HSCs through the ERK1/2 and Sp1 which up-regulated α-SMA, collagen I, and TGF-β1 synthesis. These findings indicate that TGF-β1-CD147 loop plays a key role in regulating the HSC activation and combination of TGF-β receptor inhibitor and anti-CD147 antibody might be promised to reverse fibrogenesis.

  8. Germline genetic variants disturbing the Let-7/LIN28 double-negative feedback loop alter breast cancer susceptibility.

    Directory of Open Access Journals (Sweden)

    Ao-Xiang Chen

    2011-09-01

    Full Text Available Previous studies have shown that let-7 can repress the post-transcriptional translation of LIN28, and LIN28 in turn could block the maturation of let-7, forming a double-negative feedback loop. In this study, we investigated the effect of germline genetic variants on regulation of the homeostasis of the let-7/LIN28 loop and breast cancer risk. We initially demonstrated that the T/C variants of rs3811463, a single nucleotide polymorphism (SNP located near the let-7 binding site in LIN28, could lead to differential regulation of LIN28 by let-7. Specifically, the C allele of rs3811463 weakened let-7-induced repression of LIN28 mRNA, resulting in increased production of LIN28 protein, which could in turn down-regulate the level of mature let-7. This effect was then validated at the tissue level in that the normal breast tissue of individuals with the rs3811463-TC genotype expressed significantly lower levels of let-7 and higher levels of LIN28 protein than those individuals with the rs3811463-TT genotype. Because previous in vitro and ex vivo experiments have consistently suggested that LIN28 could promote cellular transformation, we then systematically evaluated the relationship between rs3811463 as well as other common LIN28 SNPs and the risk of breast cancer in a stepwise manner. The first hospital-based association study (n = 2,300 demonstrated that two SNPs were significantly associated with breast cancer risk, one of which was rs3811463, while the other was rs6697410. The C allele of the rs3811463 SNP corresponded to an increased risk of breast cancer with an odds ratio (OR of 1.25 (P = 0.0091, which was successfully replicated in a second independent study (n = 1,156 with community-based controls. The combined P-value of the two studies was 8.0 × 10⁻⁵. Taken together, our study demonstrates that host genetic variants could disturb the regulation of the let-7/LIN28 double-negative feedback loop and alter breast cancer risk.

  9. Germline genetic variants disturbing the Let-7/LIN28 double-negative feedback loop alter breast cancer susceptibility.

    Science.gov (United States)

    Chen, Ao-Xiang; Yu, Ke-Da; Fan, Lei; Li, Ji-Yu; Yang, Chen; Huang, A-Ji; Shao, Zhi-Ming

    2011-09-01

    Previous studies have shown that let-7 can repress the post-transcriptional translation of LIN28, and LIN28 in turn could block the maturation of let-7, forming a double-negative feedback loop. In this study, we investigated the effect of germline genetic variants on regulation of the homeostasis of the let-7/LIN28 loop and breast cancer risk. We initially demonstrated that the T/C variants of rs3811463, a single nucleotide polymorphism (SNP) located near the let-7 binding site in LIN28, could lead to differential regulation of LIN28 by let-7. Specifically, the C allele of rs3811463 weakened let-7-induced repression of LIN28 mRNA, resulting in increased production of LIN28 protein, which could in turn down-regulate the level of mature let-7. This effect was then validated at the tissue level in that the normal breast tissue of individuals with the rs3811463-TC genotype expressed significantly lower levels of let-7 and higher levels of LIN28 protein than those individuals with the rs3811463-TT genotype. Because previous in vitro and ex vivo experiments have consistently suggested that LIN28 could promote cellular transformation, we then systematically evaluated the relationship between rs3811463 as well as other common LIN28 SNPs and the risk of breast cancer in a stepwise manner. The first hospital-based association study (n = 2,300) demonstrated that two SNPs were significantly associated with breast cancer risk, one of which was rs3811463, while the other was rs6697410. The C allele of the rs3811463 SNP corresponded to an increased risk of breast cancer with an odds ratio (OR) of 1.25 (P = 0.0091), which was successfully replicated in a second independent study (n = 1,156) with community-based controls. The combined P-value of the two studies was 8.0 × 10⁻⁵. Taken together, our study demonstrates that host genetic variants could disturb the regulation of the let-7/LIN28 double-negative feedback loop and alter breast cancer risk.

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

    NARCIS (Netherlands)

    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

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

    NARCIS (Netherlands)

    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 feed

  12. Phosphorylation of the transcription activator CLOCK regulates progression through a ∼ 24-h feedback loop to influence the circadian period in Drosophila.

    Science.gov (United States)

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

    2014-07-11

    Circadian (≅ 24 h) clocks control daily rhythms in metabolism, physiology, and behavior in animals, plants, and microbes. In Drosophila, these clocks keep circadian time via transcriptional feedback loops in which clock-cycle (CLK-CYC) initiates transcription of period (per) and timeless (tim), accumulating levels of PER and TIM proteins feed back to inhibit CLK-CYC, and degradation of PER and TIM allows CLK-CYC to initiate the next cycle of transcription. The timing of key events in this feedback loop are controlled by, or coincide with, rhythms in PER and CLK phosphorylation, where PER and CLK phosphorylation is high during transcriptional repression. PER phosphorylation at specific sites controls its subcellular localization, activity, and stability, but comparatively little is known about the identity and function of CLK phosphorylation sites. Here we identify eight CLK phosphorylation sites via mass spectrometry and determine how phosphorylation at these sites impacts behavioral and molecular rhythms by transgenic rescue of a new Clk null mutant. Eliminating phosphorylation at four of these sites accelerates the feedback loop to shorten the circadian period, whereas loss of CLK phosphorylation at serine 859 increases CLK activity, thereby increasing PER levels and accelerating transcriptional repression. These results demonstrate that CLK phosphorylation influences the circadian period by regulating CLK activity and progression through the feedback loop. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  13. A cell-regulatory mechanism involving feedback between contraction and tissue formation guides wound healing progression.

    Directory of Open Access Journals (Sweden)

    Clara Valero

    Full Text Available Wound healing is a process driven by cells. The ability of cells to sense mechanical stimuli from the extracellular matrix that surrounds them is used to regulate the forces that cells exert on the tissue. Stresses exerted by cells play a central role in wound contraction and have been broadly modelled. Traditionally, these stresses are assumed to be dependent on variables such as the extracellular matrix and cell or collagen densities. However, we postulate that cells are able to regulate the healing process through a mechanosensing mechanism regulated by the contraction that they exert. We propose that cells adjust the contraction level to determine the tissue functions regulating all main activities, such as proliferation, differentiation and matrix production. Hence, a closed-regulatory feedback loop is proposed between contraction and tissue formation. The model consists of a system of partial differential equations that simulates the evolution of fibroblasts, myofibroblasts, collagen and a generic growth factor, as well as the deformation of the extracellular matrix. This model is able to predict the wound healing outcome without requiring the addition of phenomenological laws to describe the time-dependent contraction evolution. We have reproduced two in vivo experiments to evaluate the predictive capacity of the model, and we conclude that there is feedback between the level of cell contraction and the tissue regenerated in the wound.

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

    Science.gov (United States)

    Frye, Stuart; Mandl, Dan; Cappelaere, Pat

    2016-01-01

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

  15. Total Reconstruction of the Afferent Loop for Treatment of Radiation-Induced Afferent Loop Obstruction with Segmental Involvement after Pancreaticoduodenectomy with Roux-en-Y Reconstruction

    Directory of Open Access Journals (Sweden)

    Konstantinos Blouhos

    2013-08-01

    Full Text Available As the literature on afferent loop obstruction (ALO after pancreaticoduodenectomy (PD is very limited, standardized rules for its management do not exist. Herein, we report the case of a 65-year-old male patient with chronic ALO who had undergone PD with single Roux-en-Y limb reconstruction and adjuvant chemoradiation therapy for pancreatic head adenocarcinoma 2 years earlier. The patient was brought to the operating room with the diagnosis of radiation enteritis of the afferent loop with segmental involvement and concurrent hepaticojejunostomy (HJ and pancreaticojejunostomy (PJ stricture. Complete mobilization of the afferent loop, removal of the affected segment and reconstruction were performed. Reconstruction of the afferent loop was a one-way option for the surgeons because the Roux-en-Y reconstruction limited endoscopic access to the afferent loop, and the segmental radiation injury of the afferent loop ruled out bypass surgery. However, mobilization of the affected segment through a field of dense adhesions and revision of the HJ and PJ were technically demanding.

  16. A Compact Ionic Polymer Metal Composite (IPMC System with Inductive Sensor for Closed Loop Feedback

    Directory of Open Access Journals (Sweden)

    Jiaqi Wang

    2015-05-01

    Full Text Available Ionic polymer metal composite (IPMC, of which a low actuating voltage (<5 V, high power efficiency and biocompatibility makes it a proven candidate for low power devices. However, due to its inherent nonlinear behaviour and time-variance, feedback control, as well as reliable sensing means, are required for accurate operations. This paper presents an IPMC actuator implemented with an inductive sensor to enhance the reliability and compactness of the overall device. A practical, low cost and importantly, compact inductive sensor fabricated on a printed circuit board (PCB is proposed here. Target material selections and coil design considerations are discussed. It is experimentally determined that the inductive sensor has comparable performance to a laser sensor. Based on a proportional-integral-derivative (PID control results the inductive sensor has demonstrated to be an alternative to a laser sensor allowing devices using IPMC actuators to be compact.

  17. Relaxation oscillations and hierarchy of feedbacks in MAPK signaling

    Science.gov (United States)

    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.

  18. Offshore Measurement System for Wave Power—Using Current Loop Feedback

    Directory of Open Access Journals (Sweden)

    Liselotte Ulvgård

    2016-12-01

    Full Text Available This paper presents the design and testing of a measurement system for wave power generators. The work is part of a project to build a robust and cheap measurement system for offshore monitoring of wave power farms. Due to the harsh offshore environment, low accessibility and high cost for installation and maintenance, it is of key importance to minimize power consumption, complexity and cost of each measurement unit. For the first prototype, the objective was to measure voltage, current and translator position inside the linear wave power generator. For this, two printed circuit boards (PCBs were developed, using a two wire current loop transmitter setup. They were tested separately and in a three phase setup inside a wave power generator during onshore tests. To ensure stability, speed and accuracy in the signal transfer, the PCBs were tested for linearity, frequency response and step response. In addition, power consumption was measured, for operational time evaluation. Results show good agreement between expected and measured performance, with an input range of ±1560 V and ±420 A for alternating current measurements and a bandwidth of 10 kHz and 7 kHz, for voltage and current measurements, respectively. The power consumption was measured to 0.5 W for each measurement unit, at 24 V feed.

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

    Science.gov (United States)

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

    2016-01-15

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

  20. An Efficient Expert System Generator for Qualitative Feed-Back Loop Analysis

    Directory of Open Access Journals (Sweden)

    Manoj Kumar Jain

    2012-04-01

    Full Text Available Quite often the variables used in system analysis are qualitative in nature. They cannot be defined precisely, whereas software development for system analysis needs a mathematical framework with precise computations. It is not trivial to capture the uncertainty in the system.
    Fuzzy sets provide us the facility to capture the uncertainty in the system. In normal crisp set where the membership of an element is always certain in a sense that it would be member or not of the given set. In contrast to this a membership functions or possibility (ranging from 0 to 1, including both values is assigned with each member. System analysis is done through system dynamics which is not very efficient. We present an efficient technique to generate expert system using fuzzy set. In our proposed approach five linguistic qualifiers are used for each variable, namely, Very Low (VL, Low (L, Medium (M, High (H, and Very High
    (VH. We capture the influence or feedback in the system with the help of if then else rules and matrices are generated for them which are used for analysis. Complete methodology and its applicability are presented here.

  1. Mutually positive regulatory feedback loop between interferons and estrogen receptor-alpha in mice: implications for sex bias in autoimmunity.

    Directory of Open Access Journals (Sweden)

    Ravichandran Panchanathan

    Full Text Available Systemic lupus erythematosus (SLE, an autoimmune disease, predominantly affects women of childbearing age. Moreover, increased serum levels of interferon-alpha (IFN-alpha are associated with the disease. Although, the female sex hormone estrogen (E2 is implicated in sex bias in SLE through up-regulation of IFN-gamma expression, the molecular mechanisms remain unknown. Here we report that activation of IFN (alpha or gamma-signaling in immune cells up-regulates expression of estrogen receptor-alpha (ERalpha; encoded by the Esr1 gene and stimulates expression of target genes.We found that treatment of mouse splenic cells and mouse cell lines with IFN (alpha or gamma increased steady-state levels of ERalpha mRNA and protein. The increase in the ERalpha mRNA levels was primarily due to the transcriptional mechanisms and it was dependent upon the activation of signal transducer and activator of transcription-1 (STAT1 factor by IFN. Moreover, the IFN-treatment of cells also stimulated transcription of a reporter gene, expression of which was driven by the promoter region of the murine Esr1 gene. Notably, splenic cells from pre-autoimmune lupus-prone (NZB x NZWF(1 female mice had relatively higher steady-state levels of mRNAs encoded by the IFN and ERalpha-responsive genes as compared to the age-matched males.Our observations identify a novel mutually positive regulatory feedback loop between IFNs and ERalpha in immune cells in mice and support the idea that activation of this regulatory loop contributes to sex bias in SLE.

  2. Mutually Positive Regulatory Feedback Loop between Interferons and Estrogen Receptor-α in Mice: Implications for Sex Bias in Autoimmunity

    Science.gov (United States)

    Panchanathan, Ravichandran; Shen, Hui; Zhang, Xiang; Ho, Shuk-mei; Choubey, Divaker

    2010-01-01

    Background Systemic lupus erythematosus (SLE), an autoimmune disease, predominantly affects women of childbearing age. Moreover, increased serum levels of interferon-α (IFN-α) are associated with the disease. Although, the female sex hormone estrogen (E2) is implicated in sex bias in SLE through up-regulation of IFN-γ expression, the molecular mechanisms remain unknown. Here we report that activation of IFN (α or γ)-signaling in immune cells up-regulates expression of estrogen receptor-α (ERα; encoded by the Esr1 gene) and stimulates expression of target genes. Methodology/Principal Findings We found that treatment of mouse splenic cells and mouse cell lines with IFN (α or γ) increased steady-state levels of ERα mRNA and protein. The increase in the ERα mRNA levels was primarily due to the transcriptional mechanisms and it was dependent upon the activation of signal transducer and activator of transcription-1 (STAT1) factor by IFN. Moreover, the IFN-treatment of cells also stimulated transcription of a reporter gene, expression of which was driven by the promoter region of the murine Esr1 gene. Notably, splenic cells from pre-autoimmune lupus-prone (NZB × NZW)F1 female mice had relatively higher steady-state levels of mRNAs encoded by the IFN and ERα-responsive genes as compared to the age-matched males. Conclusions/Significance Our observations identify a novel mutually positive regulatory feedback loop between IFNs and ERα in immune cells in mice and support the idea that activation of this regulatory loop contributes to sex bias in SLE. PMID:20526365

  3. Progress toward controlling in vivo fibrillating sheep atria using a nonlinear-dynamics-based closed-loop feedback method

    Science.gov (United States)

    Gauthier, Daniel J.; Hall, G. Martin; Oliver, Robert A.; Dixon-Tulloch, Ellen G.; Wolf, Patrick D.; Bahar, Sonya

    2002-09-01

    We describe preliminary experiments on controlling in vivo atrial fibrillation using a closed-loop feedback protocol that measures the dynamics of the right atrium at a single spatial location and applies control perturbations at a single spatial location. This study allows investigation of control of cardiac dynamics in a preparation that is physiologically close to an in vivo human heart. The spatial-temporal response of the fibrillating sheep atrium is measured using a multi-channel electronic recording system to assess the control effectiveness. In an attempt to suppress fibrillation, we implement a scheme that paces occasionally the cardiac muscle with small shocks. When successful, the inter-activation time interval is the same and electrical stimuli are only applied when the controller senses that the dynamics are beginning to depart from the desired periodic rhythm. The shock timing is adjusted in real time using a control algorithm that attempts to synchronize the most recently measured inter-activation interval with the previous interval by inducing an activation at a time projected by the algorithm. The scheme is "single-sided" in that it can only shorten the inter-activation time but not lengthen it. Using probability distributions of the inter-activation time intervals, we find that the feedback protocol is not effective in regularizing the dynamics. One possible reason for the less-than-successful results is that the controller often attempts to stimulate the tissue while it is still in the refractory state and hence it does not induce an activation.

  4. Computation of NLO Processes Involving Heavy Quarks Using Loop-Tree Duality

    CERN Document Server

    Driencourt-Mangin, Felix

    2016-01-01

    We present a new method to compute higher-order corrections to physical cross-sections, at Next-to-Leading Order and beyond. This method, based on the Loop Tree Duality, leads to locally integrable expressions in four dimensions. By introducing a physically motivated momentum mapping between the momenta involved in the real and the virtual contributions, infrared singularities naturally cancel at integrand level, without the need to introduce subtraction counter-terms. Ultraviolet singularities are dealt with by using dual representations of suitable counter-terms, with some subtleties regarding the self-energy contributions. As an example, we apply this method to compute the $1\\to2$ decay rate in the context of a scalar toy model with massive particles.

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

    LENUS (Irish Health Repository)

    Rishi, Loveena

    2014-04-10

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

  6. Healthy Change Processes-A Diary Study of Five Organizational Units. Establishing a Healthy Change Feedback Loop.

    Science.gov (United States)

    Lien, Mathilde; Saksvik, Per Øystein

    2016-10-01

    This paper explores a change process in the Central Norway Regional Health Authority that was brought about by the implementation of a new economics and logistics system. The purpose of this paper is to contribute to understanding of how employees' attitudes towards change develop over time and how attitudes differ between the five health trusts under this authority. In this paper, we argue that a process-oriented focus through a longitudinal diary method, in addition to action research and feedback loops, will provide greater understanding of the evaluation of organizational change and interventions. This is explored through the assumption that different units will have different perspectives and attitudes towards the same intervention over time because of different contextual and time-related factors. The diary method aims to capture the context, events, reflections and interactions when they occur and allows for a nuanced frame of reference for the different phases of the implementation process and how these phases are perceived by employees. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  7. Interaction of apoptotic cells with macrophages upregulates COX-2/PGE2 and HGF expression via a positive feedback loop.

    Science.gov (United States)

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

    2014-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Ji Yeon Byun

    2014-01-01

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

  9. Drosophila HP1c is regulated by an auto-regulatory feedback loop through its binding partner Woc.

    Directory of Open Access Journals (Sweden)

    Jochen Abel

    Full Text Available HP1 is a major component of chromatin and regulates gene expression through its binding to methylated histone H3. Most eukaryotes express at least three isoforms of HP1 with similar domain architecture. However, despite the common specificity for methylated histone H3, the three HP1 isoforms bind to different regions of the genome. Most of the studies so far focused on the HP1a isoform and its role in transcriptional regulation. As HP1a requires additional factors to bind methylated chromatin in vitro, we wondered whether another isoform might also require additional targeting factors. Indeed, we found that HP1c interacts with the DNA binding factors Woc and Row and requires Woc to become targeted to chromatin in vivo. Moreover, we show that the interaction between HP1c and Woc constitutes a transcriptional feedback loop that operates to balance the concentration of HP1c within the cell. This regulation may prevent HP1c from binding to methylated heterochromatin.

  10. Calculation of PDS-XADS core closed-loop transfer function by using feedback with the lumped-model

    Energy Technology Data Exchange (ETDEWEB)

    Moghassem, Alireza; Payirandeh, Ali; Abbaspour, Ali [Islamic Azad Univ., Tehran (Iran, Islamic Republic of). Nuclear Engineering Dept.

    2016-03-15

    In this paper, the PDS-XADS LBE-cooled core open-loop transfer function was calculated by considering the source importance in point-kinetic equations. For this purpose, the overall-feedback transfer function was calculated considering the lumped-model for 14-steps of subcritical levels. Following effects were considered in three steps: 1. Doppler broadening, fuel expansion, coolant density and structure expansion, 2. Delayed-reactivity and void-worth inserted to prior step, 3. Severe-accident condition, inserted to prior steps. The linear stability analysis was modeled by using the Bode diagrams, Nyquist stability criterion and Nichols chart in MATLAB for each subcritical level and six groups of delayed neutrons. For optimized subcritical level determination, a conservative severe accident was considered. According to calculation results and analysis, the PDS-XADS core is stable and in optimized subcritical level, has the higher safety margin. The results are in good agreement with SIMMER-III code and main neutronic results. The optimized subcritical level by using the lumped-model is 0.97687.

  11. Leukemia Mediated Endothelial Cell Activation Modulates Leukemia Cell Susceptibility to Chemotherapy through a Positive Feedback Loop Mechanism.

    Directory of Open Access Journals (Sweden)

    Bahareh Pezeshkian

    Full Text Available In acute myeloid leukemia (AML, the chances of achieving disease-free survival are low. Studies have demonstrated a supportive role of endothelial cells (ECs in normal hematopoiesis. Here we show that similar intercellular relationships exist in leukemia. We demonstrate that leukemia cells themselves initiate these interactions by directly modulating the behavior of resting ECs through the induction of EC activation. In this inflammatory state, activated ECs induce the adhesion of a sub-set of leukemia cells through the cell adhesion molecule E-selectin. These adherent leukemia cells are sequestered in a quiescent state and are unaffected by chemotherapy. The ability of adherent cells to later detach and again become proliferative following exposure to chemotherapy suggests a role of this process in relapse. Interestingly, differing leukemia subtypes modulate this process to varying degrees, which may explain the varied response of AML patients to chemotherapy and relapse rates. Finally, because leukemia cells themselves induce EC activation, we postulate a positive-feedback loop in leukemia that exists to support the growth and relapse of the disease. Together, the data defines a new mechanism describing how ECs and leukemia cells interact during leukemogenesis, which could be used to develop novel treatments for those with AML.

  12. The p53/miR-34a/SIRT1 Positive Feedback Loop in Quercetin-Induced Apoptosis

    Directory of Open Access Journals (Sweden)

    Guohua Lou

    2015-04-01

    Full Text Available Background: The anti-tumor effects of quercetin have been reported, but the underlying molecular mechanisms remain to be elucidated. The aim of present study was to explore the role of miRNA in the anticancer effects of quercetin. Methods: The differential miRNAs expression between the HepG2 and Huh7 cells treated by quercetin were detected by microarray. The xCELLigence, Flow cytometry, RT-PCR and Western blot were used to analyze the cell proliferation, cell apoptosis, cell cycle arrest, anti-tumor genes, and protein expression. Results: miR-34a was up-regulated in HepG2 cells treated by quercetin exhibiting wild-type p53. When inhibiting the miR-34a, the sensitivity of the cells to quercetin decreased and the expression of the SIRT1 was up-regulated, but the acetylation of p53 and the expression of some genes related to p53 down-regulated. Conclusion: miR-34a plays an important role in the anti-tumor effects of querctin in HCC, miR-34a may be a tiemolecule between the p53 and SIRT1 and is composed of a p53/miR-34a/SIRT1 signal feedback loop, which could enhance apoptosis signal and significantly promote cell apoptosis.

  13. SIRT1 is regulated by a PPARγ–SIRT1 negative feedback loop associated with senescence

    Science.gov (United States)

    Zhou, Rui; Niu, Jing; McNutt, Michael A.; Wang, Pan; Tong, Tanjun

    2010-01-01

    Human Silent Information Regulator Type 1 (SIRT1) is an NAD+-dependent deacetylase protein which is an intermediary of cellular metabolism in gene silencing and aging. SIRT1 has been extensively investigated and shown to delay senescence; however, less is known about the regulation of SIRT1 during aging. In this study, we show that the peroxisome proliferator-activated receptor-γ (PPARγ), which is a ligand-regulated modular nuclear receptor that governs adipocyte differentiation and inhibits cellular proliferation, inhibits SIRT1 expression at the transcriptional level. Moreover, both PPARγ and SIRT1 can bind the SIRT1 promoter. PPARγ directly interacts with SIRT1 and inhibits SIRT1 activity, forming a negative feedback and self-regulation loop. In addition, our data show that acetylation of PPARγ increased with increasing cell passage number. We propose that PPARγ is subject to regulation by acetylation and deacetylation via p300 and SIRT1 in cellular senescence. These results demonstrate a mutual regulation between PPARγ and SIRT1 and identify a new posttranslational modification that affects cellular senescence. PMID:20660480

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2016-09-01

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

  16. Feedback-Training für Lehrärzte in der Allgemeinmedizin [Feedback training for general practitioners involved in teaching

    Directory of Open Access Journals (Sweden)

    Engeser, Peter

    2010-02-01

    Full Text Available [english] Background: Ever since the last amendment to the German Medical Licensing Act took effect in 2002, medical students may complete four months of the Practical Year (PY in general practices. Formative feedback between the teaching general practitioner (GP and the PY student is a key element in creating a learning environment. GPs involved in teaching therefore need further education in giving feedback.Methods: A 4-hour feedback training session for GPs involved in teaching which used standardized patients and students was developed and tested in a pilot study. In role plays, GPs experienced feedback situations. Using an evaluation questionnaire, changes in self-perceived feedback skills were assessed (familiarity of feedback rules, preparation for giving feedback to PY students, possibilities to improve communication skills in doctor–patient situations.Results: Sixteen GPs who were involved or interested in PY teaching participated in the feedback training program. Afterwards, participants said they felt more comfortable in giving formative feedback and more assured in their communication skills. The confidence in their own feedback improved, especially by taking the student’s part in the role plays. An exercise between a standardized patient and a standardized stubborn student was a challenge, but proved to be extremely useful.Conclusion: The opinions of the participating GPs to the feedback training underscore its importance. Therefore, we recommend integrating such a feedback training program into the education of GPs involved in teaching.[german] Hintergrund: Seit der letzten Novelle der Approbationsordnung 2002 besteht die Möglichkeit, ein Tertial des Praktischen Jahres (PJ in Hausarztpraxen zu absolvieren. Konstruktives Feedback zwischen Arzt und PJ-Studenten ist dabei ein zentrales Element in der Gestaltung des Lernumfeldes in der Arztpraxis. Es bedarf dahingehend einer Ausbildung der in die Lehre involvierten

  17. The Persistence of Asthma requires Multiple Feedback Circuits Involving ILC2 and IL33

    Science.gov (United States)

    Christianson, Christina A.; Goplen, Nicholas P.; Zafar, Iram; Irvin, Chaoyu; Good, James T.; Rollins, Donald R.; Gorentla, Balachandra; Liu, Weimin; Gorska, Magdalena M.; Chu, HongWei; Martin, Richard J.; Alam, Rafeul

    2015-01-01

    Background Asthma in the mouse model spontaneously resolves after cessation of allergen exposure. We developed a mouse model where asthma features persisted for 6 months after cessation of allergen exposure. Objective To elucidate factors contributing to the persistence of asthma. Methods We utilized a combination of immunologic, genetic, microarray and pharmacologic approaches to dissect the mechanism of persistence of asthma. Results Elimination of T cells though antibody-mediated depletion or lethal irradiation and transplantation of Rag1−/− bone marrow in mice with chronic asthma resulted in resolution of airway inflammation but not airway hyperreactivity or remodeling. Elimination of T cells and ILC2 through lethal irradiation and transplantation of Rag2−/−γc−/− bone marrow or blockade of IL33 resulted in resolution of airway inflammation and hyperreactivity. Persistence of asthma required multiple interconnected feedback and feed forward circuits between ILC2 and epithelial cells. Epithelial IL33 induced ILC2, a rich source of IL13. The latter directly induced epithelial IL33 establishing a positive feedback circuit. IL33 auto-induced, generating another feedback circuit. IL13 upregulated IL33 receptors and facilitated IL33 auto-induction, thus establishing a feed forward circuit. Elimination of any component of these circuits resulted in resolution of chronic asthma. In agreement with the foregoing, IL33 and ILC2 were increased in the airways from asthmatic patients. IL33 correlated with disease severity. Conclusions We present a critical network of feedback and feed forward interactions between epithelial cells and ILC2 involved in maintaining chronic asthma. Although T cells contributed to the severity of chronic asthma they were redundant in maintaining airway hyperreactivity and remodeling. PMID:25617223

  18. Evolution of Double Positive Autoregulatory Feedback Loops in CYCLOIDEA2 Clade Genes Is Associated with the Origin of Floral Zygomorphy[W

    Science.gov (United States)

    Yang, Xia; Pang, Hong-Bo; Liu, Bo-Ling; Qiu, Zhi-Jing; Gao, Qiu; Wei, Lai; Dong, Yang; Wang, Yin-Zheng

    2012-01-01

    Members of the CYCLOIDEA2 (CYC2) clade of the TEOSINTE BRANCHED1, CYCLOIDEA, and PCF transcription factor genes are widely involved in controlling floral zygomorphy, a key innovation in angiosperm evolution, depending on their persistently asymmetric expression in the corresponding floral domains. However, it is unclear how this asymmetric expression is maintained throughout floral development. Selecting Primulina heterotricha as a model, we examined the expression and function of two CYC2 genes, CYC1C and CYC1D. We analyzed the role of their promoters in protein–DNA interactions and transcription activation using electrophoresis mobility shift assays, chromatin immunoprecipitation, and transient gene expression assays. We find that CYC1C and CYC1D positively autoregulate themselves and cross-regulate each other. Our results reveal a double positive autoregulatory feedback loop, evolved for a pair of CYC2 genes to maintain their expression in developing flowers. Further comparative genome analyses, together with the available expression and function data of CYC2 genes in the core eudicots, suggest that this mechanism might have led to the independent origins of floral zygomorphy, which are associated with plant–insect coevolution and the adaptive radiation of angiosperms. PMID:22649271

  19. A feedback circuit involving let-7-family miRNAs and DAF-12 integrates environmental signals and developmental timing in Caenorhabditis elegans.

    Science.gov (United States)

    Hammell, Christopher M; Karp, Xantha; Ambros, Victor

    2009-11-03

    Animal development is remarkably robust; cell fates are specified with spatial and temporal precision despite physiological and environmental contingencies. Favorable conditions cause Caenorhabditis elegans to develop rapidly through four larval stages (L1-L4) to the reproductive adult. In unfavorable conditions, L2 larvae can enter the developmentally quiescent, stress-resistant dauer larva stage, enabling them to survive for prolonged periods before completing development. A specific progression of cell division and differentiation events occurs with fidelity during the larval stages, regardless of whether an animal undergoes continuous or dauer-interrupted development. The temporal patterning of developmental events is controlled by the heterochronic genes, whose products include microRNAs (miRNAs) and regulatory proteins. One of these proteins, the DAF-12 nuclear hormone receptor, modulates the transcription of certain let-7-family miRNAs, and also mediates the choice between the continuous vs. dauer-interrupted life history. Here, we report a complex feedback loop between DAF-12 and the let-7-family miRNAs involving both the repression of DAF-12 by let-7-family miRNAs and the ligand-modulated transcriptional activation and repression of the let-7-Fam miRNAs by DAF-12. We propose that this feedback loop functions to ensure robustness of cell fate decisions and to coordinate cell fate with developmental arrest.

  20. Suppressor of cytokine signalling-6 promotes neurite outgrowth via JAK2/STAT5-mediated signalling pathway, involving negative feedback inhibition.

    Directory of Open Access Journals (Sweden)

    Sakshi Gupta

    Full Text Available BACKGROUND: Suppressors of cytokine signalling (SOCS protein family are key regulators of cellular responses to cytokines and play an important role in the nervous system. The SOCS6 protein, a less extensively studied SOCS family member, has been shown to induce insulin resistance in the retina and promote survival of the retinal neurons. But no reports are available about the role of SOCS6 in neuritogenesis. In this study, we examined the role of SOCS6 in neurite outgrowth and neuronal cell signalling. METHODOLOGY/PRINCIPAL FINDINGS: The effect of SOCS6 in neural stem cells differentiation was studied in neural stem cells and PC12 cell line. Highly elevated levels of SOCS6 were found upon neural cell differentiation both at the mRNA and protein level. Furthermore, SOCS6 over-expression lead to increase in neurite outgrowth and degree of branching, whereas SOCS6 knockdown with specific siRNAs, lead to a significant decrease in neurite initiation and extension. Insulin-like growth factor-1 (IGF-1 stimulation which enhanced neurite outgrowth of neural cells resulted in further enhancement of SOCS6 expression. Jak/Stat (Janus Kinase/Signal Transducer And Activator Of Transcription pathway was found to be involved in the SOCS6 mediated neurite outgrowth. Bioinformatics study revealed presence of putative Stat binding sites in the SOCS6 promoter region. Transcription factors Stat5a and Stat5b were involved in SOCS6 gene upregulation leading to neuronal differentiation. Following differentiation, SOCS6 was found to form a ternary complex with IGFR (Insulin Like Growth Factor-1 Receptor and JAK2 which acted in a negative feedback loop to inhibit pStat5 activation. CONCLUSION/SIGNIFICANCE: The current paradigm for the first time states that SOCS6, a SOCS family member, plays an important role in the process of neuronal differentiation. These findings define a novel molecular mechanism for Jak2/Stat5 mediated SOCS6 signalling.

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

    Science.gov (United States)

    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.

  2. Microcontroller based closed-loop control of a 2D quasi-static/resonant microscanner with on-chip piezo-resistive sensor feedback

    Science.gov (United States)

    Schroedter, Richard; Schwarzenberg, Markus; Dreyhaupt, André; Barth, Robert; Sandner, Thilo; Janschek, Klaus

    2017-02-01

    In this paper we present a 2D raster scanning quasi-static/resonant micro mirror being controlled in both axes in closed-loop with on-chip piezo-resistive sensor feedback. While the resonant axis oscillates with a given frequency, the quasi-static axis allows static as well as dynamic deflection up to its eigenfrequency because of its staggered vertical comb (SVC) drive arrangement. Due to the high quality factor of the very low damped spring-masssystem, an adapted trajectory planning using jerk limitation is applied for the quasi-static axis [1]. Nevertheless, inaccuracies of the applied nonlinear micro mirror model and external disturbances lead to undesired residual oscillation in open-loop control mode. To achieve high precise and fast beam positioning, we implement a flatness-based control algorithm with feedback to on-chip piezo-resistive deflection sensors. In comparison to previous work [2, 3], we developed a micro controller setup for driving the microscanner, that is equipped with an analog Bessel filter increasing the sensor signal quality significantly. In this study we demonstrate a small size and low power micro mirror driver including high-voltage generation and a microcontroller for real-time control as well as a head circuit board for high resolution sensing. We discuss experimental results of open-loop and closed-loop control for 2D raster scanning operation. Finally, the outlook is given to the intrinsic capability to compensate temperature drifts influencing the piezo-resistive sensor signal.

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

    Science.gov (United States)

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

    2016-05-01

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

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

    Directory of Open Access Journals (Sweden)

    Joseph H R Hetmanski

    2016-05-01

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

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

    Directory of Open Access Journals (Sweden)

    Carolina eLeon-Pinzon

    2014-06-01

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

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

    Science.gov (United States)

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

    2015-05-01

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

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

    Science.gov (United States)

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

    2016-01-28

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

  8. Coupling of a core post-translational pacemaker to a slave transcription/translation feedback loop in a circadian system.

    Directory of Open Access Journals (Sweden)

    Ximing Qin

    Full Text Available Cyanobacteria are the only model circadian clock system in which a circadian oscillator can be reconstituted in vitro. The underlying circadian mechanism appears to comprise two subcomponents: a post-translational oscillator (PTO and a transcriptional/translational feedback loop (TTFL. The PTO and TTFL have been hypothesized to operate as dual oscillator systems in cyanobacteria. However, we find that they have a definite hierarchical interdependency-the PTO is the core pacemaker while the TTFL is a slave oscillator that quickly damps when the PTO stops. By analysis of overexpression experiments and mutant clock proteins, we find that the circadian system is dependent upon the PTO and that suppression of the PTO leads to damped TTFL-based oscillations whose temperature compensation is not stable under different metabolic conditions. Mathematical modeling indicates that the experimental data are compatible with a core PTO driving the TTFL; the combined PTO/TTFL system is resilient to noise. Moreover, the modeling indicates a mechanism by which the TTFL can feed into the PTO such that new synthesis of clock proteins can phase-shift or entrain the core PTO pacemaker. This prediction was experimentally tested and confirmed by entraining the in vivo circadian system with cycles of new clock protein synthesis that modulate the phosphorylation status of the clock proteins in the PTO. In cyanobacteria, the PTO is the self-sustained core pacemaker that can operate independently of the TTFL, but the TTFL damps when the phosphorylation status of the PTO is clamped. However, the TTFL can provide entraining input into the PTO. This study is the first to our knowledge to experimentally and theoretically investigate the dynamics of a circadian clock in which a PTO is coupled to a TTFL. These results have important implications for eukaryotic clock systems in that they can explain how a TTFL could appear to be a core circadian clockwork when in fact the true

  9. Muscle involvement during intermittent contraction patterns with different target force feedback modes

    DEFF Research Database (Denmark)

    Sjøgaard, G; Jørgensen, L V; Ekner, D

    2000-01-01

    feedback) or a weight to be held in position (proprioceptive feedback) both corresponding to 30% maximal voluntary contraction. Contraction and relaxation timing of 6 and 4 s, respectively, was shown on a VDU screen as colour code identical in both conditions. RESULTS: Test contractions performed before...... and following 30 min of intermittent contractions showed larger fatigue development with proprioceptive feedback than visual feedback. Also rating of perceived exertion increased more during proprioceptive feedback than visual feedback. This may in part be explained by small differences in the mechanics during...... the two different feedback modes. In line with this, EMG recorded from four shoulder/arm muscles analyzed for amplitude and frequency showed similar activity initially; but later, during the 30 min contraction larger amplitudes were attained during proprioceptive feedback than visual feedback. CONCLUSIONS...

