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Sample records for costimulatory signals control

  1. Co-stimulatory signaling determines tumor antigen sensitivity and persistence of CAR T cells targeting PSCA+ metastatic prostate cancer.

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    Priceman, Saul J; Gerdts, Ethan A; Tilakawardane, Dileshni; Kennewick, Kelly T; Murad, John P; Park, Anthony K; Jeang, Brook; Yamaguchi, Yukiko; Yang, Xin; Urak, Ryan; Weng, Lihong; Chang, Wen-Chung; Wright, Sarah; Pal, Sumanta; Reiter, Robert E; Wu, Anna M; Brown, Christine E; Forman, Stephen J

    2018-01-01

    Advancing chimeric antigen receptor (CAR)-engineered adoptive T cells for the treatment of solid cancers is a major focus in the field of immunotherapy, given impressive recent clinical responses in hematological malignancies. Prostate cancer may be amenable to T cell-based immunotherapy since several tumor antigens, including prostate stem-cell antigen (PSCA), are widely over-expressed in metastatic disease. While antigen selectivity of CARs for solid cancers is crucial, it is problematic due to the absence of truly restricted tumor antigen expression and potential safety concerns with "on-target off-tumor" activity. Here, we show that the intracellular co-stimulatory signaling domain can determine a CAR's sensitivity for tumor antigen expression. A 4-1BB intracellular co-stimulatory signaling domain in PSCA-CARs confers improved selectivity for higher tumor antigen density, reduced T cell exhaustion phenotype, and equivalent tumor killing ability compared to PSCA-CARs containing the CD28 co-stimulatory signaling domain. PSCA-CARs exhibit robust in vivo anti-tumor activity in patient-derived bone-metastatic prostate cancer xenograft models, and 4-1BB-containing CARs show superior T cell persistence and control of disease compared with CD28-containing CARs. Our study demonstrates the importance of co-stimulation in defining an optimal CAR T cell, and also highlights the significance of clinically relevant models in developing solid cancer CAR T cell therapies.

  2. Co-stimulatory signaling determines tumor antigen sensitivity and persistence of CAR T cells targeting PSCA+ metastatic prostate cancer

    Science.gov (United States)

    Priceman, Saul J.; Gerdts, Ethan A.; Tilakawardane, Dileshni; Kennewick, Kelly T.; Murad, John P.; Park, Anthony K.; Jeang, Brook; Yamaguchi, Yukiko; Urak, Ryan; Weng, Lihong; Chang, Wen-Chung; Wright, Sarah; Pal, Sumanta; Reiter, Robert E.; Brown, Christine E.; Forman, Stephen J.

    2018-01-01

    ABSTRACT Advancing chimeric antigen receptor (CAR)-engineered adoptive T cells for the treatment of solid cancers is a major focus in the field of immunotherapy, given impressive recent clinical responses in hematological malignancies. Prostate cancer may be amenable to T cell-based immunotherapy since several tumor antigens, including prostate stem-cell antigen (PSCA), are widely over-expressed in metastatic disease. While antigen selectivity of CARs for solid cancers is crucial, it is problematic due to the absence of truly restricted tumor antigen expression and potential safety concerns with “on-target off-tumor” activity. Here, we show that the intracellular co-stimulatory signaling domain can determine a CAR's sensitivity for tumor antigen expression. A 4-1BB intracellular co-stimulatory signaling domain in PSCA-CARs confers improved selectivity for higher tumor antigen density, reduced T cell exhaustion phenotype, and equivalent tumor killing ability compared to PSCA-CARs containing the CD28 co-stimulatory signaling domain. PSCA-CARs exhibit robust in vivo anti-tumor activity in patient-derived bone-metastatic prostate cancer xenograft models, and 4-1BB-containing CARs show superior T cell persistence and control of disease compared with CD28-containing CARs. Our study demonstrates the importance of co-stimulation in defining an optimal CAR T cell, and also highlights the significance of clinically relevant models in developing solid cancer CAR T cell therapies. PMID:29308300

  3. Costimulatory signal blockade in murine relapsing experimental autoimmune encephalomyelitis

    DEFF Research Database (Denmark)

    Schaub, M; Issazadeh-Navikas, Shohreh; Stadlbauer, T H

    1999-01-01

    Blockade of the CD28-B7 or CD40L-CD40 T cell costimulatory signals prevents induction of experimental autoimmune encephalomyelitis (EAE). However, the effect of simultaneous blockade of these signals in EAE is unknown. We show that administration of either MR1 (to block CD40L) or CTLA4Ig (to block...... B7) after immunization or after the first attack protects from EAE. Treatment with a combination of CTLA4Ig and MR1 provides additive protection, and is associated with complete absence of mononuclear cell infiltrates in the central nervous system, and marked suppression of proliferation of primed T...... cells in the periphery. Selective B7-1 blockade did not protect from EAE. These observations have implications for therapy of autoimmune diseases....

  4. Antigen presenting cells costimulatory signaling during pre-implantation pregnancy 

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    Anna Sławek

    2012-09-01

    Full Text Available  Success of pregnancy depends on many factors. Three phenomena inducing immune tolerance against semi-allogeneic conceptus may play a crucial role in the pre-implantation period of pregnancy: influence of sex hormones in sex cycle, presence of oocyte or embryo and the presence of semen in the female reproductive tract. On the other hand dendritic cells are the most effective antigen-presenting cells in regulation of immune phenomena and also are considered as potent participants in inducing immune tolerance in the pregnancy. They communicate with T cells in cell contact-dependent manner or via cytokines. During cell-cell contacts, costimulatory molecules play a key role and their expression is often dependent on cytokines milieu. Both costimulatory molecules and cytokines influence generation of T regulatory cells. Interactions of these molecules are closely related. In this paper we would like to pay attention to the importance of antigen presenting cells costimulatory potency in immune regulation during a pre-implantation period of pregnancy.

  5. Expression of costimulatory molecules in the bovine corpus luteum

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    Pate Joy L

    2007-01-01

    Full Text Available Abstract Background Bovine luteal parenchymal cells express class II major histocompatibility complex (MHC molecules and stimulate class II MHC-dependent activation of T cells in vitro. The ability of a class II MHC-expressing cell type to elicit a response from T cells in vivo is also dependent on expression of costimulatory molecules by the antigen presenting cell and delivery of a costimulatory signal to the T cell. Whether bovine luteal parenchymal cells express costimulatory molecules and can deliver the costimulatory signal is currently unknown. Methods Bovine luteal tissue was collected during the early (day 5; day of estrus = day 0, mid (day 11–12, or late (day 18 luteal phase of the estrous cycle, and at 0, 0.5, 1, 4, 12 or 24 hours following administration of PGF2alpha to cows on day 10 of the estrous cycle. Northern analysis was used to measure CD80 or CD86 mRNA concentrations in luteal tissue samples. Mixed luteal parenchymal cell cultures and purified luteal endothelial cell cultures were prepared, and real-time RT-PCR was used to examine the presence of CD80 and CD86 mRNA in each culture type. Monoclonal antibodies to CD80 and CD86 were added to a mixed luteal parenchymal cell-T cell co-culture in vitro T cell proliferation assay to assess the functional significance of costimulatory molecules on activation of T lymphocytes by luteal parenchymal cells. Results Northern analysis revealed CD80 and CD86 mRNAs in luteal tissue, with greatest steady-state concentrations at midcycle. CD80 and CD86 mRNAs were detected in mixed luteal parenchymal cell cultures, but only slight amounts of CD80 (and not CD86 mRNA were detected in cultures of luteal endothelial cells. Luteinizing hormone, PGF2alpha and TNF-alpha were without effect on concentrations of CD80 or CD86 mRNA in mixed luteal parenchymal cells cultures. Anti-CD80 or anti-CD86 monoclonal antibodies inhibited T cell proliferation in the in vitro T cell proliferation assay

  6. Costimulatory Pathways: Physiology and Potential Therapeutic Manipulation in Systemic Lupus Erythematosus

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    Nien Yee Kow

    2013-01-01

    Full Text Available System lupus erythematosus (SLE is an immune-complex-mediated autoimmune condition with protean immunological and clinical manifestation. While SLE has classically been advocated as a B-cell or T-cell disease, it is unlikely that a particular cell type is more pathologically predominant than the others. Indeed, SLE is characterized by an orchestrated interplay amongst different types of immunopathologically important cells participating in both innate and adaptive immunity including the dendritic cells, macrophages, neutrophils and lymphocytes, as well as traditional nonimmune cells such as endothelial, epithelial, and renal tubular cells. Amongst the antigen-presenting cells and lymphocytes, and between lymphocytes, the costimulatory pathways which involve mutual exchange of information and signalling play an essential role in initiating, perpetuating, and, eventually, attenuating the proinflammatory immune response. In this review, advances in the knowledge of established costimulatory pathways such as CD28/CTLA-4-CD80/86, ICOS-B7RP1, CD70-CD27, OX40-OX40L, and CD137-CD137L as well as their potential roles involved in the pathophysiology of SLE will be discussed. Attempts to target these costimulatory pathways therapeutically will pave more potential treatment avenues for patients with SLE. Preliminary laboratory and clinical evidence of the potential therapeutic value of manipulating these costimulatory pathways in SLE will also be discussed in this review.

  7. Costimulatory receptors in a teleost fish: Typical CD28, elusive CTLA4

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    Bernard, D.; Riteau, B.; Hansen, J.D.; Phillips, R.B.; Michel, F.; Boudinot, P.; Benmansour, A.

    2006-01-01

    T cell activation requires both specific recognition of the peptide-MHC complex by the TCR and additional signals delivered by costimulatory receptors. We have identified rainbow trout sequences similar to CD28 (rbtCD28) and CTLA4 (rbtCTLA4). rbtCD28 and rbtCTLA4 are composed of an extracellular Ig-superfamily V domain, a transmembrane region, and a cytoplasmic tail. The presence of a conserved ligand binding site within the V domain of both molecules suggests that these receptors likely recognize the fish homologues of the B7 family. The mRNA expression pattern of rbtCD28 and rbtCTLA4 in naive trout is reminiscent to that reported in humans and mice, because rbtCTLA4 expression within trout leukocytes was quickly up-regulated following PHA stimulation and virus infection. The cytoplasmic tail of rbtCD28 possesses a typical motif that is conserved in mammalian costimulatory receptors for signaling purposes. A chimeric receptor made of the extracellular domain of human CD28 fused to the cytoplasmic tail of rbtCD28 promoted TCR-induced IL-2 production in a human T cell line, indicating that rbtCD28 is indeed a positive costimulator. The cytoplasmic tail of rtrtCTLA4 lacked obvious signaling motifs and accordingly failed to signal when fused to the huCD28 extracellular domain. Interestingly, rbtCTLA4 and rbtCD28 are not positioned on the same chromosome and thus do not belong to a unique costimulatory cluster as in mammals. Finally, oar results raise questions about the origin and evolution of positive and negative costimulation in vertebrate immune systems. Copyright ?? 2006 by The American Association of Immunologists, Inc.