  10. Midwifery students experience of teamwork projects involving mark-related peer feedback.

    Science.gov (United States)

    Hastie, Carolyn R; Fahy, Kathleen M; Parratt, Jenny A; Grace, Sandra

    2016-06-01

    Lack of teamwork skills among health care professionals endangers patients and enables workplace bullying. Individual teamwork skills are increasingly being assessed in the undergraduate health courses but rarely defined, made explicit or taught. To remedy these deficiencies we introduced a longitudinal educational strategy across all three years of the Bachelor of Midwifery program. To report on students' experiences of engaging in team based assignments which involved mark-related peer feedback. Stories of midwifery students' experiences were collected from 17 participants across the three years of the degree. These were transcribed and analysed thematically and interpreted using feminist collaborative conversations. Most participants reported being in well-functioning teams and enjoyed the experience; they spoke of 'we' and said 'Everyone was on Board'. Students in poorly functioning teams spoke of 'I' and 'they'. These students complained about the poor performance of others but they didn't speak up because they 'didn't want to make waves' and they didn't have the skills to be able to confidently manage conflict. All participants agreed 'Peer-related marks cause mayhem'. Teamwork skills should be specifically taught and assessed. These skills take time to develop. Students, therefore, should be engaged in a teamwork assignment in each semester of the entire program. Peer feedback should be moderated by the teacher and not directly related to marks. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

  11. Muscle involvement during intermittent contraction patterns with different target force feedback modes

    DEFF Research Database (Denmark)

    Sjøgaard, G; Jørgensen, L V; Ekner, D

    2000-01-01

    and following 30 min of intermittent contractions showed larger fatigue development with proprioceptive feedback than visual feedback. Also rating of perceived exertion increased more during proprioceptive feedback than visual feedback. This may in part be explained by small differences in the mechanics during...... timing and force level is generally not specified. DESIGN: Repeated measure design in which six subjects in randomized order performed two experimental conditions only differing in feedback mode. METHODS: Intermittent static elbow flexion was performed against either a fixed-force transducer (visual...... and consequently the development muscle fatigue and disorders....

  12. Mesenteric lymph node cells from neonates present a prominent IL-12 response to CpG oligodeoxynucleotide via an IL-15 feedback loop of amplification

    Directory of Open Access Journals (Sweden)

    Ferret-Bernard Stéphanie

    2011-02-01

    Full Text Available Abstract At birth, the immune system is still in development making neonates more susceptible to infections. The recognition of microbial ligands is a key step in the initiation of immune responses. It can be mimicked to stimulate the immune system by the use of synthetic ligands recognising pattern recognition receptors. In human and mouse, it has been found that neonatal cytokine responses to toll-like receptor (TLR ligands differ in many ways from those of adults but the relevant studies have been limited to cord blood and spleen cells. In this study, we compared the responses in neonate and adult sheep to CpG oligodeoxynucleotides (ODN, a TLR9 ligand, in both a mucosal and a systemic organ. We observed that in response to CpG-ODN more IL-12 was produced by neonatal than adult sheep cells from mesenteric lymph nodes (MLN and spleen. This higher IL-12 response was limited to the first 20 days after birth for MLN cells but persisted for a longer period for spleen cells. The major IL-12-producing cells were identified as CD14+CD11b+. These cells were poor producers of IL-12 in response to direct stimulation with CpG-ODN and required the cooperation of other MLN cells. The difference in response to CpG-ODN between neonates and adults can be attributed to both a higher proportion of CD14+CD11b+ cells in neonate lambs and their higher capacity to produce IL-15. The IL-15 increases IL-12 production by an amplifying feedback loop involving CD40.

  13. Downregulation of IL6 Targeted MiR-376b May Contribute to a Positive IL6 Feedback Loop During Early Liver Regeneration in Mice

    Directory of Open Access Journals (Sweden)

    Shan Lu

    2015-08-01

    Full Text Available Background/Aims: MicroRNAs (miRNAs are a group of endogenous, small, noncoding RNAs implicated in a variety of biological processes, including cell proliferation, apoptosis, differentiation and metabolism. The present study aims to explore the potential role and molecular mechanism of miR-376b during the early phase of liver regeneration. Methods: MiRNA profiling microarrays were used to assess the changes in miRNA expression. For functional analysis, cell proliferation, apoptosis assays, real time quantitative PCR and westernblot analysis were performed. Results: The comprehensive miRNA expression profiling assays on regenerating liver tissues 4 h after partial hepatectomy (PH showed that three miRNAs (miR-127, miR-376b and miR-494 located in the Dlk1-Gtl2 miRNA cluster were significantly downregulated. In vitro functional studies demonstrated that high-level interleukin 6 (IL6 inhibited the expression of miR-376b, and miR-376b mimics treatment decreased cell proliferation and increased apoptosis. Further target analysis showed that miR-376b reduced the mRNA and protein expression levels of NF-kappa-B inhibitor zeta (NFKBIZ and signal transducers and transcription activators 3 (STAT3. Additionally, IL6-induced miR-376b downregulation would, in turn, increase the expression of IL-6 possibly via a feedback loop involving NFKBIZ or/and STAT3. Conclusion: During the early phase of liver regeneration, miR-376b expression was significantly decreased. Our findings reveal that a regulatory circuitry between miR-376b and IL-6 may exist, which trigger the initiation of liver regeneration.

  14. Duration reproduction with sensory feedback delay: Differential involvement of perception and action time

    Directory of Open Access Journals (Sweden)

    Stephanie eGanzenmüller

    2012-10-01

    Full Text Available Previous research has shown that voluntary action can attract subsequent, delayed feedback events towards the action, and adaptation to the sensorimotor delay can even reverse motor-sensory temporal-order judgments. However, whether and how sensorimotor delay affects duration reproduction is still unclear. To investigate this, we injected an onset- or offset-delay to the sensory feedback signal from a duration reproduction task. We compared duration reproductions within (visual, auditory modality and across audiovisual modalities with feedback signal onset- and offset-delay manipulations. We found that the reproduced duration was lengthened in both visual and auditory feedback signal onset-delay conditions. The lengthening effect was evident immediately, on the first trial with the onset delay. However, when the onset of the feedback signal was prior to the action, the lengthening effect was diminished. In contrast, a shortening effect was found with feedback signal offset-delay, though the effect was weaker and manifested only in the auditory offset-delay condition. These findings indicate that participants tend to mix the onset of action and the feedback signal more when the feedback is delayed, and they heavily rely on motor-stop signals for the duration reproduction. Furthermore, auditory duration was overestimated compared to visual duration in crossmodal feedback conditions, and the overestimation of auditory duration (or the underestimation of visual duration was independent of the delay manipulation.

  15. PANET: a GPU-based tool for fast parallel analysis of robustness dynamics and feed-forward/feedback loop structures in large-scale biological networks.

    Science.gov (United States)

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

    2014-01-01

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

  16. PANET: a GPU-based tool for fast parallel analysis of robustness dynamics and feed-forward/feedback loop structures in large-scale biological networks.

    Directory of Open Access Journals (Sweden)

    Hung-Cuong Trinh

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

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

    Science.gov (United States)

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

    2016-01-01

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

  18. HER2 phosphorylation is maintained by a PKB negative feedback loop in response to anti-HER2 herceptin in breast cancer.

    Science.gov (United States)

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

    2010-12-21

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

  19. HER2 phosphorylation is maintained by a PKB negative feedback loop in response to anti-HER2 herceptin in breast cancer.

    Directory of Open Access Journals (Sweden)

    Merel Gijsen

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

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

    Science.gov (United States)

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

    2014-12-01

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

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

    Science.gov (United States)

    Grimm, Florian; Naros, Georgios; Gharabaghi, Alireza

    2016-01-01

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

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

    Science.gov (United States)

    Bragg-Sitton, Shannon M.; Forsbacka, Matthew

    2004-01-01

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

  3. Double negative feedback loop between reprogramming factor LIN28 and microRNA let-7 regulates aldehyde dehydrogenase 1-positive cancer stem cells

    Science.gov (United States)

    Yang, Xiaojun; Lin, Xiaojuan; Zhong, Xiaomin; Kaur, Sippy; Li, Ning; Liang, Shun; Lassus, Heini; Wang, Liping; Katsaros, Dionyssios; Montone, Kathleen; Zhao, Xia; Zhang, Youcheng; Bützow, Ralf; Coukos, George; Zhang, Lin

    2010-01-01

    A relatively rare aldehyde dehydrogenase 1 (ALDH1) positive “stem cell-like” subpopulation of tumor cells has the unique ability to initiate and perpetuate tumor growth; moreover it is highly resistant to chemotherapy and significantly associated with poor clinical outcomes. The development of more effective therapies for cancer requires targeting of this cell population. Using cDNA microarray analysis, we identified that the expression of the C. elegans lin-28 homolog (LIN28) was positively correlated with the percentage of ALDH1+ tumor cells; this was further validated in an independent set of tissue arrays (n=197). Both lose-of-function and gain-of-function studies demonstrated that LIN28 plays a critical role in the maintenance of ALDH1+ tumor cells. In addition, we found that there is a double negative feedback loop between LIN28 and let-7 in tumor cells, and that let-7 negatively regulates ALDH1+ tumor cells. Finally, we report that a LIN28/let-7 loop modulates self renewal and differentiation of mammary gland epithelial progenitor cells. Our data provide evidence that cancer stem cells may arise through a “reprogramming-like” mechanism. A rebalancing of the LIN28/let-7 regulatory loop could be a novel therapeutic strategy to target ALDH1+ cancer stem cells. PMID:21045151

  4. Connective tissue growth factor (CCN2) and microRNA-21 are components of a positive feedback loop in pancreatic stellate cells (PSC) during chronic pancreatitis and are exported in PSC-derived exosomes.

    Science.gov (United States)

    Charrier, Alyssa; Chen, Ruju; Chen, Li; Kemper, Sherri; Hattori, Takako; Takigawa, Masaharu; Brigstock, David R

    2014-06-01

    Pancreatitis is an inflammatory condition of the pancreas which, in its chronic form, involves tissue destruction, exocrine and endocrine insufficiency, increased risk of pancreatic cancer, and an extensive fibrotic pathology which is due to unrelenting collagen deposition by pancreatic stellate cells (PSC). In response to noxious agents such as alcohol-excessive consumption of which is a major cause of pancreatitis in the West-normally quiescent PSC undergo a phenotypic and functional transition to activated myofibroblasts which produce and deposit collagen at high levels. This process is regulated by connective tissue growth factor (CCN2), expression of which is highly up-regulated in activated PSC. We show that CCN2 production by activated PSC is associated with enhanced expression of microRNA-21 (miR-21) which was detected at high levels in activated PSC in a murine model of alcoholic chronic pancreatitis. A positive feedback loop between CCN2 and miR-21 was identified that resulted in enhancement of their respective expression as well as that of collagen α1(I). Both miR-21 and CCN2 mRNA were present in PSC-derived exosomes, which were characterized as 50-150 nm CD9-positive nano-vesicles. Exosomes from CCN2-GFP- or miR-21-GFP-transfected PSC were taken up by other PSC cultures, as shown by direct fluorescence or qRT-PCR for GFP. Collectively these studies establish miR-21 and CCN2 as participants in a positive feedback loop during PSC activation and as components of the molecular payload in PSC-derived exosomes that can be delivered to other PSC. Thus interactions between cellular or exosomal miR-21 and CCN2 represent novel aspects of fibrogenic regulation in PSC. Summary Chronic injury in the pancreas is associated with fibrotic pathology which is driven in large part by CCN2-dependent collagen production in pancreatic stellate cells. This study shows that CCN2 up-regulation in PSC is associated with increased expression of miR-21 which, in turn, is able to

  5. Transmesenteric hernia due to double-loop formation in the small intestine: a fatal case involving a toddler.

    Science.gov (United States)

    Kakimoto, Yu; Abiru, Hitoshi; Kotani, Hirokazu; Ozeki, Munetaka; Tsuruyama, Tatsuaki; Tamaki, Keiji

    2012-01-10

    We report a unique case of transmesenteric hernia resulting in death, which went undiagnosed during a recent hospital visit. The victim was a 2.5-year-old girl who - with the exception of chronic constipation - had no medical history. One night she complained of abdominal pains and was taken to a pediatric hospital where doctors performed an abdominal X-ray and echography. No significant findings suggesting bowel obstruction (e.g. air-fluid levels or dilation of the bowel) were obtained on examinations and bloody feces were not observed in this particular episode. As her abdominal pain gradually attenuated, the doctor allowed her to return home. A few hours later, she lost consciousness and expired despite resuscitation efforts attempted at an emergency hospital. A subsequent autopsy revealed that the small bowel had herniated through a defect in the mesentery resulting in two consecutive and inversely forming loops, in which each loop protruded on either side of the mesentery. This rare morphological anatomy seems to have progressed in a two-step process. The girl's mild abdominal pain was likely induced by herniation and formation of the first intestinal loop, followed by severe shock occurring when the subsequent intestinal segment invaginated into the same defect forming the second loop on the opposite side of the mesentery. This case illustrates the difficulty of diagnosing transmesenteric hernia due to the presentation of unspecific symptoms; especially in infants and toddlers. Furthermore, this report demonstrates the value of a complete autopsy in cases of sudden and unexpected deaths involving children. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  6. The Effects of Training, Feedback, and Participant Involvement in Behavioral Safety Observations on Office Ergonomic Behavior

    Science.gov (United States)

    Sasson, Joseph R.; Austin, John

    2005-01-01

    Eleven computer terminal operators participated in an experiment that assessed effects of several interventions aimed at increasing safe ergonomic performance. All participants received ergonomics training and performance feedback while six of them collected observations of safe behavior among the remaining five participants. Effects of…

  7. Does use of the CPREzy involve more work than CPR without feedback?

    NARCIS (Netherlands)

    Berkom, P.F. van; Noordergraaf, G.J.; Scheffer, G.J.; Noordergraaf, A.

    2008-01-01

    AIM: Feedback during CPR may facilitate quality in chest compressions, but has also been associated with caregiver complaints such as stiff wrists, the need for more force and increased fatigue. This concern about extra work is, when using the CPREzy with its own spring-loaded surface, particularly

  8. Does use of the CPREzy involve more work than CPR without feedback?

    NARCIS (Netherlands)

    Berkom, P.F. van; Noordergraaf, G.J.; Scheffer, G.J.; Noordergraaf, A.

    2008-01-01

    AIM: Feedback during CPR may facilitate quality in chest compressions, but has also been associated with caregiver complaints such as stiff wrists, the need for more force and increased fatigue. This concern about extra work is, when using the CPREzy with its own spring-loaded surface, particularly

  9. Model Predicts That MKP1 and TAB1 Regulate p38α Nuclear Pulse and Its Basal Activity through Positive and Negative Feedback Loops in Response to IL-1.

    Science.gov (United States)

    Singh, Raghvendra

    2016-01-01

    Interleukin-1 mediates inflammation and stress response through nuclear activity of p38α. Although IL-1 receptor is not degraded, p38α activation is transient. IL-1 also causes cell migration and EMT by modulating cell-cell junctions. Although molecules involved in p38 activation are known, mechanism of the transient nuclear response and its basal activity remains unknown. By mathematical modeling of IL1/p38 signaling network, we show that IL-1 induces robust p38α activation both in the nucleus and in the cytoplasm/membrane. While nuclear response consists of an acute phase, membrane response resembles a step change. Following stimulation, p38α activity returns to a basal level in absence of receptor degradation. While nuclear pulse is controlled by MKP1 through a negative feedback to pp38, its basal activity is controlled by both TAB1 and MKP1 through a positive feedback loop. Our model provides insight into the mechanism of p38α activation, reason for its transient nuclear response, and explanation of the basal activity of MKK3/6 and p38α, which has been experimentally observed by other groups.

  10. Active serine involved in the stabilization of the active site loop in the Humicola lanuginosa lipase

    DEFF Research Database (Denmark)

    Peters, Günther H.j.; Svendsen, A.; Langberg, H.;

    1998-01-01

    reveal that the hinges of the active site lid are more flexible in the wild-type Hll than in S146A. In contrast, larger fluctuations are observed in the middle region of the active site loop in S 146A than in Hll. These findings reveal that the single mutation (S146A) of the active site serine leads......We have investigated the binding properties of and dynamics in Humicola lanuginosa lipase (HII) and the inactive mutant S146A (active Ser146 substituted with Ala) using fluorescence spectroscopy and molecular dynamics simulations, respectively. Hll and S146A show significantly different binding......, whereas only small changes are observed for I-Ill suggesting that the active site Lid in the latter opens more easily and hence more lipase molecules are bound to the liposomes. These observations are in agreement with molecular dynamics simulations and subsequent essential dynamics analyses. The results...

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

    Science.gov (United States)

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

    2016-05-01

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

  12. Analysis, Design, and Optimization of Matched-Impedance Wide-Band Amplifiers With Multiple Feedback Loops Using 0.18 μm Complementary Metal Oxide Semiconductor Technology

    Science.gov (United States)

    Lin, Yo-Sheng; Lee, Tai-Hsing

    2004-10-01

    The realization of matched-impedance wide-band amplifier fabricated by 0.18 μm complementary metal oxide semiconductor (CMOS) process is reported. The technique of multiple feedback loops was used in the amplifier for terminal impedance matching and wide bandwidth simultaneously. The experimental results show that 3-dB bandwidth of 3 GHz and a gain of 10.7 dB with in-band input/output return loss more than 10 dB are obtained. These values agree well with those predicted from the analytic expressions derived for voltage gain, trans-impedance gain, bandwidth, and input/output return loss and impedance. In addition, the use of source capacitive peaking technique can improve the intrinsic over-damped characteristic of this amplifier.

  13. HTLV-1 induces a Th1-like state in CD4(+)CCR4(+) T cells that produces an inflammatory positive feedback loop via astrocytes in HAM/TSP.

    Science.gov (United States)

    Yamano, Yoshihisa; Coler-Reilly, Ariella

    2017-03-15

    The main feature of Human T-lymphotropic virus type I (HTLV-1) -associated myelopathy/tropical spastic paraparesis (HAM/TSP) pathogenesis is a virus-induced hyperactive immune response that produces chronic inflammation in the central nervous system (CNS), but the mechanism by which HTLV-1 deregulates the immune response is unknown. We recently reported a high frequency of HTLV-1-infected CCR4(+) cells, including regulatory T cells. We showed that HTLV-1 induces a Th1-like state in these CCR4(+) cells via T-bet expression. We have also found that CXCL10 plays an important role in a positive feedback loop that maintains inflammation in the CNS. Astrocytes, which were found to be the main producers of CXCL10 in the CNS, are another key player in the loop. In short, we postulate that infected CCR4(+) Th1-like T cells produce interferon-γ, which stimulates astrocytes to produce CXCL10. We now have a much better understanding of the molecular mechanisms at play in HAM/TSP pathogenesis. Copyright © 2016 Elsevier B.V. All rights reserved.

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

    Energy Technology Data Exchange (ETDEWEB)

    Unseren, M.A.

    1993-04-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Unseren, M.A.

    1993-04-01

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

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

    Science.gov (United States)

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

    2016-02-10

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

  17. Gain drift compensation with no feedback-loop developed for the X-Ray Integral Field Unit/ATHENA readout chain

    Science.gov (United States)

    Prêle, Damien; Voisin, Fabrice; Beillimaz, Cyril; Chen, Si; Goldwurm, Andrea

    2016-10-01

    The focal plane of the X-Ray Integral Field Unit (X-IFU) instrument of the Advanced Telescope for High-Energy Astrophysics observatory is composed of 3840 microcalorimeters. These sensors, based on superconducting transition edge sensors (TES), are read out through a frequency multiplexer. A "base-band feedback" suppresses all the carriers of the multiplexed signal in the superconducting quantum interference devices input coil (cryogenic readout). However, the loop gain of this feedback is too small (less than 10 in the present baseline of the phase A mission) to strongly compensate the readout gain drifts. An onboard x-ray source is considered to calibrate the gain of the full instrument. However, in-flight calibration time must be minimized, which leads to a requirement on the gain stability larger than 10-4 over a long duration (between each calibration) to reach the challenging energy resolution goal of 2.5 eV at 6 keV of the X-IFU. A significant part of this gain is provided by a low-noise amplifier in the warm front-end electronics (WFEE). To reach such gain stability over more than a dozen minutes, this noncooled amplifier has to cope with the temperature and supply voltage variations. Moreover, mainly for noise reasons, a common large loop gain with feedback cannot be used. We propose a new amplifier topology using diodes as loads of a differential amplifier to provide a fixed voltage gain, independent of the temperature and of the bias fluctuations. This amplifier is designed using 350-nm SiGe BiCMOS technology and is part of an integrated circuit developed for the WFEE. Our simulations provide the expected gain and noise performances. Comparison with standard resistive loaded differential pair clearly shows the advantages of the proposed amplifier topology with a gain drift decreased by more than an order of magnitude. Performances of this diode loaded amplifier are discussed in the context of the X-IFU requirements.

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

    Directory of Open Access Journals (Sweden)

    Fatma Aboulnasr

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

  19. Pulsed feedback defers cellular differentiation.

    Directory of Open Access Journals (Sweden)

    Joe H Levine

    2012-01-01

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

  20. Responses of primate LGN cells to moving stimuli involve a constant background modulation by feedback from area MT.

    Science.gov (United States)

    Jones, H E; Andolina, I M; Grieve, K L; Wang, W; Salt, T E; Cudeiro, J; Sillito, A M

    2013-08-29

    The feedback connections from the cortical middle temporal (MT) motion area, to layer 6 of the primary visual cortex (V1), have the capacity to drive a cascaded feedback influence from the layer 6 cortico-geniculate cells back to the lateral geniculate nucleus (LGN) relay cells. This introduces the possibility of a re-entrant motion signal affecting the relay of the retinal input through the LGN to the visual cortex. The question is whether the response of LGN cells to moving stimuli involves a component derived from this feedback. By producing a reversible focal pharmacological block of the activity of an MT direction column we show the presence of such an influence from MT on the responses of magno, parvo and koniocellular cells in the macaque LGN. The pattern of effect in the LGN reflects the direction bias of the MT location inactivated. This suggests a moving stimulus is captured by iterative interactions in the circuit formed by visual cortical areas and visual thalamus.

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

    Science.gov (United States)

    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.

  2. A Mechanism for Land-Atmosphere Feedback Involving Planetary Wave Structures

    Science.gov (United States)

    Koster, Randal D.; Chang, Yehui; Schubert, Siegfried D.

    2014-01-01

    While the ability of land surface conditions to influence the atmosphere has been demonstrated in various modeling and observational studies, the precise mechanisms by which land-atmosphere feedback occurs are still largely unknown particularly the mechanisms that allow land moisture state in one region to affect atmospheric conditions in another. Such remote impacts are examined here in the context of atmospheric general circulation model (AGCM) simulations, leading to the identification of one potential mechanism: the phase-locking and amplification of a planetary wave through the imposition of a spatial pattern of soil moisture at the land surface. This mechanism, shown here to be relevant in the AGCM, apparently also operates in nature, as suggested by supporting evidence found in reanalysis data.

  3. Coordination of Double Strand Break Repair and Meiotic Progression in Yeast by a Mek1- Ndt80 Negative Feedback Loop.

    Science.gov (United States)

    Prugar, Evelyn; Burnett, Cameron; Chen, Xiangyu; Hollingsworth, Nancy M

    2017-03-01

    During meiosis, homologous chromosomes are physically connected by crossovers and sister chromatid cohesion. Interhomolog crossovers are generated by the highly regulated repair of programmed double strand breaks (DSBs). The meiosis-specific kinase, Mek1, is critical for this regulation. Mek1 down-regulates the mitotic recombinase Rad51, indirectly promoting interhomolog strand invasion by the meiosis-specific recombinase, Dmc1. Mek1 also promotes the formation of crossovers that are distributed throughout the genome by interference and is the effector kinase for a meiosis-specific checkpoint that delays entry into Meiosis I until DSBs have been repaired. The target of this checkpoint is a meiosis-specific transcription factor, Ndt80, which is necessary to express the polo-like kinase, CDC5, and the cyclin, CLB1, thereby allowing completion of recombination and meiotic progression. This work shows that Mek1 and Ndt80 negatively feedback on each other such that when DSB levels are high, Ndt80 is inactive due to high levels of Mek1 activity. As DSBs are repaired, chromosomes synapse and Mek1 activity is reduced below a threshold that allows activation of Ndt80. Ndt80 transcription of CDC5 results in degradation of Red1, a meiosis-specific protein required for Mek1 activation, thereby abolishing Mek1 activity completely. Elimination of Mek1 kinase activity allows Rad51-mediated repair of any remaining DSBs. In this way, cells do not enter Meiosis I until recombination is complete and all DSBs are repaired.

  4. A novel double-negative feedback loop between miR-489 and the HER2-SHP2-MAPK signaling axis regulates breast cancer cell proliferation and tumor growth.

    Science.gov (United States)

    Patel, Yogin; Shah, Nirav; Lee, Ji Shin; Markoutsa, Eleni; Jie, Chunfa; Liu, Shou; Botbyl, Rachel; Reisman, David; Xu, Peisheng; Chen, Hexin

    2016-04-05

    Human epidermal growth factor receptor 2 (HER2 or ErBb2) is a receptor tyrosine kinase overexpressed in 20-30% of breast cancers and associated with poor prognosis and outcome. Dysregulation of several microRNAs (miRNAs) plays a key role in breast cancer progression and metastasis. In this study, we screened and identified miRNAs dysregualted in HER2-positive breast cancer cells. Our molecular study demonstrated that miR-489 was specifically downregulated by the HER2-downstream signaling, especially through the MAPK pathway. Restoration or overexpression of miR-489 in HER2-positive breast cancer cells significantly inhibited cell growth in vitro and decreased the tumorigenecity and tumor growth in xenograft mice. Mechanistically, we found that overexpression of miR-489 led to the decreased levels of HER2 and SHP2 and thus attenuated HER2-downstream signaling. Furthermore, we for the first time demonstrated that HER2 is a direct target of miR-489 and therefore HER2-SHP2-MAPK and miR-489 signaling pathways form a mutually inhibitory loop. Using quantitative real-time PCR analysis and Fluorescent in situ hybridization technique (FISH), we found that miR-489 was expressed at significantly lower level in tumor tissues compared to the adjacent normal tissues. Downregulation of miR-489 in breast cancers was associated with aggressive tumor phenotypes. Overall, our results define a double-negative feedback loop involving miR-489 and the HER2-SHP2-MAPK signaling axis that can regulate breast cancer cell proliferation and tumor progression and might have therapeutic relevance for HER2-positive breast cancer.

  5. Diet-induced obesity promotes murine gastric cancer growth through a nampt/sirt1/c-myc positive feedback loop.

    Science.gov (United States)

    Li, Hai-Jun; Che, Xiang-Ming; Zhao, Wei; He, Shi-Cai; Zhang, Zheng-Liang; Chen, Rui; Fan, Lin; Jia, Zong-Liang

    2013-11-01

    Obesity increases the risk of gastric cancer and may promote its growth, as was recently demonstrated by our novel in vivo mouse model. However, the underlying mechanisms of this correlation remain unclear. The purpose of this study was to investigate the precise effects of obesity on gastric cancer growth and to elucidate the potential molecular mechanisms. Diet-induced obese mice were insulin-resistant, glucose-intolerant and had high serum visfatin concentration. In the subcutaneous mouse model, tumors were more aggressive in diet-induced obese mice compared with lean mice. Tumor weights showed a significant positive correlation with mouse body weights, as well as serum insulin and visfatin concentrations. Immunohistochemical staining showed that the expression levels of iNampt, Sirt1 and c-MYC proteins were upregulated in the subcutaneous tumors from obese mice compared to those from lean animals. Furthermore, obesity not only prompted significantly murine forestomach carcinoma cell migration, proliferation, but also affected cellular apoptosis and cell cycle by endocrine mechanisms. These were associated with increased expression of the pro-survival nampt/sirt1/c-myc positive feedback loop confirmed by RT-PCR and western blotting. These results suggested that diet-induced obesity could promote murine gastric cancer growth by upregulating the expression of the nampt, sirt1 and c-myc genes.

  6. Closed Loop Identification Based on the Virtual Reference Feedback Tuning Applied to a Virtual Two-Degree-of-Freedom Control System

    Science.gov (United States)

    Kaneko, Osamu; Beak, Yong Kawn; Ohtsuka, Toshiyuki

    A new identification method with respect to the parameter tuning of a controller is presented. Here, we introduce a virtual two-degree-of-freedom control structure with a feedforward controller described by using a mathematical model of a plant with a tunable parameter. After performing a one-shot experiment, we apply the virtual reference feedback tuning (VRFT), which is a rational and effective tuning method for the parameter of a controller with only one-shot experiment data, to a virtual feedforward controller by using the experimental data obtained in the actual closed loop. We give a condition for a prefilter which is applied to the data to guarantee that the obtained parameter using the VRFT of a controller is close to the desired one. We also show that the prefilter for the identification in the proposed method has a simpler form than that obtained in the normal VRFT for two-degree-of-freedom control scheme. Finally, in order to show the validity of the proposed method, we give an experimental result on the identification of the dynamics of the opening-closing speed of an elevator door.

  7. CXCL3 contributes to CD133+ CSCs maintenance and forms a positive feedback regulation loop with CD133 in HCC via Erk1/2 phosphorylation

    Science.gov (United States)

    Zhang, Lin; Zhang, Lixing; Li, Hong; Ge, Chao; Zhao, Fangyu; Tian, Hua; Chen, Taoyang; Jiang, Guoping; Xie, Haiyang; Cui, Ying; Yao, Ming; Li, Jinjun

    2016-01-01

    Although the chemotactic cytokine CXCL3 is thought to play an important role in tumor initiation and invasion, little is known about its function in hepatocellular carcinoma (HCC). In our previous study, we found that Ikaros inhibited CD133 expression via the MAPK pathway in HCC. Here, we showed that Ikaros may indirectly down-regulate CXCL3 expression in HCC cells, which leads to better outcomes in patients with CD133+ cancer stem cell (CSC) populations. CD133 overexpression induced CXCL3 expression, and silencing of CD133 down-regulated CXCL3 in HCC cells. Knockdown of CXCL3 inhibited CD133+ HCC CSCs’ self-renewal and tumorigenesis. The serum CXCL3 level was higher in HCC patients’ samples than that in healthy individual. HCC patients with higher CXCL3 expression displayed a poor prognosis, and a high level of CXCL3 was significantly associated with vascular invasion and tumor capsule formation. Exogenous CXCL3 induced Erk1/2 and ETS1 phosphorylation and promoted CD133 expression, indicating a positive feedback loop between CXCL3 and CD133 gene expression in HCC cells via Erk1/2 activation. Together, our findings indicated that CXCL3 might be a potent therapeutic target for HCC. PMID:27255419

  8. Closed-Loop Feedback Computation Model of Dynamical Reputation Based on the Local Trust Evaluation in Business-to-Consumer E-Commerce

    Directory of Open Access Journals (Sweden)

    Bo Tian

    2016-02-01

    Full Text Available Trust and reputation are important factors that influence the success of both traditional transactions in physical social networks and modern e-commerce in virtual Internet environments. It is difficult to define the concept of trust and quantify it because trust has both subjective and objective characteristics at the same time. A well-reported issue with reputation management system in business-to-consumer (BtoC e-commerce is the “all good reputation” problem. In order to deal with the confusion, a new computational model of reputation is proposed in this paper. The ratings of each customer are set as basic trust score events. In addition, the time series of massive ratings are aggregated to formulate the sellers’ local temporal trust scores by Beta distribution. A logical model of trust and reputation is established based on the analysis of the dynamical relationship between trust and reputation. As for single goods with repeat transactions, an iterative mathematical model of trust and reputation is established with a closed-loop feedback mechanism. Numerical experiments on repeated transactions recorded over a period of 24 months are performed. The experimental results show that the proposed method plays guiding roles for both theoretical research into trust and reputation and the practical design of reputation systems in BtoC e-commerce.

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

    Science.gov (United States)

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

    2014-01-01

    The transcription factor p63, member of the p53 gene family, encodes for two main isoforms, TAp63 and ΔNp63 with distinct functions on epithelial homeostasis and cancer. Recently, we discovered that TAp63 is essential for in vitro cardiogenesis and heart development in vivo. TAp63 is expressed by embryonic endoderm and acts on cardiac progenitors by a cell-non-autonomous manner. In the present study, we search for cardiogenic secreted factors that could be regulated by TAp63 and, by ChIP-seq analysis, identified Angiomodulin (AGM), also named IGFBP7 or IGFBP-rP1. We demonstrate that AGM is necessary for cardiac commitment of embryonic stem cells (ESCs) and its regulation depends on TAp63 isoform. TAp63 directly activates both AGM and Activin-A during ESC cardiogenesis while these secreted factors modulate TAp63 gene expression by a feedback loop mechanism. The molecular circuitry controlled by TAp63 on AGM/Activin-A signaling pathway and thus on cardiogenesis emphasizes the importance of p63 during early cardiac development.

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

    Directory of Open Access Journals (Sweden)

    Zohar Wolchinsky

    2014-01-01

    Full Text Available The transcription factor p63, member of the p53 gene family, encodes for two main isoforms, TAp63 and ΔNp63 with distinct functions on epithelial homeostasis and cancer. Recently, we discovered that TAp63 is essential for in vitro cardiogenesis and heart development in vivo. TAp63 is expressed by embryonic endoderm and acts on cardiac progenitors by a cell-non-autonomous manner. In the present study, we search for cardiogenic secreted factors that could be regulated by TAp63 and, by ChIP-seq analysis, identified Angiomodulin (AGM, also named IGFBP7 or IGFBP-rP1. We demonstrate that AGM is necessary for cardiac commitment of embryonic stem cells (ESCs and its regulation depends on TAp63 isoform. TAp63 directly activates both AGM and Activin-A during ESC cardiogenesis while these secreted factors modulate TAp63 gene expression by a feedback loop mechanism. The molecular circuitry controlled by TAp63 on AGM/Activin-A signaling pathway and thus on cardiogenesis emphasizes the importance of p63 during early cardiac development.

  11. A Feedback Regulatory Loop between G3P and Lipid Transfer Proteins DIR1 and AZI1 Mediates Azelaic-Acid-Induced Systemic Immunity

    Directory of Open Access Journals (Sweden)

    Keshun Yu

    2013-04-01

    Full Text Available 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.

  12. Lnc-ATB contributes to gastric cancer growth through a MiR-141-3p/TGFβ2 feedback loop.

    Science.gov (United States)

    Lei, Kecheng; Liang, Xin; Gao, Yuwei; Xu, Baixue; Xu, Yichun; Li, Yueqi; Tao, Yiwen; Shi, Weibin; Liu, Jianwen

    2017-03-11

    The long noncoding RNA (lncRNA) ATB is an important regulator in human tumors. Here, we aimed to investigate the potential molecular mechanisms of lnc-ATB in gastric cancer (GC) tumorigenesis. RT-qPCR analysis was used to detect lnc-ATB expression level in 20 pairs of gastric cancer tissues and adjacent normal gastric mucosa tissues (ANTs). Moreover, the biological role of lnc-ATB was determined in vitro. We found that lnc-ATB was significantly upregulated in GC tissues compared to lnc-ATB expression in ANTs. These high lnc-ATB expression levels predicted poor prognosis in GC patients. Low levels of lnc-ATB inhibited GC cell proliferation and cell cycle arrest in vitro. Lnc-ATB was found to directly bind miR-141-3p. Moreover, TGF-β actives lnc-ATB and TGF-β2 directly binds mir-141-3p. Finally, we demonstrated that lnc-ATB fulfilled its oncogenic roles in a ceRNA-mediated manner. Our study suggests that lnc-ATB promotes tumor progression by interacting with miR-141-3p and that Lnc-ATB may be a valuable prognostic predictor for GC. In conclusion, the positive feedback loop of lnc-ATB/miR-141-3p/TGF-β2 may be a potential therapeutic target for the treatment of GC.

  13. Identification of a negative feedback loop between cyclic di-GMP-induced levels of IFI16 and p202 cytosolic DNA sensors and STING.