  8. Differential expression of the costimulatory molecules CD86, CD28, CD152 and PD-1 correlates with the host-parasite outcome in leprosy

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    Maria de Lourdes Palermo

    2012-12-01

    Full Text Available Leprosy is a spectral disease exhibiting two polar sides, namely, lepromatous leprosy (LL characterised by impaired T-cell responses and tuberculoid leprosy in which T-cell responses are strong. Proper T-cell activation requires signalling through costimulatory molecules expressed by antigen presenting cells and their ligands on T-cells. We studied the influence of costimulatory molecules on the immune responses of subjects along the leprosy spectrum. The expression of the costimulatory molecules was evaluated in in vitro-stimulated peripheral blood mononuclear cells of lepromatous and tuberculoid patients and healthy exposed individuals (contacts. We show that LL patients have defective monocyte CD86 expression, which likely contributes to the impairment of the antigen presentation process and to patients anergy. Accordingly, CD86 but not CD80 blockade inhibited the lymphoproliferative response to Mycobacterium leprae. Consistent with the LL anergy, there was reduced expression of the positive signalling costimulatory molecules CD28 and CD86 on the T-cells in these patients. In contrast, tuberculoid leprosy patients displayed increased expression of the negative signalling molecules CD152 and programmed death-1 (PD-1, which represents a probable means of modulating an exacerbated immune response and avoiding immunopathology. Notably, the contacts exhibited proper CD86 and CD28 expression but not exacerbated CD152 or PD-1 expression, suggesting that they tend to develop a balanced immunity without requiring immunosuppressive costimulatory signalling.

  9. Dendritic cell co-stimulatory and co-inhibitory markers in chronic HCV: An Egyptian study

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    Fouad, Hanan; Raziky, Maissa Saeed El; Aziz, Rasha Ahmed Abdel; Sabry, Dina; Aziz, Ghada Mahmoud Abdel; Ewais, Manal; Sayed, Ahmed Reda

    2013-01-01

    AIM: To assess co-stimulatory and co-inhibitory markers of dendritic cells (DCs) in hepatitis C virus (HCV) infected subjects with and without uremia. METHODS: Three subject groups were included in the study: group 1 involved 50 control subjects, group 2 involved 50 patients with chronic HCV infection and group 3 involved 50 HCV uremic subjects undergoing hemodialysis. CD83, CD86 and CD40 as co-stimulatory markers and PD-L1 as a co-inhibitory marker were assessed in peripheral blood mononuclear cells by real-time polymerase chain reaction. Interleukin-10 (IL-10) and hyaluronic acid (HA) levels were also assessed. All findings were correlated with disease activity, viral load and fibrogenesis. RESULTS: There was a significant decrease in co-stimulatory markers; CD83, CD86 and CD40 in groups 2 and 3 vs the control group. Co-stimulatory markers were significantly higher in group 3 vs group 2. There was a significant elevation in PD-L1 in both HCV groups vs the control group. PD-L1 was significantly lower in group 3 vs group 2. There was a significant elevation in IL-10 and HA levels in groups 2 and 3, where IL-10 was higher in group 3 and HA was lower in group 3 vs group 2. HA level was significantly correlated with disease activity and fibrosis grade in group 2. IL-10 was significantly correlated with fibrosis grade in group 2. There were significant negative correlations between co-stimulatory markers and viral load in groups 2 and 3, except CD83 in dialysis patients. There was a significant positive correlation between PD-L1 and viral load in both HCV groups. CONCLUSION: A significant decrease in DC co-stimulatory markers and a significant increase in a DC co-inhibitory marker were observed in HCV subjects and to a lesser extent in dialysis patients. PMID:24282359

  10. MHC class II molecules deliver costimulatory signals in human T cells through a functional linkage with IL-2-receptors

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    Odum, Niels; Kanner, S B; Ledbetter, J A

    1993-01-01

    MHC class II-positive T cells are found in tissues involved in autoimmune and infectious disorders. Because stimulation of class II molecules by mAb or bacterial superantigens induces protein tyrosine phosphorylation through activation of PTK3 in T cells, we hypothesized that class II signals play...... tyrosine phosphorylation of specific substrates including PLC-gamma 1. Combined stimulation of IL-2R and class II molecules had an additive effect on tyrosine phosphorylation. Pretreatment of T cells with a protein tyrosine kinase inhibitor, herbimycin A, inhibited IL-2 and class II-induced proliferation...... a regulatory function in T cell activation. Here, we show that cross-linking HLA-DR and -DP but not -DQ molecules by immobilized mAb enhanced proliferative T cell responses to IL-2. In contrast, class II stimulation had no effect on IL-4-induced proliferation. The costimulatory effect was most pronounced...

  11. Expression of major histocompatibility complex class II and costimulatory molecules in oral carcinomas in vitro.

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    Villarroel-Dorrego, Mariana; Speight, Paul M; Barrett, A William

    2005-01-01

    Recognition in the 1980 s that keratinocytes can express class II molecules of the Major Histocompatibility Complex (MHC) first raised the possibility that these cells might have an immunological function, and may even act as antigen presenting cells (APC). For effective T lymphocyte activation, APC require, in addition to MHC II, appropriate costimulatory signals. The aim of this study was to determine the expression of MHC class II and the co-stimulatory molecules CD40, CD80 and CD86 in keratinocytes derived from healthy oral mucosa and oral carcinomas. Using flow cytometry, it was confirmed that oral keratinocytes, switch on, expression of MHC class II molecules after stimulation with IFNgamma in vitro. All keratinocyte lines expressed CD40 constitutively; by contrast, CD80 and CD86 were universally absent. Loss of CD80 and CD86 may be one means whereby tumours escape immunological surveillance.

  12. Peptide-Conjugated Nanoparticles Reduce Positive Co-stimulatory Expression and T Cell Activity to Induce Tolerance.

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    Kuo, Robert; Saito, Eiji; Miller, Stephen D; Shea, Lonnie D

    2017-07-05

    Targeted approaches to treat autoimmune diseases would improve upon current therapies that broadly suppress the immune system and lead to detrimental side effects. Antigen-specific tolerance was induced using poly(lactide-co-glycolide) nanoparticles conjugated with disease-relevant antigen to treat a model of multiple sclerosis. Increasing the nanoparticle dose and amount of conjugated antigen both resulted in more durable immune tolerance. To identify active tolerance mechanisms, we investigated downstream cellular and molecular events following nanoparticle internalization by antigen-presenting cells. The initial cell response to nanoparticles indicated suppression of inflammatory signaling pathways. Direct and functional measurement of surface MHC-restricted antigen showed positive correlation with both increasing particle dose from 1 to 100 μg/mL and increasing peptide conjugation by 2-fold. Co-stimulatory analysis of cells expressing MHC-restricted antigen revealed most significant decreases in positive co-stimulatory molecules (CD86, CD80, and CD40) following high doses of nanoparticles with higher peptide conjugation, whereas expression of a negative co-stimulatory molecule (PD-L1) remained high. T cells isolated from mice immunized against myelin proteolipid protein (PLP 139-151 ) were co-cultured with antigen-presenting cells administered PLP 139-151 -conjugated nanoparticles, which resulted in reduced T cell proliferation, increased T cell apoptosis, and a stronger anti-inflammatory response. These findings indicate several potential mechanisms used by peptide-conjugated nanoparticles to induce antigen-specific tolerance. Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

  13. The co-stimulatory effects of MyD88-dependent Toll-like receptor signaling on activation of murine γδ T cells.

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    Jinping Zhang

    Full Text Available γδ T cells express several different toll-like receptor (TLRs. The role of MyD88- dependent TLR signaling in TCR activation of murine γδ T cells is incompletely defined. Here, we report that Pam3CSK4 (PAM, TLR2 agonist and CL097 (TLR7 agonist, but not lipopolysaccharide (TLR4 agonist, increased CD69 expression and Th1-type cytokine production upon anti-CD3 stimulation of γδ T cells from young adult mice (6-to 10-week-old. However, these agonists alone did not induce γδ T cell activation. Additionally, we noted that neither PAM nor CL097 synergized with anti-CD3 in inducing CD69 expression on γδ T cells of aged mice (21-to 22-month-old. Compared to young γδ T cells, PAM and CL097 increased Th-1 type cytokine production with a lower magnitude from anti-CD3- stimulated, aged γδ T cells. Vγ1+ and Vγ4+ cells are two subpopulations of splenic γδ T cells. PAM had similar effects in anti-CD3-activated control and Vγ4+ subset- depleted γδ T cells; whereas CL097 induced more IFN-γ production from Vγ4+ subset-depleted γδ T cells than from the control group. Finally, we studied the role of MyD88-dependent TLRs in γδ T cell activation during West Nile virus (WNV infection. γδ T cell, in particular, Vγ1+ subset expansion was significantly reduced in both MyD88- and TLR7- deficient mice. Treatment with TLR7 agonist induced more Vγ1+ cell expansion in wild-type mice during WNV infection. In summary, these results suggest that MyD88-dependent TLRs provide co-stimulatory signals during TCR activation of γδ T cells and these have differential effects on distinct subsets.

  14. Expression of CD80 and CD86 costimulatory molecules are potential markers for better survival in nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Chang, Cheng-Shyong; Chang, Julia H; Hsu, Nicholas C; Lin, Hsuan-Yu; Chung, Chih-Yuan

    2007-01-01

    B7 Costimulatory signal is essential to trigger T-cell activation upon the recognition of tumor antigens. This study examined the expression of B7-1 (CD80) and B7-2 (CD86) costimulatory molecules along with HLA-DR and the presence of infiltrating lymphocytes and dendritic cells to assess their significance in patients with nasopharyngeal carcinoma (NPC). Expression of CD80, CD86, HLA-DR, S-100 protein and the presence of infiltrating lymphocytes and follicular dendritic reticulum cells were immunohistochemically examined on the paraffin-embedded tissue blocks from newly diagnosed NPC patients (n = 50). The results were correlated with clinical outcome of patients. CD80 and CD86 were each expressed in 10 of 50 cases in which they co-expressed in 9 cases. Univariate analysis revealed that patients with CD80/CD86 expression had significantly better overall survival than those without it (P = 0.017), but after adjustment for stage, nodal status, and treatment, the expression of CD80/CD86 did not significantly correlate with overall survival. Expression of HLA-DR and the presence of infiltrating lymphocytes and dendritic cells did not appear to have impact on the survival of patients. Expression of CD80 and CD86 costimulatory molecules appears to be a marker of better survival in patient with NPC

  15. Mixed Signals: Co-Stimulation in Invariant Natural Killer T Cell-Mediated Cancer Immunotherapy

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    Susannah C. Shissler

    2017-11-01

    Full Text Available Invariant natural killer T (iNKT cells are an integral component of the immune system and play an important role in antitumor immunity. Upon activation, iNKT cells can directly kill malignant cells as well as rapidly produce cytokines that stimulate other immune cells, making them a front line defense against tumorigenesis. Unfortunately, iNKT cell number and activity are reduced in multiple cancer types. This anergy is often associated with upregulation of co-inhibitory markers such as programmed death-1. Similar to conventional T cells, iNKT cells are influenced by the conditions of their activation. Conventional T cells receive signals through the following three types of receptors: (1 T cell receptor (TCR, (2 co-stimulation molecules, and (3 cytokine receptors. Unlike conventional T cells, which recognize peptide antigen presented by MHC class I or II, the TCRs of iNKT cells recognize lipid antigen in the context of the antigen presentation molecule CD1d (Signal 1. Co-stimulatory molecules can positively and negatively influence iNKT cell activation and function and skew the immune response (Signal 2. This study will review the background of iNKT cells and their co-stimulatory requirements for general function and in antitumor immunity. We will explore the impact of monoclonal antibody administration for both blocking inhibitory pathways and engaging stimulatory pathways on iNKT cell-mediated antitumor immunity. This review will highlight the incorporation of co-stimulatory molecules in antitumor dendritic cell vaccine strategies. The use of co-stimulatory intracellular signaling domains in chimeric antigen receptor-iNKT therapy will be assessed. Finally, we will explore the influence of innate-like receptors and modification of immunosuppressive cytokines (Signal 3 on cancer immunotherapy.

  16. Decreased Expression of T-Cell Costimulatory Molecule CD28 on CD4 and CD8 T Cells of Mexican Patients with Pulmonary Tuberculosis

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    German Bernal-Fernandez

    2010-01-01

    Full Text Available Patients with tuberculosis frequently develop anergy, a state of T-cell hyporesponsiveness in which defective T-cell costimulation could be a factor. To know if the expression of T-cell costimulatory molecules was altered in tuberculosis, we analyzed the peripheral blood T-cell phenotype of 23 Mexican patients with pulmonary tuberculosis. There was severe CD4 (P<.001 and CD8 (P<.01 lymphopenia and upregulation of costimulatory molecule CD30 on CD4 and CD8 T cells (P<.05; this increase was higher in relapsing tuberculosis. The main finding was severe downregulation of the major costimulatory molecule CD28 on both CD8 and CD4 T cells (P<.001. Depletion of the CD4/CD28 subset, a hitherto undescribed finding, is relevant because CD4 T cells constitute the main arm of the cell-mediated antimycobacterial immune response.

  17. Pro- and anti-apoptotic CD95 signaling in T cells

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    Janssen Ottmar

    2011-04-01

    Full Text Available Abstract The TNF receptor superfamily member CD95 (Fas, APO-1, TNFRSF6 is known as the prototypic death receptor in and outside the immune system. In fact, many mechanisms involved in apoptotic signaling cascades were solved by addressing consequences and pathways initiated by CD95 ligation in activated T cells or other "CD95-sensitive" cell populations. As an example, the binding of the inducible CD95 ligand (CD95L to CD95 on activated T lymphocytes results in apoptotic cell death. This activation-induced cell death was implicated in the control of immune cell homeostasis and immune response termination. Over the past years, however, it became evident that CD95 acts as a dual function receptor that also exerts anti-apoptotic effects depending on the cellular context. Early observations of a potential non-apoptotic role of CD95 in the growth control of resting T cells were recently reconsidered and revealed quite unexpected findings regarding the costimulatory capacity of CD95 for primary T cell activation. It turned out that CD95 engagement modulates TCR/CD3-driven signal initiation in a dose-dependent manner. High doses of immobilized CD95 agonists or cellular CD95L almost completely silence T cells by blocking early TCR-induced signaling events. In contrast, under otherwise unchanged conditions, lower amounts of the same agonists dramatically augment TCR/CD3-driven activation and proliferation. In the present overview, we summarize these recent findings with a focus on the costimulatory capacity of CD95 in primary T cells and discuss potential implications for the T cell compartment and the interplay between T cells and CD95L-expressing cells including antigen-presenting cells.

  18. Targeting immune co-stimulatory effects of PD-L1 and PD-L2 might represent an effective therapeutic strategy in stroke

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    Sheetal eBodhankar

    2014-08-01

    Full Text Available Stroke outcome is worsened by the infiltration of inflammatory immune cells into ischemic brains. Our recent study demonstrated that PD-L1- and to a lesser extent PD-L2-deficient mice had smaller brain infarcts and fewer brain-infiltrating cells vs. WT mice, suggesting a pathogenic role for PD-Ligands in experimental stroke. We sought to ascertain PD-L1 and PD-L2-expressing cell types that affect T-cell activation, post-stroke in the context of other known co-stimulatory molecules. Thus, cells from male WT and PD-L-deficient mice undergoing 60 min of middle cerebral artery occlusion (MCAO followed by 96h of reperfusion were treated with neutralizing antibodies to study co-stimulatory and co-inhibitory interactions between CD80, CTLA-4, PD-1 and PD-Ls that regulate CD8+ and CD4+ T-cell activation. We found that antibody neutralization of PD-1 and CTLA-4 signaling post-MCAO resulted in higher proliferation in WT CD8+ and CD4+ T-cells, confirming an inhibitory role of PD-1 and CTLA-4 on T-cell activation. Also, CD80/CD28 interactions played a prominent regulatory role for the CD8+ T-cells and the PD-1/PD-L2 interactions were dominant in controlling the CD4+ T-cell responses in WT mice after stroke. A suppressive phenotype in PD-L1-deficient mice was attributed to CD80/CTLA-4 and PD-1/PD-L2 interactions. PD-L2 was crucial in modulating CD4+ T-cell responses, whereas PD-L1 regulated both CD8+ and CD4+ T-cells. To establish the contribution of PD-L1 and PD-L2 on regulatory B-cells (Bregs, infarct volumes were evaluated in male PD-L1- and PD-L2-deficient mice receiving IL-10+ B-cells 4h post-MCAO. PD-L2- but not PD-L1-deficient recipients of IL-10+ B-cells had markedly reduced infarct volumes, indicating a regulatory role of PD-L2 on Bregs. These results imply that PD-L1 and PD-L2 differentially control induction of T- and Breg-cell responses after MCAO, thus suggesting that selective targeting of PD-L1 and PD-L2 might represent a valuable therapeutic

  19. Molecular pathway profiling of T lymphocyte signal transduction pathways; Th1 and Th2 genomic fingerprints are defined by TCR and CD28-mediated signaling

    NARCIS (Netherlands)

    Smeets, Ruben L.; Fleuren, Wilco W. M.; He, Xuehui; Vink, Paul M.; Wijnands, Frank; Gorecka, Monika; Klop, Henri; Bauerschmidt, Sussane; Garritsen, Anja; Koenen, Hans J. P. M.; Joosten, Irma; Boots, Annemieke M. H.; Alkema, Wynand

    2012-01-01

    Background: T lymphocytes are orchestrators of adaptive immunity. Naive T cells may differentiate into Th1, Th2, Th17 or iTreg phenotypes, depending on environmental co-stimulatory signals. To identify genes and pathways involved in differentiation of Jurkat T cells towards Th1 and Th2 subtypes we

  20. Molecular pathway profiling of T lymphocyte signal transduction pathways; Th1 and Th2 genomic fingerprints are defined by TCR and CD28-mediated signaling.

    NARCIS (Netherlands)

    Smeets, R.L.; Fleuren, W.W.M.; He, X.; Vink, P.M.; Wijnands, F.; Gorecka, M.; Klop, H.; Bauerschmidt, S.; Garritsen, A.; Koenen, H.J.P.M.; Joosten, I.; Boots, A.M.H.; Alkema, W.

    2012-01-01

    BACKGROUND: T lymphocytes are orchestrators of adaptive immunity. Naive T cells may differentiate into Th1, Th2, Th17 or iTreg phenotypes, depending on environmental co-stimulatory signals. To identify genes and pathways involved in differentiation of Jurkat T cells towards Th1 and Th2 subtypes we

  1. CD80 and CD86 Costimulatory Molecules Differentially Regulate OT-II CD4+ T Lymphocyte Proliferation and Cytokine Response in Cocultures with Antigen-Presenting Cells Derived from Pregnant and Pseudopregnant Mice

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    Tomasz Maj

    2014-01-01

    Full Text Available Immune phenomena during the preimplantation period of pregnancy are poorly understood. The aim of our study was to assess the capacity for antigen presentation of splenic antigen-presenting cells (APCs derived from pregnant and pseudopregnant mice in in vitro conditions. Therefore, sorted CD11c+ dendritic cells and macrophages F4/80+ and CD11b+ presenting ovalbumin (OVA were cocultured with CD4+ T cells derived from OT-II mice’s (C57BL6/J-Tg(TcraTcrb1100Mjb/J spleen. After 132 hours of cell culture, proliferation of lymphocytes (ELISA-BrdU, activation of these cells (flow cytometry, cytokine profile (ELISA, and influence of costimulatory molecules blocking on these parameters were measured. We did not detect any differences in regulation of Th1/Th2 cytokine balance. CD86 seems to be the main costimulatory molecule involved in the proliferation response but CD80 is the main costimulatory molecule influencing cytokine secretion in pregnant mice. In conclusion, this study showed that CD80 and CD86 costimulatory molecules regulate OT-II CD4+ T lymphocyte proliferation and cytokine response in cocultures with antigen-presenting cells derived from pregnant and pseudopregnant mice. The implications of these changes still remain unclear.

  2. CD70 reverse signaling enhances NK cell function and immunosurveillance in CD27-expressing B-cell malignancies.

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    Al Sayed, Mohamad F; Ruckstuhl, Carla A; Hilmenyuk, Tamara; Claus, Christina; Bourquin, Jean-Pierre; Bornhauser, Beat C; Radpour, Ramin; Riether, Carsten; Ochsenbein, Adrian F

    2017-07-20

    The interaction of the tumor necrosis factor receptor (TNFR) CD27 with its ligand CD70 is an emerging target to treat cancer. CD27 signaling provides costimulatory signals to cytotoxic T cells but also increases the frequency of regulatory T cells. Similar to other TNFR ligands, CD70 has been shown to initiate intracellular signaling pathways (CD70 reverse signaling). CD27 is expressed on a majority of B-cell non-Hodgkin lymphoma, but its role in the immune control of lymphoma and leukemia is unknown. We therefore generated a cytoplasmic deletion mutant of CD27 (CD27-trunc) to study the role of CD70 reverse signaling in the immunosurveillance of B-cell malignancies in vivo. Expression of CD27-trunc on malignant cells increased the number of tumor-infiltrating interferon γ-producing natural killer (NK) cells. In contrast, the antitumoral T-cell response remained largely unchanged. CD70 reverse signaling in NK cells was mediated via the AKT signaling pathway and increased NK cell survival and effector function. The improved immune control by activated NK cells prolonged survival of CD27-trunc-expressing lymphoma-bearing mice. Finally, CD70 reverse signaling enhanced survival and effector function of human NK cells in a B-cell acute lymphoblastic leukemia xenotransplants model. Therefore, CD70 reverse signaling in NK cells contributes to the immune control of CD27-expressing B-cell lymphoma and leukemia. © 2017 by The American Society of Hematology.