    Science.gov (United States)

    Panchanathan, Ravichandran; Liu, Hongzhu; Xin, Duan; Choubey, Divaker

    2014-10-01

    A host type I IFN response is induced by cytosolic sensing of the bacterial second messenger cyclic-di-GMP (c-di-GMP) by STING (stimulator of IFN genes). Because the STING, an adaptor protein, links the cytosolic detection of DNA by the cytosolic DNA sensors such as the IFN-inducible human IFI16 and murine p202 proteins to the TBK1/IRF3 axis, we investigated whether c-di-GMP-induced signaling could regulate expression of IFI16 and p202 proteins. Here, we report that activation of c-di-GMP-induced signaling in human and murine cells increased steady-state levels of IFI16 and p202 proteins. The increase was c-di-GMP concentration- and time-dependent. Unexpectedly, treatment of cells with type I IFN decreased levels of the adaptor protein STING. Therefore, we investigated whether the IFI16 or p202 protein could regulate the expression of STING and activation of the TBK1/IRF3 axis. We found that constitutive knockdown of IFI16 or p202 expression in cells increased steady-state levels of STING. Additionally, the knockdown of IFI16 resulted in activation of the TBK1/IRF3 axis. Accordingly, increased levels of the IFI16 or p202 protein in cells decreased STING levels. Together, our observations identify a novel negative feedback loop between c-di-GMP-induced levels of IFI16 and p202 cytosolic DNA sensors and the adaptor protein STING.

  14. GAS5 suppresses malignancy of human glioma stem cells via a miR-196a-5p/FOXO1 feedback loop.

    Science.gov (United States)

    Zhao, Xihe; Liu, Yunhui; Zheng, Jian; Liu, Xiaobai; Chen, Jiajia; Liu, Libo; Wang, Ping; Xue, Yixue

    2017-10-01

    Glioma stem cells (GSCs) make up highly tumorigenic subpopulations within gliomas, and aberrant expression of GSC genes is a major underlying cause of glioma pathogenesis and treatment failure. The present study characterized the expression and function of long non-coding RNA growth arrest specific 5 (GAS5) in GSCs in order to elucidate the molecular mechanisms by which GAS5 contributes to glioma pathogenesis. We demonstrate that GAS5 suppresses GSC malignancy by binding to miR-196a-5p. miR-196a-5p, an onco-miRNA, stimulates GSC proliferation, migration, and invasion, in addition to reducing levels of apoptosis. miR-196a-5p specifically downregulates the expression of forkhead box protein O1 (FOXO1) by targeting its 3' untranslated region (3'-UTR). FOXO1 upregulates expression of phosphotyrosine interaction domain containing 1 (PID1), thereby inhibiting GSC tumorigenicity and growth. FOXO1 also upregulates migration and invasion inhibitory protein (MIIP), resulting in attenuation of migration and invasion activities. Interestingly, we also show that FOXO1 promotes GAS5 transcription, thus forminga positive feedback loop. These data provide insights into potential new pathways for GSC molecular therapy and suggest that GAS5 may be an efficacious target for glioma treatments. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. HP1a/KDM4A is involved in the autoregulatory loop of the oncogene gene c-Jun.

    Science.gov (United States)

    Liu, Yan; Zhang, Daoyong

    2015-01-01

    The proto-oncogene c-Jun plays crucial roles in tumorigenesis, and its aberrant expression has been implicated in many cancers. Previous studies have shown that the c-Jun gene is positively autoregulated by its product. Notably, it has also been reported that c-Jun proteins are enriched in its gene body region. However, the role of c-Jun proteins in its gene body region has yet to be uncovered. HP1a is an evolutionarily conserved heterochromatin-associated protein, which plays an essential role in heterochromatin-mediated gene silencing. Interestingly, accumulating evidence shows that HP1a is also localized to euchromatic regions to positively regulate gene transcription. However, the underlying mechanism has not been defined. In this study, we demonstrate that HP1a is involved in the positive autoregulatory loop of the Jra gene, the c-Jun homolog in Drosophila. Jra recruits the HP1a/KDM4A complex to its gene body region upon osmotic stress to reduce H3K36 methylation levels and disrupt H3K36 methylation-dependent histone deacetylation, resulting in high levels of histone acetylation in the Jra gene body region, thus promoting gene transcription. These results not only expand our knowledge toward the mechanism of c-Jun regulation, but also reveal the mechanism by which HP1a exerts its positive regulatory function in gene expression.

  16. Autism and genius: is there a link? The involvement of central brain loops and hypotheses for functional testing.

    Science.gov (United States)

    Boso, M; Emanuele, E; Prestori, Francesca; Politi, P; Barale, F; D'Angelo, E

    2010-01-01

    Mental processing is the product of the huge number of synaptic interactions that occur in the brain. It is easier to understand how brain functions can deteriorate than how they might be boosted. Lying at the border between the humanities, cognitive science and neurophysiology, some mental diseases offer new angles on this problematic issue. Despite their social deficits, autistic subjects can display unexpected and extraordinary skills in numerous fields, including music, the arts, calculation and memory. The advanced skills found in a subgroup of people with autism may be explained by their special mental functioning, in particular by their weak central coherence, one of the pivotal characteristics of the disorder. As a result of the increasing interest in autistic talent, there has recently emerged a tendency to screen any eccentric artist or scientist for traits of the autistic spectrum. Following this trend, we analyze the eccentricity of the popular pianist Glenn Gould and briefly discuss the major functional hypotheses on autistic hyperfunctioning, advancing proposals for functional testing. In particular, the potential involvement of rhythm-entrained systems and cerebro-cerebellar loops opens up new perspectives for the investigation of autistic disorders and brain hyperfunctioning.

  17. Closed-Loop Feedback Computer-Controlled Phenylephrine for Maintenance of Blood Pressure During Spinal Anesthesia for Cesarean Delivery: A Randomized Trial Comparing Automated Boluses Versus Infusion.

    Science.gov (United States)

    Ngan Kee, Warwick D; Tam, Yuk-Ho; Khaw, Kim S; Ng, Floria F; Lee, Shara W Y

    2017-07-01

    We previously described the use of closed-loop feedback computer-controlled infusion of phenylephrine for maintaining blood pressure (BP) during spinal anesthesia for cesarean delivery. In this study, we report a modified system in which phenylephrine is delivered by intermittent boluses rather than infusion. We hypothesized that the use of computer-controlled boluses would result in more precise control of BP compared with infusions. Two hundred fourteen healthy patients having spinal anesthesia for elective cesarean delivery were randomized to have their systolic BP maintained by phenylephrine administered by computer-controlled continuous infusion or computer-controlled intermittent boluses. From induction of anesthesia until the time of uterine incision, a noninvasive BP monitor was set to cycle at 1-minute intervals. In the infusion group, the infusion rate was automatically adjusted after each BP measurement using a previously described algorithm. In the bolus group, the algorithm was modified so that the mass of drug that would have been delivered over 1 minute was instead injected as a rapid intravenous bolus after each BP measurement. The precision of BP control was assessed using performance error calculations and compared between groups, with the primary outcome defined as median absolute performance error, and the latter being a measure of inaccuracy showing an average of the magnitudes of the differences of measured BP values above or below the target values. The precision of BP control was greater, as shown by smaller values for median absolute performance error, in the bolus group (median 4.38 [quartiles 3.22, 6.25] %) versus the infusion group (5.39 [4.12, 7.04] %, P = .008). In the bolus group, phenylephrine consumption was smaller; this was associated with smaller values for median performance error compared with the continuous infusion group (P control was more precise when computer-controlled phenylephrine was delivered using intermittent

  18. Downregulation of COMMD1 by miR-205 promotes a positive feedback loop for amplifying inflammatory- and stemness-associated properties of cancer cells.

    Science.gov (United States)

    Yeh, D-W; Chen, Y-S; Lai, C-Y; Liu, Y-L; Lu, C-H; Lo, J-F; Chen, L; Hsu, L-C; Luo, Y; Xiang, R; Chuang, T-H

    2016-05-01

    Sustained activation of nuclear factor-κB (NF-κB) in cancer cells has been shown to promote inflammation, expansion of cancer stem cell (CSC) population, and tumor development. In contrast, recent studies reveal that CSCs exhibit increased inflammation due to constitutive NF-κB activation; however, the underlying molecular mechanism remains unclear. In the present study, the analysis of microarray data revealed upregulation of NF-κB-regulated pro-inflammatory genes and downregulation of copper metabolism MURR1 domain-containing 1 (COMMD1) during the enrichment for stemness in SAS head and neck squamous-cell carcinoma (HNSCC) cells. The 3'-UTR of COMMD1 mRNA contains microRNA (miR)-205 target site. Parallel studies with HNSCC and NSCLC cells indicated that miR-205 is upregulated upon NF-κB activation and suppresses COMMD1 expression in stemness-enriched cancer cells. COMMD1 negatively regulates the inflammatory responses induced by TLR agonists, IL-1β, and TNF-α by targeting RelA for degradation. The shRNA-mediated downregulation of COMMD1 in cancer cells enhanced inflammatory response, generating favorable conditions for macrophage recruitment. In addition, genes associated with stemness were also upregulated in these cells, which exhibited increased potential for anchorage-independent growth. Furthermore, COMMD1 downregulation promoted in vivo tumorigenesis and tumor growth, and tumors derived from COMMD1-knockdown cells displayed elevated level of NF-κB activation, increased expression of inflammatory- and stemness-associated genes, and contain expanded population of tumor-associated leukocytes and stemness-enriched cancer cells. These results suggest that COMMD1 downregulation by miR-205 promotes tumor development by modulating a positive feedback loop that amplifies inflammatory- and stemness-associated properties of cancer cells.

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

    Science.gov (United States)

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

    2015-10-15

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

  20. Shrimp with knockdown of LvSOCS2, a negative feedback loop regulator of JAK/STAT pathway in Litopenaeus vannamei, exhibit enhanced resistance against WSSV.

    Science.gov (United States)

    Wang, Sheng; Song, Xuan; Zhang, Zijian; Li, Haoyang; L, Kai; Yin, Bin; He, Jianguo; Li, Chaozheng

    2016-12-01

    JAK/STAT pathway is one of cytokine signaling pathways and mediates diversity immune responses to protect host from viral infection. In this study, LvSOCS2, a member of suppressor of cytokine signaling (SOCS) families, has been cloned and identified from Litopenaeus vannamei. The full length of LvSOCS2 is 1601 bp, including an 1194 bp open reading frame (ORF) coding for a putative protein of 397 amino acids with a calculated molecular weight of ∼42.3 kDa. LvSOCS2 expression was most abundant in gills and could respond to the challenge of LPS, Vibrio parahaemolyticus, Staphhylococcus aureus, Poly (I: C) and white spot syndrome virus (WSSV). There are several STAT binding motifs presented in the proximal promoter region of LvSOCS2 and its expression was induced by LvJAK or LvSTAT protein in a dose dependent manner, suggesting LvSOCS2 could be the transcriptional target gene of JAK/STAT pathway. Moreover, the transcription of DmVir-1, a read out of the activation of JAK/STAT pathway in Drosophila, was promoted by LvJAK but inhibited by LvSOCS2, indicating that LvSOCS2 could be a negative regulator in this pathway and thus can form a negative feedback loop. Our previous study indicated that shrimp JAK/STAT pathway played a positive role against WSSV. In this study, RNAi-mediated knockdown of LvSOCS2 shrimps showed lower susceptibility to WSSV infection and caused lessened virus loads, which further demonstrated that the JAK/STAT pathway could function as an anti-viral immunity in shrimp.

  1. A Positive Feedback Loop between Glial Cells Missing 1 and Human Chorionic Gonadotropin (hCG) Regulates Placental hCGβ Expression and Cell Differentiation

    Science.gov (United States)

    Cheong, Mei-Leng; Wang, Liang-Jie; Chuang, Pei-Yun; Chang, Ching-Wen; Lee, Yun-Shien; Lo, Hsiao-Fan; Tsai, Ming-Song

    2015-01-01

    Human chorionic gonadotropin (hCG) is composed of a common α subunit and a placenta-specific β subunit. Importantly, hCG is highly expressed in the differentiated and multinucleated syncytiotrophoblast, which is formed via trophoblast cell fusion and stimulated by cyclic AMP (cAMP). Although the ubiquitous activating protein 2 (AP2) transcription factors TFAP2A and TFAP2C may regulate hCGβ expression, it remains unclear how cAMP stimulates placenta-specific hCGβ gene expression and trophoblastic differentiation. Here we demonstrated that the placental transcription factor glial cells missing 1 (GCM1) binds to a highly conserved promoter region in all six hCGβ paralogues by chromatin immunoprecipitation-on-chip (ChIP-chip) analyses. We further showed that cAMP stimulates GCM1 and the CBP coactivator to activate the hCGβ promoter through a GCM1-binding site (GBS1), which also constitutes a previously identified AP2 site. Given that TFAP2C may compete with GCM1 for GBS1, cAMP enhances the association between the hCGβ promoter and GCM1 but not TFAP2C. Indeed, the hCG-cAMP-protein kinase A (PKA) signaling pathway also stimulates Ser269 and Ser275 phosphorylation of GCM1, which recruits CBP to mediate GCM1 acetylation and stabilization. Consequently, hCG stimulates the expression of GCM1 target genes, including the fusogenic protein syncytin-1, to promote placental cell fusion. Our study reveals a positive feedback loop between GCM1 and hCG regulating placental hCGβ expression and cell differentiation. PMID:26503785

  2. Loss of the oncogenic phosphatase PRL-3 promotes a TNF-R1 feedback loop that mediates triple-negative breast cancer growth.

    Science.gov (United States)

    Gari, H H; DeGala, G D; Lucia, M S; Lambert, J R

    2016-08-15

    Stimulating tumor cell senescence and apoptosis are proven methods for therapeutically combating cancer. However, senescence and apoptosis are conventionally viewed as parallel, not sequential, processes. We have discovered that the metastasis-promoting phosphatase, PRL-3, is transcriptionally regulated by the NF-ĸB pathway in triple-negative breast cancer (TNBC) cells, and that PRL-3 knockdown elicits an autocrine tumor necrosis factor receptor 1 (TNF-R1) feedback loop that results in TNBC cell senescence followed by apoptosis. Knockdown of PRL-3 leads to rapid G1 cell cycle arrest and induction of a strong TNFα cytokine response that promotes a period of cellular senescence through TNF-R1-mediated activation of NF-ĸB. Senescent PRL-3 knockdown cells subsequently underwent apoptosis as a result of increased TNF-R1 signaling through the TNFα-associated extrinsic death pathway, shunting signaling away from the NF-ĸB cascade. These data suggest that TNF-R1 signaling dynamically re-programs after PRL-3 knockdown, from sustaining cell senescence through NF-ĸB to promoting apoptosis through TNF-R1 internalization and caspase-8 activation. The molecular mechanisms that determine the survival-death balance of TNF-R1 signaling are poorly understood, despite the fact that TNF-R1 has been extensively studied. Our results describe PRL-3 knockdown as a novel survival-death balance modifier of the TNF-R1 pathway, and show that senescent TNBC tumor cells can be sensitized to undergo apoptosis in a sequential manner.

  3. Oridonin induces apoptosis and autophagy in murine fibrosarcoma L929 cells partly via NO-ERK-p53 positive-feedback loop signaling pathway

    Institute of Scientific and Technical Information of China (English)

    Yuan-chao YE; Hong-ju WANG; Lei XU; Wei-wei LIU; Bin-bin LIU; Shin-lchi TASHIRO; Satoshi ONODERA; Takashi IKEJIMA

    2012-01-01

    Aim:To investigate the role of nitric oxide (NO) in oridonin-induced apoptosis and autophagy in murine fibrosarcoma L929 Cells and the underlying molecular mechanisms.Methods; Cell viability was measured using MTT assay.Intracellular NO level,SubG1 cell ratio and autophagy cell ratios were analyzed with flow cytometry after diaminofluorescein-2 diacetate (DAF-2DA),propidium iodide (PI) and monodansylcadaverine (MDC) staining,respectively.Protein expression was examined using Western blot analysis.Results:Exposure of L929 cells to oridonin (50 μmol/L) for 24 h led to intracellular NO production.Pretreatment with NOS inhibitor 1400w or L-NAME inhibited oridonin-induced apoptosis and autophagy in L929 cells.The pretreatment decreased the apoptosisrelated protein Bax translocation and cytochrome c release,increased Bcl-2 level,reversed the autophay-associated protein Beclin 1 increase and conversion of LC3 Ⅰ to LC3 Ⅱ.Furthermore,pretreatment with NO scavenger DTT completely inhibited oridonin-induced apoptosis and autophagy in L929 cells.In addition,oridonin (50 μmol/L) activated ERK and p53 in L929 cells,and the interruption of ERK and p53 activation by PD 98059,pifithrin-α,or ERK siRNA decreased oridonin-induced apoptosis and autophagy.The inhibition of NO production reduced oridonin-induced ERK and p53 activation,and NO production was down-regulated by blocking ERK and p53activation.Conclusion:NO played a pivotal role in oridonin-induced apoptosis and autophagy in L929 cells.Taken together with our previous finding that ERK contributes to p53 activation,it appears that NO,ERK,and p53 form a positive feedback loop.Consequently,we suggest that oridonin-induced apoptosis and autophagy are modulated by the NO-ERK-p53 molecular signaling mechanism in L929 cells.

  4. Fault Tolerant Feedback Control

    DEFF Research Database (Denmark)

    Stoustrup, Jakob; Niemann, H.

    2001-01-01

    An architecture for fault tolerant feedback controllers based on the Youla parameterization is suggested. It is shown that the Youla parameterization will give a residual vector directly in connection with the fault diagnosis part of the fault tolerant feedback controller. It turns out...... that there is a separation be-tween the feedback controller and the fault tolerant part. The closed loop feedback properties are handled by the nominal feedback controller and the fault tolerant part is handled by the design of the Youla parameter. The design of the fault tolerant part will not affect the design...... of the nominal feedback con-troller....

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

    Science.gov (United States)

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

    2016-01-01

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

  6. Growth factor TGF-β induces intestinal epithelial cell (IEC-6) differentiation: miR-146b as a regulatory component in the negative feedback loop.

    Science.gov (United States)

    Liao, Yalin; Zhang, Man; Lönnerdal, Bo

    2013-01-01

    TGF-β is a potent pleiotropic factor that promotes small intestinal cell differentiation. The role of microRNAs in the TGF-β induction of intestinal epithelial phenotype is largely unknown. We hypothesized that microRNAs are functionally involved in TGF-β-induced intestinal cell growth. In this study, TGF-β caused a morphological change of IEC-6 cells and stimulated expression of the epithelial cell markers alkaline phosphatase, villin, and aminopeptidase N. By global microRNA profiling during TGF-β-induced intestinal crypt cell (IEC-6) differentiation, we identified 19 differentially expressed microRNAs. We showed by real-time Q-PCR that miR-146b expression increased rapidly after TGF-β treatment; sequence analysis and in vitro assays revealed that miR-146b targets SIAH2, an E3 ubiquitin ligase, with decreased protein expression upon IEC-6 cell differentiation. Transfection of miR-146b inhibitor before TGF-β treatment blocked the down-regulation of SIAH2 in response to TGF-β. Moreover, SIAH2 over-expression during TGF-β treatment caused a significant decrease in Smad7 protein expression in IEC-6 cells. Furthermore, activation of the ERK1/2 pathway is active in the up-regulation of miR-146b by TGF-β. These findings suggest a novel mechanism whereby TGF-β signaling during IEC-6 cell differentiation may be modulated in part by microRNAs, and we propose a key role for miR-146b in the homeostasis of growth factor TGF-β signaling through a negative feedback regulation involving down-regulation of SIAH2 repressed Smad7 activities.

  7. Exploration and Feedback Mechanism on Training Mode of Closed-loop Talents for Characteristic Specialty%特色专业闭环人才培养模式的探索和反馈机制

    Institute of Scientific and Technical Information of China (English)

    徐忠四; 梁益宁; 高雪琴

    2016-01-01

    Every segment of Professional talent cultivation should form a closed-loop system. During the course of talent cultivation, every segment could dynamically adjust to change according to the talent market demands. The cultivation objectives of closed-loop talents were set forth, and the basis thinking of training modeof closed-loop talents was analyzed. Taking the armored vehicle engineering specialty of North University of China for example, Training mode of closed-loop talents for characteristic specialty and feedback mechanism improving the undergraduate cultivation quality was explored on practice, which will form a solid foundation for the sustainable development of the specialty.%专业人才培养各个环节之间应该形成一个闭环,各个环节根据市场对人才需求的变化进行动态调整。阐述闭环人才的培养目标,分析闭环人才培养的基本思路。以中北大学装甲车辆工程专业为例,从实践上探索特色专业闭环人才的培养模式和提高本科生培养质量的反馈机制,为本专业的可持续发展奠定坚实的基础。

  8. Circadian clock feedback cycle through NAMPT-mediated NAD+ biosynthesis.

    Science.gov (United States)

    Ramsey, Kathryn Moynihan; Yoshino, Jun; Brace, Cynthia S; Abrassart, Dana; Kobayashi, Yumiko; Marcheva, Biliana; Hong, Hee-Kyung; Chong, Jason L; Buhr, Ethan D; Lee, Choogon; Takahashi, Joseph S; Imai, Shin-Ichiro; Bass, Joseph

    2009-05-01

    The circadian clock is encoded by a transcription-translation feedback loop that synchronizes behavior and metabolism with the light-dark cycle. Here we report that both the rate-limiting enzyme in mammalian nicotinamide adenine dinucleotide (NAD+) biosynthesis, nicotinamide phosphoribosyltransferase (NAMPT), and levels of NAD+ display circadian oscillations that are regulated by the core clock machinery in mice. Inhibition of NAMPT promotes oscillation of the clock gene Per2 by releasing CLOCK:BMAL1 from suppression by SIRT1. In turn, the circadian transcription factor CLOCK binds to and up-regulates Nampt, thus completing a feedback loop involving NAMPT/NAD+ and SIRT1/CLOCK:BMAL1.

  9. The effect of performance agreement, employee involvement, facilitation, assessment and feedback towards employee performance: a study in Pt. Surya Pamenang, Jawa Timur Province, Indonesia

    OpenAIRE

    ANSORY AL FADJAR; SALIM UBUD; SUDIRO ACHMAD; KHUSNIAH NUR

    2016-01-01

    Facing ASEAN Economic Community to deal with foreign companies from various countries needs optimal resources so that local enterprises could increase the employee performance. This study aims to analyze the influence of performance agreement, facilitation, assessment, feedback, employee involvement towards employee performance. The inferential statistical analysis used was SEM (Structural Equation Modeling) by collecting data through a survey at PT. Surya Pamenang, Kediri, Jawa Timur Provinc...

  10. General anesthetic action at an internal protein site involving the S4-S5 cytoplasmic loop of a neuronal K(+) channel.

    Science.gov (United States)

    Harris, T; Shahidullah, M; Ellingson, J S; Covarrubias, M

    2000-02-18

    The structural bases of general anesthetic action on a neuronal K(+) channel were investigated using the series of homologous 1-alkanols, electrophysiology, and mutational analysis. Domain swapping between dShaw2 (alkanol-sensitive) and hKv3.4 (alkanol-resistant) and site-directed mutagenesis demonstrated that a 13-amino acid cytoplasmic loop (S4-S5) determines the selective inhibition of native dShaw2 channels by 1-alkanols. The S4-S5 loop may contribute to a receptor for both 1-alkanols and the inactivation particle, because the enhanced 1-alkanol sensitivity of hKv3.4 channels hosting S4-S5 mutations correlates directly with disrupted channel inactivation. Evidence of a discrete protein site was also obtained from the analysis of the relationship between potency and alkyl chain length, which begins to level off after 1-hexanol. Rapid application to the cytoplasmic side of inside-out membrane patches shows that the interaction between dShaw2 channels and 1-alkanols equilibrates in 1000-fold slower when the drug is applied externally to outside-out membrane patches. The data strongly favor a mechanism of inhibition involving a discrete internal site for 1-alkanols in dShaw2 K(+) channels. A new working hypothesis proposes that 1-alkanols lock dShaw2 channels in their closed conformation by a direct interaction at a crevice formed by the S4-S5 loop.

  11. Analytic Evaluation of Three Different Five-Electron Atomic Integrals Involving Exponentially Correlated Functions of $r_{ij}$ With $r_{ij}$'s Not Forming A Closed Loop

    CERN Document Server

    Padhy, B

    2016-01-01

    The simple method outlined in our earlier paper [B.Padhy, Orissa Journal of Physics, vol.19, No.1, p.1, February 2012] has been utilized here for analytic evaluation of three different five-electron atomic integrals with integrands involving products of s Slater-type orbitals and exponentially correlated functions of the form $r_{ij} exp(-\\lambda_{ij} r_{ij})$. Only products of those $r_{ij}$'s which do not form a closed loop by themselves, are considered.

  12. A chopper current-feedback instrumentation amplifier with a 1 mHz 1/f noise corner and an AC-coupled ripple reduction loop

    NARCIS (Netherlands)

    Wu, R.; Makinwa, K.A.A.; Huijsing, J.H.

    2009-01-01

    This paper presents a chopper instrumentation amplifier for interfacing precision thermistor bridges. For high CMRR and DC gain, the amplifier employs a three-stage current-feedback topology with nested-Miller compensation. By chopping both the input and intermediate stages of the amplifier, a 1 mHz

  13. Balanced bridge feedback control system

    Science.gov (United States)

    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.

  14. Bandwidth enhancement and time-delay signature suppression of chaotic signal from an optical feedback semiconductor laser by using cross phase modulation in a highly nonlinear fiber loop mirror

    Science.gov (United States)

    Wang, Liang-Yan; Zhong, Zhu-Qiong; Wu, Zheng-Mao; Lu, Dong; Chen, Xi; Chen, Jun; Xia, Guang-Qiong

    2016-11-01

    Based on a nonlinear fiber loop mirror (NOLM) composed of a fiber coupler (FC) and a highly nonlinear fiber (HNLF), a scheme is proposed to simultaneously realize the bandwidth enhancement and the time-delay signature (TDS) suppression of a chaotic signal generated from an external cavity optical feedback semiconductor laser. The simulation results show that, after passing through the NOLM, the bandwidth of chaotic signal can be efficiently enhanced and the TDS can be well suppressed under suitable operation parameters. Furthermore, the influences of the power-splitting ratio of the FC, the averaged power of the chaotic signal entering into the FC and the length of the HNLF on the chaotic bandwidth and TDS are analyzed, and the optimized parameters are determined.

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

    Science.gov (United States)

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

    2015-10-27

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

  16. Feedback control of quantum system

    Institute of Scientific and Technical Information of China (English)

    DONG Dao-yi; CHEN Zong-hai; ZHANG Chen-bin; CHEN Chun-lin

    2006-01-01

    Feedback is a significant strategy for the control of quantum system.Information acquisition is the greatest difficulty in quantum feedback applications.After discussing several basic methods for information acquisition,we review three kinds of quantum feedback control strategies:quantum feedback control with measurement,coherent quantum feedback,and quantum feedback control based on cloning and recognition.The first feedback strategy can effectively acquire information,but it destroys the coherence in feedback loop.On the contrary,coherent quantum feedback does not destroy the coherence,but the capability of information acquisition is limited.However,the third feedback scheme gives a compromise between information acquisition and measurement disturbance.

  17. Pirfenidone controls the feedback loop of the AT1R/p38 MAPK/renin-angiotensin system axis by regulating liver X receptor-α in myocardial infarction-induced cardiac fibrosis

    Science.gov (United States)

    Li, Chunmei; Han, Rui; Kang, Le; Wang, Jianping; Gao, Yonglin; Li, Yanshen; He, Jie; Tian, Jingwei

    2017-01-01

    Pirfenidone (PFD), an anti-fibrotic small molecule drug, is used to treat fibrotic diseases, but its effects on myocardial infarction (MI)-induced cardiac fibrosis are unknown. The aim of this study was to determine the effects of PFD on MI-induced cardiac fibrosis and the possible underlying mechanisms in rats. After establishment of the model, animals were administered PFD by gavage for 4 weeks. During the development of MI-induced cardiac fibrosis, we found activation of a positive feedback loop between the angiotensin II type 1 receptor (AT1R)/phospho-p38 mitogen-activated protein kinase (p38 MAPK) pathway and renin-angiotensin system (RAS), which was accompanied by down-regulation of liver X receptor-α (LXR-α) expression. PFD attenuated body weight, heart weight, left ventricular weight, left ventricular systolic pressure, and ±dp/dtmax changes induced by MI, which were associated with a reduction in cardiac fibrosis, infarct size, and hydroxyproline concentration. Moreover, PFD inhibited the AT1R/p38 MAPK pathway, corrected the RAS imbalance [decreased angiotensin-converting enzyme (ACE), angiotensin II, and angiotensin II type 1 receptor expression, but increased ACE2 and angiotensin (1-7) activity and Mas expression] and strongly enhanced heart LXR-α expression. These results indicate that the cardioprotective effects of PFD may be due, in large part, to controlling the feedback loop of the AT1R/p38 MAPK/RAS axis by activation of LXR-α. PMID:28091615

  18. 电励磁同步电动机转矩角截止负反馈闭环控制%Torque-Angle Cut-Off Negative Feedback Closed-Loop Control Strategy of Electrical Excited Synchronous Motor

    Institute of Scientific and Technical Information of China (English)

    谢慕君; 步伟明; 冯敬芳; 王志乾

    2013-01-01

    针对电励磁同步电动机负载变化易失步的问题,通过对转矩角特性分析,提出了一种基于转矩角截止负反馈的控制策略。阐述了利用转矩角控制防止失步的原理,建立了基于同步电动机磁链观测的转矩角数学模型,并设计了转矩角外环、励磁电流内环的双闭环控制系统。仿真结果表明,该控制策略与常规控制相比,适应负载变化的能力显著提高,有效抑制了电机的失步,为电机的稳定控制开辟了新途径。%Aiming at the problem that the electrical synchronous excited motor will be out of step with the load changes, this paper raised a control strategy based on torque-angle cut-off feedback via the analysis of torque-angle characteristics. Discussion was made to the principle using torque-angle control to prevent out-of-step. The mathematical model of torque-angle was constructed based on the flux linkage observation of synchronous motors and the double closed-loop control system for the outer loop adopting torque-angle and the inner loop adopting field current were designed. The simulation results show that compared with conventional control, this control strategy obviously met the requirements of load changes, effectively restraining out-of-step of motors, which opens up a new way for stable control of motors.

  19. Regenerative feedback resonant circuit

    Science.gov (United States)

    Jones, A. Mark; Kelly, James F.; McCloy, John S.; McMakin, Douglas L.

    2014-09-02

    A regenerative feedback resonant circuit for measuring a transient response in a loop is disclosed. The circuit includes an amplifier for generating a signal in the loop. The circuit further includes a resonator having a resonant cavity and a material located within the cavity. The signal sent into the resonator produces a resonant frequency. A variation of the resonant frequency due to perturbations in electromagnetic properties of the material is measured.

  20. Dynamic aspects of the tubuloglomerular feedback mechanism

    DEFF Research Database (Denmark)

    Holstein-Rathlou, N H

    1992-01-01

    unlikely, it cannot be excluded that a vascular pacemaker is involved in the underlying oscillatory mechanism. To test the hypothesis that the oscillations are caused by the TGF system, a series of dynamic mathematical models of the TGF system have been developed.(ABSTRACT TRUNCATED AT 400 WORDS)......Tubuloglomerular feedback (TGF) is an important intrarenal regulatory mechanism, which acts to stabilize renal blood flow, GFR, and the tubular flow rate. The anatomical basis for this negative feedback system is the Juxtaglomerular Apparatus (JGA). This is located at the point of contact between...... the thick ascending limb of the loop of Henle (TAL) and the vascular pole of the glomerulus. The JGA includes the macula densa, a specialized plaque of cells in the TAL thought to be responsible for the sensing step in the feedback mechanism; the mesangial cells, a cushion of cells separating the macula...

  1. A prototype framework for models of socio-hydrology: identification of key feedback loops with application to two Australian case-studies

    Directory of Open Access Journals (Sweden)

    Y. Elshafei

    2014-01-01

    Full Text Available It is increasingly acknowledged that, in order to sustainably manage global freshwater resources, it is critical that we better understand the nature of human-hydrology interactions at the broader catchment system-scale. Yet to date, a generic conceptual framework for building models of catchment systems that include adequate representation of socioeconomic systems – and the dynamic feedbacks between human and natural systems – has remained elusive. In an attempt to work towards such a model, this paper outlines a generic framework for a model of socio-hydrology that posits a novel construct, a composite Community Sensitivity state variable, as a key link to elucidate the drivers of behavioural response in a hydrological context. The framework provides for both macro-scale contextual parameters, which allow it to be applied across climate, socioeconomic and political gradients, and catchment-specific conditions, by way of tailored "closure relationships", in order to ensure that site-specific and application-specific contexts of socio-hydrologic problems can be accommodated. To demonstrate how such a framework would be applied, two different socio-hydrological case studies, taken from the Australian experience, are presented and discussed. It is envisioned that the application of this framework across study sites and gradients will aid in developing our understanding of the fundamental interactions and feedbacks in such complex human-hydrology systems, and allow hydrologists to participate in the growing field of social-ecological systems modelling.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1992-01-01

    This paper brings out a control algorithm for VSI fed induction motor drives based on the converter DC link current feedback. It is shown that the speed and flux can be controlled over the wide speed and load range quite satisfactorily for simpler drives. The base commands of both the inverter voltage and frequency are proportional to the reference speed, but each of them is further modified by the signals derived from the DC current sensor. The algorithm is based on the equations well known from the vector control theory, and is aimed to obtain the constant rotor flux and proportionality between the electrical torque, the slip frequency and the active component of the stator current. In this way, the problems of slip compensation, Ri compensation and correction of U/f characteristics are solved in the same time. Analytical considerations and computer simulations of the proposed control structure are in close agreement with the experimental results measured on a prototype drive.

  3. Audio Feedback -- Better Feedback?

    Science.gov (United States)

    Voelkel, Susanne; Mello, Luciane V.

    2014-01-01

    National Student Survey (NSS) results show that many students are dissatisfied with the amount and quality of feedback they get for their work. This study reports on two case studies in which we tried to address these issues by introducing audio feedback to one undergraduate (UG) and one postgraduate (PG) class, respectively. In case study one…

  4. A Possible Feedback Mechanism Involving the Arctic Freshwater,the Arctic Sea Ice, and the North Atlantic Drift

    Institute of Scientific and Technical Information of China (English)

    Odd Helge OTTER(A); Helge DRANGE

    2004-01-01

    Model studies point to enhanced warming and to increased freshwater fluxes to high northern latitudes in response to global warming. In order to address possible feedbacks in the ice-ocean system in response to such changes, the combined effect of increased freshwater input to the Arctic Ocean and Arctic warming--the latter manifested as a gradual melting of the Arctic sea ice--is examined using a 3-D isopycnic coordinate ocean general circulation model. A suite of three idealized experiments is carried out: one control integration, one integration with a doubling of the modern Arctic river runoff, and a third more extreme case, where the river runoff is five times the modern value. In the two freshwater cases, the sea ice thickness is reduced by 1.5-2 m in the central Arctic Ocean over a 50-year period. The modelled ocean response is qualitatively the same for both perturbation experiments: freshwater propagates into the Atlantic Ocean and the Nordic Seas, leading to an initial weakening of the North Atlantic Drift.Furthermore, changes in the geostrophic currents in the central Arctic and melting of the Arctic sea ice lead to an intensified Beaufort Gyre, which in turn increases the southward volume transport through the Canadian Archipelago. To compensate for this southward transport of mass, more warm and saline Atlantic water is carried northward with the North Atlantic Drift. It is found that the increased transport of salt into the northern North Atlantic and the Nordic Seas tends to counteract the impact of the increased freshwater originating from the Arctic, leading to a stabilization of the North Atlantic Drift.

  5. An educational intervention, involving feedback of routinely collected computer data, to improve cardiovascular disease management in UK primary care.

    Science.gov (United States)

    de Lusignan, S

    2007-01-01

    To report the lessons learned from eight years of feeding back routinely collected cardiovascular data in an educational context There are distinct educational and technical components. The educational component provides peer-led learning opportunities based on comparative analysis of quality of care, as represented in computer records. The technical part ensures that relevant evidence-based audit criteria are identified; an appropriate dataset is extracted and processed to facilitate quality improvement. Anonymised data are used to provide inter-practice comparisons, with lists of identifiable patients who need interventions left in individual practices. The progressive improvement in cholesterol management in ischaemic heart disease (IHD) is used as an exemplar of the changes achieved. Over three iterations of the cardiovascular programme the standardised prevalence of IHD recorded in GP computer systems rose from 3.8% to 4.0%. Cholesterol recording rose from 47.6% to 89.0%; and the mean cholesterol level fell from 5.18 to 4.67 mmol/L; while statin prescribing rose from 46% to 57% to 68%. The atrial fibrillation, heart failure and renal programmes (more people with chronic kidney disease go on to die from cardiovascular cause than from end-stage renal disease) are used to demonstrate the range of cardiovascular interventions amenable to this approach. Technical progress has meant that larger datasets can be extracted and processed. Feedback of routinely collected data in an educational context is acceptable to practitioners and results in quality improvement. Further research is needed to assess its utility as a strategy and cost-effectiveness compared with other methods.

  6. The key residue within the second extracellular loop of human EP3 involved in selectively turning down PGE2- and retaining PGE1-mediated signaling in live cells.