  3. Differential TCR signals for T helper cell programming.

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    Morel, Penelope A

    2018-05-02

    Upon encounter with their cognate antigen naïve CD4 T cells become activated and are induced to differentiate into several possible T helper (Th) cell subsets. This differentiation depends on a number of factors including antigen presenting cells, cytokines and costimulatory molecules. The strength of the T cell receptor (TCR) signal, related to the affinity of TCR for antigen and antigen dose, has emerged as a dominant factor in determining Th cell fate. Recent studies have revealed that TCR signals of high or low strength do not simply induce quantitatively different signals in the T cells, but rather qualitatively distinct pathways can be induced based on TCR signal strength. This review examines the recent literature in this area and highlights important new developments in our understanding of Th cell differentiation and TCR signal strength. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  4. Constitutive expression of a costimulatory ligand on antigen-presenting cells in the nervous system drives demyelinating disease

    DEFF Research Database (Denmark)

    Zehntner, Simone P; Brisebois, Marcel; Tran, Elise

    2003-01-01

    that transgenic mice constitutively expressing the costimulatory ligand B7.2/CD86 on microglia in the central nervous system (CNS) and on related cells in the proximal peripheral nervous tissue spontaneously develop autoimmune demyelinating disease. Disease-affected nervous tissue in transgenic mice showed...... recipients but not into non-transgenic recipients. These data provide evidence that B7/CD28 interactions within the nervous tissue are critical determinants of disease development. Our findings have important implications for understanding the etiology of nervous system autoimmune diseases such as multiple...

  5. IL-6 trans-Signaling-Dependent Rapid Development of Cytotoxic CD8+ T Cell Function

    Directory of Open Access Journals (Sweden)

    Jan P. Böttcher

    2014-09-01

    Full Text Available Immune control of infections with viruses or intracellular bacteria relies on cytotoxic CD8+ T cells that use granzyme B (GzmB for elimination of infected cells. During inflammation, mature antigen-presenting dendritic cells instruct naive T cells within lymphoid organs to develop into effector T cells. Here, we report a mechanistically distinct and more rapid process of effector T cell development occurring within 18 hr. Such rapid acquisition of effector T cell function occurred through cross-presenting liver sinusoidal endothelial cells (LSECs in the absence of innate immune stimulation and known costimulatory signaling. Rather, interleukin-6 (IL-6 trans-signaling was required and sufficient for rapid induction of GzmB expression in CD8+ T cells. Such LSEC-stimulated GzmB-expressing CD8+ T cells further responded to inflammatory cytokines, eliciting increased and protracted effector functions. Our findings identify a role for IL-6 trans-signaling in rapid generation of effector function in CD8+ T cells that may be beneficial for vaccination strategies.

  6. The role of CD154-CD40 versus CD28-B7 costimulatory pathways in regulating allogeneic Th1 and Th2 responses in vivo

    DEFF Research Database (Denmark)

    Kishimoto, K; Dong, V M; Issazadeh-Navikas, Shohreh

    2000-01-01

    We used signal transducer and activator of transcription 4 (STAT4) and STAT6 gene knockout (-/-) mice as recipients of fully mismatched cardiac allografts to study the role of T-cell costimulatory pathways in regulating allogeneic T-helper 1 (Th1) versus Th2 responses in vivo. STAT4(-/-) mice have...... impaired Th1 responses, whereas STAT6(-/-) mice do not generate normal Th2 responses. Cardiac allografts from C57BL/6 mice were transplanted into normal wild-type (WT), STAT4(-/-), and STAT6(-/-) BALB/c recipients. STAT4(-/-) and STAT6(-/-) mice rejected their grafts with the same tempo as untreated WT....... Furthermore, there was a similar differential effect of CD28-B7 versus CD154-CD40 blockade in inhibiting immune responses in animals immunized with ovalbumin and complete Freund's adjuvant. These novel data indicate that Th1 and Th2 cells are differentially regulated by CD28-B7 versus CD154-CD40 costimulation...

  7. Impaired Upregulation of the Costimulatory Molecules, CD27 and CD28, on CD4+ T Cells from HIV Patients Receiving ART Is Associated with Poor Proliferative Responses.

    Science.gov (United States)

    Tanaskovic, Sara; Price, Patricia; French, Martyn A; Fernandez, Sonia

    2017-02-01

    HIV patients beginning antiretroviral therapy (ART) with advanced immunodeficiency often retain low CD4 + T cell counts despite virological control. We examined proliferative responses and upregulation of costimulatory molecules, following anti-CD3 stimulation, in HIV patients with persistent CD4 + T cell deficiency on ART. Aviremic HIV patients with nadir CD4 + T cell counts cells/μL and who had received ART for a median time of 7 (range 1-11) years were categorized into those achieving low (cells/μL; n = 13) or normal (>500 cells/μL; n = 20) CD4 + T cell counts. Ten healthy controls were also recruited. CD4 + T cell proliferation (Ki67) and upregulation of costimulatory molecules (CD27 and CD28) after anti-CD3 stimulation were assessed by flow cytometry. Results were related to proportions of CD4 + T cells expressing markers of T cell senescence (CD57), activation (HLA-DR), and apoptotic potential (Fas). Expression of CD27 and/or CD28 on uncultured CD4 + T cells was similar in patients with normal CD4 + T cell counts and healthy controls, but lower in patients with low CD4 + T cell counts. Proportions of CD4 + T cells expressing CD27 and/or CD28 correlated inversely with CD4 + T cell expression of CD57, HLA-DR, and Fas. After anti-CD3 stimulation, induction of CD27 hi CD28 hi expression was independent of CD4 + T cell counts, but lower in HIV patients than in healthy controls. Induction of CD27 hi CD28 hi expression correlated with induction of Ki67 expression in total, naïve, and CD31 + naïve CD4 + T cells from patients. In HIV patients responding to ART, impaired induction of CD27 and CD28 on CD4 + T cells after stimulation with anti-CD3 is associated with poor proliferative responses as well as greater CD4 + T cell activation and immunosenescence.

  8. NK cell activation: distinct stimulatory pathways counterbalancing inhibitory signals.

    Science.gov (United States)

    Bakker, A B; Wu, J; Phillips, J H; Lanier, L L

    2000-01-01

    A delicate balance between positive and negative signals regulates NK cell effector function. Activation of NK cells may be initiated by the triggering of multiple adhesion or costimulatory molecules, and can be counterbalanced by inhibitory signals induced by receptors for MHC class I. A common pathway of inhibitory signaling is provided by immunoreceptor tyrosine-based inhibitory motifs (ITIMs) in the cytoplasmic domains of these receptors which mediate the recruitment of SH2 domain-bearing tyrosine phosphate-1 (SHP-1). In contrast to the extensive progress that has been made regarding the negative regulation of NK cell function, our knowledge of the signals that activate NK cells is still poor. Recent studies of the activating receptor complexes have shed new light on the induction of NK cell effector function. Several NK receptors using novel adaptors with immunoreceptor tyrosine-based activation motifs (ITAMs) and with PI 3-kinase recruiting motifs have been implicated in NK cell stimulation.

  9. Suppressive effects of anti-allergic agent suplatast tosilate (IPD-1151T on the expression of co-stimulatory molecules on mouse splenocytes in vivo

    Directory of Open Access Journals (Sweden)

    Masatsugu Kurokawa

    2001-01-01

    Full Text Available The effects of IPD-1151T on the expression of costimulatory molecules, CD40, CD80 and CD86, were investigated in vivo using mice with allergic disorders. BALB/c mice were immunized intraperitoneally with two doses of dinitrophenylated ovalbumin (DNP-OVA at 1-week intervals. These mice then were treated intraperitoneally with 100μg/kg of IPD1151T once a day for 14 days, starting 7 days after the first immunization. On day 21, some mice were challenged intraperitoneally with DNP-OVA and the other mice were not challenged. All mice were autopsied on day 22 and assayed for immunoglobulin E, interleuken (IL-4 and IL-5 productions following DNP-OVA immunization. The intraperitoneal treatment with IPD-1151T strongly suppressed immunoglobulin E contents in serum, which were enhanced by DNA-OVA immunization. IPD-1151T also caused a decrease in both IL-4 and IL-5 levels in splenic lymphocytes. We next examined the influence of IPD1151T on co-stimulatory molecule expression on splenic lymphocytes. IPD-1151T caused suppression of CD40 and CD86 expression; however, the treatments did not affect CD80 expression.

  10. Expression of the costimulatory molecule B7-H3 is associated with prolonged survival in human pancreatic cancer

    International Nuclear Information System (INIS)

    Loos, Martin; Hedderich, Dennis M; Ottenhausen, Malte; Giese, Nathalia A; Laschinger, Melanie; Esposito, Irene; Kleeff, Jörg; Friess, Helmut

    2009-01-01

    Costimulatory signaling has been implicated as a potential regulator of antitumor immunity in various human cancers. In contrast to the negative prognostic value of aberrant B7-H1 expression by pancreatic cancer cells, the role of B7-H3 is still unknown. Therefore, we investigated the expression pattern and clinical significance of B7-H3 expression in human pancreatic cancer. B7-H3 expression was evaluated by immunohistochemistry in 68 patients with pancreatic cancer who underwent surgical tumor resection. Expression data was correlated with clinicopathologic features and with the number of tumor-infiltrating T cells. B7-H3 expression was significantly upregulated in pancreatic cancer compared to normal pancreas (p < 0.05). In 60 of 68 examined tumors B7-H3 protein was detectable in pancreatic cancer cells. Patients with high tumor B7-H3 levels had a significantly better postoperative prognosis than patients with low tumor B7-H3 levels (p = 0.0067). Furthermore, tumor B7-H3 expression significantly correlated with the number of tumor-infiltrating CD8+ T cells (p = 0.018). We demonstrate for the first time that B7-H3 is abundantly expressed in pancreatic cancer and that tumor-associated B7-H3 expression significantly correlates with prolonged postoperative survival. Our findings suggest that B7-H3 might play an important role as a potential stimulator of antitumor immune response in pancreatic cancer

  11. Parallels between immune driven-hematopoiesis and T cell activation: 3 signals that relay inflammatory stress to the bone marrow

    Energy Technology Data Exchange (ETDEWEB)

    Libregts, Sten F.W.M.; Nolte, Martijn A., E-mail: m.nolte@sanquin.nl

    2014-12-10

    Quiescence, self-renewal, lineage commitment and differentiation of hematopoietic stem cells (HSCs) towards fully mature blood cells are a complex process that involves both intrinsic and extrinsic signals. During steady-state conditions, most hematopoietic signals are provided by various resident cells inside the bone marrow (BM), which establish the HSC micro-environment. However, upon infection, the hematopoietic process is also affected by pathogens and activated immune cells, which illustrates an effective feedback mechanism to hematopoietic stem and progenitor cells (HSPCs) via immune-mediated signals. Here, we review the impact of pathogen-associated molecular patterns (PAMPs), damage-associated molecular patterns (DAMPs), costimulatory molecules and pro-inflammatory cytokines on the quiescence, proliferation and differentiation of HSCs and more committed progenitors. As modulation of HSPC function via these immune-mediated signals holds an interesting parallel with the “three-signal-model” described for the activation and differentiation of naïve T-cells, we propose a novel “three-signal” concept for immune-driven hematopoiesis. In this model, the recognition of PAMPs and DAMPs will activate HSCs and induce proliferation, while costimulatory molecules and pro-inflammatory cytokines confer a second and third signal, respectively, which further regulate expansion, lineage commitment and differentiation of HSPCs. We review the impact of inflammatory stress on hematopoiesis along these three signals and we discuss whether they act independently from each other or that concurrence of these signals is important for an adequate response of HSPCs upon infection. - Highlights: • Inflammation and infection have a direct impact on hematopoiesis in the bone marrow. • We draw a striking parallel between immune-driven hematopoiesis and T cell activation. • We review how PAMPs and DAMPs, costimulation and cytokines influence HSPC function.

  12. Parallels between immune driven-hematopoiesis and T cell activation: 3 signals that relay inflammatory stress to the bone marrow

    International Nuclear Information System (INIS)

    Libregts, Sten F.W.M.; Nolte, Martijn A.

    2014-01-01

    Quiescence, self-renewal, lineage commitment and differentiation of hematopoietic stem cells (HSCs) towards fully mature blood cells are a complex process that involves both intrinsic and extrinsic signals. During steady-state conditions, most hematopoietic signals are provided by various resident cells inside the bone marrow (BM), which establish the HSC micro-environment. However, upon infection, the hematopoietic process is also affected by pathogens and activated immune cells, which illustrates an effective feedback mechanism to hematopoietic stem and progenitor cells (HSPCs) via immune-mediated signals. Here, we review the impact of pathogen-associated molecular patterns (PAMPs), damage-associated molecular patterns (DAMPs), costimulatory molecules and pro-inflammatory cytokines on the quiescence, proliferation and differentiation of HSCs and more committed progenitors. As modulation of HSPC function via these immune-mediated signals holds an interesting parallel with the “three-signal-model” described for the activation and differentiation of naïve T-cells, we propose a novel “three-signal” concept for immune-driven hematopoiesis. In this model, the recognition of PAMPs and DAMPs will activate HSCs and induce proliferation, while costimulatory molecules and pro-inflammatory cytokines confer a second and third signal, respectively, which further regulate expansion, lineage commitment and differentiation of HSPCs. We review the impact of inflammatory stress on hematopoiesis along these three signals and we discuss whether they act independently from each other or that concurrence of these signals is important for an adequate response of HSPCs upon infection. - Highlights: • Inflammation and infection have a direct impact on hematopoiesis in the bone marrow. • We draw a striking parallel between immune-driven hematopoiesis and T cell activation. • We review how PAMPs and DAMPs, costimulation and cytokines influence HSPC function

  13. Engineering tolerance using biomaterials to target and control antigen presenting cells.

    Science.gov (United States)

    Tostanoski, Lisa H; Gosselin, Emily A; Jewell, Christopher M

    2016-05-01

    Autoimmune diseases occur when cells of the adaptive immune system incorrectly recognize and attack "self" tissues. Importantly, the proliferation and differentiation of these cells is triggered and controlled by interactions with antigen presenting cells (APCs), such as dendritic cells. Thus, modulating the signals transduced by APCs (e.g., cytokines, costimulatory surface proteins) has emerged as a promising strategy to promote tolerance for diseases such as multiple sclerosis, type 1 diabetes, and lupus. However, many approaches have been hindered by non-specific activity of immunosuppressive or immunoregulatory cues, following systemic administration of soluble factors via traditional injections routes (e.g., subcutaneous, intravenous). Biomaterials offer a unique opportunity to control the delivery of tolerogenic signals in vivo via properties such as controlled particle size, tunable release kinetics, and co-delivery of multiple classes of cargo. In this review, we highlight recent reports that exploit these properties of biomaterials to target APCs and promote tolerance via three strategies, i) passive or active targeting of particulate carriers to APCs, ii) biomaterial-mediated control over antigen localization and processing, and iii) targeted delivery of encapsulated or adsorbed immunomodulatory signals. These reports represent exciting advances toward the goal of more effective therapies for autoimmune diseases, without the broad suppressive effects associated with current clinically-approved therapies.

  14. Diabetes: Models, Signals and control

    Science.gov (United States)

    Cobelli, C.

    2010-07-01

    Diabetes and its complications impose significant economic consequences on individuals, families, health systems, and countries. The control of diabetes is an interdisciplinary endeavor, which includes significant components of modeling, signal processing and control. Models: first, I will discuss the minimal (coarse) models which describe the key components of the system functionality and are capable of measuring crucial processes of glucose metabolism and insulin control in health and diabetes; then, the maximal (fine-grain) models which include comprehensively all available knowledge about system functionality and are capable to simulate the glucose-insulin system in diabetes, thus making it possible to create simulation scenarios whereby cost effective experiments can be conducted in silico to assess the efficacy of various treatment strategies - in particular I will focus on the first in silico simulation model accepted by FDA as a substitute to animal trials in the quest for optimal diabetes control. Signals: I will review metabolic monitoring, with a particular emphasis on the new continuous glucose sensors, on the crucial role of models to enhance the interpretation of their time-series signals, and on the opportunities that they present for automation of diabetes control. Control: I will review control strategies that have been successfully employed in vivo or in silico, presenting a promise for the development of a future artificial pancreas and, in particular, I will discuss a modular architecture for building closed-loop control systems, including insulin delivery and patient safety supervision layers.

  15. Dividing traffic cluster into parts by signal control

    Science.gov (United States)

    Nagatani, Takashi

    2018-02-01

    When a cluster of vehicles with various speeds moves through the series of signals, the cluster breaks down by stopping at signals and results in smaller groups of vehicles. We present the nonlinear-map model of the motion of vehicles controlled by the signals. We study the breakup of a cluster of vehicles through the series of signals. The cluster of vehicles is divided into various groups by controlling the cycle time of signals. The vehicles within each group move with the same mean velocity. The breakup of the traffic cluster depends highly on the signal control. The dependence of dividing on both cycle time and vehicular speed is clarified. Also, we investigate the effect of the irregular interval between signals on dividing.

  16. CD80 and CD86 IgC domains are important for quaternary structure, receptor binding and co-signaling function.

    Science.gov (United States)

    Girard, Tanya; Gaucher, Denis; El-Far, Mohamed; Breton, Gaëlle; Sékaly, Rafick-Pierre

    2014-09-01

    CD86 and CD80, the ligands for the co-stimulatory molecules CD28 and CTLA-4, are members of the Ig superfamily. Their structure includes Ig variable-like (IgV) domains, Ig constant-like (IgC) domains and intracellular domains. Although crystallographic studies have clearly identified the IgV domain to be responsible for receptor interactions, earlier studies suggested that both Ig domains are required for full co-signaling function. Herein, we have used deletion and chimeric human CD80 and CD86 molecules in co-stimulation assays to study the impact of the multimeric state of IgV and IgC domains on receptor binding properties and on co-stimulatory function in a peptide-specific T cell activation model. We report for the first time the presence of CD80 dimers and CD86 monomers in living cells. Moreover, we show that the IgC domain of both molecules inhibits multimer formation and greatly affects binding to the co-receptors CD28 and CTLA-4. Finally, both IgC and intracellular domains are required for full co-signaling function. These findings reveal the distinct but complementary roles of CD80 and CD86 IgV and IgC domains in T cell activation. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Supraphysiologic control over HIV-1 replication mediated by CD8 T cells expressing a re-engineered CD4-based chimeric antigen receptor.

    Directory of Open Access Journals (Sweden)

    Rachel S Leibman

    2017-10-01

    Full Text Available HIV is adept at avoiding naturally generated T cell responses; therefore, there is a need to develop HIV-specific T cells with greater potency for use in HIV cure strategies. Starting with a CD4-based chimeric antigen receptor (CAR that was previously used without toxicity in clinical trials, we optimized the vector backbone, promoter, HIV targeting moiety, and transmembrane and signaling domains to determine which components augmented the ability of T cells to control HIV replication. This re-engineered CAR was at least 50-fold more potent in vitro at controlling HIV replication than the original CD4 CAR, or a TCR-based approach, and substantially better than broadly neutralizing antibody-based CARs. A humanized mouse model of HIV infection demonstrated that T cells expressing optimized CARs were superior at expanding in response to antigen, protecting CD4 T cells from infection, and reducing viral loads compared to T cells expressing the original, clinical trial CAR. Moreover, in a humanized mouse model of HIV treatment, CD4 CAR T cells containing the 4-1BB costimulatory domain controlled HIV spread after ART removal better than analogous CAR T cells containing the CD28 costimulatory domain. Together, these data indicate that potent HIV-specific T cells can be generated using improved CAR design and that CAR T cells could be important components of an HIV cure strategy.

  18. CD28-CD80 interactions control regulatory T cell motility and immunological synapse formation1,2

    Science.gov (United States)

    Thauland, Timothy J.; Koguchi, Yoshinobu; Dustin, Michael L.; Parker, David C.

    2014-01-01

    Regulatory T cells (Tregs) are essential for tolerance to self and environmental antigens, acting in part by downmodulating costimulatory molecules on the surface of dendritic cells (DCs) and altering naïve CD4 T cell-DC interactions. Here, we show that Tregs form stable conjugates with DCs before, but not after, they decrease surface expression of the costimulatory molecule CD80 on the DCs. We use supported planar bilayers to show that Tregs dramatically slow down, but maintain a highly polarized and motile phenotype after recognizing antigen in the absence of costimulation. These motile cells are characterized by distinct accumulations of LFA-1-ICAM-1 in the lamella and TCR-MHC in the uropod, consistent with a motile immunological synapse or ‘kinapse’. However, in the presence of high, but not low, concentrations of CD80, Tregs form stationary, symmetrical synapses. Using blocking antibodies, we show that, while CTLA-4 is required for CD80 downmodulation, CD28-CD80 interactions are critical for modulating Treg motility in the presence of antigen. Together, these results support the hypothesis that Tregs are tuned to alter their motility depending on costimulatory signals. PMID:25355918

  19. Toward Small-Molecule Inhibition of Protein-Protein Interactions: General Aspects and Recent Progress in Targeting Costimulatory and Coinhibitory (Immune Checkpoint) Interactions.