    Science.gov (United States)

    Akasaka, Hironari; Thaliachery, Natasha; Zheng, Xianghai; Blumenthal, Marissa; Nikhar, Sameer; Murdoch, Emma E; Ling, Qinglan; Ruan, Ke-He

    2017-02-15

    Key residues and binding mechanisms of PGE1 and PGE2 on prostanoid receptors are poorly understood due to the lack of X-ray structures for the receptors. We constructed a human EP3 (hEP3) model through integrative homology modeling using the X-ray structure of the β2-adrenergic receptor transmembrane domain and NMR structures of the thromboxane A2 receptor extracellular loops. PGE1 and PGE2 docking into the hEP3 model showed differing configurations within the extracellular ligand recognition site. While PGE2 could form possible binding contact with S211, PGE1 is unable to form similar contacts. Therefore, S211 could be the critical residue for PGE2 recognition, but is not a significant for PGE1. This prediction was confirmed using HEK293 cells transfected with hEP3 S211L cDNA. The S211L cells lost PGE2 binding and signaling. Interestingly, the S211L cells retained PGE1-mediated signaling. It indicates that S211 within the second extracellular loop is a key residue involved in turning down PGE2 signaling. Our study provided information that S211L within EP3 is the key residue to distinguish PGE1 and PGE2 binding to mediate diverse biological functions at the initial recognition step. The S211L mutant could be used as a model for studying the binding mechanism and signaling pathway specifically mediated by PGE1. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. X-37 separation from a B-52H: application of multi-body dynamics and closed-loop feedback using overset CFD

    Energy Technology Data Exchange (ETDEWEB)

    Jolly, B.; Rizk, M. [Jacobs Sverdrup Tech., TEAS Group, Elgin AFB, Florida (United States)]. Email: jollyb@eglin.af.mil; Moran, R. [United States Air Force, Elgin AFB, Florida (United States)

    2005-07-01

    The Air Force SEEK EAGLE Office (AFSEO) provided independent aerodynamic data, which was key in the separation analysis for the X-37 Approach and Landing Test Vehicle (ALTV). To ensure the best aerodynamic B-52H interference database would be generated for the analysis, NASA contracted both NASA Johnson Space Center (JSC) and the AFSEO via the 412th Flight Test Squadron (Edwards AFB CA) to run independent Computational Fluid Dynamics (CFD) studies. These data were then compared to the existing database from Boeing to establish confidence and determine areas of uncertainty. NASA requested CFD data from the AFSEO primarily for static and carriage solutions of the X-37 at various positions under the B-52H. In addition, several dynamic simulations of X-37 trajectories used rate feedback control to deflect the control surfaces to stabilize the X-37. The AFSEO CFD team calculated 140 static, unsteady solutions and 9 dynamic time-accurate trajectory simulations between April 2003 and June 2004 to support the NASA X-37 ALTV program. The computational models used structured adjacent and overlapping grids with the total computational domain consisting of 25 million points in 315 grids. The rate-control autopilot commanded both yaw and roll in four control surfaces; pitch commands were preset. The results show significant increase in stability of the X-37 trajectory from the B-52H. (author)

  8. Closed Loop Subspace Identification

    Directory of Open Access Journals (Sweden)

    Geir W. Nilsen

    2005-07-01

    Full Text Available A new three step closed loop subspace identifications algorithm based on an already existing algorithm and the Kalman filter properties is presented. The Kalman filter contains noise free states which implies that the states and innovation are uneorre lated. The idea is that a Kalman filter found by a good subspace identification algorithm will give an output which is sufficiently uncorrelated with the noise on the output of the actual process. Using feedback from the output of the estimated Kalman filter in the closed loop system a subspace identification algorithm can be used to estimate an unbiased model.

  9. Performance of a closed-loop feedback computer-controlled infusion system for maintaining blood pressure during spinal anaesthesia for caesarean section: a randomized controlled comparison of norepinephrine versus phenylephrine.

    Science.gov (United States)

    Ngan Kee, Warwick D; Khaw, Kim S; Tam, Yuk-Ho; Ng, Floria F; Lee, Shara W

    2017-06-01

    Closed-loop feedback computer-controlled vasopressor infusion has been previously described for maintaining blood pressure during spinal anaesthesia for caesarean section but there are limited data available comparing the relative performance of different vasopressors. The aim of this study was to compare the performance of norepinephrine versus phenylephrine in this system. Data from a randomized, two-arm parallel group, double-blinded controlled trial were reanalyzed. 104 patients scheduled for elective caesarean section under spinal anaesthesia were randomized to receive computer-controlled closed-loop infusion of either norepinephrine 5 µg ml(-1) or phenylephrine 100 µg ml(-1). This was started immediately after induction of spinal anaesthesia and used an algorithm designed to maintain systolic blood pressure near baseline until fetal delivery. Performance error calculations were used to compare the performance of the two vasopressors. The primary outcome was defined as the median absolute performance error. Median performance error, wobble and divergence were also compared. Median absolute performance error was smaller in the norepinephrine group (median 3.79 [interquartile range 2.82-5.17] %) versus the phenylephrine group (4.70 [3.23-6.57] %, P = 0.028). In addition, median performance error was smaller (0.75 [-1.56-2.52] %) versus 2.61 [0.83-4.57] %, P = 0.002) and wobble was smaller (2.85 [2.07-5.17] %) versus 3.39 [2.62-4.90] %, P = 0.028) in the norepinephrine group versus the phenylephrine group. Divergence was similar between groups. The precision of the control of blood pressure was greater with norepinephrine compared with phenylephrine at the drug concentrations used.

  10. Output Feedback Adaptive Stabilization of Uncertain Nonholonomic Systems

    Directory of Open Access Journals (Sweden)

    Yuanyuan Wu

    2014-01-01

    Full Text Available This paper investigates the problem of output feedback adaptive stabilization control design for a class of nonholonomic chained systems with uncertainties, involving virtual control coefficients, unknown nonlinear parameters, and unknown time delays. The objective is to design a robust nonlinear output-feedback switching controller, which can guarantee the stabilization of the closed loop systems. An observer and an estimator are employed for states and parameters estimates, respectively. A constructive controller design procedure is proposed by applying input-state scaling transformation, parameter separation technique, and backstepping recursive approach. Simulation results are provided to show the effectiveness of the proposed method.

  11. Output feedback controller design for uncertain piecewise linear systems

    Institute of Scientific and Technical Information of China (English)

    Jianxiong ZHANG; Wansheng TANG

    2007-01-01

    This paper proposes output feedback controller design methods for uncertain piecewise linear systems based on piecewise quadratic Lyapunov function. The α-stability of closed-loop systems is also considered. It is shown that the output feedback controller design procedure of uncertain piecewise linear systems with α-stability constraint can be cast as solving a set of bilinear matrix inequalities (BMIs). The BMIs problem in this paper can be solved iteratively as a set of two convex optimization problems involving linear matrix inequalities (LMIs) which can be solved numerically efficiently. A numerical example shows the effectiveness of the proposed methods.

  12. A positive feedback loop links opposing functions of P-TEFb/Cdk9 and histone H2B ubiquitylation to regulate transcript elongation in fission yeast.

    Directory of Open Access Journals (Sweden)

    Miriam Sansó

    Full Text Available Transcript elongation by RNA polymerase II (RNAPII is accompanied by conserved patterns of histone modification. Whereas histone modifications have established roles in transcription initiation, their functions during elongation are not understood. Mono-ubiquitylation of histone H2B (H2Bub1 plays a key role in coordinating co-transcriptional histone modification by promoting site-specific methylation of histone H3. H2Bub1 also regulates gene expression through an unidentified, methylation-independent mechanism. Here we reveal bidirectional communication between H2Bub1 and Cdk9, the ortholog of metazoan positive transcription elongation factor b (P-TEFb, in the fission yeast Schizosaccharomyces pombe. Chemical and classical genetic analyses indicate that lowering Cdk9 activity or preventing phosphorylation of its substrate, the transcription processivity factor Spt5, reduces H2Bub1 in vivo. Conversely, mutations in the H2Bub1 pathway impair Cdk9 recruitment to chromatin and decrease Spt5 phosphorylation. Moreover, an Spt5 phosphorylation-site mutation, combined with deletion of the histone H3 Lys4 methyltransferase Set1, phenocopies morphologic and growth defects due to H2Bub1 loss, suggesting independent, partially redundant roles for Cdk9 and Set1 downstream of H2Bub1. Surprisingly, mutation of the histone H2B ubiquitin-acceptor residue relaxes the Cdk9 activity requirement in vivo, and cdk9 mutations suppress cell-morphology defects in H2Bub1-deficient strains. Genome-wide analyses by chromatin immunoprecipitation also demonstrate opposing effects of Cdk9 and H2Bub1 on distribution of transcribing RNAPII. Therefore, whereas mutual dependence of H2Bub1 and Spt5 phosphorylation indicates positive feedback, mutual suppression by cdk9 and H2Bub1-pathway mutations suggests antagonistic functions that must be kept in balance to regulate elongation. Loss of H2Bub1 disrupts that balance and leads to deranged gene expression and aberrant cell

  13. Probabilistic models for feedback systems.

    Energy Technology Data Exchange (ETDEWEB)

    Grace, Matthew D.; Boggs, Paul T.

    2011-02-01

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

  14. INFLUENZA-INDUCED UP-REGULATION OF TLR3 IN RESPIRATORY EPITHELIAL CELLS MAY OCCUR THROUGH A POSITIVE FEEDBACK LOOP INVOLVING TYPE I INTERFERON

    Science.gov (United States)

    Toll-like receptor 3 (TLR3) plays an important role in the host defense responses against viral infections, including Influenza virus infections. Based on our previous observations showing that Influenza infection of respiratory epithelial cells results in an up-regulation of Tol...

  15. INFLUENZA-INDUCED UP-REGULATION OF TLR3 IN RESPIRATORY EPITHELIAL CELLS MAY OCCUR THROUGH A POSITIVE FEEDBACK LOOP INVOLVING TYPE I INTERFERON

    Science.gov (United States)

    Toll-like receptor 3 (TLR3) plays an important role in the host defense responses against viral infections, including Influenza virus infections. Based on our previous observations showing that Influenza infection of respiratory epithelial cells results in an up-regulation of Tol...

  16. Finite Feedback Cycling in Structural Equation Models

    Science.gov (United States)

    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…

  17. Simple Optoelectronic Feedback in Microwave Oscillators

    Science.gov (United States)

    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.

  18. The prostaglandin E2 receptor EP4 is integral to a positive feedback loop for prostaglandin E2 production in human macrophages infected with Mycobacterium tuberculosis.

    Science.gov (United States)

    Nishimura, Tomoyasu; Zhao, Xiaomin; Gan, Huixian; Koyasu, Shigeo; Remold, Heinz G

    2013-09-01

    Prostaglandin E2 (PGE2) is an important biological mediator involved in the defense against Mycobacterium tuberculosis (Mtb) infection. Previously, we reported that in macrophages (Mϕs), infection with avirulent Mtb H37Ra resulted in inhibition of necrosis by an inhibitory effect on mitochondrial permeability transition via the PGE2 receptor EP2. However, human Mϕs also express EP4, a PGE2 receptor functionally closely related to EP2 that also couples to stimulatory guanine nucleotide binding protein, but the functional differences between EP2 and EP4 in Mtb-infected Mϕs have been unclear. EP4 antagonist addition to H37Ra-infected Mϕs inhibited the expression of cyclooxygenase 2 (COX2) and microsomal prostaglandin E synthase-1 (mPGES-1), which are involved in PGE2 production. Moreover, H37Ra infection induced PGE2 production through the Toll-like receptor (TLR) 2/p38 mitogen-activated protein kinase (MAPK) signaling pathway. Induction of COX2 and mPGES-1 expression by TLR2 stimulation or Mtb infection was increased after additional stimulation with EP4 agonist. Hence, in Mtb-infected Mϕs, PGE2 production induced by pathogen recognition receptors/p38 MAPK signaling is up-regulated by EP4-triggered signaling to maintain an effective PGE2 concentration.

  19. Induction of an inflammatory loop by interleukin-1β and tumor necrosis factor-α involves NF-kB and STAT-1 in differentiated human neuroprogenitor cells.

    Directory of Open Access Journals (Sweden)

    Subbiah Pugazhenthi

    Full Text Available Proinflammatory cytokines secreted from microglia are known to induce a secondary immune response in astrocytes leading to an inflammatory loop. Cytokines also interfere with neurogenesis during aging and in neurodegenerative diseases. The present study examined the mechanism of induction of inflammatory mediators at the transcriptional level in human differentiated neuroprogenitor cells (NPCs. Interleukin-1β (IL-1β and tumor necrosis factor-α (TNF-α induced the expression of cytokines and chemokines in differentiated human NPCs as shown by an immune pathway-specific array. Network motif (NM analysis of these genes revealed 118 three-node NMs, suggesting complex interactions between inflammatory mediators and transcription factors. Immunofluorescent staining showed increases in the levels of IL-8 and CXCL10 proteins in neurons and glial cells. Findings from Taqman low density array suggested the synergistic actions of IL-1β and TNF-α in the induction of a majority of inflammatory genes by a mechanism involving NF-kB and STAT-1. Nuclear localization of these transcription factors in differentiated NPCs was observed following exposure to IL-1α and TNF-α. Further studies on CXCL10, a chemokine known to be elevated in the Alzheimer's brain, showed that TNF-α is a stronger inducer of CXCL10 promoter when compared to IL-1β. The synergy between these cytokines was lost when ISRE or kB elements in CXCL10 promoter were mutated. Our findings suggest that the activation of inflammatory pathways in neurons and astrocytes through transcription factors including NF-kB and STAT-1 play important roles in neuroglial interactions and in sustaining the vicious cycle of inflammatory response.

  20. Basic helix-loop-helix transcription factor Bmsage is involved in regulation of fibroin H-chain gene via interaction with SGF1 in Bombyx mori.

    Science.gov (United States)

    Zhao, Xiao-Ming; Liu, Chun; Li, Qiong-Yan; Hu, Wen-Bo; Zhou, Meng-Ting; Nie, Hong-Yi; Zhang, Yin-Xia; Peng, Zhang-Chuan; Zhao, Ping; Xia, Qing-You

    2014-01-01

    Silk glands are specialized in the synthesis of several secretory proteins. Expression of genes encoding the silk proteins in Bombyx mori silk glands with strict territorial and developmental specificities is regulated by many transcription factors. In this study, we have characterized B. mori sage, which is closely related to sage in the fruitfly Drosophila melanogaster. It is termed Bmsage; it encodes transcription factor Bmsage, which belongs to the Mesp subfamily, containing a basic helix-loop-helix motif. Bmsage transcripts were detected specifically in the silk glands of B. mori larvae through RT-PCR analysis. Immunoblotting analysis confirmed the Bmsage protein existed exclusively in B. mori middle and posterior silk gland cells. Bmsage has a low level of expression in the 4th instar molting stages, which increases gradually in the 5th instar feeding stages and then declines from the wandering to the pupation stages. Quantitative PCR analysis suggested the expression level of Bmsage in a high silk strain was higher compared to a lower silk strain on day 3 of the larval 5th instar. Furthermore, far western blotting and co-immunoprecipitation assays showed the Bmsage protein interacted with the fork head transcription factor silk gland factor 1 (SGF1). An electrophoretic mobility shift assay showed the complex of Bmsage and SGF1 proteins bound to the A and B elements in the promoter of fibroin H-chain gene(fib-H), respectively. Luciferase reporter gene assays confirmed the complex of Bmsage and SGF1 proteins increased the expression of fib-H. Together, these results suggest Bmsage is involved in the regulation of the expression of fib-H by being together with SGF1 in B. mori PSG cells.

  1. What Controls DNA Looping?

    Directory of Open Access Journals (Sweden)

    Pamela J. Perez

    2014-08-01

    Full Text Available The looping of DNA provides a means of communication between sequentially distant genomic sites that operate in tandem to express, copy, and repair the information encoded in the DNA base sequence. The short loops implicated in the expression of bacterial genes suggest that molecular factors other than the naturally stiff double helix are involved in bringing the interacting sites into close spatial proximity. New computational techniques that take direct account of the three-dimensional structures and fluctuations of protein and DNA allow us to examine the likely means of enhancing such communication. Here, we describe the application of these approaches to the looping of a 92 base-pair DNA segment between the headpieces of the tetrameric Escherichia coli Lac repressor protein. The distortions of the double helix induced by a second protein—the nonspecific nucleoid protein HU—increase the computed likelihood of looping by several orders of magnitude over that of DNA alone. Large-scale deformations of the repressor, sequence-dependent features in the DNA loop, and deformability of the DNA operators also enhance looping, although to lesser degrees. The correspondence between the predicted looping propensities and the ease of looping derived from gene-expression and single-molecule measurements lends credence to the derived structural picture.

  2. Strategies for effective feedback.

    Science.gov (United States)

    Kritek, Patricia A

    2015-04-01

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

  3. Supervisor Feedback.

    Science.gov (United States)

    Hayman, Marilyn J.

    1981-01-01

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

  4. The crosstalk between Sirt1 and Keap1/Nrf2/ARE anti-oxidative pathway forms a positive feedback loop to inhibit FN and TGF-β1 expressions in rat glomerular mesangial cells.

    Science.gov (United States)

    Huang, Kaipeng; Gao, Xiang; Wei, Wentao

    2017-10-03

    Oxidative stress aroused by advanced glycation-end products (AGEs) is a culprit in the pathological progression of diabetic nephropathy. Both Sirt1 and the Keap1/Nrf2/ARE anti-oxidative pathway exert crucial inhibitory effects on the development of diabetic nephropathy. Our previous study has confirmed that Sirt1 activation can inhibit the upregulation of fibronectin (FN) and transforming growth factor-β1 (TGF-β1) by promoting Keap1/Nrf2/ARE pathway in glomerular mesangial cells (GMCs) challenged with AGEs. However, the underlying mechanism needs further investigation. Here, we found that concomitant with deacetylating and reducing the ubiquitination levels of Nrf2, Sirt1 significantly enhanced the activity of Keap1/Nrf2/ARE pathway including decreasing Keap1 expression, promoting the nuclear content, ARE-binding ability, and transcriptional activity of Nrf2, augmenting the protein levels of heme oxygenase 1, a target gene of Nrf2, which eventually quenched ROS overproduction and alleviating FN and TGF-β1 accumulation in AGEs-treated GMCs. And depletion of Nrf2 blocked those renoprotective effects of Sirt1. Interestingly, Nrf2 also positively regulated Sirt1 at the protein expression and deacetylase activity levels as evidenced by tert-Butylhydroquinone and specific siRNA targeting Nrf2 to downregulate FN and TGF-β1. In conclusion, the current study basically demonstrated that the crosstalk between Sirt1 and Keap1/Nrf2/ARE anti-oxidative pathway forms a positive feedback loop to inhibit the protein expressions of FN and TGF-β1 in AGEs-treated GMCs. Copyright © 2017. Published by Elsevier Inc.

  5. A positive feedback loop between HEAT SHOCK PROTEIN101 and HEAT STRESS-ASSOCIATED 32-KD PROTEIN modulates long-term acquired thermotolerance illustrating diverse heat stress responses in rice varieties.

    Science.gov (United States)

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

    2014-04-01

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

  6. Feedback traps for virtual potentials

    CERN Document Server

    Gavrilov, Momčilo

    2016-01-01

    Feedback traps are tools for trapping and manipulating single charged objects, such as molecules in solution. An alternative to optical tweezers and other single-molecule techniques, they use feedback to counteract the Brownian motion of a molecule of interest. The trap first acquires information about a molecule's position and then applies an electric feedback force to move the molecule. Since electric forces are stronger than optical forces at small scales, feedback traps are the best way to trap single molecules without "touching" them. Feedback traps can do more than trap molecules: They can also subject a target object to forces that are calculated to be the gradient of a desired potential function U(x). If the feedback loop is fast enough, it creates a virtual potential whose dynamics will be very close to those of a particle in an actual potential U(x). But because the dynamics are entirely a result of the feedback loop--absent the feedback, there is only an object diffusing in a fluid--we are free to ...

  7. TUNE FEEDBACK AT RHIC

    Energy Technology Data Exchange (ETDEWEB)

    CAMERON,P.; CERNIGLIA,P.; CONNOLLY,R.; CUPOLO,J.; DAWSON,W.C.; DEGEN,C.; DELLAPENNA,A.; DELONG,J.; DREES,A.; HUHN,A.; KESSELMAN,M.; MARUSIC,A.; OERTER,B.; MEAD,J.; SCHULTHEISS,C.; SIKORA,R.; VAN ZEIJTS,J.

    2001-06-18

    Preliminary phase-locked loop betatron tune measurement results were obtained during RHIC 2000 with a resonant Beam Position Monitor. These results suggested the possibility of incorporating PLL tune measurement into a tune feedback system for RHIC 2001. Tune feedback is useful in a superconducting accelerator, where the machine cycle time is long and inefficient acceleration due to resonance crossing is not comfortably tolerated. This is particularly true with the higher beam intensities planned for RHIC 2001. We present descriptions of a PLL tune measurement system implemented in the DSP/FPGA environment of a RHIC BPM electronics module and the feedback system into which the measurement is incorporated to regulate tune. In addition, we present results from the commissioning of this system during RHIC 2001.

  8. LoopIng: a template-based tool for predicting the structure of protein loops.

    KAUST Repository

    Messih, Mario Abdel

    2015-08-06

    Predicting the structure of protein loops is very challenging, mainly because they are not necessarily subject to strong evolutionary pressure. This implies that, unlike the rest of the protein, standard homology modeling techniques are not very effective in modeling their structure. However, loops are often involved in protein function, hence inferring their structure is important for predicting protein structure as well as function.We describe a method, LoopIng, based on the Random Forest automated learning technique, which, given a target loop, selects a structural template for it from a database of loop candidates. Compared to the most recently available methods, LoopIng is able to achieve similar accuracy for short loops (4-10 residues) and significant enhancements for long loops (11-20 residues). The quality of the predictions is robust to errors that unavoidably affect the stem regions when these are modeled. The method returns a confidence score for the predicted template loops and has the advantage of being very fast (on average: 1 min/loop).www.biocomputing.it/loopinganna.tramontano@uniroma1.itSupplementary data are available at Bioinformatics online.

  9. Investigation of Inner Loop Flight Control Strategies for High-Speed Research

    Science.gov (United States)

    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.

  10. Closed/Open-loop Sub-optimal Control of Structures Based on Output Feedbacks%基于输出反馈的建筑结构闭开环次优控制

    Institute of Scientific and Technical Information of China (English)

    宋刚; 谭川; 陈果

    2015-01-01

    ,especially for some high-order systems,the proposed control strategy only requires the measurement of a partial state.In the calculation of a state tran-sition matrix,which is required to solve a differential equation,large rounding errors may occur when the time-step size is excessively small.To overcome this limitation,we introduce a precise integration algorithm to solve the differential equation.This algorithm is always numerically sta-ble and yields very high precision solutions for numerical integration problems.To demonstrate the effectiveness of the proposed control strategy,we investigated the undamped vibration of a three-story building subjected to horizontal seismic forces.We assumed that the columns of the building are massless and that the mass of the structure is concentrated at floor levels.We imple-mented control using actuators exerting forces on each story.We also assumed that floor veloci-ties can be measured in real time by sensors installed in every story unit.We used the NS compo-nent of the 1 940 El Centro earthquake ground acceleration record as the excitation source and per-formed calculations for its entire duration.We modeled the columns of the building as linear elas-tic springs and assumed the response mitigation effect of the actuators to be sufficient for the building to behave in a linear elastic manner during earthquake excitation.We did not consider the soil-structure interaction or the dynamic characteristics of the actuators.We investigated the con-trolled and uncontrolled behavior of the three-story undamped building and compared the relative displacement,velocity,acceleration,and inter-story displacement responses.Our numerical sim-ulation results show that the proposed closed/open-loop sub-optimal output feedback control strategy can significantly reduce structural earthquake responses.

  11. An external loop region of domain III of dengue virus type 2 envelope protein is involved in serotype-specific binding to mosquito but not mammalian cells.

    Science.gov (United States)

    Hung, Jan-Jong; Hsieh, Meng-Ti; Young, Ming-Jer; Kao, Chuan-Liang; King, Chwan-Chuen; Chang, Wen

    2004-01-01

    Dengue virus (DV) is a flavivirus and infects mammalian cells through mosquito vectors. This study investigates the roles of domain III of DV type 2 envelope protein (EIII) in DV binding to the host cell. Recombinant EIII interferes with DV infection to BHK21 and C6/36 cells by blocking dengue virion adsorption to these cells. Inhibition of EIII on BHK21 cells was broad with no serotype specificity; however, inhibition of EIII on C6/36 cells was relatively serotype specific. Soluble heparin completely blocks binding of EIII to BHK21 cells, suggesting that domain III binds mainly to cell surface heparan sulfates. This suggestion is supported by the observation that EIII binds very weakly to gro2C and sog9 mutant mammalian cell lines that lack heparan sulfate. In contrast, heparin does not block binding of EIII to mosquito cells. Furthermore, a synthetic peptide that includes amino acids (aa) 380 to 389 of EIII, IGVEPGQLKL, inhibits binding of EIII to C6/36 but not BHK21 cells. This peptide corresponds to a lateral loop region on domain III of E protein, indicating a possible role of this loop in binding to mosquito cells. In summary, these results suggest that EIII plays an important role in binding of DV type 2 to host cells. In addition, EIII interacts with heparan sulfates when binding to BHK21 cells, and a loop region containing aa 380 to 389 of EIII may participate in DV type 2 binding to C6/36 cells.

  12. Multi-bunch feedback systems

    CERN Document Server

    Lonza, M

    2008-01-01

    Coupled-bunch instabilities excited by the interaction of the particle beam with its surroundings can seriously limit the performance of circular particle accelerators. These instabilities can be cured by the use of active feedback systems based on sensors capable of detecting the unwanted beam motion and actuators that apply the feedback correction to the beam. The advances in electronic technology now allow the implementation of feedback loops using programmable digital systems. Besides important advantages in terms of flexibility and reproducibility, digital systems open the way to the use of novel diagnostic tools and additional features. The lecture will first introduce coupled-bunch instabilities analysing the equation of motion of charged particles and the different modes of oscillation of a multi-bunch beam, showing how they can be observed and measured. Different types of feedbacks systems will then be presented as examples of real implementations that belong to the history of multi-bunch feedback sy...

  13. Multi-bunch Feedback Systems

    CERN Document Server

    Lonza, M.

    2014-12-19

    Coupled-bunch instabilities excited by the interaction of the particle beam with its surroundings can seriously limit the performance of circular particle accelerators. These instabilities can be cured by the use of active feedback systems based on sensors capable of detecting the unwanted beam motion and actuators that apply the feedback correction to the beam. Advances in electronic technology now allow the implementation of feedback loops using programmable digital systems. Besides important advantages in terms of flexibility and reproducibility, digital systems open the way to the use of novel diagnostic tools and additional features. We first introduce coupled-bunch instabilities, analysing the equation of motion of charged particles and the different modes of oscillation of a multi-bunch beam, showing how they can be observed and measured. Different types of feedback systems will then be presented as examples of real implementations that belong to the history of multi-bunch feedback systems. The main co...

  14. On interconnections, control, and feedback

    NARCIS (Netherlands)

    Willems, JC

    1997-01-01

    The purpose of this paper is to study interconnections and control of dynamical systems in a behavioral context. We start with an extensive physical example which serves to illustrate that the familiar input-output feedback loop structure is not as universal as we have been taught to believe, This l

  15. On interconnections, control, and feedback

    NARCIS (Netherlands)

    Willems, JC

    The purpose of this paper is to study interconnections and control of dynamical systems in a behavioral context. We start with an extensive physical example which serves to illustrate that the familiar input-output feedback loop structure is not as universal as we have been taught to believe, This

  16. On COBACC (COntinental Biosphere-Aerosol-Cloud-Climate) feedback

    Science.gov (United States)

    Kulmala, Markku

    2016-04-01

    Anthropogenic emissions of GHGs have increased substantially during the past century. Elevated concentrations of CO2 and methane are the most important forcing agents causing global warming. However, it is not straightforward to attribute or predict the climate change in detail, as the internal variability of climate is only partially understood, aerosol forcings are still highly uncertain, and there are many feedback mechanisms that are difficult to quantify. It has been recognized for decades that the biosphere plays an important role in climate. For example, Kulmala et al. (2004) suggested a negative climate feedback mechanism whereby higher temperatures and CO2-levels boost continental biomass production, leading to increased biogenic secondary organic aerosol (BSOA) and cloud condensation nuclei (CCN) concentrations, tending to cause cooling. This COBACC (COntinental Biosphere-Aerosol-Cloud-Climate) feedback is similar to the so-called CLAW-hypothesis by Charlson et al. (1987) which connects the ocean biochemistry and climate via a negative feedback loop involving CCN production due to sulphur emissions from plankton. The first quantification of the COBACC feedback loop (Kulmala et al. 2014) was based on continuous comprehensive observations at SMEAR II (Station for Measuring Forest Ecosystem-Atmosphere Relations) station in Hyytiälä, Finland, and showed that a 10 ppm increase in atmospheric CO2 concentration leads to a significant (several percent) increase in both carbon sink and aerosol source. These effects operate through changes in gross primary production, volatile organic compound (VOC) emissions and secondary aerosol formation associated with atmospheric oxidation of VOCs. Here we will describe the present knowledge from processes level understanding to whole COBACC feedback including some hints on biogenic and anthropogenic contributions to global aerosol number load. References: Charlson, R. J. et al. Nature 326, 655 1987 Kulmala, M. et al. Atmos

  17. Loop-to-loop coupling.

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-05-01

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

  18. Computer modelling reveals new conformers of the ATP binding loop of Na+/K+-ATPase involved in the transphosphorylation process of the sodium pump

    Science.gov (United States)

    Tejral, Gracian; Sopko, Bruno; Necas, Alois; Schoner, Wilhelm

    2017-01-01

    Hydrolysis of ATP by Na+/K+-ATPase, a P-Type ATPase, catalyzing active Na+ and K+ transport through cellular membranes leads transiently to a phosphorylation of its catalytical α-subunit. Surprisingly, three-dimensional molecular structure analysis of P-type ATPases reveals that binding of ATP to the N-domain connected by a hinge to the P-domain is much too far away from the Asp369 to allow the transfer of ATP’s terminal phosphate to its aspartyl-phosphorylation site. In order to get information for how the transfer of the γ-phosphate group of ATP to the Asp369 is achieved, analogous molecular modeling of the M4–M5 loop of ATPase was performed using the crystal data of Na+/K+-ATPase of different species. Analogous molecular modeling of the cytoplasmic loop between Thr338 and Ile760 of the α2-subunit of Na+/K+-ATPase and the analysis of distances between the ATP binding site and phosphorylation site revealed the existence of two ATP binding sites in the open conformation; the first one close to Phe475 in the N-domain, the other one close to Asp369 in the P-domain. However, binding of Mg2+•ATP to any of these sites in the “open conformation” may not lead to phosphorylation of Asp369. Additional conformations of the cytoplasmic loop were found wobbling between “open conformation”  “semi-open conformation  “closed conformation” in the absence of 2Mg2+•ATP. The cytoplasmic loop’s conformational change to the “semi-open conformation”—characterized by a hydrogen bond between Arg543 and Asp611—triggers by binding of 2Mg2+•ATP to a single ATP site and conversion to the “closed conformation” the phosphorylation of Asp369 in the P-domain, and hence the start of Na+/K+-activated ATP hydrolysis. PMID:28316890

  19. Computer modelling reveals new conformers of the ATP binding loop of Na+/K+-ATPase involved in the transphosphorylation process of the sodium pump

    Directory of Open Access Journals (Sweden)

    Gracian Tejral

    2017-03-01

    Full Text Available Hydrolysis of ATP by Na+/K+-ATPase, a P-Type ATPase, catalyzing active Na+ and K+ transport through cellular membranes leads transiently to a phosphorylation of its catalytical α-subunit. Surprisingly, three-dimensional molecular structure analysis of P-type ATPases reveals that binding of ATP to the N-domain connected by a hinge to the P-domain is much too far away from the Asp369 to allow the transfer of ATP’s terminal phosphate to its aspartyl-phosphorylation site. In order to get information for how the transfer of the γ-phosphate group of ATP to the Asp369 is achieved, analogous molecular modeling of the M4–M5 loop of ATPase was performed using the crystal data of Na+/K+-ATPase of different species. Analogous molecular modeling of the cytoplasmic loop between Thr338 and Ile760 of the α2-subunit of Na+/K+-ATPase and the analysis of distances between the ATP binding site and phosphorylation site revealed the existence of two ATP binding sites in the open conformation; the first one close to Phe475 in the N-domain, the other one close to Asp369 in the P-domain. However, binding of Mg2+•ATP to any of these sites in the “open conformation” may not lead to phosphorylation of Asp369. Additional conformations of the cytoplasmic loop were found wobbling between “open conformation”  “semi-open conformation  “closed conformation” in the absence of 2Mg2+•ATP. The cytoplasmic loop’s conformational change to the “semi-open conformation”—characterized by a hydrogen bond between Arg543 and Asp611—triggers by binding of 2Mg2+•ATP to a single ATP site and conversion to the “closed conformation” the phosphorylation of Asp369 in the P-domain, and hence the start of Na+/K+-activated ATP hydrolysis.

  20. Formativ Feedback

    DEFF Research Database (Denmark)

    Hyldahl, Kirsten Kofod

    Denne bog undersøger, hvordan lærere kan anvende feedback til at forbedre undervisningen i klasselokalet. I denne sammenhæng har John Hattie, professor ved Melbourne Universitet, udviklet en model for feedback, hvilken er baseret på synteser af meta-analyser. I 2009 udgav han bogen "Visible...

  1. Iterative LQG Controller Design Through Closed-Loop Identification

    Science.gov (United States)

    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.

  2. Comparison of the domain and frequency domain state feedbacks

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, S.Y.

    1986-01-01

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

  3. Closed-loop approach to thermodynamics

    CERN Document Server

    Goupil, C; Herbert, E; Benenti, G; D'Angelo, Y; Lecoeur, Ph

    2016-01-01

    We present the closed-loop approach to linear nonequilibrium thermodynamics considering a generic heat engine dissipatively connected to two temperature baths. The system is usually quite generally characterized by two parameters: the output power $P$ and the conversion efficiency $\\eta$, to which we add a third one, the working frequency $\\omega$. We establish that a detailed understanding of the effects of the dissipative coupling on the energy conversion process, necessitates the knowledge of only two quantities: the system's feedback factor $\\beta$ and its open-loop gain $A_{0}$, the product of which, $A_{0}\\beta$, characterizes the interplay between the efficiency, the output power and the operating rate of the system. The feedback loop approach thus provides a versatile and economical, hence efficient, tool for the study of any conversion engine operation for which a feedback factor may be defined as illustrated with a thermoelectric system.

  4. Closed-loop approach to thermodynamics

    Science.gov (United States)

    Goupil, C.; Ouerdane, H.; Herbert, E.; Benenti, G.; D'Angelo, Y.; Lecoeur, Ph.

    2016-09-01

    We present the closed-loop approach to linear nonequilibrium thermodynamics considering a generic heat engine dissipatively connected to two temperature baths. The system is usually quite generally characterized by two parameters: the output power P and the conversion efficiency η , to which we add a third one, the working frequency ω . We establish that a detailed understanding of the effects of the dissipative coupling on the energy conversion process requires only knowing two quantities: the system's feedback factor β and its open-loop gain A0, which product A0β characterizes the interplay between the efficiency, the output power, and the operating rate of the system. By raising the abstract hermodynamic analysis to a higher level, the feedback loop approach provides a versatile and economical, hence fairly efficient, tool for the study of any conversion engine operation for which a feedback factor can be defined.

  5. Open-loop versus closed-loop control of MEMS devices: choices and issues

    Science.gov (United States)

    Borovic, B.; Liu, A. Q.; Popa, D.; Cai, H.; Lewis, F. L.

    2005-10-01

    From a controls point of view, micro electromechanical systems (MEMS) can be driven in an open-loop and closed-loop fashion. Commonly, these devices are driven open-loop by applying simple input signals. If these input signals become more complex by being derived from the system dynamics, we call such control techniques pre-shaped open-loop driving. The ultimate step for improving precision and speed of response is the introduction of feedback, e.g. closed-loop control. Unlike macro mechanical systems, where the implementation of the feedback is relatively simple, in the MEMS case the feedback design is quite problematic, due to the limited availability of sensor data, the presence of sensor dynamics and noise, and the typically fast actuator dynamics. Furthermore, a performance comparison between open-loop and closed-loop control strategies has not been properly explored for MEMS devices. The purpose of this paper is to present experimental results obtained using both open- and closed-loop strategies and to address the comparative issues of driving and control for MEMS devices. An optical MEMS switching device is used for this study. Based on these experimental results, as well as computer simulations, we point out advantages and disadvantages of the different control strategies, address the problems that distinguish MEMS driving systems from their macro counterparts, and discuss criteria to choose a suitable control driving strategy.