    Science.gov (United States)

    Bojadzic, Damir; Buchwald, Peter

    2018-05-30

    Protein-protein interactions (PPIs) that are part of the costimulatory and coinhibitory (immune checkpoint) signaling are critical for adequate T cell response and are important therapeutic targets for immunomodulation. Biologics targeting them have already achieved considerable clinical success in the treatment of autoimmune diseases or transplant recipients (e.g., abatacept, belatacept, and belimumab) as well as cancer (e.g., ipilimumab, nivolumab, pembrolizumab, atezolizumab, durvalumab, and avelumab). In view of such progress, there have been only relatively limited efforts toward developing small-molecule PPI inhibitors (SMPPIIs) targeting these cosignaling interactions, possibly because they, as all other PPIs, are difficult to target by small molecules and were not considered druggable. Nevertheless, substantial progress has been achieved during the last decade. SMPPIIs proving the feasibility of such approaches have been identified through various strategies for a number of cosignaling interactions including CD40-CD40L, OX40-OX40L, BAFFR-BAFF, CD80-CD28, and PD-1-PD-L1s. Here, after an overview of the general aspects and challenges of SMPPII-focused drug discovery, we review them briefly together with relevant structural, immune-signaling, physicochemical, and medicinal chemistry aspects. While so far only a few of these SMPPIIs have shown activity in animal models (DRI-C21045 for CD40-D40L, KR33426 for BAFFR-BAFF) or reached clinical development (RhuDex for CD80-CD28, CA-170 for PD-1-PD-L1), there is proof-of-principle evidence for the feasibility of such approaches in immunomodulation. They can result in products that are easier to develop/manufacture and are less likely to be immunogenic or encounter postmarket safety events than corresponding biologics, and, contrary to them, can even become orally bioavailable. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  20. Safety Impacts of the Actuated Signal Control at Urban Intersections

    Directory of Open Access Journals (Sweden)

    Sang Hyuk Lee

    2016-02-01

    Full Text Available To reduce travel time, the actuated signal controls have been implemented at urban intersections. However, the safety impacts of actuated signal controls thus far have rarely been examined. In this assessment of the safety impact of urban intersections with semi-actuated signal controls, the safety performance functions and EB approaches were applied. The semi-actuated signal controls have increased injuries and total crashes in all crash types by around 5.9% and 3.8%, respectively. Regarding the most common crash types, such as angle, sideswipe & rear-end, and head-on crashes, semi-actuated signal controls have been seen to decrease injuries by 7.7%. Total crashes have been reduced by over 9.2% through the use of semi-actuated signal controls. This may be result of optimal signal timings considering traffic conditions during peak time periods. In conclusion, safety impact factors which have been established in this study can be used to improve safety and minimize travel times using semi-actuated signal controls.

  1. development of an electronic vehicular traffic signal controller

    African Journals Online (AJOL)

    INTRODUCTION ... The SCOOT (Split Cycle Offset Optimization Technique) signal control system implements an adaptive ... An electronic traffic signal controller is basically a sequential machine whose operation can be modeled using finite ...

  2. SDF-1/CXCR4 expression in bladder cancer tissue and the correlation with negative costimulatory molecule PD-L1, cell apoptosis and invasion

    Directory of Open Access Journals (Sweden)

    Ming-Bao Ye

    2017-06-01

    Full Text Available Objective: To study the SDF-1/CXCR4 expression in bladder cancer tissue and the correlation with negative costimulatory molecule PD-L1, cell apoptosis and invasion. Methods: A total of 118 cases of bladder cancer tissue and para-carcinoma tissue surgically removed in our hospital between May 2014 and May 2016 were selected as the research samples, the RNA was extracted and then reverse-transcribed into cDNA, and the expression levels of SDF-1/ CXCR4, PD-L1/PD-1, cell apoptosis-related molecules and cell invasion-related molecules were detected. Results: SDF-1 and CXCR4 mRNA expression in bladder cancer tissue were significantly higher than those in para-carcinoma tissue; PD-L1, PD-1, Rec1, Survivin, MRPS5, Nanog, BCAPP2Ac, TRPM8, TRPV2, ILK, β-catenin and GUGBP1 mRNA expression in bladder cancer tissue were significantly higher than those in para-carcinoma tissue and positively correlated with SDF-1 and CXCR4 mRNA expression. Conclusion: Highly expressed SDF-1/CXCR4 in bladder cancer tissue are closely related to the high expression of negative costimulatory molecule PD-L1, pro-proliferation molecules and proinvasion molecules, and SDF-1/CXCR4 can promote the immune escape, proliferation and invasion of bladder cancer cells.

  3. Distributed traffic signal control using fuzzy logic

    Science.gov (United States)

    Chiu, Stephen

    1992-01-01

    We present a distributed approach to traffic signal control, where the signal timing parameters at a given intersection are adjusted as functions of the local traffic condition and of the signal timing parameters at adjacent intersections. Thus, the signal timing parameters evolve dynamically using only local information to improve traffic flow. This distributed approach provides for a fault-tolerant, highly responsive traffic management system. The signal timing at an intersection is defined by three parameters: cycle time, phase split, and offset. We use fuzzy decision rules to adjust these three parameters based only on local information. The amount of change in the timing parameters during each cycle is limited to a small fraction of the current parameters to ensure smooth transition. We show the effectiveness of this method through simulation of the traffic flow in a network of controlled intersections.

  4. Brushless DC motor control system responsive to control signals generated by a computer or the like

    Science.gov (United States)

    Packard, Douglas T. (Inventor); Schmitt, Donald E. (Inventor)

    1987-01-01

    A control system for a brushless DC motor responsive to digital control signals is disclosed. The motor includes a multiphase wound stator and a permanent magnet rotor. The rotor is arranged so that each phase winding, when energized from a DC source, will drive the rotor through a predetermined angular position or step. A commutation signal generator responsive to the shaft position provides a commutation signal for each winding. A programmable control signal generator such as a computer or microprocessor produces individual digital control signals for each phase winding. The control signals and commutation signals associated with each winding are applied to an AND gate for that phase winding. Each gate controls a switch connected in series with the associated phase winding and the DC source so that each phase winding is energized only when the commutation signal and the control signal associated with that phase winding are present. The motor shaft may be advanced one step at a time to a desired position by applying a predetermined number of control signals in the proper sequence to the AND gates and the torque generated by the motor may be regulated by applying a separate control signal to each AND gate which is pulse width modulated to control the total time that each switch connects its associated winding to the DC source during each commutation period.

  5. CD137 is induced by the CD40 signal on chronic lymphocytic leukemia B cells and transduces the survival signal via NF-κB activation.

    Directory of Open Access Journals (Sweden)

    Yukana Nakaima

    Full Text Available CD137 is a member of the tumor necrosis factor receptor family that is expressed on activated T cells. This molecule provides a co-stimulatory signal that enhances the survival, and differentiation of cells, and has a crucial role in the development of CD8 cytotoxic T cells and anti-tumor immunity. Here we report that CD137 expression is also induced on normal or malignant human B cells by CD40 ligation by its ligand CD154. This CD137 induction was more prominent in chronic lymphocytic leukemia (CLL cells than in other types of B cells. CD137 stimulation on B cells by its ligand induced the nuclear translocation of p52 (a non-canonical NF-κB factor. In agreement with this finding, expression of the survival factor BCL-XL was upregulated. Consequently, the CD137 signal augmented the survival of CD154-stimulated CLL B cells in vitro. This unexpected induction of CD137 on B cells by CD40 signal may influence the clinical course of CLL.

  6. Pedestrian Friendly Traffic Signal Control.

    Science.gov (United States)

    2016-01-01

    This project continues research aimed at real-time detection and use of pedestrian : traffic flow information to enhance adaptive traffic signal control in urban areas : where pedestrian traffic is substantial and must be given appropriate attention ...

  7. Control of striatal signaling by G protein regulators

    Directory of Open Access Journals (Sweden)

    Keqiang eXie

    2011-08-01

    Full Text Available Signaling via heterotrimeric G proteins plays a crucial role in modulating the responses of striatal neurons that ultimately shape core behaviors mediated by the basal ganglia circuitry, such as reward valuation, habit formation and movement coordination. Activation of G-protein-coupled receptors (GPCRs by extracellular signals activates heterotrimeric G proteins by promoting the binding of GTP to their α subunits. G proteins exert their effects by influencing the activity of key effector proteins in this region, including ion channels, second messenger enzymes and protein kinases. Striatal neurons express a staggering number of GPCRs whose activation results in the engagement of downstream signaling pathways and cellular responses with unique profiles but common molecular mechanisms. Studies over the last decade have revealed that the extent and duration of GPCR signaling are controlled by a conserved protein family named Regulator of G protein Signaling (RGS. RGS proteins accelerate GTP hydrolysis by the α subunits of G proteins, thus promoting deactivation of GPCR signaling. In this review, we discuss the progress made in understanding the roles of RGS proteins in controlling striatal G protein signaling and providing integration and selectivity of signal transmission. We review evidence on the formation of a macromolecular complex between RGS proteins and other components of striatal signaling pathways, their molecular regulatory mechanisms and impacts on GPCR signaling in the striatum obtained from biochemical studies and experiments involving genetic mouse models. Special emphasis is placed on RGS9-2, a member of the RGS family that is highly enriched in the striatum and plays critical roles in drug addiction and motor control.

  8. Digital signal processing in power system protection and control

    CERN Document Server

    Rebizant, Waldemar; Wiszniewski, Andrzej

    2011-01-01

    Digital Signal Processing in Power System Protection and Control bridges the gap between the theory of protection and control and the practical applications of protection equipment. Understanding how protection functions is crucial not only for equipment developers and manufacturers, but also for their users who need to install, set and operate the protection devices in an appropriate manner. After introductory chapters related to protection technology and functions, Digital Signal Processing in Power System Protection and Control presents the digital algorithms for signal filtering, followed

  9. Signal differentiation in position tracking control of dc motors

    International Nuclear Information System (INIS)

    Beltran-Carbajal, F; Valderrabano-Gonzalez, A; Rosas-Caro, J C

    2015-01-01

    An asymptotic differentiation approach with respect to time is used for on-line estimation of velocity and acceleration signals in controlled dc motors. The attractive feature of this differentiator of signals is that it does not require any system mathematical model, which allows its use in engineering systems that require the signal differentiation for its control, identification, fault detection, among other applications. Moreover, it is shown that the differentiation approach can be applied for output signals showing a chaotic behavior. In addition a differential flatness control scheme with additional integral compensation of the output error is proposed for tracking tasks of position reference trajectories for direct current electric motors using angular position measurements only

  10. Net analyte signal based statistical quality control

    NARCIS (Netherlands)

    Skibsted, E.T.S.; Boelens, H.F.M.; Westerhuis, J.A.; Smilde, A.K.; Broad, N.W.; Rees, D.R.; Witte, D.T.

    2005-01-01

    Net analyte signal statistical quality control (NAS-SQC) is a new methodology to perform multivariate product quality monitoring based on the net analyte signal approach. The main advantage of NAS-SQC is that the systematic variation in the product due to the analyte (or property) of interest is

  11. Intersection signal control multi-objective optimization based on genetic algorithm

    OpenAIRE

    Zhanhong Zhou; Ming Cai

    2014-01-01

    A signal control intersection increases not only vehicle delay, but also vehicle emissions and fuel consumption in that area. Because more and more fuel and air pollution problems arise recently, an intersection signal control optimization method which aims at reducing vehicle emissions, fuel consumption and vehicle delay is required heavily. This paper proposed a signal control multi-object optimization method to reduce vehicle emissions, fuel consumption and vehicle delay simultaneously at ...

  12. Programs for control of an analog-signal switching network

    International Nuclear Information System (INIS)

    D'Ottavio, T.; Enriquez, R.; Katz, R.; Skelly, J.

    1989-01-01

    A suite of programs has been developed to control the network of analog-signal switching multiplexers in the AGS complex. The software is driven by a relational database which describes the architecture of the multiplexer tree and the set of available analog signals. Signals are routed through a three-layer multiplexer tree, to be made available at four consoles each with three 4-trace oscilloscopes. A menu-structured operator interface program is available at each console, to accept requests to route any available analog signal to any of that console's 12 oscilloscope traces. A common routing-server program provides automatic routing-server program provides automatic routing of requested signals through the layers of multiplexers, maintaining a reservation database to denote free and in-use trunks. Expansion of the analog signal system is easily accommodated in software by adding new signals, trunks, multiplexers, or consoles to the database. Programmatic control of the triggering signals for each of the oscilloscopes is also provided. 3 refs., 4 figs., 3 tabs

  13. Continuous residual reinforcement learning for traffic signal control optimization

    NARCIS (Netherlands)

    Aslani, Mohammad; Seipel, Stefan; Wiering, Marco

    2018-01-01

    Traffic signal control can be naturally regarded as a reinforcement learning problem. Unfortunately, it is one of the most difficult classes of reinforcement learning problems owing to its large state space. A straightforward approach to address this challenge is to control traffic signals based on

  14. Power system small signal stability analysis and control

    CERN Document Server

    Mondal, Debasish; Sengupta, Aparajita

    2014-01-01

    Power System Small Signal Stability Analysis and Control presents a detailed analysis of the problem of severe outages due to the sustained growth of small signal oscillations in modern interconnected power systems. The ever-expanding nature of power systems and the rapid upgrade to smart grid technologies call for the implementation of robust and optimal controls. Power systems that are forced to operate close to their stability limit have resulted in the use of control devices by utility companies to improve the performance of the transmission system against commonly occurring power system

  15. Route-Based Signal Preemption Control of Emergency Vehicle

    Directory of Open Access Journals (Sweden)

    Haibo Mu

    2018-01-01

    Full Text Available This paper focuses on the signal preemption control of emergency vehicles (EV. A signal preemption control method based on route is proposed to reduce time delay of EV at intersections. According to the time at which EV is detected and the current phase of each intersection on the travelling route of EV, the calculation methods of the earliest start time and the latest start time of green light at each intersection are given. Consequently, the effective time range of green light at each intersection is determined in theory. A multiobjective programming model, whose objectives are the minimal residence time of EV at all intersections and the maximal passing numbers of general society vehicles, is presented. Finally, a simulation calculation is carried out. Calculation results indicate that, by adopting the signal preemption method based on route, the delay of EV is reduced and the number of society vehicles passing through the whole system is increased. The signal preemption control method of EV based on route can reduce the time delay of EV and improve the evacuation efficiency of the system.

  16. FireSignal application Node for subsystem control

    International Nuclear Information System (INIS)

    Duarte, A.S.; Santos, B.; Pereira, T.; Carvalho, B.B.; Fernandes, H.; Neto, A.; Janky, F.; Cahyna, P.; Pisacka, J.; Hron, M.

    2010-01-01

    Modern fusion experiments require the presence of several subsystems, responsible for the different parameters involved in the operation of the machine. With the migration from the pre-programmed to the real-time control paradigm, their integration in Control, Data Acquisition, and Communication (CODAC) systems became an important issue, as this implies not only the connection to a main central coordination system, but also communications with related diagnostics and actuators. A subsystem for the control and operation of the vacuum, gas injection and baking was developed and installed in the COMPASS tokamak. These tasks are performed by dsPIC microcontrollers that receive commands from a hub computer and send information regarding the status of the operation. Communications are done in the serial protocol RS-232 through fibre optics. Java software, with an intuitive graphical user interface, for controlling and monitoring of the subsystem was developed and installed in a hub computer. In order to allow operators to perform these tasks remotely besides locally, this was integrated in the FireSignal system. Taking advantage of FireSignal features, it was possible to provide the users with, not only the same functionalities of the local application but also a similar user interface. An independent FireSignal Java Node bridges the central server and the control application. This design makes possible to easily reuse the Node for other subsystems or integrate the vacuum slow control in the other CODAC systems. The complete system, with local and remote control, has been installed successfully on COMPASS and has been in operation since April this year.

  17. FireSignal Application Node for Subsystem Control

    Energy Technology Data Exchange (ETDEWEB)

    Duarte, A.; Santos, B.; Pereira, T.; Carvalho, B.; Fernandes, H. [Instituto de Plasmas e Fusao Nuclear - Instituto Superior Tecnico, Lisbon (Portugal); Cahyna, P.; Pisacka, J.; Hron, M. [Institute of Plasma Physics AS CR, Association EURATOM/IPP.CR, Prague (Czech Republic)

    2009-07-01

    Modern fusion experiments require the presence of several sub-systems, responsible for the different parameters involved in the operation of the machine. With the migration from the pre-programmed to the real-time control paradigm, their integration in Control, Data Acquisition, and Communication (CODAC) systems became an important issue, as this implies not only the connection to a main central coordination system, but also communications with related diagnostics and actuators. A sub-system for the control and operation of the vacuum, gas injection and baking was developed and installed in the COMPASS tokamak. These tasks are performed by 'dsPIC' micro-controllers that receive commands from a computer and send information regarding the status of the operation. Communications are done in the serial protocol RS-232 through fibre optics at speeds up to 1 Mbaud. A Java software, with an intuitive graphical user interface, for controlling and monitoring the sub-system was developed and installed in a hub computer. In order to allow operators to perform these tasks remotely besides locally, this was integrated in the FireSignal system. Taking advantage of FireSignal features, it was possible to provide the users with, not only the same functionalities of the local application but also a similar user interface. An independent FireSignal Java node bridges the central server and the control application. This design makes possible to easily reuse the node for other subsystems or integrate the vacuum slow control in the other CODAC systems. This document is composed of an abstract and a poster. (authors)

  18. Current Views of Toll-Like Receptor Signaling Pathways

    Directory of Open Access Journals (Sweden)

    Masahiro Yamamoto

    2010-01-01

    Full Text Available On microbial invasion, the host immediately evokes innate immune responses. Recent studies have demonstrated that Toll-like receptors (TLRs play crucial roles in innate responses that lead not only to the clearance of pathogens but also to the efficient establishment of acquired immunity by directly detecting molecules from microbes. In terms of intracellular TLR-mediated signaling pathways, cytoplasmic adaptor molecules containing Toll/IL-1R (TIR domains play important roles in inflammatory immune responses through the production of proinflammatory cytokines, nitric oxide, and type I interferon, and upregulation of costimulatory molecules. In this paper, we will describe our current understanding of the relationship between TLRs and their ligands derived from pathogens such as viruses, bacteria, fungi, and parasites. Moreover, we will review the historical and current literature to describe the mechanisms behind TLR-mediated activation of innate immune responses.

  19. Myoelectric signal processing for control of powered limb prostheses.

    Science.gov (United States)

    Parker, P; Englehart, K; Hudgins, B

    2006-12-01

    Progress in myoelectric control technology has over the years been incremental, due in part to the alternating focus of the R&D between control methodology and device hardware. The technology has over the past 50 years or so moved from single muscle control of a single prosthesis function to muscle group activity control of multifunction prostheses. Central to these changes have been developments in the means of extracting information from the myoelectric signal. This paper gives an overview of the myoelectric signal processing challenge, a brief look at the challenge from an historical perspective, the state-of-the-art in myoelectric signal processing for prosthesis control, and an indication of where this field is heading. The paper demonstrates that considerable progress has been made in providing clients with useful and reliable myoelectric communication channels, and that exciting work and developments are on the horizon.

  20. Simulation of traffic control signal systems

    Science.gov (United States)

    Connolly, P. J.; Concannon, P. A.; Ricci, R. C.

    1974-01-01

    In recent years there has been considerable interest in the development and testing of control strategies for networks of urban traffic signal systems by simulation. Simulation is an inexpensive and timely method for evaluating the effect of these traffic control strategies since traffic phenomena are too complex to be defined by analytical models and since a controlled experiment may be hazardous, expensive, and slow in producing meaningful results. This paper describes the application of an urban traffic corridor program, to evaluate the effectiveness of different traffic control strategies for the Massachusetts Avenue TOPICS Project.

  1. Chaos control applied to cardiac rhythms represented by ECG signals

    International Nuclear Information System (INIS)

    Borem Ferreira, Bianca; Amorim Savi, Marcelo; Souza de Paula, Aline

    2014-01-01

    The control of irregular or chaotic heartbeats is a key issue in cardiology. In this regard, chaos control techniques represent a good alternative since they suggest treatments different from those traditionally used. This paper deals with the application of the extended time-delayed feedback control method to stabilize pathological chaotic heart rhythms. Electrocardiogram (ECG) signals are employed to represent the cardiovascular behavior. A mathematical model is employed to generate ECG signals using three modified Van der Pol oscillators connected with time delay couplings. This model provides results that qualitatively capture the general behavior of the heart. Controlled ECG signals show the ability of the strategy either to control or to suppress the chaotic heart dynamics generating less-critical behaviors. (paper)

  2. Robust control of dielectric elastomer diaphragm actuator for human pulse signal tracking

    Science.gov (United States)

    Ye, Zhihang; Chen, Zheng; Asmatulu, Ramazan; Chan, Hoyin

    2017-08-01

    Human pulse signal tracking is an emerging technology that is needed in traditional Chinese medicine. However, soft actuation with multi-frequency tracking capability is needed for tracking human pulse signal. Dielectric elastomer (DE) is one type of soft actuating that has great potential in human pulse signal tracking. In this paper, a DE diaphragm actuator was designed and fabricated to track human pulse pressure signal. A physics-based and control-oriented model has been developed to capture the dynamic behavior of DE diaphragm actuator. Using the physical model, an H-infinity robust control was designed for the actuator to reject high-frequency sensing noises and disturbances. The robust control was then implemented in real-time to track a multi-frequency signal, which verified the tracking capability and robustness of the control system. In the human pulse signal tracking test, a human pulse signal was measured at the City University of Hong Kong and then was tracked using DE actuator at Wichita State University in the US. Experimental results have verified that the DE actuator with its robust control is capable of tracking human pulse signal.

  3. Digital Signal Processing and Control for the Study of Gene Networks

    Science.gov (United States)

    Shin, Yong-Jun

    2016-04-01

    Thanks to the digital revolution, digital signal processing and control has been widely used in many areas of science and engineering today. It provides practical and powerful tools to model, simulate, analyze, design, measure, and control complex and dynamic systems such as robots and aircrafts. Gene networks are also complex dynamic systems which can be studied via digital signal processing and control. Unlike conventional computational methods, this approach is capable of not only modeling but also controlling gene networks since the experimental environment is mostly digital today. The overall aim of this article is to introduce digital signal processing and control as a useful tool for the study of gene networks.