  6. Self-oscillating loop based piezoelectric power converter

    DEFF Research Database (Denmark)

    2013-01-01

    The present invention relates to a piezoelectric power converter comprising an input driver electrically coupled directly to an input or primary electrode of the piezoelectric transformer without any intervening series or parallel inductor. A feedback loop is operatively coupled between an output...... voltage of the piezoelectric transformer and the input driver to provide a self-oscillation loop around a primary section of the piezoelectric transformer oscillating at an excitation frequency. Electrical characteristics of the feedback loop are configured to set the excitation frequency of the self......- oscillation loop within a zero-voltage-switching (ZVS) operation range of the piezoelectric transformer....

  7. Feedback regulation between autophagy and PKA

    Science.gov (United States)

    Torres-Quiroz, Francisco; Filteau, Marie; Landry, Christian R

    2015-01-01

    Protein kinase A (PKA) controls diverse cellular processes and homeostasis in eukaryotic cells. Many processes and substrates of PKA have been described and among them are direct regulators of autophagy. The mechanisms of PKA regulation and how they relate to autophagy remain to be fully understood. We constructed a reporter of PKA activity in yeast to identify genes affecting PKA regulation. The assay systematically measures relative protein-protein interactions between the regulatory and catalytic subunits of the PKA complex in a systematic set of genetic backgrounds. The candidate PKA regulators we identified span multiple processes and molecular functions (autophagy, methionine biosynthesis, TORC signaling, protein acetylation, and DNA repair), which themselves include processes regulated by PKA. These observations suggest the presence of many feedback loops acting through this key regulator. Many of the candidate regulators include genes involved in autophagy, suggesting that not only does PKA regulate autophagy but that autophagy also sends signals back to PKA. PMID:26046386

  8. Feedback regulation between autophagy and PKA.

    Science.gov (United States)

    Torres-Quiroz, Francisco; Filteau, Marie; Landry, Christian R

    2015-01-01

    Protein kinase A (PKA) controls diverse cellular processes and homeostasis in eukaryotic cells. Many processes and substrates of PKA have been described and among them are direct regulators of autophagy. The mechanisms of PKA regulation and how they relate to autophagy remain to be fully understood. We constructed a reporter of PKA activity in yeast to identify genes affecting PKA regulation. The assay systematically measures relative protein-protein interactions between the regulatory and catalytic subunits of the PKA complex in a systematic set of genetic backgrounds. The candidate PKA regulators we identified span multiple processes and molecular functions (autophagy, methionine biosynthesis, TORC signaling, protein acetylation, and DNA repair), which themselves include processes regulated by PKA. These observations suggest the presence of many feedback loops acting through this key regulator. Many of the candidate regulators include genes involved in autophagy, suggesting that not only does PKA regulate autophagy but that autophagy also sends signals back to PKA.

  9. Cfs1p, a Novel Membrane Protein in the PQ-Loop Family, Is Involved in Phospholipid Flippase Functions in Yeast

    Directory of Open Access Journals (Sweden)

    Takaharu Yamamoto

    2017-01-01

    Full Text Available Type 4 P-type ATPases (P4-ATPases function as phospholipid flippases, which translocate phospholipids from the exoplasmic leaflet to the cytoplasmic leaflet of the lipid bilayer, to generate and maintain asymmetric distribution of phospholipids at the plasma membrane and endosomal/Golgi membranes. The budding yeast Saccharomyces cerevisiae has four heteromeric flippases (Drs2p, Dnf1p, Dnf2p, and Dnf3p, associated with the Cdc50p family noncatalytic subunit, and one monomeric flippase, Neo1p. They have been suggested to function in vesicle formation in membrane trafficking pathways, but details of their mechanisms remain to be clarified. Here, to search for novel factors that functionally interact with flippases, we screened transposon insertional mutants for strains that suppressed the cold-sensitive growth defect in the cdc50Δ mutant. We identified a mutation of YMR010W encoding a novel conserved membrane protein that belongs to the PQ-loop family including the cystine transporter cystinosin and the SWEET sugar transporters. We named this gene CFS1 (cdc fifty suppressor 1. GFP-tagged Cfs1p was partially colocalized with Drs2p and Neo1p to endosomal/late Golgi membranes. Interestingly, the cfs1Δ mutation suppressed growth defects in all flippase mutants. Accordingly, defects in membrane trafficking in the flippase mutants were also suppressed. These results suggest that Cfs1p and flippases function antagonistically in membrane trafficking pathways. A growth assay to assess sensitivity to duramycin, a phosphatidylethanolamine (PE-binding peptide, suggested that the cfs1Δ mutation changed PE asymmetry in the plasma membrane. Cfs1p may thus be a novel regulator of phospholipid asymmetry.

  10. A regulatory loop involving miR-22, Sp1, and c-Myc modulates CD147 expression in breast cancer invasion and metastasis.

    Science.gov (United States)

    Kong, Ling-Min; Liao, Cheng-Gong; Zhang, Yang; Xu, Jing; Li, Yu; Huang, Wan; Zhang, Yi; Bian, Huijie; Chen, Zhi-Nan

    2014-07-15

    Breast cancer is the most common cancer in women for which the metastatic process is still poorly understood. CD147 is upregulated in breast cancer and has been associated with tumor progression, but little is known about its regulatory mechanisms. In this study, we demonstrated that CD147 was overexpressed in breast cancer tissues and cell lines, and the high expression correlated with tumor invasion and metastasis. We also found that the transcription factors Sp1 and c-Myc could bind to the CD147 promoter and enhance its expression. The CD147 mRNA has a 748-bp 3'-untranslated region (UTR) with many miRNA target sites, suggesting possible regulation by miRNAs. We discovered that miR-22 repressed CD147 expression by directly targeting the CD147 3'UTR. We also determined that miR-22 could indirectly participate in CD147 modulation by downregulating Sp1 expression. miR-22 could form an autoregulatory loop with Sp1, which repressed miR-22 transcription by binding to the miR-22 promoter. Together with the c-Myc-mediated inhibition of miR-22 expression, our investigation identified a miR-22/Sp1/c-Myc network that regulates CD147 gene transcription. In addition, miR-22 overexpression suppressed breast cancer cell invasion, metastasis, and proliferation by targeting CD147 in vitro and in vivo. Furthermore, we found that miR-22 was significantly downregulated in breast cancer tissues and that its expression was inversely correlated with the tumor-node-metastasis stage and lymphatic metastasis in patients. Our study provides the first evidence that an miR-22/Sp1/c-Myc network regulates CD147 upregulation in breast cancer and that miR-22 represses breast cancer invasive and metastatic capacities.

  11. MiR-208a stimulates the cocktail of SOX2 and β-catenin to inhibit the let-7 induction of self-renewal repression of breast cancer stem cells and formed miR208a/let-7 feedback loop via LIN28 and DICER1.

    Science.gov (United States)

    Sun, Xin; Jiang, Shiwen; Liu, Jian; Wang, Huangzhen; Zhang, Yiwen; Tang, Shou-Ching; Wang, Jichang; Du, Ning; Xu, Chongwen; Wang, Chenguang; Qin, Sida; Zhang, Jia; Liu, Dapeng; Zhang, Yunfeng; Li, Xiaojun; Wang, Jiansheng; Dong, Jun; Wang, Xin; Xu, Shaohua; Tao, Zhen; Xu, Fei; Zhou, Jie; Wang, Tao; Ren, Hong

    2015-10-20

    MiR-208a stimulates cardiomyocyte hypertrophy, fibrosis and β-MHC (β-myosin heavy chain) expression, being involved in cardiovascular diseases. Although miR-208a is known to play a role in cardiovascular diseases, its role in cancer and cancer stem cells (CSCs) remains uncertain. We identified an inverse relationship between miR-208a and let-7a in breast cancer specimens, and found that SOX2, β-catenin and LIN28 are highly expressed in patients with advanced breast cancer opposed to lesser grades. Further, we isolated ALDH1+ CSCs from ZR75-1 and MDA-MB-231 (MM-231) breast cancer cell lines to test the role of miR-208a in breast CSCs (BrCSCs). Our studies showed that overexpression of miR-208a in these cells strongly promoted the proportion of ALDH1+ BrCSCs and continuously stimulated the self-renewal ability of BrCSCs. By using siRNAs of SOX2 and/or β-catenin, we found that miR-208a increased LIN28 through stimulation of both SOX2 and β-catenin. The knockdown of either SOX2 or β-catenin only partially attenuated the functions of miR-208a. Let-7a expression was strongly inhibited in miR-208a overexpressed cancer cells, which was achieved by miR-208a induction of LIN28, and the restoration of let-7a significantly inhibited the miR-208a induction of the number of ALDH1+ cells, inhibiting the propagations of BrCSCs. In let-7a overexpressed ZR75-1 and MM-231 cells, DICER1 activity was significantly inhibited with decreased miR-208a. Let-7a failed to decrease miR-208a expression in ZR75-1 and MM-231 cells with DICER1 knockdown. Our research revealed the mechanisms through which miR-208a functioned in breast cancer and BrCSCs, and identified the miR-208a-SOX2/β-catenin-LIN28-let-7a-DICER1 regulatory feedback loop in regulations of stem cells renewal.

  12. Linear Quadratic Gaussian Controller Design Using Loop Transfer Recovery for a Flexible Missile Model

    Science.gov (United States)

    1993-12-01

    Feedback Control System with Feedback Perturbation and Loop Broken at the Uncertainty ..................................... 42 Figure 19. General A-P...the observability matrix is given by 23 ’g = [C T ATC T A 2CT. .ATWICT] (38) The optimal output feedback control system is represented below. This...State Space Model of the Optimal Output Feedback Control System . The acceleration time response of the closed-loop system to a unit step acceleration

  13. Implementation of integral feedback control in biological systems.

    Science.gov (United States)

    Somvanshi, Pramod R; Patel, Anilkumar K; Bhartiya, Sharad; Venkatesh, K V

    2015-01-01

    Integral control design ensures that a key variable in a system is tightly maintained within acceptable levels. This approach has been widely used in engineering systems to ensure offset free operation in the presence of perturbations. Several biological systems employ such an integral control design to regulate cellular processes. An integral control design motif requires a negative feedback and an integrating process in the network loop. This review describes several biological systems, ranging from bacteria to higher organisms in which the presence of integral control principle has been hypothesized. The review highlights that in addition to the negative feedback, occurrence of zero-order kinetics in the process is a key element to realize the integral control strategy. Although the integral control motif is common to these systems, the mechanisms involved in achieving it are highly specific and can be incorporated at the level of signaling, metabolism, or at the phenotypic levels. © 2015 Wiley Periodicals, Inc.

  14. Strong feedback limit of the Goodwin circadian oscillator

    Science.gov (United States)

    Woller, Aurore; Gonze, Didier; Erneux, Thomas

    2013-03-01

    The three-variable Goodwin model constitutes a prototypical oscillator based on a negative feedback loop. It was used as a minimal model for circadian oscillations. Other core models for circadian clocks are variants of the Goodwin model. The Goodwin oscillator also appears in many studies of coupled oscillator networks because of its relative simplicity compared to other biophysical models involving a large number of variables and parameters. Because the synchronization properties of Goodwin oscillators still remain difficult to explore mathematically, further simplifications of the Goodwin model have been sought. In this paper, we investigate the strong negative feedback limit of Goodwin equations by using asymptotic techniques. We find that Goodwin oscillations approach a sequence of decaying exponentials that can be described in terms of a single-variable leaky integrated-and-fire model.

  15. Feature saliency and feedback information interactively impact visual category learning.

    Science.gov (United States)

    Hammer, Rubi; Sloutsky, Vladimir; Grill-Spector, Kalanit

    2015-01-01

    Visual category learning (VCL) involves detecting which features are most relevant for categorization. VCL relies on attentional learning, which enables effectively redirecting attention to object's features most relevant for categorization, while 'filtering out' irrelevant features. When features relevant for categorization are not salient, VCL relies also on perceptual learning, which enables becoming more sensitive to subtle yet important differences between objects. Little is known about how attentional learning and perceptual learning interact when VCL relies on both processes at the same time. Here we tested this interaction. Participants performed VCL tasks in which they learned to categorize novel stimuli by detecting the feature dimension relevant for categorization. Tasks varied both in feature saliency (low-saliency tasks that required perceptual learning vs. high-saliency tasks), and in feedback information (tasks with mid-information, moderately ambiguous feedback that increased attentional load, vs. tasks with high-information non-ambiguous feedback). We found that mid-information and high-information feedback were similarly effective for VCL in high-saliency tasks. This suggests that an increased attentional load, associated with the processing of moderately ambiguous feedback, has little effect on VCL when features are salient. In low-saliency tasks, VCL relied on slower perceptual learning; but when the feedback was highly informative participants were able to ultimately attain the same performance as during the high-saliency VCL tasks. However, VCL was significantly compromised in the low-saliency mid-information feedback task. We suggest that such low-saliency mid-information learning scenarios are characterized by a 'cognitive loop paradox' where two interdependent learning processes have to take place simultaneously.

  16. Hard Loops, Soft Loops, and High Density Effective Field Theory

    CERN Document Server

    Schäfer, T

    2003-01-01

    We study several issues related to the use of effective field theories in QCD at large baryon density. We show that the power counting is complicated by the appearance of two scales inside loop integrals. Hard dense loops involve the large scale $mu^2$ and lead to phenomena such as screening and damping at the scale $gmu$. Soft loops only involve small scales and lead to superfluidity and non-Fermi liquid behavior at exponentially small scales. Four-fermion operators in the effective theory are suppressed by powers of $1/mu$, but they get enhanced by hard loops. As a consequence their contribution to the pairing gap is only suppressed by powers of the coupling constant, and not powers of $1/mu$. We determine the coefficients of four-fermion operators in the effective theory by matching quark-quark scattering amplitudes. Finally, we introduce a perturbative scheme for computing corrections to the gap parameter in the superfluid phase

  17. BK Induces cPLA2 Expression via an Autocrine Loop Involving COX-2-Derived PGE2 in Rat Brain Astrocytes.

    Science.gov (United States)

    Lin, Chih-Chung; Hsieh, Hsi-Lung; Liu, Shiau-Wen; Tseng, Hui-Ching; Hsiao, Li-Der; Yang, Chuen-Mao

    2015-01-01

    Bradykinin (BK) is a proinflammatory mediator and elevated in several brain injury and inflammatory diseases. The deleterious effects of BK on brain astrocytes may aggravate brain inflammation mediated through the upregulation of cytosolic phospholipase A2 (cPLA2)/cyclooxygenase-2 (COX-2)-derived prostaglandin E2 (PGE2) production. However, the signaling mechanisms underlying BK-induced cPLA2 expression in brain astrocytes remain unclear. Herein, we investigated the effects of activation of cPLA2/COX-2 system on BK-induced cPLA2 upregulation in rat brain astrocytes (RBA-1). The data obtained with Western blotting, RT-PCR, and immunofluorescent staining analyses showed that BK-induced de novo cPLA2 expression was mediated through activation of cPLA2/COX-2 system. Upregulation of native cPLA2/COX-2 system by BK through activation of PKCδ, c-Src, MAPKs (ERK1/2 and JNK1/2) cascades led to PGE2 biosynthesis and release. Subsequently, the released PGE2 induced cPLA2 expression via the same signaling pathways (PKCδ, c-Src, ERK1/2, and JNK1/2) and then activated the cyclic AMP response element-binding protein (CREB) via B2 BK receptor-mediated cPLA2/COX-2 system-derived PGE2/EP-dependent manner. Finally, upregulation of cPLA2 by BK may promote more PGE2 production. These results demonstrated that in RBA-1, activation of CREB by PGE2/EP-mediated PKCδ/c-Src/MAPK cascades is essential for BK-induced de novo cPLA2 protein. More importantly, upregulation of cPLA2 by BK through native cPLA2/COX-2 system may be a positive feedback mechanism that enhances prolonged brain inflammatory responses. Understanding the mechanisms of cPLA2/COX-2 system upregulated by BK on brain astrocytes may provide rational therapeutic interventions for brain injury and inflammatory diseases.

  18. Glucagon-like peptide-1 secretion is influenced by perfusate glucose concentration and by a feedback mechanism involving somatostatin in isolated perfused porcine ileum

    DEFF Research Database (Denmark)

    Hansen, Lene; Hartmann, Bolette; Mineo, Hitoshi;

    2004-01-01

    Glucagon-like peptide-1 (GLP-1) is released from intestinal L-cells in response to ingestion of meals. The mechanisms regulating its secretion are not clear, but local somatostatin (SS) restrains GLP-1 secretion. We investigated feedback and substrate regulation of GLP-1 and SS secretion, using...... the effect of proglucagon products, glucagon (10 nM), GLP-1 and GLP-2 (0.1, 1, and 10 nM) on GLP-1 and SS secretion, as well as on glucagon-like peptide-2 (GLP-2), peptide YY (PYY) and GIP secretion, all possible product of L-cells or neighbour cells. Perfusate glucose concentration dose......-dependently stimulated GLP-1 secretion (p=0.011). Insulin had no effect. Glucagon weakly stimulated GIP secretion. GLP-1 stimulated SS secretion and motor activity, but inhibited GLP-2, GIP and PYY secretion and perfusion pressure. GLP-2 weakly stimulated SS secretion. We conclude (a) that GLP-1 secretion is influenced...

  19. Feedback on household electricity consumption

    DEFF Research Database (Denmark)

    Grønhøj, Alice; Thøgersen, John

    2011-01-01

    consumption, we evaluate the effects of giving households detailed feedback about their electricity consumption on a small liquid crystal display (LCD) screen. Twenty Danish households participated in the study over a 5-month period. A new feedback system was developed in a user-involved innovation process...

  20. Linearizing Intra-Train Beam-Beam Deflection Feedback

    Energy Technology Data Exchange (ETDEWEB)

    Smith, S.R.; /SLAC

    2006-02-22

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

  1. Feedback and Incentives

    DEFF Research Database (Denmark)

    Eriksson, Tor Viking; Poulsen, Anders; Villeval, Marie Claire

    2009-01-01

    This paper experimentally investigates the impact of different pay schemes and relative performance feedback policies on employee effort. We explore three feedback rules: no feedback on relative performance, feedback given halfway through the production period, and continuously updated feedback. ...

  2. Marine vehicle path following using inner-outer loop control.

    Digital Repository Service at National Institute of Oceanography (India)

    Maurya, P.K.; Agular, A.P.; Pascoal, A.M.

    borrow from nonlinear control theory, whereby the cas- cade and feedback systems of interest are characterized in terms of their IOS properties. To derive quantitative relationships for proper controller tuning an IOS small- gain theorem is used... controller is designed as the combination of a kinematic outer-loop that issues heading commands to an inner loop consisting of the feedback combination of the vehicle itself and a heading controller (heading autopilot). The speed of the vehicle may be kept...

  3. Kalman Orbit Optimized Loop Tracking

    Science.gov (United States)

    Young, Lawrence E.; Meehan, Thomas K.

    2011-01-01

    Under certain conditions of low signal power and/or high noise, there is insufficient signal to noise ratio (SNR) to close tracking loops with individual signals on orbiting Global Navigation Satellite System (GNSS) receivers. In addition, the processing power available from flight computers is not great enough to implement a conventional ultra-tight coupling tracking loop. This work provides a method to track GNSS signals at very low SNR without the penalty of requiring very high processor throughput to calculate the loop parameters. The Kalman Orbit-Optimized Loop (KOOL) tracking approach constitutes a filter with a dynamic model and using the aggregate of information from all tracked GNSS signals to close the tracking loop for each signal. For applications where there is not a good dynamic model, such as very low orbits where atmospheric drag models may not be adequate to achieve the required accuracy, aiding from an IMU (inertial measurement unit) or other sensor will be added. The KOOL approach is based on research JPL has done to allow signal recovery from weak and scintillating signals observed during the use of GPS signals for limb sounding of the Earth s atmosphere. That approach uses the onboard PVT (position, velocity, time) solution to generate predictions for the range, range rate, and acceleration of the low-SNR signal. The low- SNR signal data are captured by a directed open loop. KOOL builds on the previous open loop tracking by including feedback and observable generation from the weak-signal channels so that the MSR receiver will continue to track and provide PVT, range, and Doppler data, even when all channels have low SNR.

  4. Baseband feedback for SAFARI-SPICA using Frequency Domain Multiplexing

    Science.gov (United States)

    Bounab, A.; de Korte, P.; Cros, A.; van der Kuur, J.; van Leeuwen, B. J.; Monna, B.; Mossel, R.; Nieuwenhuizen, A.; Ravera, L.

    We report on the performance of the digital baseband feedback circuit developed to readout and process signals from arrays of transition edge sensors for SPICA-SAFARI in frequency domain multiplexing (FDM). The standard procedure to readout the SQUID current amplifiers is to use a feedback loop (flux-locked loop: FLL). However the achievable FFL bandwidth is limited by the cable transport delay t_d, which makes standard feedback inconvenient. A much better approach is to use baseband feedback. We have developed a model of the electronic readout chain for SPICA-SAFARI instrument by using an Anlog-digital co-simulation based on Simulink-System Generator environment.

  5. Efficiency at maximum power of a discrete feedback ratchet

    Science.gov (United States)

    Jarillo, Javier; Tangarife, Tomás; Cao, Francisco J.

    2016-01-01

    Efficiency at maximum power is found to be of the same order for a feedback ratchet and for its open-loop counterpart. However, feedback increases the output power up to a factor of five. This increase in output power is due to the increase in energy input and the effective entropy reduction obtained as a consequence of feedback. Optimal efficiency at maximum power is reached for time intervals between feedback actions two orders of magnitude smaller than the characteristic time of diffusion over a ratchet period length. The efficiency is computed consistently taking into account the correlation between the control actions. We consider a feedback control protocol for a discrete feedback flashing ratchet, which works against an external load. We maximize the power output optimizing the parameters of the ratchet, the controller, and the external load. The maximum power output is found to be upper bounded, so the attainable extracted power is limited. After, we compute an upper bound for the efficiency of this isothermal feedback ratchet at maximum power output. We make this computation applying recent developments of the thermodynamics of feedback-controlled systems, which give an equation to compute the entropy reduction due to information. However, this equation requires the computation of the probability of each of the possible sequences of the controller's actions. This computation becomes involved when the sequence of the controller's actions is non-Markovian, as is the case in most feedback ratchets. We here introduce an alternative procedure to set strong bounds to the entropy reduction in order to compute its value. In this procedure the bounds are evaluated in a quasi-Markovian limit, which emerge when there are big differences between the stationary probabilities of the system states. These big differences are an effect of the potential strength, which minimizes the departures from the Markovianicity of the sequence of control actions, allowing also to

  6. Closing the loop: towards strategic defence management

    NARCIS (Netherlands)

    S. de Spiegeleire; P. van Hooft; C. Culpepper; R. Willems

    2009-01-01

    How do defence-organisations (or organisations with comparable profiles) of other countries map out policy goals and how are policy goals related to activities and capabilities and the required financial means, and finally how does the feedback loop on the performance in all these areas take place?

  7. 17α-Ethinylestradiol (EE2) treatment of wild roach (Rutilus rutilus) during early life development disrupts expression of genes directly involved in the feedback cycle of estrogen.

    Science.gov (United States)

    Nikoleris, Lina; Hultin, Cecilia L; Hallgren, Per; Hansson, Maria C

    2016-02-01

    Fish are more sensitive to introduced disturbances from synthetic endocrine disrupting compounds during early life phases compared with mature stages. 17α-Ethinylestradiol (EE2), which is the active compound in human oral contraceptives and hormone replacement therapies, is today ever present in the effluents from sewage treatment plants. EE2 targets and interacts with the endogenous biological systems of exposed vertebrates resulting in to large extents unknown short- and long-term effects. We investigated how EE2 exposure affects expression profiles of a large number of target genes during early life of roach (Rutilus rutilus). We exposed fertilized roach eggs collected from a lake in Southern Sweden to EE2 for 12weeks together with 1+-year-old roach in aquaria. We measured the gene expression of the estrogen receptor (esr)1/2a/2b, androgen receptor (ar), vitellogenin, cytochrome P450 (cyp)19a1a/1b in fertilized eggs; newly hatched larvae; 12-week-old fry; and juvenile wild roach (1+-year-old). Results shows that an EE2 concentration as low as 0.5ng/L significantly affects gene expression during early development. Gene expression responses vary both among life stages and molecular receptors. We also show that the gene profile of the estrogen feedback cycle to a large extent depends on the relationship between the three esr genes and the two cyp19a1 genes, which are all up-regulated with age. Results indicate that a disruption of the natural activity of the dominant esr gene could lead to detrimental biological effects if EE2 exposure occurs during development, even if this exposure occurred for only a short period.

  8. A tracking system with space virtual feedback

    Institute of Scientific and Technical Information of China (English)

    Zheng MAO; Xiaojun QU; Fuling WEI; Yali WANG

    2008-01-01

    In this paper,a tracking system with space virtual feedback(SVF)is presented.The whole tracking system is closed by the space virtual feedback line that is the line of sight(LOS),but the parts in the system,such as the tracking subsystem and the servo subsystem.are in the state of open-loop.Because the SVF tracking model is used.the correcting loops can be removed in this system architecture.So the tracking speed and accuracy of the system are greatly improved.

  9. Chaos Generation and Synchronization Using Driven TWT amplifiers having delayed feedback

    Science.gov (United States)

    Larsen, P.; Booske, J. H.; Bhattacharjee, S.; Marchewka, C.; Sengele, S.; Koch, S.; Ryskin, N.; Titov, V.

    2004-11-01

    Development of high power sources of chaotic waveforms in the microwave frequency regime is important for communications, noise radar, and other applications. We have demonstrated that driven traveling wave tube (TWT) amplifiers with delayed feedback are excellent sources of chaotic radiation with numerous experimental advantages. The configuration involves a TWT oscillator (using an external feedback loop) which is driven by an external coherent generator. Two types of chaos have been observed in these experiments: a period doubling type and a "loss-of-synchronization" type of chaos. Characterizations have identified single frequency oscillation, self-modulation, and chaos within the parameter space defined by the drive power, drive frequency, and feedback attenuation level. Current investigations are examining synchronization between a pair of driven TWT oscillators.

  10. Feedback traps for virtual potentials

    Science.gov (United States)

    Gavrilov, Momčilo; Bechhoefer, John

    2017-03-01

    Feedback traps are tools for trapping and manipulating single charged objects, such as molecules in solution. An alternative to optical tweezers and other single-molecule techniques, they use feedback to counteract the Brownian motion of a molecule of interest. The trap first acquires information about a molecule's position and then applies an electric feedback force to move the molecule. Since electric forces are stronger than optical forces at small scales, feedback traps are the best way to trap single molecules without `touching' them (e.g. by putting them in a small box or attaching them to a tether). Feedback traps can do more than trap molecules: they can also subject a target object to forces that are calculated to be the gradient of a desired potential function U(x). If the feedback loop is fast enough, it creates a virtual potential whose dynamics will be very close to those of a particle in an actual potential U(x). But because the dynamics are entirely a result of the feedback loop-absent the feedback, there is only an object diffusing in a fluid-we are free to specify and then manipulate in time an arbitrary potential U(x,t). Here, we review recent applications of feedback traps to studies on the fundamental connections between information and thermodynamics, a topic where feedback plays an even more fundamental role. We discuss how recursive maximum-likelihood techniques allow continuous calibration, to compensate for drifts in experiments that last for days. We consider ways to estimate work and heat, using them to measure fluctuating energies to a precision of ±0.03 kT over these long experiments. Finally, we compare work and heat measurements of the costs of information erasure, the Landauer limit of kT ln 2 per bit of information erased. We argue that, when you want to know the average heat transferred to a bath in a long protocol, you should measure instead the average work and then infer the heat using the first law of thermodynamics. This

  11. Nonlinear feedback control of Timoshenko beam

    Institute of Scientific and Technical Information of China (English)

    冯德兴; 张维弢

    1995-01-01

    This note is concerned with nonlinear boundary feedback control of a Timoshenko beam. Under some nonlinear boundary feedback control, first the nonlinear semigroup theory is used to show the existence and uniqueness of solution for the corresponding closed loop system. Then by using the Lyapunov method, it is proved that the vibration of the beam under the proposed control action decays in a negative power of time t as t→.

  12. Understanding the hysteresis loop conundrum in pharmacokinetic/pharmacodynamic relationships.

    Science.gov (United States)

    Louizos, Christopher; Yáñez, Jaime A; Forrest, M Laird; Davies, Neal M

    2014-01-01

    Hysteresis loops are phenomena that sometimes are encountered in the analysis of pharmacokinetic and pharmacodynamic relationships spanning from pre-clinical to clinical studies. When hysteresis occurs it provides insight into the complexity of drug action and disposition that can be encountered. Hysteresis loops suggest that the relationship between drug concentration and the effect being measured is not a simple direct relationship, but may have an inherent time delay and disequilibrium, which may be the result of metabolites, the consequence of changes in pharmacodynamics or the use of a non-specific assay or may involve an indirect relationship. Counter-clockwise hysteresis has been generally defined as the process in which effect can increase with time for a given drug concentration, while in the case of clockwise hysteresis the measured effect decreases with time for a given drug concentration. Hysteresis loops can occur as a consequence of a number of different pharmacokinetic and pharmacodynamic mechanisms including tolerance, distributional delay, feedback regulation, input and output rate changes, agonistic or antagonistic active metabolites, uptake into active site, slow receptor kinetics, delayed or modified activity, time-dependent protein binding and the use of racemic drugs among other factors. In this review, each of these various causes of hysteresis loops are discussed, with incorporation of relevant examples of drugs demonstrating these relationships for illustrative purposes. Furthermore, the effect that pharmaceutical formulation has on the occurrence and potential change in direction of the hysteresis loop, and the major pharmacokinetic / pharmacodynamic modeling approaches utilized to collapse and model hysteresis are detailed.

  13. Indirect Identification of Linear Stochastic Systems with Known Feedback Dynamics

    Science.gov (United States)

    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.

  14. Feedback-charging a metallic island

    Science.gov (United States)

    Schaller, Gernot

    2017-03-01

    We consider electronic transport through a single-electron quantum dot that is tunnel-coupled to an electronic lead and a metallic island. A background reservoir keeps the metallic island at a thermal state with the ambient temperature, while the charge accumulated on the island is reflected in a time-dependent chemical potential. Without feedback, a current would flow through the system until the chemical potentials of island and lead are equilibrated. A feedback loop can be implemented by a quantum point contact detecting the dot state, classical processing of the result and appropriate feedback actions on the electronic tunneling rates taken, with the objective to direct the current in a preferred direction. Since we directly take the detector counting statistics into account, this automatically includes measurement errors in the description. When mainly the rates are modified but hardly any energy is exchanged with the system, this feedback loop effectively implements a Maxwell demon, capable of transporting electrons against an electric bias and thereby charging the metallic island. Once the feedback protocol is stopped, the metallic island simply discharges. We find that a quantitative detector model may be useful for a realistic statistical description of feedback loops.

  15. Current control loop design and analysis based on resonant regulators for microgrid applications

    DEFF Research Database (Denmark)

    Federico, de Bosio; Pastorelli, Michelle; de Sousa Ribeiro, Luiz Antonio

    2015-01-01

    Voltage and current control loops play an important role in the performance of microgrids employing power electronics voltage source inverters. Correct design of feedback loops is essential for the proper operation of these systems. This paper analyzes the influence of state feedback cross......-coupling in the design of resonant regulators for inner current loops in power converters operating in standalone microgrids. It is also demonstrated that the effect of state feedback cross-coupling degrades the performance of the control loops by increasing the steady-state error. Different resonant regulators...... structures are analyzed and compared, performing experimental tests to validate the results of the theoretical analysis....

  16. Alternative loop rings

    CERN Document Server

    Goodaire, EG; Polcino Milies, C

    1996-01-01

    For the past ten years, alternative loop rings have intrigued mathematicians from a wide cross-section of modern algebra. As a consequence, the theory of alternative loop rings has grown tremendously. One of the main developments is the complete characterization of loops which have an alternative but not associative, loop ring. Furthermore, there is a very close relationship between the algebraic structures of loop rings and of group rings over 2-groups. Another major topic of research is the study of the unit loop of the integral loop ring. Here the interaction between loop rings and group ri

  17. The new BNL AGS phase, radial and synchronization loops

    Energy Technology Data Exchange (ETDEWEB)

    Onillon, E.; Brennan, J.M.

    1996-07-01

    The AGS and the RHIC must be synchronized before bunch-to-bucket transfer of the beam. A feedback loop has been designed and an improvement has been made to the AGS phase and radial loops. In both cases, the design uses a state variable representation to achieve greater stability and smaller errors. The state variables are beam phase, frequency and radius , the integral of the difference between the radius and its reference and the phase deviation of the bunch from the synchronous phase. Furthermore, the feedback gains are programmed as a function of the beam parameters to keep the same loop performances through the acceleration cycle.

  18. Loop Quantum Cosmology

    Directory of Open Access Journals (Sweden)

    Bojowald Martin

    2008-07-01

    Full Text Available Quantum gravity is expected to be necessary in order to understand situations in which classical general relativity breaks down. In particular in cosmology one has to deal with initial singularities, i.e., the fact that the backward evolution of a classical spacetime inevitably comes to an end after a finite amount of proper time. This presents a breakdown of the classical picture and requires an extended theory for a meaningful description. Since small length scales and high curvatures are involved, quantum effects must play a role. Not only the singularity itself but also the surrounding spacetime is then modified. One particular theory is loop quantum cosmology, an application of loop quantum gravity to homogeneous systems, which removes classical singularities. Its implications can be studied at different levels. The main effects are introduced into effective classical equations, which allow one to avoid the interpretational problems of quantum theory. They give rise to new kinds of early-universe phenomenology with applications to inflation and cyclic models. To resolve classical singularities and to understand the structure of geometry around them, the quantum description is necessary. Classical evolution is then replaced by a difference equation for a wave function, which allows an extension of quantum spacetime beyond classical singularities. One main question is how these homogeneous scenarios are related to full loop quantum gravity, which can be dealt with at the level of distributional symmetric states. Finally, the new structure of spacetime arising in loop quantum gravity and its application to cosmology sheds light on more general issues, such as the nature of time.

  19. Loop Quantum Cosmology

    Directory of Open Access Journals (Sweden)

    Bojowald Martin

    2005-12-01

    Full Text Available Quantum gravity is expected to be necessary in order to understand situations where classical general relativity breaks down. In particular in cosmology one has to deal with initial singularities, i.e., the fact that the backward evolution of a classical space-time inevitably comes to an end after a finite amount of proper time. This presents a breakdown of the classical picture and requires an extended theory for a meaningful description. Since small length scales and high curvatures are involved, quantum effects must play a role. Not only the singularity itself but also the surrounding space-time is then modified. One particular realization is loop quantum cosmology, an application of loop quantum gravity to homogeneous systems, which removes classical singularities. Its implications can be studied at different levels. Main effects are introduced into effective classical equations which allow to avoid interpretational problems of quantum theory. They give rise to new kinds of early universe phenomenology with applications to inflation and cyclic models. To resolve classical singularities and to understand the structure of geometry around them, the quantum description is necessary. Classical evolution is then replaced by a difference equation for a wave function which allows to extend space-time beyond classical singularities. One main question is how these homogeneous scenarios are related to full loop quantum gravity, which can be dealt with at the level of distributional symmetric states. Finally, the new structure of space-time arising in loop quantum gravity and its application to cosmology sheds new light on more general issues such as time.

  20. The Impact of Telemedicine Interventions Involving Routine Transmission of Blood Glucose Data with Clinician Feedback on Metabolic Control in Youth with Type 1 Diabetes: A Systematic Review and Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Palmert MarkR

    2010-07-01

    Full Text Available Our objective was to determine the impact of telemedicine (TM interventions on the management of type 1 diabetes (T1DM in youth. We performed a systematic review of randomized trials that evaluated TM interventions involving transmission of blood glucose data followed by unsolicited scheduled clinician feedback. We found no apparent effect of the TM interventions on hemoglobin A1c (HbA1c, severe hypoglycemia, or diabetic ketoacidosis. The limited data available on patient satisfaction, quality of life, and cost also suggested no differences between groups. It is unlikely that TM interventions, as performed in the assessed studies, had a substantial effect on glycemic control or acute complications. However, it remains possible that there are other benefits of TM not adequately reported, that newer TM strategies may be more effective and that interventions may benefit subgroups of youth, such as those with the poor glycemic control, adolescents, or those living in remote areas.

  1. Causal Loop Analysis of coastal geomorphological systems

    Science.gov (United States)

    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

  2. Closed-loop neuronal computations: focus on vibrissa somatosensation in rat.

    Science.gov (United States)

    Ahissar, Ehud; Kleinfeld, David

    2003-01-01

    Two classes of neuronal architectures dominate in the ongoing debate on the nature of computing by nervous systems. The first is a predominantly feedforward architecture, in which local interactions among neurons within each processing stage play a less influential role compared with the drive of the input to that stage. The second class is a recurrent network architecture, in which the local interactions among neighboring neurons dominate the dynamics of neuronal activity so that the input acts only to bias or seed the state of the network. The study of sensorimotor networks, however, serves to highlight a third class of architectures, which is neither feedforward nor locally recurrent and where computations depend on large-scale feedback loops. Findings that have emerged from our laboratories and those of our colleagues suggest that the vibrissa sensorimotor system is involved in such closed-loop computations. In particular, single unit responses from vibrissa sensory and motor areas show generic signatures of phase-sensitive detection and control at the level of thalamocortical and corticocortical loops. These loops are likely to be components within a greater closed-loop vibrissa sensorimotor system, which optimizes sensory processing.

  3. Haptic gas pedal feedback.

    Science.gov (United States)

    Mulder, M; Mulder, M; van Paassen, M M; Abbink, D A

    2008-11-01

    Active driver support systems either automate a control task or present warnings to drivers when their safety is seriously degraded. In a novel approach, utilising neither automation nor discrete warnings, a haptic gas pedal (accelerator) interface was developed that continuously presents car-following support information, keeping the driver in the loop. This interface was tested in a fixed-base driving simulator. Twenty-one drivers between the ages of 24 and 30 years participated in a driving experiment to investigate the effects of haptic gas pedal feedback on car-following behaviour. Results of the experiment indicate that when haptic feedback was presented to the drivers, some improvement in car-following performance was achieved, while control activity decreased. Further research is needed to investigate the effectiveness of the system in more varied driving conditions. Haptics is an under-used modality in the application of human support interfaces, which usually draw on vision or hearing. This study demonstrates how haptics can be used to create an effective driver support interface.

  4. Premature Sister Chromatid Separation Is Poorly Detected by the Spindle Assembly Checkpoint as a Result of System-Level Feedback

    Directory of Open Access Journals (Sweden)

    Mihailo Mirkovic

    2015-10-01

    Full Text Available Sister chromatid cohesion, mediated by the cohesin complex, is essential for faithful mitosis. Nevertheless, evidence suggests that the surveillance mechanism that governs mitotic fidelity, the spindle assembly checkpoint (SAC, is not robust enough to halt cell division when cohesion loss occurs prematurely. The mechanism behind this poor response is not properly understood. Using developing Drosophila brains, we show that full sister chromatid separation elicits a weak checkpoint response resulting in abnormal mitotic exit after a short delay. Quantitative live-cell imaging approaches combined with mathematical modeling indicate that weak SAC activation upon cohesion loss is caused by weak signal generation. This is further attenuated by several feedback loops in the mitotic signaling network. We propose that multiple feedback loops involving cyclin-dependent kinase 1 (Cdk1 gradually impair error-correction efficiency and accelerate mitotic exit upon premature loss of cohesion. Our findings explain how cohesion defects may escape SAC surveillance.

  5. nf2 contributions to fermionic four-loop form factors

    Science.gov (United States)

    Lee, Roman N.; Smirnov, Alexander V.; Smirnov, Vladimir A.; Steinhauser, Matthias

    2017-07-01

    We compute the four-loop contributions to the photon quark and Higgs quark form factors involving two closed fermion loops. We present analytical results for all nonplanar master integrals of the two nonplanar integral families which enter our calculation.

  6. Augmenting Environmental Interaction in Audio Feedback Systems

    Directory of Open Access Journals (Sweden)

    Seunghun Kim

    2016-04-01

    Full Text Available Audio feedback is defined as a positive feedback of acoustic signals where an audio input and output form a loop, and may be utilized artistically. This article presents new context-based controls over audio feedback, leading to the generation of desired sonic behaviors by enriching the influence of existing acoustic information such as room response and ambient noise. This ecological approach to audio feedback emphasizes mutual sonic interaction between signal processing and the acoustic environment. Mappings from analyses of the received signal to signal-processing parameters are designed to emphasize this specificity as an aesthetic goal. Our feedback system presents four types of mappings: approximate analyses of room reverberation to tempo-scale characteristics, ambient noise to amplitude and two different approximations of resonances to timbre. These mappings are validated computationally and evaluated experimentally in different acoustic conditions.

  7. Feedback control of superconducting quantum circuits

    NARCIS (Netherlands)

    Ristè, D.

    2014-01-01

    Superconducting circuits have recently risen to the forefront of the solid-state prototypes for quantum computing. Reaching the stage of robust quantum computing requires closing the loop between measurement and control of quantum bits (qubits). This thesis presents the realization of feedback contr

  8. Haptic feedback helps bipedal coordination.

    Science.gov (United States)

    Roelofsen, Eefje G J; Bosga, Jurjen; Rosenbaum, David A; Nijhuis-van der Sanden, Maria W G; Hullegie, Wim; van Cingel, Robert; Meulenbroek, Ruud G J

    2016-10-01

    The present study investigated whether special haptic or visual feedback would facilitate the coordination of in-phase, cyclical feet movements of different amplitudes. Seventeen healthy participants sat with their feet on sliding panels that were moved externally over the same or different amplitudes. The participants were asked to generate simultaneous knee flexion-extension movements, or to let their feet be dragged, resulting in reference foot displacements of 150 mm and experimental foot displacements of 150, 120, or 90 mm. Four types of feedback were given: (1) special haptic feedback, involving actively following the motions of the sliders manipulated by two confederates, (2) haptic feedback resulting from passive motion, (3) veridical visual feedback, and (4) enhanced visual feedback. Both with respect to amplitude assimilation effects, correlations and standard deviation of relative phase, the results showed that enhanced visual feedback did not facilitate bipedal independence, but haptic feedback with active movement did. Implications of the findings for movement rehabilitation contexts are discussed.

  9. Direct laser additive fabrication system with image feedback control

    Energy Technology Data Exchange (ETDEWEB)

    Griffith, Michelle L. (Albuquerque, NM); Hofmeister, William H. (Nashville, TN); Knorovsky, Gerald A. (Albuquerque, NM); MacCallum, Danny O. (Edgewood, NM); Schlienger, M. Eric (Albuquerque, NM); Smugeresky, John E. (Pleasanton, CA)

    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.

  10. Multichannel electrotactile feedback for simultaneous and proportional myoelectric control

    Science.gov (United States)

    Patel, Gauravkumar K.; Dosen, Strahinja; Castellini, Claudio; Farina, Dario

    2016-10-01

    Objective. Closing the loop in myoelectric prostheses by providing artificial somatosensory feedback to the user is an important need for prosthetic users. Previous studies investigated feedback strategies in combination with the control of one degree of freedom of simple grippers. Modern hands, however, are sophisticated multifunction systems. In this study, we assessed multichannel electrotactile feedback integrated with an advanced method for the simultaneous and proportional control of individual fingers of a dexterous hand. Approach. The feedback used spatial and frequency coding to provide information on the finger positions (normalized flexion angles). A comprehensive set of conditions have been investigated in 28 able-bodied subjects, including feedback modalities (visual, electrotactile and no feedback), control tasks (fingers and grasps), systems (virtual and real hand), control methods (ideal and realistic) and range of motion (low and high). The task for the subjects was to operate the hand using closed-loop myoelectric control and generate the desired movement (e.g., selected finger or grasp at a specific level of closure). Main results. The subjects could perceive the multichannel and multivariable electrotactile feedback and effectively exploit it to improve the control performance with respect to open-loop grasping. The improvement however depended on the reliability of the feedforward control, with less consistent control exhibiting performance trends that were more complex across the conditions. Significance. The results are promising for the potential application of advanced feedback to close the control loop in sophisticated prosthetic systems.

  11. The Youla Parameterization for Nonlinear Feedback Systems with Additive Disturbances

    NARCIS (Netherlands)

    Paice, A.D.B.; Schaft, A.J. van der

    1995-01-01

    Building on the work presented previously, a construction of the Youla Parameterization for nonlinear feedback systems is presented in which the feedback loop is disturbed by additive disturbances. The construction of the Youla parameterization may then be shown to be stable and well-posed in the

  12. Vacuum Energy Sequestering and Graviton Loops

    CERN Document Server

    Kaloper, Nemanja

    2016-01-01

    We recently formulated a local mechanism of vacuum energy sequester. This mechanism automatically removes all matter loop contributions to vacuum energy from the stress energy tensor which sources the curvature. Here we adapt the local vacuum energy sequestering mechanism to also cancel all the vacuum energy loops involving virtual gravitons, in addition to the vacuum energy generated by matter fields alone.

  13. Vacuum Energy Sequestering and Graviton Loops

    OpenAIRE

    Kaloper, Nemanja; Padilla, Antonio

    2016-01-01

    We recently formulated a local mechanism of vacuum energy sequester. This mechanism automatically removes all matter loop contributions to vacuum energy from the stress energy tensor which sources the curvature. Here we adapt the local vacuum energy sequestering mechanism to also cancel all the vacuum energy loops involving virtual gravitons, in addition to the vacuum energy generated by matter fields alone.

  14. The anti-waggle dance: use of the stop signal as negative feedback

    Directory of Open Access Journals (Sweden)

    Parry Macdonald Kietzman

    2015-02-01

    Full Text Available Numerous activities within honey bee (Apis mellifera L. colonies rely on feedback loops for organization at the group level. Classic examples of these self-organizing behaviors occur during foraging and swarm nest site selection. The waggle dance provides positive feedback, promoting foraging at a specific location or increased scouting at a potential nest site. Rather less well known than the waggle dance, the stop signal, a short vibration often delivered while butting against a dancing bee, is currently best understood as a counter to the waggle dance, offering negative feedback towards the advertised foraging location or nest site. When the stop signal is received by a waggle dancer she is more likely to terminate her dance early and retire from the dance floor. Bees that experienced danger or overcrowding at a food source are more likely to perform the stop signal upon their return to the colony, resulting in an inhibition of foraging at that location. During a swarm’s nest site selection process, scout bees that visited a different site than the one being advertised are more likely to stop-signal the waggle dancer than are scouts that had visited the same site. Over time, the scout bees build recruitment to a single site until a quorum is reached and the swarm can move to it. The balance between the positive feedback from the waggle dance and the negative feedback from the stop signal allows for a more sensitive adjustment of response from the colony as a unit. Many of the processes associated with the feedback loops organizing a honey bee colony’s activities are in striking parallel to other systems, such as intercellular interactions involved in motor neuron function.

  15. Tracking controller for robot manipulators via composite nonlinear feedback law

    Institute of Scientific and Technical Information of China (English)

    Peng Wendong; Su Jianbo

    2009-01-01

    A composite nonlinear feedback tracking controller for motion control of robot manipulators is de-scribed. The structure of the controller is composed of a composite nonlinear feedback law plus full robot nonlinear dynamics compensation. The stability is carried out in the presence of friction. The controller takes advantage of varying damping ratios induced by the composite nonlinear feedback control, so the transient performance of the closed-loop is remarkably improved. Simulation results demonstrate the feasibility of the proposed method.

  16. Experimental demonstration of coherent feedback control on optical field squeezing

    CERN Document Server

    Iida, Sanae; Yonezawa, Hidehiro; Yamamoto, Naoki; Furusawa, Akira

    2011-01-01

    Coherent feedback is a non-measurement based, hence a back-action free, method of control for quantum systems. A typical application of this control scheme is squeezing enhancement, a purely non-classical effect in quantum optics. In this paper we report its first experimental demonstration that well agrees with the theory taking into account time delays and losses in the coherent feedback loop. The results clarify both the benefit and the limitation of coherent feedback control in a practical situation.

  17. A cryo-amplifier working in a double loop-flux locked loop scheme for SQUID readout of TES detectors

    Science.gov (United States)

    Torrioli, Guido; Bastia, Paolo; Piro, Luigi; Macculi, Claudio; Colasanti, Luca

    2010-07-01

    In this paper we report on a novel SQUID readout scheme, called Double Loop-Flux Locked loop (DL-FLL), that we are investigating in the frame of ASI and ESA technological development contracts. This scheme is based on the realization of a cryogenic amplifier which is used in order to readout TES detectors in the Frequency Division Multiplexing technique, where high loop-gain is required up to few MHz. Loop-gain in feedback systems is, usually, limited by the propagation delay of the signals traveling in the loop because of the distance between the feedback loop elements. This problem is particularly evident in the case of SQUID systems, where the elements of the feedback loop are placed both at cryogenic and room temperature. To solve this issue we propose a low power dissipation cryo-amplifier capable to work at cryogenic temperatures so that it can be placed close to the SQUID realizing a local cryogenic loop. The adoption of the DL-FLL scheme allows to simplify considerably the cryo-amplifier which, being AC-coupled, don't require the features of a precision DC-coupled amplifier and can be made with a limited number of electronic components and with a consequent reduction of power dissipation.

  18. Transfigured Loop Shaping Controller and its Application to Underwater Vehicle

    Institute of Scientific and Technical Information of China (English)

    Xian-Ku Zhang; Yi-Cheng Jin

    2005-01-01

    A kind of transfigured loop shaping controller is presented in this paper. A transfigured loop shaping system puts a controller K in a feedback loop, while putting the dc gain of the controller K on the reference signal line. It is shown through frequency domain analysis and simulation that a transfigured controller can improve the dynamic behavior of a system. The transfigured loop shaping controller method is simple and effective and corresponds to the mixed sensitivity method of robust control theory, which improves the behavior of a system by iterative tuning of weighting functions. Satisfactory control results are obtained when it is applied to the design of an underwater vehicle.

  19. Theoretical Design of a Depolarized Interferometric Fiber-Optic Gyroscope (IFOG) on SMF-28 Single-Mode Standard Optical Fiber Based on Closed-Loop Sinusoidal Phase Modulation with Serrodyne Feedback Phase Modulation Using Simulation Tools for Tactical and Industrial Grade Applications.

    Science.gov (United States)

    Pérez, Ramón José; Álvarez, Ignacio; Enguita, José María

    2016-04-27

    This article presents, by means of computational simulation tools, a full analysis and design of an Interferometric Fiber-Optic Gyroscope (IFOG) prototype based on a closed-loop configuration with sinusoidal bias phase- modulation. The complete design of the different blocks, optical and electronic, is presented, including some novelties as the sinusoidal bias phase-modulation and the use of an integrator to generate the serrodyne phase-modulation signal. The paper includes detailed calculation of most parameter values, and the plots of the resulting signals obtained from simulation tools. The design is focused in the use of a standard single-mode optical fiber, allowing a cost competitive implementation compared to commercial IFOG, at the expense of reduced sensitivity. The design contains an IFOG model that accomplishes tactical and industrial grade applications (sensitivity ≤ 0.055 °/h). This design presents two important properties: (1) an optical subsystem with advanced conception: depolarization of the optical wave by means of Lyot depolarizers, which allows to use a sensing coil made by standard optical fiber, instead by polarization maintaining fiber, which supposes consequent cost savings and (2) a novel and simple electronic design that incorporates a linear analog integrator with reset in feedback chain, this integrator generating a serrodyne voltage-wave to apply to Phase-Modulator (PM), so that it will be obtained the interferometric phase cancellation. This particular feedback design with sawtooth-wave generated signal for a closed-loop configuration with sinusoidal bias phase modulation has not been reported till now in the scientific literature and supposes a considerable simplification with regard to previous designs based on similar configurations. The sensing coil consists of an 8 cm average diameter spool that contains 300 m of standard single-mode optical-fiber (SMF-28 type) realized by quadrupolar winding. The working wavelength will be

  20. Theoretical Design of a Depolarized Interferometric Fiber-Optic Gyroscope (IFOG) on SMF-28 Single-Mode Standard Optical Fiber Based on Closed-Loop Sinusoidal Phase Modulation with Serrodyne Feedback Phase Modulation Using Simulation Tools for Tactical and Industrial Grade Applications

    Science.gov (United States)

    Pérez, Ramón José; Álvarez, Ignacio; Enguita, José María

    2016-01-01

    This article presents, by means of computational simulation tools, a full analysis and design of an Interferometric Fiber-Optic Gyroscope (IFOG) prototype based on a closed-loop configuration with sinusoidal bias phase- modulation. The complete design of the different blocks, optical and electronic, is presented, including some novelties as the sinusoidal bias phase-modulation and the use of an integrator to generate the serrodyne phase-modulation signal. The paper includes detailed calculation of most parameter values, and the plots of the resulting signals obtained from simulation tools. The design is focused in the use of a standard single-mode optical fiber, allowing a cost competitive implementation compared to commercial IFOG, at the expense of reduced sensitivity. The design contains an IFOG model that accomplishes tactical and industrial grade applications (sensitivity ≤ 0.055 °/h). This design presents two important properties: (1) an optical subsystem with advanced conception: depolarization of the optical wave by means of Lyot depolarizers, which allows to use a sensing coil made by standard optical fiber, instead by polarization maintaining fiber, which supposes consequent cost savings and (2) a novel and simple electronic design that incorporates a linear analog integrator with reset in feedback chain, this integrator generating a serrodyne voltage-wave to apply to Phase-Modulator (PM), so that it will be obtained the interferometric phase cancellation. This particular feedback design with sawtooth-wave generated signal for a closed-loop configuration with sinusoidal bias phase modulation has not been reported till now in the scientific literature and supposes a considerable simplification with regard to previous designs based on similar configurations. The sensing coil consists of an 8 cm average diameter spool that contains 300 m of standard single-mode optical-fiber (SMF-28 type) realized by quadrupolar winding. The working wavelength will be

  1. Theoretical Design of a Depolarized Interferometric Fiber-Optic Gyroscope (IFOG on SMF-28 Single-Mode Standard Optical Fiber Based on Closed-Loop Sinusoidal Phase Modulation with Serrodyne Feedback Phase Modulation Using Simulation Tools for Tactical and Industrial Grade Applications

    Directory of Open Access Journals (Sweden)

    Ramón José Pérez

    2016-04-01

    Full Text Available This article presents, by means of computational simulation tools, a full analysis and design of an Interferometric Fiber-Optic Gyroscope (IFOG prototype based on a closed-loop configuration with sinusoidal bias phase- modulation. The complete design of the different blocks, optical and electronic, is presented, including some novelties as the sinusoidal bias phase-modulation and the use of an integrator to generate the serrodyne phase-modulation signal. The paper includes detailed calculation of most parameter values, and the plots of the resulting signals obtained from simulation tools. The design is focused in the use of a standard single-mode optical fiber, allowing a cost competitive implementation compared to commercial IFOG, at the expense of reduced sensitivity. The design contains an IFOG model that accomplishes tactical and industrial grade applications (sensitivity ≤ 0.055 °/h. This design presents two important properties: (1 an optical subsystem with advanced conception: depolarization of the optical wave by means of Lyot depolarizers, which allows to use a sensing coil made by standard optical fiber, instead by polarization maintaining fiber, which supposes consequent cost savings and (2 a novel and simple electronic design that incorporates a linear analog integrator with reset in feedback chain, this integrator generating a serrodyne voltage-wave to apply to Phase-Modulator (PM, so that it will be obtained the interferometric phase cancellation. This particular feedback design with sawtooth-wave generated signal for a closed-loop configuration with sinusoidal bias phase modulation has not been reported till now in the scientific literature and supposes a considerable simplification with regard to previous designs based on similar configurations. The sensing coil consists of an 8 cm average diameter spool that contains 300 m of standard single-mode optical-fiber (SMF-28 type realized by quadrupolar winding. The working

  2. A True Open-Loop Synchronization Technique

    DEFF Research Database (Denmark)

    Golestan, Saeed; Vidal, Ana; Yepes, Alejandro G.

    2016-01-01

    to worsen in the presence of frequency drifts. To deal with this problem, two approaches are often recommended in the literature: Adapting OLS techniques to grid frequency variations by feeding back the frequency estimated by them or using the frequency estimated by a secondary frequency detector...... in a parallel manner. In the presence of the frequency feedback loop, nevertheless, the OLS technique may not be truly open-loop, which makes a deep study of stability necessary. Using the secondary frequency detector, on the other hand, increases the computational effort and implementation complexity. Another...

  3. The finite Bruck Loops

    CERN Document Server

    Baumeister, Barbara

    2009-01-01

    We continue the work by Aschbacher, Kinyon and Phillips [AKP] as well as of Glauberman [Glaub1,2] by describing the structure of the finite Bruck loops. We show essentially that a finite Bruck loop $X$ is the direct product of a Bruck loop of odd order with either a soluble Bruck loop of 2-power order or a product of loops related to the groups $PSL_2(q)$, $q= 9$ or $q \\geq 5$ a Fermat prime. The latter possibillity does occur as is shown in [Nag1, BS]. As corollaries we obtain versions of Sylow's, Lagrange's and Hall's Theorems for loops.

  4. A Theory of Circular Organization and Negative Feedback: Defining Life in a Cybernetic Context

    Science.gov (United States)

    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.

  5. Combining experimental observation and modelling in investigating feedback and emotions in repeated selection tasks

    NARCIS (Netherlands)

    Fischer, A.R.H.; Blommaert, F.J.J.; Midden, C.J.H.

    2005-01-01

    People seem to learn tasks even without formal training. This can be modelled as the outcome of a feedback system that accumulates experience. In this paper we investigate such a feedback system, following an iterative research approach. A feedback loop is specified that is detailed using contempora

  6. Combining experimental observation and modelling in investigating feedback and emotions in repeated selection tasks

    NARCIS (Netherlands)

    Fischer, A.R.H.; Blommaert, F.J.J.; Midden, C.J.H.

    2005-01-01

    People seem to learn tasks even without formal training. This can be modelled as the outcome of a feedback system that accumulates experience. In this paper we investigate such a feedback system, following an iterative research approach. A feedback loop is specified that is detailed using

  7. On Teacher’s Feedback from the Perspective of Communication

    Institute of Scientific and Technical Information of China (English)

    张芳

    2011-01-01

    Classroom interaction involves many aspects,among which teacher’s feedback is an important element.This paper aimes at studying teacher’s feedback from the perspective of communication.It first discusses the definition of teacher’s feedback and analyses the functions of teacher’s feedback in the classroom interaction and then explores some strategies for effective feedback based on communication theory.

  8. A Critical Examination of Frequency-Fixed Second-Order Generalized Integrator-Based Phase-Locked Loops

    DEFF Research Database (Denmark)

    Golestan, Saeed; Mousazadeh Mousavi, Seyyed-Yousef; Guerrero, Josep M.

    2017-01-01

    The implementation of a large number of single-phase phase-locked loops (PLLs) involves creating a fictitious quadrature signal. A popular approach for this purpose is using a second-order generalized integrator-based quadrature signal generator (SOGIQSG) because it results in an acceptable speed....../accuracy tradeoff. The SOGI-QSG based PLL (or briefly the SOGI-PLL), in its standard form, involves a frequency feedback loop for adjusting the SOGI resonance frequency under frequency drifts. Some recent research works have reported that the speed/accuracy tradeoff of the SOGI-PLL can be considerably enhanced......-based PLLs (FFSOGI-PLLs) to highlight their real advantages and disadvantages....

  9. Pseudonoise code tracking loop

    Science.gov (United States)

    Laflame, D. T. (Inventor)

    1980-01-01

    A delay-locked loop is presented for tracking a pseudonoise (PN) reference code in an incoming communication signal. The loop is less sensitive to gain imbalances, which can otherwise introduce timing errors in the PN reference code formed by the loop.

  10. Going Full Circle With Teacher Feedback

    Directory of Open Access Journals (Sweden)

    Jo-Anne L. Manswell Butty

    2015-07-01

    Full Text Available Research on the evaluation of early childhood programs focuses mainly on its outcomes rather than its process with often little attention given to the role that feedback to teachers in pre-kindergarten (pre-k programs plays in the larger cycle of the evaluation process. This article provides a case example of a multiyear evaluation of community-based pre-k programs serving about 360 three- and four-year old children over a 5-year period in the District of Columbia. The Closing the Loop Evaluation Model proposed represents a responsive evaluation approach that illustrates the interconnected interactions between teacher feedback during the evaluation process and two supporting evaluation methodologies that emphasize social justice and utility. Findings from the case example highlight the responsive evaluation approach, feedback process, and ensuing conceptual and instrumental changes that occurred among stakeholders from whole-group feedback to small-group “report card” meetings with add-ons such as technical assistance, teacher-generated action plans, and teacher follow-up and feedback to close the evaluation loop. The authors discuss lessons learned about the evaluation process from the case example around aspects of feedback, including timing, audience, and function. Findings highlight the importance of feedback being timely and prompt, high quality in focus and content, non-punitive, collaborative, concise, and useful. The authors conclude that an evaluation process that includes teacher feedback, couched in social justice and utility, can have positive outcomes for all stakeholders and will likely lead to higher quality early childhood education programs.

  11. Enhanced Negative Feedback Responses in Remitted Depression

    OpenAIRE

    Pizzagalli, Diego; Meites, Tiffany M.; Deveney, Christen M; Holmes, Avram J.; Bogdan, Ryan; Steele, Katherine T.; Santesso, Diane L.

    2008-01-01

    Major depressive disorder (MDD)is characterized by hypersensitivity to negative feedback that might involve frontocingulate dysfunction. MDD patients exhibit enhanced electrophysiological responses to negative internal (errors) and external (feedback) cues. Whether this dysfunction extends to remitted depressed (RD) individuals with a history of MDD is currently unknown. To address this issue, we examined the feedback-related negativity in RD and control participants using a probabilistic pun...

  12. Automatic Loop Parallelization via Compiler Guided Refactoring

    DEFF Research Database (Denmark)

    Larsen, Per; Ladelsky, Razya; Lidman, Jacob

    For many parallel applications, performance relies not on instruction-level parallelism, but on loop-level parallelism. Unfortunately, many modern applications are written in ways that obstruct automatic loop parallelization. Since we cannot identify sufficient parallelization opportunities...... for these codes in a static, off-line compiler, we developed an interactive compilation feedback system that guides the programmer in iteratively modifying application source, thereby improving the compiler’s ability to generate loop-parallel code. We use this compilation system to modify two sequential...... benchmarks, finding that the code parallelized in this way runs up to 8.3 times faster on an octo-core Intel Xeon 5570 system and up to 12.5 times faster on a quad-core IBM POWER6 system. Benchmark performance varies significantly between the systems. This suggests that semi-automatic parallelization should...

  13. Parallelizing More Loops with Compiler Guided Refactoring

    DEFF Research Database (Denmark)

    Larsen, Per; Ladelsky, Razya; Lidman, Jacob

    2012-01-01

    The performance of many parallel applications relies not on instruction-level parallelism but on loop-level parallelism. Unfortunately, automatic parallelization of loops is a fragile process; many different obstacles affect or prevent it in practice. To address this predicament we developed...... an interactive compilation feedback system that guides programmers in iteratively modifying their application source code. This helps leverage the compiler’s ability to generate loop-parallel code. We employ our system to modify two sequential benchmarks dealing with image processing and edge detection......, resulting in scalable parallelized code that runs up to 8.3 times faster on an eightcore Intel Xeon 5570 system and up to 12.5 times faster on a quad-core IBM POWER6 system. Benchmark performance varies significantly between the systems. This suggests that semi-automatic parallelization should be combined...

  14. Generalized modal analysis for closed-loop piezoelectric devices

    Science.gov (United States)

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

    2015-08-01

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

  15. Inner Current Loop Analysis and Design Based on Resonant Regulators for Isolated Microgrids

    DEFF Research Database (Denmark)

    Federico, de Bosio; de Sousa Ribeiro, Luiz Antonio; Soares Lima, Marcel

    2015-01-01

    coupling in the design of proportional resonant controllers for these inner loops in voltage source inverters operating in islanded microgrids. It is also shown that the state feedback coupling has an important effect in the performance of the control loops by increasing the steady-state error......Inner current and voltage loops are fundamental in achieving good performance of microgrids based on power electronics voltage source inverters. The analysis and design of these loops are essential for the adequate operation of these systems. This paper investigates the effect of state feedback....... A comparison between different types of proportional+resonant controllers is done. Experimental results verify the theoretical assumptions done....

  16. Extended Lock Range Zero-Crossing Digital Phase-Locked Loop with Time Delay

    OpenAIRE

    Nasir Qassim

    2005-01-01

    The input frequency limit of the conventional zero-crossing digital phase-locked loop (ZCDPLL) is due to the operating time of the digital circuitry inside the feedback loop. A solution that has been previously suggested is the introduction of a time delay in the feedback path of the loop to allow the digital circuits to complete their sample processing before the next sample is received. However, this added delay will limit the stable operation range and hence lock range of the loop. The ob...

  17. Price Coordination of Closed-Loop Supply Chain Involving Third-Party Recycling%第三方负责回收的闭环供应链差别定价协调契约设计

    Institute of Scientific and Technical Information of China (English)

    张克勇; 周国华

    2011-01-01

    Based on the game theory, the differential price coordination is addressed in this paper for a closed-loop supply chain with third-party collection of used products. First, the decentralized and centralized differential pricing models are established. With them, the optimal pricing strategy and the optimal profit for the members in a closed-loop supply chain are analyzed. Then,it is found that efficiency is lost in the decentralized closed-loop supply chain. Finally,it puts forward a profit-sharing coordination contract to coordinate the closed-loop supply chain, which makes the profit of the decentralized closed-loop supply chain equal to that of the integrated closed-loop supply chain.%以博弈论为基本研究方法,研究了第三方负责回收的闭环供应链系统差别定价协调契约的设计问题.构建了三方非合作分散决策情形和合作集中决策情形下的系统差别定价模型,分析得到了两种情形下闭环供应链系统成员的最优定价策略和利润,发现三方分散决策会造成系统效率的损失.由此,提出了一种收益分享协调契约,实现了闭环供应链系统的协调,并使供应链系统整体利润达到集中决策时的利润水平.

  18. Corrective feedback, learner uptake, and feedback perception in a Chinese as a foreign language classroom

    Directory of Open Access Journals (Sweden)

    Tingfeng Fu

    2016-03-01

    Full Text Available The role of corrective feedback in second language classrooms has received considerable research attention in the past few decades. However, most of this research has been conducted in English-teaching settings, either ESL or EFL. This study examined teacher feedback, learner uptake as well as learner and teacher perception of feedback in an adult Chinese as a foreign language classroom. Ten hours of classroom interactions were videotaped, transcribed and coded for analysis. Lyster and Ranta’s (1997 coding system involving six types of feedback was initially used to identify feedback frequency and learner uptake. However, the teacher was found to use a number of additional feedback types. Altogether, 12 types of feedback were identified: recasts, delayed recasts, clarification requests, translation, metalinguistic feedback, elicitation, explicit correction, asking a direct question, repetition, directing question to other students, re-asks, and using L1-English. Differences were noted in the frequency of some of the feedback types as well as learner uptake compared to what had been reported in some previous ESL and EFL studies. With respect to the new feedback types, some led to noticeable uptake. As for the students’ and teacher’s perceptions, they did not match and both the teacher and the students were generally not accurate in perceiving the frequency of each feedback type. The findings are discussed in terms of the role of context in affecting the provision and effectiveness of feedback and its relationship to student and teacher perception of feedback.

  19. Supersymmetric Wilson loops at two loops

    CERN Document Server

    Bassetto, Antonio; Pucci, Fabrizio; Seminara, Domenico

    2008-01-01

    We study the quantum properties of certain BPS Wilson loops in ${\\cal N}=4$ supersymmetric Yang-Mills theory. They belong to a general family, introduced recently, in which the addition of particular scalar couplings endows generic loops on $S^3$ with a fraction of supersymmetry. When restricted to $S^2$, their quantum average has been further conjectured to be exactly computed by the matrix model governing the zero-instanton sector of YM$_2$ on the sphere. We perform a complete two-loop analysis on a class of cusped Wilson loops lying on a two-dimensional sphere, finding perfect agreement with the conjecture. The perturbative computation reproduces the matrix-model expectation through a highly non-trivial interplay between ladder diagrams and self-energies/vertex contributions, suggesting the existence of a localization procedure.

  20. Feature-saliency and feedback-information interactively impact visual category learning

    Directory of Open Access Journals (Sweden)

    Rubi eHammer

    2015-02-01

    Full Text Available Visual category learning (VCL involves detecting which features are most relevant for categorization. This requires attentional learning, which allows effectively redirecting attention to object’s features most relevant for categorization while also filtering out irrelevant features. When features relevant for categorization are not salient VCL relies also on perceptual learning, which enable becoming more sensitive to subtle yet important differences between objects. Little is known about how attentional learning and perceptual learning interact when VCL relies on both processes at the same time. Here we tested this interaction. Participants performed VCL tasks that varied in feature-saliency (low-saliency tasks that required perceptual learning vs. high-saliency tasks, and in feedback-information (tasks with mid-information, moderately ambiguous feedback that increased attentional load vs. tasks with high-information non-ambiguous feedback. Participants were required learning to categorize novel stimuli by detecting the feature-dimension relevant for categorization. We found that mid-information and high-information feedback were similarly effective for VCL in high-saliency tasks. This suggests that an increased attentional load associated with the processing of moderately ambiguous feedback does not compromise VCL when both the task relevant feature and irrelevant features are salient. In low-saliency VCL tasks performance improvement relied on slower perceptual learning, but when the feedback was highly-informative participants were ultimately capable reaching performances matching those observed in high-saliency VCL tasks. However, VCL was much compromised when features were with low-saliency and the feedback was ambiguous. We suggest that this later learning scenario is characterized by a ‘cognitive loop paradox’ where two interdependent learning processes have to take place simultaneously.

  1. 闭环肌松注射系统反馈调节苯磺顺阿曲库铵用药的精确性研究%Investigation of Feedback Regulation of Close-loop Muscle Relaxant Injection System on Accuracy of Cisatracurium Besilate Usage

    Institute of Scientific and Technical Information of China (English)

    郭瑞; 李建宾; 王立勋; 何婉雯; 李辉; 陈友利

    2015-01-01

    Objective To investigate feedback regulation of close-loop muscle relaxant injection system on accuracy of cisatracurium besilate usage. Methods Two hundred patients undergoing laparoscopic cholecystectomy surgery, aged 20 to 40 years old, at ASA Ⅰ or Ⅱ, were randomly divided into two groups:control group and treatment group (n=100 each group).In the control group, the patients received injection of cisatracurium besilate with closed-loop muscle relaxant injection system at 1.5-2.0 μg·kg-1 ·min-1 , until 30 min before the end of surgery;if the muscle relaxant level could not meet the requirement of the operation, extra 0.05 mg·kg-1 was added.The treatment group was adopted closed-loop muscle relaxant monitoring under negative feedback regulation of infusion cisatracurium, and the close-loop control parameters were set to: drug was added when TOF was 8%, and injection speed was 2. 5 μg · kg-1 · min-1 , maintaining speed was 0. 33 μg · kg-1 · min-1 , the stimulus current for monitoring muscle relaxant was 60 mA , and the pulse width was 200μs.The Cooper score, cisatracurium dosage, and muscle recovery index, TOFr75 and TOFr90 of the two groups were compared. Prediction probability ( Pk ) of NI on awakening period of eye opening and directional force recovery of the two groups were detected, and regression equation was established to predict ED50 and ED95 related NI . Results Cooper score was significantly higher in the treatment group than in the control group ( P0.05) . Conclusion The accuracy of closed loop muscle relaxant injection system is higher than that of the traditional method, it provides better muscle relaxation effect for tracheal intubation, reduces recovery time, increases the Pk of NI on patient awakening.%目的 观察闭环肌松注射系统反馈调节苯磺顺阿曲库铵用药的精确性. 方法 选择拟行腹腔镜下胆囊切除手术患者200例(年龄20~40岁,ASAⅠ或Ⅱ级) ,采用随机数字表法分为两组.

  2. Self-oscillating loop based piezoelectric power converter

    OpenAIRE

    Rødgaard, Martin Schøler; Andersen, Michael A. E.; Esbern, Andreas; Meyer, Kasper Sinding

    2013-01-01

    The present invention relates to a piezoelectric power converter comprising an input driver electrically coupled directly to an input or primary electrode of the piezoelectric transformer without any intervening series or parallel inductor. A feedback loop is operatively coupled between an output voltage of the piezoelectric transformer and the input driver to provide a self-oscillation loop around a primary section of the piezoelectric transformer oscillating at an excitation frequency. Elec...

  3. REGULARIZATION OF SINGULAR SYSTEMS BY OUTPUT FEEDBACK

    Institute of Scientific and Technical Information of China (English)

    De-lin Chu; Da-yong Cai

    2000-01-01

    Problem of regularization of a singular system by derivative and proportional output feedback is studied. Necessary and sufficient conditions are obtained under which a singular system can be regularized into a closed-loop system that is regular and of index at most one. The reduced form is given that can easily explore the system properties as well as the feedback to be determined. The main results of the present paper are based on orthogonal transformations. Therefore, they can be implemented by numerically stable ways.

  4. AtRH57, a DEAD-box RNA helicase, is involved in feedback inhibition of glucose-mediated abscisic acid accumulation during seedling development and additively affects pre-ribosomal RNA processing with high glucose.

    Science.gov (United States)

    Hsu, Yi-Feng; Chen, Yun-Chu; Hsiao, Yu-Chun; Wang, Bing-Jyun; Lin, Shih-Yun; Cheng, Wan-Hsing; Jauh, Guang-Yuh; Harada, John J; Wang, Co-Shine

    2014-01-01

    The Arabidopsis thaliana T-DNA insertion mutant rh57-1 exhibited hypersensitivity to glucose (Glc) and abscisic acid (ABA). The other two rh57 mutants also showed Glc hypersensitivity similar to rh57-1, strongly suggesting that the Glc-hypersensitive feature of these mutants results from mutation of AtRH57. rh57-1 and rh57-3 displayed severely impaired seedling growth when grown in Glc concentrations higher than 3%. The gene, AtRH57 (At3g09720), was expressed in all Arabidopsis organs and its transcript was significantly induced by ABA, high Glc and salt. The new AtRH57 belongs to class II DEAD-box RNA helicase gene family. Transient expression of AtRH57-EGFP (enhanced green fluorescent protein) in onion cells indicated that AtRH57 was localized in the nucleus and nucleolus. Purified AtRH57-His protein was shown to unwind double-stranded RNA independent of ATP in vitro. The ABA biosynthesis inhibitor fluridone profoundly redeemed seedling growth arrest mediated by sugar. rh57-1 showed increased ABA levels when exposed to high Glc. Quantitative real time polymerase chain reaction analysis showed that AtRH57 acts in a signaling network downstream of HXK1. A feedback inhibition of ABA accumulation mediated by AtRH57 exists within the sugar-mediated ABA signaling. AtRH57 mutation and high Glc conditions additively caused a severe defect in small ribosomal subunit formation. The accumulation of abnormal pre-rRNA and resistance to protein synthesis-related antibiotics were observed in rh57 mutants and in the wild-type Col-0 under high Glc conditions. These results suggested that AtRH57 plays an important role in rRNA biogenesis in Arabidopsis and participates in response to sugar involving Glc- and ABA signaling during germination and seedling growth.

  5. Sensory Processing: Advances in Understanding Structure and Function of Pitch-Shifted Auditory Feedback in Voice Control

    Directory of Open Access Journals (Sweden)

    Charles R Larson

    2016-02-01

    Full Text Available The pitch-shift paradigm has become a widely used method for studying the role of voice pitch auditory feedback in voice control. This paradigm introduces small, brief pitch shifts in voice auditory feedback to vocalizing subjects. The perturbations trigger a reflexive mechanism that counteracts the change in pitch. The underlying mechanisms of the vocal responses are thought to reflect a negative feedback control system that is similar to constructs developed to explain other forms of motor control. Another use of this technique requires subjects to voluntarily change the pitch of their voice when they hear a pitch shift stimulus. Under these conditions, short latency responses are produced that change voice pitch to match that of the stimulus. The pitch-shift technique has been used with magnetoencephalography (MEG and electroencephalography (EEG recordings, and has shown that at vocal onset there is normally a suppression of neural activity related to vocalization. However, if a pitch-shift is also presented at voice onset, there is a cancellation of this suppression, which has been interpreted to mean that one way in which a person distinguishes self-vocalization from vocalization of others is by a comparison of the intended voice and the actual voice. Studies of the pitch shift reflex in the fMRI environment show that the superior temporal gyrus (STG plays an important role in the process of controlling voice F0 based on auditory feedback. Additional studies using fMRI for effective connectivity modeling show that the left and right STG play critical roles in correcting for an error in voice production. While both the left and right STG are involved in this process, a feedback loop develops between left and right STG during perturbations, in which the left to right connection becomes stronger, and a new negative right to left connection emerges along with the emergence of other feedback loops within the cortical network tested.

  6. Cosmic string loop shapes

    CERN Document Server

    Blanco-Pillado, Jose J; Shlaer, Benjamin

    2015-01-01

    We analyze the shapes of cosmic string loops found in large-scale simulations of an expanding-universe string network. The simulation does not include gravitational back reaction, but we model that process by smoothing the loop using Lorentzian convolution. We find that loops at formation consist of generally straight segments separated by kinks. We do not see cusps or any cusp-like structure at the scale of the entire loop, although we do see very small regions of string that move with large Lorentz boosts. However, smoothing of the string almost always introduces two cusps on each loop. The smoothing process does not lead to any significant fragmentation of loops that were in non-self-intersecting trajectories before smoothing.

  7. Coxeter-Chein Loops

    CERN Document Server

    Blok, Rieuwert J

    2011-01-01

    In 1974 Orin Chein discovered a new family of Moufang loops which are now called Chein loops. Such a loop can be created from any group $W$ together with $\\mathbb{Z}_2$ by a variation on a semi-direct product. We study these loops in the case where $W$ is a Coxeter group and show that it has what we call a Chein-Coxeter system, a small set of generators of order 2, together with a set of relations closely related to the Coxeter relations and Chein relations. As a result we are able to give amalgam presentations for Coxeter-Chein loops. This is to our knowledge the first such presentation for a Moufang loop.

  8. Remarks on correlators of Polyakov Loops

    CERN Document Server

    Neuberger, Herbert

    2013-01-01

    Polyakov loop eigenvalues and their N-dependence are studied in 2 and 4 dimensional SU(N) YM theory. The connected correlation function of the single eigenvalue distributions of two separated Polyakov loops in 2D YM is calculated and is found to have a structure differing from the one of corresponding hermitian random matrix ensembles. No large $N$ non-analyticities are found for two point functions in the confining regime. Suggestions are made for situations in which large-N phase transitions involving Polyakov loops might occur.

  9. Wilson Loop Form Factors: A New Duality

    OpenAIRE

    Chicherin, Dmitry; Heslop, Paul; Korchemsky, Gregory P.; Sokatchev, Emery

    2016-01-01

    We find a new duality for form factors of lightlike Wilson loops in planar $\\mathcal N=4$ super-Yang-Mills theory. The duality maps a form factor involving an $n$-sided lightlike polygonal super-Wilson loop together with $m$ external on-shell states, to the same type of object but with the edges of the Wilson loop and the external states swapping roles. This relation can essentially be seen graphically in Lorentz harmonic chiral (LHC) superspace where it is equivalent to planar graph duality....

  10. A method for closed loop automatic tuning of PID controllers

    Directory of Open Access Journals (Sweden)

    Tor S. Schei

    1992-07-01

    Full Text Available A simple method for the automatic tuning of PID controllers in closed loop is proposed. A limit cycle is generated through a nonlinear feedback path from the process output to the controller reference signal. The frequency of this oscillation is above the crossover frequency and below the critical frequency of the loop transfer function. The amplitude and frequency of the oscillation are estimated and the control parameters are adjusted iteratively such that the closed loop transfer function from the controller reference to the process output attains a specified amplitude at the oscillation frequency.

  11. Feedback control system for walking in man.

    Science.gov (United States)

    Petrofsky, J S; Phillips, C A; Heaton, H H

    1984-01-01

    A computer control stimulation system is described which has been successfully tested by allowing a paraplegic subject to stand and walk through closed loop control. This system is a Z80 microprocessor system with eight channels of analog to digital and 16 channels of digital to analog control. Programming is written in CPM and works quite successfully for maintaining lower body postural control in paraplegics. Further expansion of this system would enable a feedback control system for multidirectional walking in man.

  12. Coxeter-Chein Loops

    OpenAIRE

    Blok, Rieuwert J.; Gagola III, Stephen

    2011-01-01

    In 1974 Orin Chein discovered a new family of Moufang loops which are now called Chein loops. Such a loop can be created from any group $W$ together with $\\mathbb{Z}_2$ by a variation on a semi-direct product. We study these loops in the case where $W$ is a Coxeter group and show that it has what we call a Chein-Coxeter system, a small set of generators of order 2, together with a set of relations closely related to the Coxeter relations and Chein relations. As a result we are able to give am...

  13. Observational Evidence for Loop-Loop Interaction

    Science.gov (United States)

    Guiping, W.; Guangli, H.; Yuhua, T.; Aoao, X.

    2004-01-01

    Through analysis of the data including the hard x-ray(BASTE) microwave(NoRP) and magnetogram(MDI from SOHO) as well as the images of soft x-ray(YHKOH) and EIT(SOHO) on Apr. 151998 solar flare in the active region 8203(N30W12) we found: (1) there are similar quasi period oscillation in the profile of hard x-ray flux (25-5050-100keV) and microwave flux(1GHz) with duration of 85+/-25s every peak includes two sub-peak structures; (2) in the preheat phase of the flare active magnetic field changes apparently and a s-pole spot emerges ; (3) several EIT and soft x-ray loops exist and turn into bright . All of these may suggest that loop-loop interaction indeed exist. Through reconnection the electrons may be accelerated and the hard x-ray and microwave emission take place.

  14. Pulse energy control through dual loop electronic feedback

    CSIR Research Space (South Africa)

    Jacobs, Cobus

    2006-07-01

    Full Text Available surgery • Better accuracy in laser-based scientific measurements Pulse Energy Control handptright Cobus Jacobs et al. head2righthead2rightPump/Gain • Duration & intensity of pump determine energy stored in laser medium barb2rightbarb2right Problem...

  15. Regulation of pollen tube polarity: Feedback loops rule

    Science.gov (United States)

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

  16. Birhythmicity and Hard Excitation from Coupled Synthetic Feedback Loops

    Directory of Open Access Journals (Sweden)

    Aimin Chen

    2014-01-01

    Full Text Available Synthetic biology opens up the possibility of creating circuits that would not survive in the natural world and studying their behaviors in living cells, expanding our notion of biology. Based on this, we analyze on a synthetic biological system the effect of coupling between two instability-generating mechanisms. The systems considered are two topologically equivalent synthetic networks. In addition to simple periodic oscillations and stable steady state, the system can exhibit a variety of new modes of dynamic behavior: coexistence between two stable periodic regimes (birhythmicity and coexistence of a stable periodic regime with a stable steady state (hard excitation. Birhythmicity and hard excitation have been proved to exist in biochemical networks. Through bifurcation analysis on these two synthetic cellular networks, we analyze the function of network structure for the collapse and revival of birhythmicity and hard excitation with the variation of parameters. The results have illustrated that the bifurcation space can be divided into four subspaces for which the dynamical behaviors of the system are generically distinct. Our analysis corroborates the results obtained by numerical simulation of the dynamics.

  17. Extracellular matrix proteins: A positive feedback loop in lung fibrosis?

    NARCIS (Netherlands)

    Blaauboer, M.E.; Boeijen, F.R.; Emson, C.L.; Turner, S.M.; Zandieh-Doulabi, B.; Hanemaaijer, R.; Smit, T.H.; Stoop, R.; Everts, V.

    2014-01-01

    Lung fibrosis is characterized by excessive deposition of extracellular matrix. This not only affects tissue architecture and function, but it also influences fibroblast behavior and thus disease progression. Here we describe the expression of elastin, type V collagen and tenascin C during the

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

    Science.gov (United States)

    Eres, D.; Sharp, J.W.

    1996-07-30

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

  19. Tutorial on beam-based feedback systems for linacs

    Energy Technology Data Exchange (ETDEWEB)

    Hendrickson, L.; Allison, S.; Gromme, T.; Grossberg, P.; Himel, T.; Krauter, K.; MacKenzie, R.; Ross, M.; Sass, R.; Shoaee, H.

    1994-08-01

    A generalized fast feedback system stabilizes beams in the SLC. It performs measurements and modifies actuator settings to control beam states such as position, angle, energy and intensity on a pulse to pulse basis. An adaptive cascade feature allows communication between a series of linac loops, avoiding overcorrection problems. The system is based on the state space formalism of digital control theory. Due to the database-driven design, new loops are added without requiring software modifications. Recent enhancements support the monitoring and control of nonlinear states such as beam phase using excitation techniques. In over three years of operation, the feedback system has grown from its original eight loops to more than fifty loops, and it has been invaluable in stabilizing the machine.

  20. Effects of unwanted feedback on synchronized chaotic optical communications.

    Science.gov (United States)

    Li, Xiaofeng; Pan, Wei; Luo, Bin; Ma, Dong

    2006-04-10

    The effects of unwanted external optical feedback on synchronized chaotic optical communication systems are studied numerically. We consider an open-loop configuration consisting of a transmitter laser with double external optical feedbacks and a receiver laser with optical injection from the transmitter laser. First, including the effects of unwanted optical feedback, the synchronization performances of both the complete synchronization and the generalized synchronization are examined. Then the encoding and decoding performances of the generalized synchronization and the effects of the introduced feedback are investigated, respectively. Finally, we study the control of the unwanted feedback on the dynamics of the transmitter laser and briefly discuss the system security when the transmitter laser is driven to operate in a steady state or periodic oscillation state by the additional feedback.

  1. Conserved stem-loop structures in the HIV-1 RNA region containing the A3 3' splice site and its cis-regulatory element: possible involvement in RNA splicing.

    Science.gov (United States)

    Jacquenet, S; Ropers, D; Bilodeau, P S; Damier, L; Mougin, A; Stoltzfus, C M; Branlant, C

    2001-01-15

    The HIV-1 transcript is alternatively spliced to over 30 different mRNAs. Whether RNA secondary structure can influence HIV-1 RNA alternative splicing has not previously been examined. Here we have determined the secondary structure of the HIV-1/BRU RNA segment, containing the alternative A3, A4a, A4b, A4c and A5 3' splice sites. Site A3, required for tat mRNA production, is contained in the terminal loop of a stem-loop structure (SLS2), which is highly conserved in HIV-1 and related SIVcpz strains. The exon splicing silencer (ESS2) acting on site A3 is located in a long irregular stem-loop structure (SLS3). Two SLS3 domains were protected by nuclear components under splicing condition assays. One contains the A4c branch points and a putative SR protein binding site. The other one is adjacent to ESS2. Unexpectedly, only the 3' A residue of ESS2 was protected. The suboptimal A3 polypyrimidine tract (PPT) is base paired. Using site-directed mutagenesis and transfection of a mini-HIV-1 cDNA into HeLa cells, we found that, in a wild-type PPT context, a mutation of the A3 downstream sequence that reinforced SLS2 stability decreased site A3 utilization. This was not the case with an optimized PPT. Hence, sequence and secondary structure of the PPT may cooperate in limiting site A3 utilization.

  2. A key region in the human parietal cortex for processing proprioceptive hand feedback during reaching movements.

    Science.gov (United States)

    Reichenbach, Alexandra; Thielscher, Axel; Peer, Angelika; Bülthoff, Heinrich H; Bresciani, Jean-Pierre

    2014-01-01

    Seemingly effortless, we adjust our movements to continuously changing environments. After initiation of a goal-directed movement, the motor command is under constant control of sensory feedback loops. The main sensory signals contributing to movement control are vision and proprioception. Recent neuroimaging studies have focused mainly on identifying the parts of the posterior parietal cortex (PPC) that contribute to visually guided movements. We used event-related TMS and force perturbations of the reaching hand to test whether the same sub-regions of the left PPC contribute to the processing of proprioceptive-only and of multi-sensory information about hand position when reaching for a visual target. TMS over two distinct stimulation sites elicited differential effects: TMS applied over the posterior part of the medial intraparietal sulcus (mIPS) compromised reaching accuracy when proprioception was the only sensory information available for correcting the reaching error. When visual feedback of the hand was available, TMS over the anterior intraparietal sulcus (aIPS) prolonged reaching time. Our results show for the first time the causal involvement of the posterior mIPS in processing proprioceptive feedback for online reaching control, and demonstrate that distinct cortical areas process proprioceptive-only and multi-sensory information for fast feedback corrections.

  3. Synthetic gene network restoring endogenous pituitary-thyroid feedback control in experimental Graves' disease.

    Science.gov (United States)

    Saxena, Pratik; Charpin-El Hamri, Ghislaine; Folcher, Marc; Zulewski, Henryk; Fussenegger, Martin

    2016-02-02

    Graves' disease is an autoimmune disorder that causes hyperthyroidism because of autoantibodies that bind to the thyroid-stimulating hormone receptor (TSHR) on the thyroid gland, triggering thyroid hormone release. The physiological control of thyroid hormone homeostasis by the feedback loops involving the hypothalamus-pituitary-thyroid axis is disrupted by these stimulating autoantibodies. To reset the endogenous thyrotrophic feedback control, we designed a synthetic mammalian gene circuit that maintains thyroid hormone homeostasis by monitoring thyroid hormone levels and coordinating the expression of a thyroid-stimulating hormone receptor antagonist (TSHAntag), which competitively inhibits the binding of thyroid-stimulating hormone or the human autoantibody to TSHR. This synthetic control device consists of a synthetic thyroid-sensing receptor (TSR), a yeast Gal4 protein/human thyroid receptor-α fusion, which reversibly triggers expression of the TSHAntag gene from TSR-dependent promoters. In hyperthyroid mice, this synthetic circuit sensed pathological thyroid hormone levels and restored the thyrotrophic feedback control of the hypothalamus-pituitary-thyroid axis to euthyroid hormone levels. Therapeutic plug and play gene circuits that restore physiological feedback control in metabolic disorders foster advanced gene- and cell-based therapies.

  4. Sensory feedback in interlimb coordination

    DEFF Research Database (Denmark)

    Gervasio, Sabata; Voigt, Michael; Kersting, Uwe G.

    2017-01-01

    direct communication between the two sides without the need for the involvement of higher centers. These may also exist in humans since sensory feedback elicited by tibial nerve stimulation on one side (ipsilateral) can affect the muscles activation in the opposite side (contralateral), provoking short......-latency crossed responses (SLCRs). The current study investigated whether contralateral afferent feedback contributes to the mechanism controlling the SLCR in human gastrocnemius muscle. Surface electromyogram, kinematic and kinetic data were recorded from subjects during normal walking and hybrid walking (with.......04). Moreover, estimated spindle secondary afferent and Golgi tendon organ activity were significantly different (P ≤ 0.01) when opposite responses have been observed, that is during normal (facilitation) and hybrid walking (inhibition) conditions. Contralateral sensory feedback, specifically spindle secondary...

  5. Feedback Scheduling of Priority-Driven Control Networks

    CERN Document Server

    Xia, Feng; Tian, Yu-Chu

    2008-01-01

    With traditional open-loop scheduling of network resources, the quality-of-control (QoC) of networked control systems (NCSs) may degrade significantly in the presence of limited bandwidth and variable workload. The goal of this work is to maximize the overall QoC of NCSs through dynamically allocating available network bandwidth. Based on codesign of control and scheduling, an integrated feedback scheduler is developed to enable flexible QoC management in dynamic environments. It encompasses a cascaded feedback scheduling module for sampling period adjustment and a direct feedback scheduling module for priority modification. The inherent characteristics of priority-driven control networks make it feasible to implement the proposed feedback scheduler in real-world systems. Extensive simulations show that the proposed approach leads to significant QoC improvement over the traditional open-loop scheduling scheme under both underloaded and overloaded network conditions.

  6. Design of Cognitive Interfaces for Personal Informatics Feedback

    DEFF Research Database (Denmark)

    Jensen, Camilla Birgitte Falk

    to personal informatics systems, and propose an approach to design cognitive interfaces, which considers both users’ motivations, needs, and goals. In this thesis I propose a new personal informatics framework, the feedback loop, which incorporates lean agile design principles. Including hierarchical modeling....... For instance, examining emotional responses to pleasant and unpleasant media content from brain activity, reveals the large amount of data and extensive analysis required to apply this to future personal informatics systems. In addition we analyse challenges related to temporal aspects of the feedback loop...

  7. BOUNDARY FEEDBACK STABILIZATION OF NONUNIFORM TIMOSHENKO BEAM WITH A TIPLOAD

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The boundary stabilization problem of a Timoshenko beam attached with a mass at one end is studied. First, with linear boundary force feedback and moment control simultaneously at the end attached with the load, the energy corresponding to the closed loop system is proven to be exponentially convergent to zero as time t -- oo. Then, some counterexamples are given to show that, in other cases, the corresponding closed loop system is, in general, not stable asymtotically, let alone exponentially.

  8. BOUNDARY FEEDBACK STABILIZATION OF NONUNIFORM TIMOSHENKO BEAM WITH A TIPLOAD

    Institute of Scientific and Technical Information of China (English)

    YANQINGXU; FENGDEXING

    2001-01-01

    The boundary stabilization problem of a Timoshenko beam attached with a mass at one end is studied. First, with linear boundary force feedback and moment control simultaneously at the end attached with the load, the energy corresponding to the closed loop system is proven to be exponentially convergent to zero as time t→∞. Then, some counterexamples are given to show that, in other cases, the corresponding closed loop system is, in general, not stable asymtotically, let alone exponentially.

  9. Feedback control of flow alignment in sheared liquid crystals.

    Science.gov (United States)

    Strehober, David A; Schöll, Eckehard; Klapp, Sabine H L

    2013-12-01

    Based on a continuum theory, we investigate the manipulation of the nonequilibrium behavior of a sheared liquid crystal via closed-loop feedback control. Our goal is to stabilize a specific dynamical state, that is, the stationary "flow alignment," under conditions where the uncontrolled system displays oscillatory director dynamics with in-plane symmetry. To this end we employ time-delayed feedback control (TDFC), where the equation of motion for the ith component q(i)(t) of the order parameter tensor is supplemented by a control term involving the difference q(i)(t)-q(i)(t-τ). In this diagonal scheme, τ is the delay time. We demonstrate that the TDFC method successfully stabilizes flow alignment for suitable values of the control strength K and τ; these values are determined by solving an exact eigenvalue equation. Moreover, our results show that only small values of K are needed when the system is sheared from an isotropic equilibrium state, contrary to the case where the equilibrium state is nematic.

  10. Reliability and Feedback of Multiple Hop Wireless Networks

    Institute of Scientific and Technical Information of China (English)

    N. Eva Wu; Sudha Thavamani; Xiaohua Li

    2007-01-01

    This paper analyzes fault-tolerance over the entire design life of a class of multiple-hop wireless networks, where cooperative transmission schemes are used. The networks are subject to both node failure and random channel fading. A node lifetime distribution is modeled with an increasing failure rate, where the node power consumption level enters the parameters of the distribution. A method for assessing both link and network reliabilities projected at the network's design life is developed. Link reliability is enhanced through use of redundant nodes. The number of redundant nodes is restricted by the cooperative transmission scheme used.The link reliability is then used to establish a re-transmission control policy that minimizes an expected cost involving power, bandwidth expenditures, and packet loss. The benefit and cost of feedback in network operations are examined. The results of a simulation study under specific node processing times are presented. The study quantifies the effect of loop closure frequency, acknowledgment deadline, and nodes' storage capacity on the performance of the network in terms of network lifetime, packet loss rate, and false alarm rate. The study concludes that in a network where energy is severely constrained, feedback must be applied judiciously.

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

    Science.gov (United States)

    Fei, Juntao; Lu, Cheng

    2017-03-06

    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 z-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.

  12. Effects of Differential Feedback on Students' Examination Performance

    Science.gov (United States)

    Lipnevich, Anastasiya A.; Smith, Jeffrey K.

    2009-01-01

    The effects of feedback on performance and factors associated with it were examined in a large introductory psychology course. The experiment involved college students (N = 464) working on an essay examination under 3 conditions: no feedback, detailed feedback that was perceived by participants to be provided by the course instructor, and detailed…

  13. Remote Robot Control With High Force-Feedback Gain

    Science.gov (United States)

    Kim, Won S.

    1993-01-01

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

  14. Estimation of Parametric Fault in Closed-loop Systems

    DEFF Research Database (Denmark)

    Niemann, Hans Henrik; Poulsen, Niels Kjølstad

    2015-01-01

    The aim of this paper is to present a method for estimation of parametric faults in closed-loop systems. The key technology applied in this paper is coprime factorization of both the dynamic system as well as the feedback controller. Using the Youla-Jabr-Bongiorno-Kucera (YJBK) parameterization...

  15. Pilot-in-the-Loop Analysis of Propulsive-Only Flight Control Systems

    Science.gov (United States)

    Chou, Hwei-Lan; Biezad, Daniel J.

    1996-01-01

    Longitudinal control system architectures are presented which directly couple flight stick motions to throttle commands for a multi-engine aircraft. This coupling enables positive attitude control with complete failure of the flight control system. The architectures chosen vary from simple feedback gains to classical lead-lag compensators with and without prefilters. Each architecture is reviewed for its appropriateness for piloted flight. The control systems are then analyzed with pilot-in-the-loop metrics related to bandwidth required for landing. Results indicate that current and proposed bandwidth requirements should be modified for throttles only flight control. Pilot ratings consistently showed better ratings than predicted by analysis. Recommendations are made for more robust design and implementation. The use of Quantitative Feedback Theory for compensator design is discussed. Although simple and effective augmented control can be achieved in a wide variety of failed configurations, a few configuration characteristics are dominant for pilot-in-the-loop control. These characteristics will be tested in a simulator study involving failed flight controls for a multi-engine aircraft.

  16. Testing loop quantum cosmology

    Science.gov (United States)

    Wilson-Ewing, Edward

    2017-03-01

    Loop quantum cosmology predicts that quantum gravity effects resolve the big-bang singularity and replace it by a cosmic bounce. Furthermore, loop quantum cosmology can also modify the form of primordial cosmological perturbations, for example by reducing power at large scales in inflationary models or by suppressing the tensor-to-scalar ratio in the matter bounce scenario; these two effects are potential observational tests for loop quantum cosmology. In this article, I review these predictions and others, and also briefly discuss three open problems in loop quantum cosmology: its relation to loop quantum gravity, the trans-Planckian problem, and a possible transition from a Lorentzian to a Euclidean space-time around the bounce point.

  17. Control of open-loop neutrally stable systems subject to actuator saturation and external disturbances

    NARCIS (Netherlands)

    Wang, Xu; Saberi, Ali; Grip, H°avard Fjær; Stoorvogel, Antonie Arij

    2013-01-01

    In this paper, we study the disturbance response of open-loop neutrally stable linear systems with saturating linear feedback controller. It is shown that the closed-loop states remain bounded if the disturbances con- sists of those signals that do not have large sustained frequency components

  18. Modeling T cell antigen discrimination based on feedback control of digital ERK responses.

    Directory of Open Access Journals (Sweden)

    2005-11-01

    Full Text Available T-lymphocyte activation displays a remarkable combination of speed, sensitivity, and discrimination in response to peptide-major histocompatibility complex (pMHC ligand engagement of clonally distributed antigen receptors (T cell receptors or TCRs. Even a few foreign pMHCs on the surface of an antigen-presenting cell trigger effective signaling within seconds, whereas 1 x 10(5-1 x 10(6 self-pMHC ligands that may differ from the foreign stimulus by only a single amino acid fail to elicit this response. No existing model accounts for this nearly absolute distinction between closely related TCR ligands while also preserving the other canonical features of T-cell responses. Here we document the unexpected highly amplified and digital nature of extracellular signal-regulated kinase (ERK activation in T cells. Based on this observation and evidence that competing positive- and negative-feedback loops contribute to TCR ligand discrimination, we constructed a new mathematical model of proximal TCR-dependent signaling. The model made clear that competition between a digital positive feedback based on ERK activity and an analog negative feedback involving SH2 domain-containing tyrosine phosphatase (SHP-1 was critical for defining a sharp ligand-discrimination threshold while preserving a rapid and sensitive response. Several nontrivial predictions of this model, including the notion that this threshold is highly sensitive to small changes in SHP-1 expression levels during cellular differentiation, were confirmed by experiment. These results combining computation and experiment reveal that ligand discrimination by T cells is controlled by the dynamics of competing feedback loops that regulate a high-gain digital amplifier, which is itself modulated during differentiation by alterations in the intracellular concentrations of key enzymes. The organization of the signaling network that we model here may be a prototypic solution to the problem of achieving

  19. Effective Instructor Feedback: Perceptions of Online Graduate Students

    Directory of Open Access Journals (Sweden)

    Beverley Getzlaf

    2009-07-01

    Full Text Available This descriptive study explored online graduate students' perceptions of effective instructor feedback. The objectives of the study were to determine the students’ perceptions of the content of effective instructor feedback (“what should be included in effective feedback?” and the process of effective instructor feedback (“how should effective feedback be provided?”. The participants were students completing health-related graduate courses offered exclusively online. Data were collected via a survey that included open ended questions inviting participants to share their perspectives regarding effective online instructor feedback. Thematic analysis revealed five major themes: student involvement/individualization, gentle guidance, being positively constructive, timeliness and future orientation. We conclude that effective instructor feedback has positive outcomes for the students. Future studies are warranted to investigate strategies to make feedback a mutual process between instructor and student that supports an effective feedback cycle.

  20. Audio versus Written Feedback: Exploring Learners' Preference and the Impact of Feedback Format on Students' Academic Performance

    Science.gov (United States)

    Morris, Cecile; Chikwa, Gladson

    2016-01-01

    Very little is known about the impact of the different types of feedback on students' academic performance. This article explores students' preference in the use of audio and written feedback and how each type of feedback received by students impacts their academic performance in subsequent assignments. The study involved 68 students who were…

  1. Feedback Augmented Sub-Ranging (FASR) Quantizer

    Science.gov (United States)

    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. Uranyl Nitrate Flow Loop

    Energy Technology Data Exchange (ETDEWEB)

    Ladd-Lively, Jennifer L [ORNL

    2008-10-01

    The objectives of the work discussed in this report were to: (1) develop a flow loop that would simulate the purified uranium-bearing aqueous stream exiting the solvent extraction process in a natural uranium conversion plant (NUCP); (2) develop a test plan that would simulate normal operation and disturbances that could be anticipated in an NUCP; (3) use the flow loop to test commercially available flowmeters for use as safeguards monitors; and (4) recommend a flowmeter for production-scale testing at an NUCP. There has been interest in safeguarding conversion plants because the intermediate products [uranium dioxide (UO{sub 2}), uranium tetrafluoride (UF{sub 4}), and uranium hexafluoride (UF{sub 6})] are all suitable uranium feedstocks for producing special nuclear materials. Furthermore, if safeguards are not applied virtually any nuclear weapons program can obtain these feedstocks without detection by the International Atomic Energy Agency (IAEA). Historically, IAEA had not implemented safeguards until the purified UF{sub 6} product was declared as feedstock for enrichment plants. H. A. Elayat et al. provide a basic definition of a safeguards system: 'The function of a safeguards system on a chemical conversion plant is in general terms to verify that no useful nuclear material is being diverted to use in a nuclear weapons program'. The IAEA now considers all highly purified uranium compounds as candidates for safeguarding. DOE is currently interested in 'developing instruments, tools, strategies, and methods that could be of use to the IAEA in the application of safeguards' for materials found in the front end of the nuclear fuel cycle-prior to the production of the uranium hexafluoride or oxides that have been the traditional starting point for IAEA safeguards. Several national laboratories, including Oak Ridge, Los Alamos, Lawrence Livermore, and Brookhaven, have been involved in developing tools or techniques for safeguarding conversion

  3. Rateless feedback codes

    DEFF Research Database (Denmark)

    Sørensen, Jesper Hemming; Koike-Akino, Toshiaki; Orlik, Philip

    2012-01-01

    This paper proposes a concept called rateless feedback coding. We redesign the existing LT and Raptor codes, by introducing new degree distributions for the case when a few feedback opportunities are available. We show that incorporating feedback to LT codes can significantly decrease both...... the coding overhead and the encoding/decoding complexity. Moreover, we show that, at the price of a slight increase in the coding overhead, linear complexity is achieved with Raptor feedback coding....

  4. Feedback on Involvement of Medical Social Workers from Hospitalized Psychiatric Patients%住院精神病患者对医务社工介入的反馈及需求调查

    Institute of Scientific and Technical Information of China (English)

    朱转娥; 陈瑞莲; 郑丽松; 黄双火

    2014-01-01

    目的:了解住院精神病患者对医务社工介入医院服务的反馈和需求情况,为医务社工引入精神病医院服务提供依据。方法自行设计问卷,随机抽取2012年6月-2013年5月在我院住院的90例精神病患者进行调查。结果住院精神病患者对已开展的社工服务总体满意度达73%,52%的患者表示遇到困惑时愿意寻求社工的帮助;在患者对医务社工服务内容需求的调查中,改善住院环境、争取情感支持、开展文娱体育活动的需求排在前3项;对社工服务方式的需求中,小组方法分值最高,为(5.19±1.12)分;在对医务社工服务频次需求调查中,选择每周开展3~4次和5~6次的频数最多(2项之和超过了50%)。结论精神病患者的康复需要多元的服务方式,医务社工引入精神病患者的康复服务中已被患者所接受,应针对患者所需服务内容和频次要求开展活动,以期更好地帮助患者配合完成治疗护理计划。%Objective To investigate feedback on involvement of medical social workers from hospitalized psychiatric patients and its demand for the involvement. Methods A self-designed questionnaire was applied to survey ninety patients from June 2012 to May 2013. Results The overall satisfaction rate with the intervention of medical social workers among patients reached 73% and 52% of the patients would turned to medical social workers. The improvement of hospital environment, emotional support and the development of cultural and sports activities topped the service list and most patients preferred medical social workers could provide their service as groups (an average score of 5.19 ±1.12) and with frequency of 3~4 times or 5~6 times per week. Conclusion Diversified services are needed among patients undergoing mental rehabilitation and rehabilitation service provided by medical social workers can effectively enriches psychiatric rehabilitation means.

  5. Preventing Feedback Fizzle

    Science.gov (United States)

    Brookhart, Susan M.

    2012-01-01

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

  6. Developing Sustainable Feedback Practices

    Science.gov (United States)

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

    2011-01-01

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

  7. Numerical multi-loop integrals and applications

    CERN Document Server

    Freitas, Ayres

    2016-01-01

    Higher-order radiative corrections play an important role in precision studies of the electroweak and Higgs sector, as well as for the detailed understanding of large backgrounds to new physics searches. For corrections beyond the one-loop level and involving many independent mass and momentum scales, it is in general not possible to find analytic results, so that one needs to resort to numerical methods instead. This article presents an overview over a variety of numerical loop integration techniques, highlighting their range of applicability, suitability for automatization, and numerical precision and stability. In a second part of this article, the application of numerical loop integration methods in the area of electroweak precision tests is illustrated. Numerical methods were essential for obtaining full two-loop predictions for the most important precision observables within the Standard Model. The theoretical foundations for these corrections will be described in some detail, including aspects of the r...

  8. Capillary fluid loop developments in Astrium

    Energy Technology Data Exchange (ETDEWEB)

    Figus, C.; Ounougha, L.; Bonzom, P. [Astrium SAS, Toulouse (France); Supper, W. [ESA/ESTEC, Noordwijk (Netherlands); Puillet, C. [CNES, Toulouse (France)

    2003-06-01

    Over the past decade, Astrium has been involved in the development of capillary pumped fluid loops. In the frame of the French technological demonstrator spacecraft called STENTOR, Astrium has gained experience on capillary fluid loop design and manufacturing. After the STENTOR cylindrical evaporator type was successfully tested and qualified, Astrium has developed miniaturised fluid loops for thermal dissipation of electronic devices. For such applications, the use of a flat shape evaporator is very promising, limiting the volume and the mass of the thermal hardware. Both technologies have been submitted to a comprehensive one-g test program and will be flight-tested in the near future. Through a comparative of the reached performances, some main advantages and drawbacks of each design are listed and a definition of what should be the next generation of Astrium fluid loops is given. (author)

  9. Coherent feedback control of a single qubit in diamond

    Science.gov (United States)

    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

  10. Decouple Design of Current Loop Parameters for PWM Converters Based on Multi-resonant Controllers and Capacitor Current Feedback Active Damping%基于多谐振控制器和电容电流反馈有源阻尼的PWM变换器电流环参数解耦设计

    Institute of Scientific and Technical Information of China (English)

    吕永灿; 林桦; 杨化承; 罗咏

    2013-01-01

    To track the given sinusoidal current under stationary frame and suppress the effect of the low harmonics in the grid, a multi-resonant proportional resonant (PR) controller was adopted for pulse width modulation (PWM) converter with LCL filter based on capacitor current feedback active damping. Because the system is of high order, many parameters and complicated, the effects of the control parameters on the current-loop performance were investigated with frequency theory, i.e. the stability, steady-state error and phase margin. Based on this, a decoupling-simplified analytic design method was proposed. According to the requests of the stability, steady-state error and phase margin, the capacitor-current-feedback coefficient, the relative resonant gain factor and the proportional factor could be designed separately. The proposed method uses the analytic method and simplifies the couple of the parameters without trial-and-error procedure. Finally, a battery storage power conversion system (PCS) was built. Experiment results verify the effectiveness of the proposed design method.%基于电容电流反馈有源阻尼的LCL型脉宽调制(pulse width modulation,PWM)变换器并网电流控制中,通常采用多谐振比例谐振(proportional resonant,PR)控制器来实现静止αβ坐标系下正弦电流给定的无静差跟踪和抑制电网电压特定次谐波影响。针对电流环控制器复杂、参数多、设计难的问题,采用频率域理论分析电容电流反馈系数和准PR控制器各参数对电流环性能的影响。在此基础上,提出一种电流环控制器参数解耦简化解析设计方法,根据稳定性、稳态误差和相位裕度要求,分别设计电容电流反馈系数及PR控制器相对谐振增益系数和比例系数。该设计方法简化了控制器参数之间的耦合关系,且多采用解析计算,不需要反复试凑。实验结果验证了所提出的参数解耦解析设计方法是可行和有效的。

  11. Closing the Loop: Integrating Body, Muscle and Environment with Locomotion Central Pattern Generators

    Science.gov (United States)

    2013-06-30

    simple closed-loop model in which a CPG produces a pattern of muscle activation which is modified by sensory feedback related to body curvature . (a...by a complex interaction of the neural circuits in the spinal cord and brain, the body, the muscles, sensory organs and the environment. With- out...feedback related to body curvature . 2.1 Computation of optimal feedback for the control of locomotion We have a developed a general method of computing

  12. Quantum feedback channels

    CERN Document Server

    Bowen, G

    2002-01-01

    In classical information theory the capacity of a noisy communication channel cannot be increased by the use of feedback. In quantum information theory the no-cloning theorem means that noiseless copying and feedback of quantum information cannot be achieved. In this paper, quantum feedback is defined as the unlimited use of a noiseless quantum channel from receiver to sender. Given such quantum feedback, it is shown to provide no increase in the entanglement-assisted capacities of a noisy quantum channel, in direct analogy to the classical case. It is also shown that in various cases of non-assisted capacities, feedback can increase the capacity of many quantum channels.

  13. Natively unstructured loops differ from other loops.

    Directory of Open Access Journals (Sweden)

    Avner Schlessinger

    2007-07-01

    Full Text Available Natively unstructured or disordered protein regions may increase the functional complexity of an organism; they are particularly abundant in eukaryotes and often evade structure determination. Many computational methods predict unstructured regions by training on outliers in otherwise well-ordered structures. Here, we introduce an approach that uses a neural network in a very different and novel way. We hypothesize that very long contiguous segments with nonregular secondary structure (NORS regions differ significantly from regular, well-structured loops, and that a method detecting such features could predict natively unstructured regions. Training our new method, NORSnet, on predicted information rather than on experimental data yielded three major advantages: it removed the overlap between testing and training, it systematically covered entire proteomes, and it explicitly focused on one particular aspect of unstructured regions with a simple structural interpretation, namely that they are loops. Our hypothesis was correct: well-structured and unstructured loops differ so substantially that NORSnet succeeded in their distinction. Benchmarks on previously used and new experimental data of unstructured regions revealed that NORSnet performed very well. Although it was not the best single prediction method, NORSnet was sufficiently accurate to flag unstructured regions in proteins that were previously not annotated. In one application, NORSnet revealed previously undetected unstructured regions in putative targets for structural genomics and may thereby contribute to increasing structural coverage of large eukaryotic families. NORSnet found unstructured regions more often in domain boundaries than expected at random. In another application, we estimated that 50%-70% of all worm proteins observed to have more than seven protein-protein interaction partners have unstructured regions. The comparative analysis between NORSnet and DISOPRED2 suggested

  14. Natively unstructured loops differ from other loops.

    Science.gov (United States)

    Schlessinger, Avner; Liu, Jinfeng; Rost, Burkhard

    2007-07-01

    Natively unstructured or disordered protein regions may increase the functional complexity of an organism; they are particularly abundant in eukaryotes and often evade structure determination. Many computational methods predict unstructured regions by training on outliers in otherwise well-ordered structures. Here, we introduce an approach that uses a neural network in a very different and novel way. We hypothesize that very long contiguous segments with nonregular secondary structure (NORS regions) differ significantly from regular, well-structured loops, and that a method detecting such features could predict natively unstructured regions. Training our new method, NORSnet, on predicted information rather than on experimental data yielded three major advantages: it removed the overlap between testing and training, it systematically covered entire proteomes, and it explicitly focused on one particular aspect of unstructured regions with a simple structural interpretation, namely that they are loops. Our hypothesis was correct: well-structured and unstructured loops differ so substantially that NORSnet succeeded in their distinction. Benchmarks on previously used and new experimental data of unstructured regions revealed that NORSnet performed very well. Although it was not the best single prediction method, NORSnet was sufficiently accurate to flag unstructured regions in proteins that were previously not annotated. In one application, NORSnet revealed previously undetected unstructured regions in putative targets for structural genomics and may thereby contribute to increasing structural coverage of large eukaryotic families. NORSnet found unstructured regions more often in domain boundaries than expected at random. In another application, we estimated that 50%-70% of all worm proteins observed to have more than seven protein-protein interaction partners have unstructured regions. The comparative analysis between NORSnet and DISOPRED2 suggested that long

  15. Introduction to Loop Heat Pipes

    Science.gov (United States)

    Ku, Jentung

    2015-01-01

    This is the presentation file for the short course Introduction to Loop Heat Pipes, to be conducted at the 2015 Thermal Fluids and Analysis Workshop, August 3-7, 2015, Silver Spring, Maryland. This course will discuss operating principles and performance characteristics of a loop heat pipe. Topics include: 1) pressure profiles in the loop; 2) loop operating temperature; 3) operating temperature control; 4) loop startup; 4) loop shutdown; 5) loop transient behaviors; 6) sizing of loop components and determination of fluid inventory; 7) analytical modeling; 8) examples of flight applications; and 9) recent LHP developments.

  16. The autoregulatory loop: A common mechanism of regulation of key sex determining genes in insects

    Indian Academy of Sciences (India)

    Suresh Kumar Kumar; Gajula Gopinath; Nagraj Sambrani; Kallare P Arunkumar

    2016-06-01

    Sex determination in most insects is structured as a gene cascade, wherein a primary signal is passed through a series of sex-determining genes, culminating in a downstream double-switch known as doublesex that decides the sexual fate of the embryo. From the literature available on sex determination cascades, it becomes apparent that sex determination mechanisms have evolved rapidly. The primary signal that provides the cue to determine the sex of the embryo varies remarkably, not only among taxa, but also within taxa. Furthermore, the upstream key gene in the cascade also varies between species and even among closely related species. The order Insecta alone provides examples of astoundingly complex diversity of upstream key genes in sex determination mechanisms. Besides, unlike key upstream genes, the downstream double-switch gene is alternatively spliced to form functional sex-specific isoforms. This sex-specific splicing is conserved across insect taxa. The genes involved in the sex determination cascade such as Sex-lethal (Sxl) in Drosophila melanogaster, transformer (tra) in many other dipterans, coleopterans and hymenopterans, Feminizer (fem) in Apis mellifera, and IGF-II mRNA-binding protein (Bmimp) in Bombyx mori are reported to be regulated by an autoregulatory positive feedback loop. In this review, by taking examples from various insects, we propose the hypothesis that autoregulatory loop mechanisms of sex determination might be a general strategy. We also discuss the possible reasons for the evolution of autoregulatory loops in sex determination cascades and their impact on binary developmental choices.

  17. Focal Dystonia and the Sensory-Motor Integrative Loop for Enacting (SMILE

    Directory of Open Access Journals (Sweden)

    David ePerruchoud

    2014-06-01

    Full Text Available Performing accurate movements requires preparation, execution, and monitoring mechanisms. The first two are coded by the motor system, and the latter by the sensory system. To provide an adaptive neural basis to overt behaviors, motor and sensory information has to be properly integrated in a reciprocal feedback loop. Abnormalities in this sensory-motor loop are involved in movement disorders such as focal dystonia, a hyperkinetic alteration affecting only a specific body part and characterized by sensory and motor deficits in the absence of basic motor impairments. Despite the fundamental impact of sensory-motor integration mechanisms on daily life, the general principles of healthy and pathological anatomic-functional organization of sensory-motor integration remain to be clarified. Based on the available data from experimental psychology, neurophysiology, and neuroimaging, we propose a bio-computational model of sensory-motor integration: the Sensory-Motor Integrative Loop for Enacting (SMILE. Aiming at direct therapeutic implementations and with the final target of implementing novel intervention protocols for motor rehabilitation, our main goal is to provide the information necessary for further validating the SMILE model. By translating neuroscientific hypotheses into empirical investigations and clinically relevant questions, the prediction based on the SMILE model can be further extended to other pathological conditions characterized by impaired sensory-motor integration.

  18. The autoregulatory loop: A common mechanism of regulation of key sex determining genes in insects.

    Science.gov (United States)

    Sawanth, Suresh Kumar; Gopinath, Gajula; Sambrani, Nagraj; Arunkumar, Kallare P

    2016-06-01

    Sex determination in most insects is structured as a gene cascade, wherein a primary signal is passed through a series of sex-determining genes, culminating in a downstream double-switch known as doublesex that decides the sexual fate of the embryo. From the literature available on sex determination cascades, it becomes apparent that sex determination mechanisms have evolved rapidly. The primary signal that provides the cue to determine the sex of the embryo varies remarkably, not only among taxa, but also within taxa. Furthermore, the upstream key gene in the cascade also varies between species and even among closely related species. The order Insecta alone provides examples of astoundingly complex diversity of upstream key genes in sex determination mechanisms. Besides, unlike key upstream genes, the downstream double-switch gene is alternatively spliced to form functional sex-specific isoforms. This sex-specific splicing is conserved across insect taxa. The genes involved in the sex determination cascade such as Sex-lethal (Sxl) in Drosophila melanogaster, transformer (tra) in many other dipterans, coleopterans and hymenopterans, Feminizer (fem) in Apis mellifera, and IGF-II mRNA-binding protein (Bmimp) in Bombyx mori are reported to be regulated by an autoregulatory positive feedback loop. In this review, by taking examples from various insects, we propose the hypothesis that autoregulatory loop mechanisms of sex determination might be a general strategy. We also discuss the possible reasons for the evolution of autoregulatory loops in sex determination cascades and their impact on binary developmental choices.

  19. Control-structure interaction in precision pointing servo loops

    Science.gov (United States)

    Spanos, John T.

    1989-01-01

    The control-structure interaction problem is addressed via stability analysis of a generic linear servo loop model. With the plant described by the rigid body mode and a single elastic mode, structural flexibility is categorized into one of three types: (1) appendage, (2) in-the-loop minimum phase, and (3) in-the-loop nonminimum phase. Closing the loop with proportional-derivative (PD) control action and introducing sensor roll-off dynamics in the feedback path, stability conditions are obtained. Trade studies are conducted with modal frequency, modal participation, modal damping, loop bandwidth, and sensor bandwidth treated as free parameters. Results indicate that appendage modes are most likely to produce instability if they are near the sensor rolloff, whereas in-the-loop modes are most dangerous near the loop bandwidth. The main goal of this paper is to provide a fundamental understanding of the control-structure interaction problem so that it may benefit the design of complex spacecraft and pointing system servo loops. In this framework, the JPL Pathfinder gimbal pointer is considered as an example.

  20. Spatiotemporal adaptation through corticothalamic loops A hypothesis

    CERN Document Server

    Hillenbrand, U; Hillenbrand, Ulrich

    2000-01-01

    The thalamus is the major gate to the cortex and its control over cortical responses is well established. Cortical feedback to the thalamus is, in turn, the anatomically dominant input to relay cells, yet its influence on thalamic processing has been difficult to interpret. For an understanding of complex sensory processing, detailed concepts of the corticothalamic interplay need yet to be established. Drawing on various physiological and anatomical data, we elaborate the novel hypothesis that the visual cortex controls the spatiotemporal structure of cortical receptive fields via feedback to the lateral geniculate nucleus. Furthermore, we present and analyze a model of corticogeniculate loops that implements this control, and exhibit its ability of object segmentation by statistical motion analysis in the visual field.

  1. Situated Formative Feedback

    DEFF Research Database (Denmark)

    Lukassen, Niels Bech; Wahl, Christian; Sorensen, Elsebeth Korsgaard

    2016-01-01

    This study addresses the conceptual challenge of providing students with good quality feedback to enhance student learning in an online community of practice (COP). The aim of the study is to identify feedback mechanisms in a virtual learning environment (VLE) and to create a full formative...... feedback episode (FFE) through an online dialogue. The paper argues that dialogue is crucial for student learning and that feedback is not only something the teacher gives to the student. Viewing good quality feedback as social, situated, formative, emphasis is put on the establishment of dialogue. We...... refer to this type of feedback as, Situated Formative Feedback (SFF). As a basis for exploring, identifying and discussing relevant aspects of SFF the paper analyses qualitative data from a Moodle dialogue. Data are embedded in the qualitative analytic program Nvivo and are analysed with a system...

  2. Feedback and Incentives

    DEFF Research Database (Denmark)

    Eriksson, Tor Viking; Poulsen, Anders; Villeval, Marie Claire

    2009-01-01

    This paper experimentally investigates the impact of different pay schemes and relative performance feedback policies on employee effort. We explore three feedback rules: no feedback on relative performance, feedback given halfway through the production period, and continuously updated feedback. We...... use two pay schemes, a piece rate and a tournament. We find that overall feedback does not improve performance. In contrast to the piece-rate pay scheme there is some evidence of positive peer effects in tournaments since the underdogs almost never quit the competition even when lagging significantly...... behind, and front runners do not slack off. But in both pay schemes relative performance feedback reduces the quality of the low performers' work; we refer to this as a "negative quality peer effect"....

  3. Enhanced Negative Feedback Responses in Remitted Depression

    Science.gov (United States)

    Santesso, Diane L.; Steele, Katherine T.; Bogdan, Ryan; Holmes, Avram J.; Deveney, Christen M.; Meites, Tiffany M.; Pizzagalli, Diego A.

    2011-01-01

    Major depressive disorder (MDD) is characterized by hypersensitivity to negative feedback that might involve frontocingulate dysfunction. MDD subjects exhibit enhanced electrophysiological responses to negative internal (errors) and external (feedback) cues. Whether this dysfunction extends to remitted depressed (RD) subjects with a history of MDD is currently unknown. To address this issue, we examined the feedback-related negativity (FRN) in RD and control subjects using a probabilistic punishment learning task. Despite equivalent behavioral performance, RD subjects showed larger FRNs to negative feedback relative to controls; group differences remained after accounting for residual anxiety and depressive symptoms. The present findings suggest that abnormal responses to negative feedback extend to samples at increased risk for depressive episodes in the absence of current symptoms. PMID:18580576

  4. Effective Feedback Procedures in Games for Health.

    Science.gov (United States)

    Baranowski, Moderator Tom; Bower, Participants Kelly; Krebs, Paul; Lamoth, Claudine J; Lyons, Elizabeth J

    2013-12-01

    Feedback on game performance can be provided in many ways (e.g., cumulative points on game achievements, points on selected aspects of game play, biofeedback, brief statements offered during gameplay on choices made, verbal feedback at end of gameplay on overall performance, etc.). Feedback could be used motivationally to maintain player interest and involvement, informationally to guide the player in more effective choices, to build player confidence, and for a variety of other purposes. Although diverse feedback types and purposes are possible, some are more likely to be useful and effective. We have contacted several accomplished game designers and game researchers to obtain their insights into issues in feedback in Games for Health Journal.

  5. Closed-loop neuromorphic benchmarks

    CSIR Research Space (South Africa)

    Stewart

    2015-11-01

    Full Text Available Benchmarks   Terrence C. Stewart 1* , Travis DeWolf 1 , Ashley Kleinhans 2 , Chris Eliasmith 1   1 University of Waterloo, Canada, 2 Council for Scientific and Industrial Research, South Africa   Submitted to Journal:   Frontiers in Neuroscience   Specialty... the study was exempt from ethical approval procedures.) Did the study presented in the manuscript involve human or animal subjects: No I v i w 1Closed-loop Neuromorphic Benchmarks Terrence C. Stewart 1,∗, Travis DeWolf 1, Ashley Kleinhans 2 and Chris...

  6. A loop quantum multiverse?

    CERN Document Server

    Bojowald, Martin

    2013-01-01

    Inhomogeneous space-times in loop quantum cosmology have come under better control with recent advances in effective methods. Even highly inhomogeneous situations, for which multiverse scenarios provide extreme examples, can now be considered at least qualitatively.

  7. Blind loop syndrome

    Science.gov (United States)

    ... part of the stomach) and operations for extreme obesity As a complication of inflammatory bowel disease Diseases such as diabetes or scleroderma may slow down movement in a segment of the intestine, leading to blind loop syndrome.

  8. Diffusion of Wilson Loops

    CERN Document Server

    Brzoska, A M; Negele, J W; Thies, M

    2004-01-01

    A phenomenological analysis of the distribution of Wilson loops in SU(2) Yang-Mills theory is presented in which Wilson loop distributions are described as the result of a diffusion process on the group manifold. It is shown that, in the absence of forces, diffusion implies Casimir scaling and, conversely, exact Casimir scaling implies free diffusion. Screening processes occur if diffusion takes place in a potential. The crucial distinction between screening of fundamental and adjoint loops is formulated as a symmetry property related to the center symmetry of the underlying gauge theory. The results are expressed in terms of an effective Wilson loop action and compared with various limits of SU(2) Yang-Mills theory.

  9. From Loops to Surfaces

    CERN Document Server

    Neuberger, H

    2010-01-01

    The generating function for all antisymmetric characters of a Wilson loop matrix in SU(N) Yang Mills theory is the partition function of a fermion living on the curve describing the loop. This generalizes to fermion subsystems living on higher dimensional submanifolds, for example, surfaces. This write-up also contains some extra background, in response to some questions raised during the oral presentation.

  10. Observer-based H-infinity output feedback control with feedback gain and observer gain variations for Delta operator system

    Institute of Scientific and Technical Information of China (English)

    Ruiquan LIN; Fuwen YANG; Renchong PENG

    2009-01-01

    Considering that the controller feedback gain and the observer gain are of additive norm-bounded variations, a design method of observer-based H-infinity output feedback controller for uncertain Delta operator systems is proposed in this paper. A sufficient condition of such controllers is presented in linear matrix inequality (LMI) forms. A numerical example is then given to illustrate the effectiveness of this method, that is, the obtained controller guarantees the closed-loop system asymptotically stable and the expected H-infinity performance even if the controller feedback gain and the observer gain are varied.

  11. Discussing Feedback System Thinking in Relation to a Balanced Scorecard, Inspired by an Actual Case

    DEFF Research Database (Denmark)

    Nielsen, Steen; Nielsen, Erland Hejn

    may the feedback systems thinking and causal loop reasoning be conducted within BSC. In contrast to previous literature on BSC this paper focuses on a System Dynamics Modeling approach to transform a static BSC into a dynamic and analytical closed loop management model by incorporating both time-lags...

  12. Multiple model-informed open-loop control of uncertain intracellular signaling dynamics.

    Directory of Open Access Journals (Sweden)

    Jeffrey P Perley

    2014-04-01

    Full Text Available Computational approaches to tune the activation of intracellular signal transduction pathways both predictably and selectively will enable researchers to explore and interrogate cell biology with unprecedented precision. Techniques to control complex nonlinear systems typically involve the application of control theory to a descriptive mathematical model. For cellular processes, however, measurement assays tend to be too time consuming for real-time feedback control and models offer rough approximations of the biological reality, thus limiting their utility when considered in isolation. We overcome these problems by combining nonlinear model predictive control with a novel adaptive weighting algorithm that blends predictions from multiple models to derive a compromise open-loop control sequence. The proposed strategy uses weight maps to inform the controller of the tendency for models to differ in their ability to accurately reproduce the system dynamics under different experimental perturbations (i.e. control inputs. These maps, which characterize the changing model likelihoods over the admissible control input space, are constructed using preexisting experimental data and used to produce a model-based open-loop control framework. In effect, the proposed method designs a sequence of control inputs that force the signaling dynamics along a predefined temporal response without measurement feedback while mitigating the effects of model uncertainty. We demonstrate this technique on the well-known Erk/MAPK signaling pathway in T cells. In silico assessment demonstrates that this approach successfully reduces target tracking error by 52% or better when compared with single model-based controllers and non-adaptive multiple model-based controllers. In vitro implementation of the proposed approach in Jurkat cells confirms a 63% reduction in tracking error when compared with the best of the single-model controllers. This study provides an experimentally

  13. Multiple model-informed open-loop control of uncertain intracellular signaling dynamics.

    Science.gov (United States)

    Perley, Jeffrey P; Mikolajczak, Judith; Harrison, Marietta L; Buzzard, Gregery T; Rundell, Ann E

    2014-04-01

    Computational approaches to tune the activation of intracellular signal transduction pathways both predictably and selectively will enable researchers to explore and interrogate cell biology with unprecedented precision. Techniques to control complex nonlinear systems typically involve the application of control theory to a descriptive mathematical model. For cellular processes, however, measurement assays tend to be too time consuming for real-time feedback control and models offer rough approximations of the biological reality, thus limiting their utility when considered in isolation. We overcome these problems by combining nonlinear model predictive control with a novel adaptive weighting algorithm that blends predictions from multiple models to derive a compromise open-loop control sequence. The proposed strategy uses weight maps to inform the controller of the tendency for models to differ in their ability to accurately reproduce the system dynamics under different experimental perturbations (i.e. control inputs). These maps, which characterize the changing model likelihoods over the admissible control input space, are constructed using preexisting experimental data and used to produce a model-based open-loop control framework. In effect, the proposed method designs a sequence of control inputs that force the signaling dynamics along a predefined temporal response without measurement feedback while mitigating the effects of model uncertainty. We demonstrate this technique on the well-known Erk/MAPK signaling pathway in T cells. In silico assessment demonstrates that this approach successfully reduces target tracking error by 52% or better when compared with single model-based controllers and non-adaptive multiple model-based controllers. In vitro implementation of the proposed approach in Jurkat cells confirms a 63% reduction in tracking error when compared with the best of the single-model controllers. This study provides an experimentally

  14. A review of control strategies in closed-loop neuroprosthetic systems

    Directory of Open Access Journals (Sweden)

    James Wright

    2016-07-01

    Full Text Available 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.

  15. Expected optimal feedback with Time-Varying Parameters

    NARCIS (Netherlands)

    Tucci, M.P.; Kendrick, D.A.; Amman, H.M.

    2011-01-01

    In this paper we derive the closed loop form of the Expected Optimal Feedback rule, sometimes called passive learning stochastic control, with time varying parameters. As such this paper extends the work of Kendrick (1981,2002, Chapter 6) where parameters are assumed to vary randomly around a known

  16. Synthesis of human-nature feedbacks

    Directory of Open Access Journals (Sweden)

    Vanessa Hull

    2015-09-01

    Full Text Available In today's globalized world, humans and nature are inextricably linked. The coupled human and natural systems (CHANS framework provides a lens with which to understand such complex interactions. One of the central components of the CHANS framework involves examining feedbacks among human and natural systems, which form when effects from one system on another system feed back to affect the first system. Despite developments in understanding feedbacks in single disciplines, interdisciplinary research on CHANS feedbacks to date is scant and often site-specific, a shortcoming that prevents complex coupled systems from being fully understood. The special feature "Exploring Feedbacks in Coupled Human and Natural Systems (CHANS" makes strides to fill this critical gap. Here, as an introduction to the special feature, we provide an overview of CHANS feedbacks. In addition, we synthesize key CHANS feedbacks that emerged in the papers of this special feature across agricultural, forest, and urban landscapes. We also examine emerging themes explored across the papers, including multilevel feedbacks, time lags, and surprises as a result of feedbacks. We conclude with recommendations for future research that can build upon the foundation provided in the special feature.

  17. Arbitrarily low sensitivity (ALS) in linear distributed systems using pointwise linear feedback

    NARCIS (Netherlands)

    Kelemen, Matei; Kennai, Yakar; Horowitz, Isaac

    1990-01-01

    The sensitivity problem is defined for feedback systems with plants described by linear partial differential operators having constant coefficients, in a bounded one-dimensional domain. there are also finitely many observation points and finitely many lumped feedback loops, and a finite number of di

  18. Arbitrarily low sensitivity (ALS) in linear distributed systems using pointwise linear feedback

    NARCIS (Netherlands)

    Kelemen, Matei; Kennai, Yakar; Horowitz, Isaac

    1990-01-01

    The sensitivity problem is defined for feedback systems with plants described by linear partial differential operators having constant coefficients, in a bounded one-dimensional domain. there are also finitely many observation points and finitely many lumped feedback loops, and a finite number of

  19. A Case Study of Representing Signal Transduction in Liver Cells as a Feedback Control Problem

    Science.gov (United States)

    Singh, Abhay; Jayaraman, Arul; Hahn, Juergen

    2007-01-01

    Cell signaling pathways often contain feedback loops where proteins are produced that regulate signaling. While feedback regulatory mechanisms are commonly found in signaling pathways, there is no example available in the literature that is simple enough to be presented in an undergraduate control class. This paper presents a simulation study of…

  20. The Quadratic Matrix Inequality in Singular H∞ Control with State Feedback

    NARCIS (Netherlands)

    Stoorvogel, A.A.; Trentelman, H.L.

    1990-01-01

    In this paper the standard H∞ control problem using state feedback is considered. Given a linear, time-invariant, finite-dimensional system, this problem consists of finding a static state feedback such that the resulting closed-loop transfer matrix has H∞ norm smaller than some a priori given upper

  1. A novel approach to negative feedback in RX front-ends

    DEFF Research Database (Denmark)

    Vandi, Luca; Andreani, Pietro; Tired, Tobias

    2006-01-01

    A new approach to negative feedback is proposed and applied to active mixer cells based on Gilbert multiplier. The feedback can be exploited in several ways, and different configurations are derived. A dual-loop topology provides a solution for inductor-less broad-band receiver stages. The nature...

  2. Sufficient Conditions for Dynamical Output Feedback Stabilization Via the Circle Criterion

    OpenAIRE

    2003-01-01

    This paper suggests sufficient conditions for asymptotically stable dynamical output feedback controller design based on the circle criterion. It is shown that a dynamic output feedback stabilization problem with impending problems of finite escape time, previously attacked by observer-based design, can be successfully solved using circle criterion design. Stability of the closed-loop system is global and robust to parameter uncertainty.

  3. The Use of Feedback Mechanisms in Interpreting the Robustness of a Neoliberal Educational Assemblage

    Science.gov (United States)

    Demerath, Peter; Mattheis, Allison

    2015-01-01

    This article demonstrates how using feedback mechanisms or "loops" as heuristic devices can help ethnographers explain the interior logic, robustness and contradictions within complex educational assemblages. After reviewing the use of feedback mechanisms in the natural and social sciences, particularly practice theory, the article…

  4. Two forms of feedback inhibition determine the dynamical state of a small hippocampal network

    NARCIS (Netherlands)

    Zeldenrust, F.; Wadman, W.J.

    2009-01-01

    Pyramidal cells in the hippocampus are part of a small neuronal network that performs computations on external input. The network consists of principal cells and various forms of feedback inhibition. Experimental evidence indicates at least two functionally distinct inhibitory feedback loops in the

  5. Bandwidth limitations in current mode and voltage mode integrated feedback amplifiers

    DEFF Research Database (Denmark)

    Bruun, Erik

    1995-01-01

    loop bandwidth remains constant for a feedback amplifier. The constant-bandwidth relations of such amplifier designs are reviewed in this paper and they are combined with the constraints imposed by technology when the feedback amplifier is to be designed in an integrated technology. From this analysis...

  6. Multi-loop calculations: numerical methods and applications arXiv

    CERN Document Server

    Borowka, S.; Jahn, S.; Jones, S.P.; Kerner, M.; Schlenk, J.

    We briefly review numerical methods for calculations beyond one loop and then describe new developments within the method of sector decomposition in more detail. We also discuss applications to two-loop integrals involving several mass scales.

  7. Delayed excitatory and inhibitory feedback shape neural information transmission

    Science.gov (United States)

    Chacron, Maurice J.; Longtin, André; Maler, Leonard

    2017-01-01

    Feedback circuitry with conduction and synaptic delays is ubiquitous in the nervous system. Yet the effects of delayed feedback on sensory processing of natural signals are poorly understood. This study explores the consequences of delayed excitatory and inhibitory feedback inputs on the processing of sensory information. We show, through numerical simulations and theory, that excitatory and inhibitory feedback can alter the firing frequency response of stochastic neurons in opposite ways by creating dynamical resonances, which in turn lead to information resonances (i.e., increased information transfer for specific ranges of input frequencies). The resonances are created at the expense of decreased information transfer in other frequency ranges. Using linear response theory for stochastically firing neurons, we explain how feedback signals shape the neural transfer function for a single neuron as a function of network size. We also find that balanced excitatory and inhibitory feedback can further enhance information tuning while maintaining a constant mean firing rate. Finally, we apply this theory to in vivo experimental data from weakly electric fish in which the feedback loop can be opened. We show that it qualitatively predicts the observed effects of inhibitory feedback. Our study of feedback excitation and inhibition reveals a possible mechanism by which optimal processing may be achieved over selected frequency ranges. PMID:16383655

  8. Genetic Programming with Simple Loops

    Institute of Scientific and Technical Information of China (English)

    QI Yuesheng; WANG Baozhong; KANG Lishan

    1999-01-01

    A kind of loop function LoopN inGenetic Programming (GP) is proposed.Different from other forms of loopfunction, such as While-Do and Repeat-Until, LoopNtakes only oneargument as its loop body and makes its loop body simply run N times,soinfinite loops will never happen. The problem of how to avoid too manylayers ofloops in Genetic Programming is also solved. The advantage ofLoopN in GP is shown bythe computational results in solving the mowerproblem.

  9. Improving Convergence of Iterative Feedback Tuning using Optimal External Perturbations

    DEFF Research Database (Denmark)

    Huusom, Jakob Kjøbsted; Hjalmarsson, Håkon; Poulsen, Niels Kjølstad

    2008-01-01

    Iterative feedback tuning constitutes an attractive control loop tuning method for processes in the absence of sufficient process insight. It is a purely data driven approach to optimization of the loop performance. The standard formulation ensures an unbiased estimate of the loop performance cost...... function gradient, which is used in a search algorithm. A slow rate of convergence of the tuning method is often experienced when tuning for disturbance rejection. This is due to a poor signal to noise ratio in the process data. A method is proposed for increasing the information content in data...... by introducing an optimal perturbation signal in the tuning algorithm. For minimum variance control design the optimal design of an external perturbation signal is derived in terms of the asymptotic accuracy of the iterative feedback tuning method....

  10. Feedback control of torsion balance in measurement of gravitational constant G with angular acceleration method.

    Science.gov (United States)

    Quan, Li-Di; Xue, Chao; Shao, Cheng-Gang; Yang, Shan-Qing; Tu, Liang-Cheng; Wang, Yong-Ji; Luo, Jun

    2014-01-01

    The performance of the feedback control system is of central importance in the measurement of the Newton's gravitational constant G with angular acceleration method. In this paper, a PID (Proportion-Integration-Differentiation) feedback loop is discussed in detail. Experimental results show that, with the feedback control activated, the twist angle of the torsion balance is limited to [Formula: see text] at the signal frequency of 2 mHz, which contributes a [Formula: see text] uncertainty to the G value.

  11. RF feedback for KEKB

    Energy Technology Data Exchange (ETDEWEB)

    Ezura, Eizi; Yoshimoto, Shin-ichi; Akai, Kazunori [National Lab. for High Energy Physics, Tsukuba, Ibaraki (Japan)

    1996-08-01

    This paper describes the present status of the RF feedback development for the KEK B-Factory (KEKB). A preliminary experiment concerning the RF feedback using a parallel comb-filter was performed through a choke-mode cavity and a klystron. The RF feedback has been tested using the beam of the TRISTAN Main Ring, and has proved to be effective in damping the beam instability. (author)

  12. Neural cryptography with feedback

    Science.gov (United States)

    Ruttor, Andreas; Kinzel, Wolfgang; Shacham, Lanir; Kanter, Ido

    2004-04-01

    Neural cryptography is based on a competition between attractive and repulsive stochastic forces. A feedback mechanism is added to neural cryptography which increases the repulsive forces. Using numerical simulations and an analytic approach, the probability of a successful attack is calculated for different model parameters. Scaling laws are derived which show that feedback improves the security of the system. In addition, a network with feedback generates a pseudorandom bit sequence which can be used to encrypt and decrypt a secret message.

  13. Neural cryptography with feedback.

    Science.gov (United States)

    Ruttor, Andreas; Kinzel, Wolfgang; Shacham, Lanir; Kanter, Ido

    2004-04-01

    Neural cryptography is based on a competition between attractive and repulsive stochastic forces. A feedback mechanism is added to neural cryptography which increases the repulsive forces. Using numerical simulations and an analytic approach, the probability of a successful attack is calculated for different model parameters. Scaling laws are derived which show that feedback improves the security of the system. In addition, a network with feedback generates a pseudorandom bit sequence which can be used to encrypt and decrypt a secret message.

  14. Extended Lock Range Zero-Crossing Digital Phase-Locked Loop with Time Delay

    Directory of Open Access Journals (Sweden)

    Nasir Qassim

    2005-01-01

    Full Text Available The input frequency limit of the conventional zero-crossing digital phase-locked loop (ZCDPLL is due to the operating time of the digital circuitry inside the feedback loop. A solution that has been previously suggested is the introduction of a time delay in the feedback path of the loop to allow the digital circuits to complete their sample processing before the next sample is received. However, this added delay will limit the stable operation range and hence lock range of the loop. The objective of this work is to extend the lock range of ZCDPLL with time delay by using a chaos control. The tendency of the loop to diverge is measured and fed back as a form of linear stabilization. The lock range extension has been confirmed through the use of a bifurcation diagram, and Lyapunov exponent.

  15. Extended Lock Range Zero-Crossing Digital Phase-Locked Loop with Time Delay

    Directory of Open Access Journals (Sweden)

    Nasir Qassim

    2005-01-01

    Full Text Available The input frequency limit of the conventional zero-crossing digital phase-locked loop (ZCDPLL is due to the operating time of the digital circuitry inside the feedback loop. A solution that has been previously suggested is the introduction of a time delay in the feedback path of the loop to allow the digital circuits to complete their sample processing before the next sample is received. However, this added delay will limit the stable operation range and hence lock range of the loop. The objective of this work is to extend the lock range of ZCDPLL with time delay by using a chaos control. The tendency of the loop to diverge is measured and fed back as a form of linear stabilization. The lock range extension has been confirmed through the use of a bifurcation diagram, and Lyapunov exponent.

  16. Human-in-the loop issues for demining

    Science.gov (United States)

    Herman, Herman; Iglesias, Diego

    1999-08-01

    The effectiveness and robustness of any landmine detector ultimately depend on its operator. This is especially true for hand-held landmine detectors, since the operator handles both the scanning motion and the interpretation of the data. Therefore, it is important that the human-in-the-loop issues are addressed as an integral part of the detector design, not as an afterthought. Two critical issues that we have identified are the lack of position feedback for the operator and the lack of 2D map of the detector output. The position feedback will allow the operator to obtain feedback with respect to the sweep rate, detector height and orientation. The position feedback can also be integrated with the detector output to generate a 2D map for the operator. In addition, the 2D map enables 2D image processing techniques, which are more robust and effective than 1D signal processing techniques.

  17. Engineering applications of a dynamical state feedback chaotification method

    Science.gov (United States)

    Şahin, Savaş; Güzeliş, Cüneyt

    2012-09-01

    This paper presents two engineering applications of a chaotification method which can be applied to any inputstate linearizable (nonlinear) system including linear controllable ones as special cases. In the used chaotification method, a reference chaotic and linear system can be combined into a special form by a dynamical state feedback increasing the order of the open loop system to have the same chaotic dynamics with the reference chaotic system. Promising dc motor applications of the method are implemented by the proposed dynamical state feedback which is based on matching the closed loop dynamics to the well known Chua and also Lorenz chaotic systems. The first application, which is the chaotified dc motor used for mixing a corn syrup added acid-base mixture, is implemented via a personal computer and a microcontroller based circuit. As a second application, a chaotified dc motor with a taco-generator used in the feedback is realized by using fully analog circuit elements.

  18. Disconnected Loops with Twisted Mass Lattice QCD

    CERN Document Server

    Wilcox, W; Morgan, R; Lewis, R; Wilcox, Walter; Darnell, Dean; Morgan, Ron; Lewis, Randy

    2005-01-01

    We give a general introduction and discussion of the issues involved in using the twisted mass formulation of lattice fermions in the context of disconnected loop calculations, including a short orientation on the present experimental situation for nucleon strange quark form factors. A prototype calculation of the disconnected part of the nucleon scalar form factor is described.

  19. Framing of Feedback Impacts Student's Satisfaction, Self-Efficacy and Performance

    Science.gov (United States)

    van de Ridder, J. M. Monica; Peters, Claudia M. M.; Stokking, Karel M.; de Ru, J. Alexander; ten Cate, Olle Th. J.

    2015-01-01

    Feedback is considered important to acquire clinical skills. Research evidence shows that feedback does not always improve learning and its effects may be small. In many studies, a variety of variables involved in feedback provision may mask either one of their effects. E.g., there is reason to believe that the way oral feedback is framed may…

  20. Loop electrosurgical excisional procedure.

    Science.gov (United States)

    Mayeaux, E J; Harper, M B

    1993-02-01

    Loop electrosurgical excisional procedure, or LEEP, also known as loop diathermy treatment, loop excision of the transformation zone (LETZ), and large loop excision of the transformation zone (LLETZ), is a new technique for outpatient diagnosis and treatment of dysplastic cervical lesions. This procedure produces good specimens for cytologic evaluation, carries a low risk of affecting childbearing ability, and is likely to replace cryotherapy or laser treatment for cervical neoplasias. LEEP uses low-current, high-frequency electrical generators and thin stainless steel or tungsten loops to excise either lesions or the entire transformation zone. Complication rates are comparable to cryotherapy or laser treatment methods and include bleeding, incomplete removal of the lesion, and cervical stenosis. Compared with other methods, the advantages of LEEP include: removal of abnormal tissue in a manner permitting cytologic study, low cost, ease of acquiring necessary skills, and the ability to treat lesions with fewer visits. Patient acceptance of the procedure is high. Widespread use of LEEP by family physicians can be expected.