  4. 30 CFR 77.515 - Bare signal or control wires; voltage.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Bare signal or control wires; voltage. 77.515 Section 77.515 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR COAL MINE... COAL MINES Electrical Equipment-General § 77.515 Bare signal or control wires; voltage. The voltage on...

  5. Signal validation and failure correction algorithms for PWR steam generator feedwater control

    International Nuclear Information System (INIS)

    Nasrallah, C.N.; Graham, K.F.

    1986-01-01

    A critical contributor to the reliability of a nuclear power plant is the reliability of the control systems which maintain plant operating parameters within desired limits. The most difficult system to control in a PWR nuclear power plant and the one which causes the most reactor trips is the control of the feedwater flow to the steam generators. The level in the steam generator must be held within relatively narrow limits, with reactor trips set for both too high and too low a level. The steam generator level is inherently unstable in that it is an open integrator of feedwater flow steam flow mismatch. The steam generator feedwater control system relies on sensed variables in order to generate the appropriate feedwater valve control signal. In current systems, each of these sensed variables comes from a single sensor which may be a separate control sensor or one of the redundant protection sensors that is manually selected by the operator. In case this single signal is false, either due to sensor malfunction or due to a test signal being substituted during periodic test and maintenance, the control system will generate a wrong control signal to the feedwater control valve. This will initiate a steam generator level upset. The solution to this problem is for the control system to sense a given variable with more than one redundant sensor. Normally there are three or four sensors for each variable monitored by the reactor protection system. The techniques discussed allow the control system to compare these redundant sensor signals and generate a validated signal for each measured variable that is insensitive to false signals

  6. Robust Bio-Signal Based Control of an Intelligent Wheelchair

    Directory of Open Access Journals (Sweden)

    Dongyi Chen

    2013-09-01

    Full Text Available In this paper, an adaptive human-machine interaction (HMI method that is based on surface electromyography (sEMG signals is proposed for the hands-free control of an intelligent wheelchair. sEMG signals generated by the facial movements are obtained by a convenient dry electrodes sensing device. After the signals features are extracted from the autoregressive model, control data samples are updated and trained by an incremental online learning algorithm in real-time. Experimental results show that the proposed method can significantly improve the classification accuracy and training speed. Moreover, this method can effectively reduce the influence of muscle fatigue during a long time operation of sEMG-based HMI.

  7. CD28 Aptamers as Powerful Immune Response Modulators

    Directory of Open Access Journals (Sweden)

    Fernando Pastor

    2013-01-01

    Full Text Available CD28 is one of the main costimulatory receptors responsible for the proper activation of T lymphocytes. We have isolated two aptamers that bind to the CD28 receptor. As a monomer, one of them interfered with the binding of CD28 to its ligand (B7, precluding the costimulatory signal, whereas the other one was inactive. However, dimerization of any of the anti-CD28 aptamers was sufficient to provide an artificial costimulatory signal. No antibody has featured a dual function (i.e., the ability to work as agonist and antagonist to date. Two different agonistic structures were engineered for each anti-CD28 aptamer. One showed remarkably improved costimulatory properties, surpassing the agonistic effect of an anti-CD28 antibody. Moreover, we showed in vivo that the CD28 agonistic aptamer is capable of enhancing the cellular immune response against a lymphoma idiotype and of prolonging survival of mice which receive the aptamer together with an idiotype vaccine. The CD28 aptamers described in this work could be used to modulate the immune response either blocking the interaction with B7 or enhancing vaccine-induced immune responses in cancer immunotherapy.

  8. Control of earphone produced binaural signals

    DEFF Research Database (Denmark)

    Hammershøi, Dorte; Hoffmann, Pablo F.

    2011-01-01

    While most people keep a high attention to the significance of the binaural recording method, whether it is e.g. individual or non-individual (as e.g. artificial head recording), many pay less attention to the type of earphone used to reproduce the binaural signals, and to the accurate control...

  9. Light signals for road traffic control.

    NARCIS (Netherlands)

    Schreuder, D.A.

    1981-01-01

    Signals for road traffic control are a major constituent of the modern traffic scene, particularly in built-up areas. A vast amount of research has been executed in the last two decennia, resulting in a fairly generally accepted view on what the requirements for effective traffic lights are. For the

  10. Decentralized Hierarchical Controller Design for Selective Damping of Inter Area Oscillations Using PMU Signals

    Directory of Open Access Journals (Sweden)

    Ashfaque Ahmed Hashmani

    2011-07-01

    Full Text Available This paper deals with the decentralized hierarchical PSS (Power System Stabilizer controller design to achieve a better damping of specific inter-area oscillations. The two-level decentralized hierarchical structure consists of two PSS controllers. The first level controller is a local PSS controller for each generator to damp local mode in the area where controller is located. This controller uses only local signals as input signals. The local signal comes from the generator at which the controller is located. The secondary level controller is a multivariable decentralized global PSS controller to damp inter-area modes. This controller uses selected suitable wide area PMU (Phasor Measurement Units signals as inputs. The PMU or global signals are taken from network locations where the oscillations are well observable. The global controller uses only those global input signals in which the assigned single inter-area mode is most observable and is located at a generator that is most effective in controlling the assigned mode. The global controller works mainly in a frequency band given by the natural frequency of the assigned mode. The effectiveness of the resulting hierarchical controller is demonstrated through simulation studies conducted on a test power system.

  11. Pak2 Controls Acquisition of NKT Cell Fate by Regulating Expression of the Transcription Factors PLZF and Egr2

    Science.gov (United States)

    O’Hagan, Kyle L.; Zhao, Jie; Pryshchep, Olga; Wang, Chyung-Ru

    2015-01-01

    NKT cells constitute a small population of T cells developed in the thymus that produce large amounts of cytokines and chemokines in response to lipid Ags. Signaling through the Vα14-Jα18 TCR instructs commitment to the NKT cell lineage, but the precise signaling mechanisms that instruct their lineage choice are unclear. In this article, we report that the cytoskeletal remodeling protein, p21-activated kinase 2 (Pak2), was essential for NKT cell development. Loss of Pak2 in T cells reduced stage III NKT cells in the thymus and periphery. Among different NKT cell subsets, Pak2 was necessary for the generation and function of NKT1 and NKT2 cells, but not NKT17 cells. Mechanistically, expression of Egr2 and promyelocytic leukemia zinc finger (PLZF), two key transcription factors for acquiring the NKT cell fate, were markedly diminished in the absence of Pak2. Diminished expression of Egr2 and PLZF were not caused by aberrant TCR signaling, as determined using a Nur77-GFP reporter, but were likely due to impaired induction and maintenance of signaling lymphocyte activation molecule 6 expression, a TCR costimulatory receptor required for NKT cell development. These data suggest that Pak2 controls thymic NKT cell development by providing a signal that links Egr2 to induce PLZF, in part by regulating signaling lymphocyte activation molecule 6 expression. PMID:26519537

  12. Intersection signal control multi-objective optimization based on genetic algorithm

    Directory of Open Access Journals (Sweden)

    Zhanhong Zhou

    2014-04-01

    Full Text Available A signal control intersection increases not only vehicle delay, but also vehicle emissions and fuel consumption in that area. Because more and more fuel and air pollution problems arise recently, an intersection signal control optimization method which aims at reducing vehicle emissions, fuel consumption and vehicle delay is required heavily. This paper proposed a signal control multi-object optimization method to reduce vehicle emissions, fuel consumption and vehicle delay simultaneously at an intersection. The optimization method combined the Paramics microscopic traffic simulation software, Comprehensive Modal Emissions Model (CMEM, and genetic algorithm. An intersection in Haizhu District, Guangzhou, was taken for a case study. The result of the case study shows the optimal timing scheme obtained from this method is better than the Webster timing scheme.

  13. Warts signaling controls organ and body growth through regulation of ecdysone

    DEFF Research Database (Denmark)

    Møller, Morten Erik; Nagy, Stanislav; Gerlach, Stephan Uwe

    2017-01-01

    Coordination of growth between individual organs and the whole body is essential during development to produce adults with appropriate size and proportions [1, 2]. How local organ-intrinsic signals and nutrient-dependent systemic factors are integrated to generate correctly proportioned organisms...... under different environmental conditions is poorly understood. In Drosophila, Hippo/Warts signaling functions intrinsically to regulate tissue growth and organ size [3, 4], whereas systemic growth is controlled via antagonistic interactions of the steroid hormone ecdysone and nutrient-dependent insulin....../insulin-like growth factor (IGF) (insulin) signaling [2, 5]. The interplay between insulin and ecdysone signaling regulates systemic growth and controls organismal size. Here, we show that Warts (Wts; LATS1/2) signaling regulates systemic growth in Drosophila by activating basal ecdysone production, which negatively...

  14. Development of remote control software for multiformat test signal generator

    Directory of Open Access Journals (Sweden)

    Gao Yang

    2017-01-01

    Full Text Available The multi format test signal generator mentioned in this paper is the video signal generator named TG8000 produced by Tektronix Company. I will introduce the function about remote control for signal generator, how to connect the computer to the instrument, and how to remote control. My topic uses my computer to connect the instrument through the 10/100/1000 BASE-T port on the rear panel of TG8000. Then I write program to transmit SCPI (Standard Commands for Programmable Instruments to control TG8000. The application is running on the Windows operating system, the programming language is C#, development environment is Microsoft Visual Studio 2010, using the TCP/IP protocol based on Socket. And the method of remote control refers to the application called TGSetup which is developed by Tektronix Company. This paper includes a brief summary of the basic principle, and introduce for details about the process of remote control software development, and how to use my software. In the end, I will talk about the advantages of my software compared with another one.

  15. Hedonic and incentive signals for body weight control.

    Science.gov (United States)

    Egecioglu, Emil; Skibicka, Karolina P; Hansson, Caroline; Alvarez-Crespo, Mayte; Friberg, P Anders; Jerlhag, Elisabet; Engel, Jörgen A; Dickson, Suzanne L

    2011-09-01

    Here we review the emerging neurobiological understanding of the role of the brain's reward system in the regulation of body weight in health and in disease. Common obesity is characterized by the over-consumption of palatable/rewarding foods, reflecting an imbalance in the relative importance of hedonic versus homeostatic signals. The popular 'incentive salience theory' of food reward recognises not only a hedonic/pleasure component ('liking') but also an incentive motivation component ('wanting' or 'reward-seeking'). Central to the neurobiology of the reward mechanism is the mesoaccumbal dopamine system that confers incentive motivation not only for natural rewards such as food but also by artificial rewards (eg. addictive drugs). Indeed, this mesoaccumbal dopamine system receives and integrates information about the incentive (rewarding) value of foods with information about metabolic status. Problematic over-eating likely reflects a changing balance in the control exerted by hypothalamic versus reward circuits and/or it could reflect an allostatic shift in the hedonic set point for food reward. Certainly, for obesity to prevail, metabolic satiety signals such as leptin and insulin fail to regain control of appetitive brain networks, including those involved in food reward. On the other hand, metabolic control could reflect increased signalling by the stomach-derived orexigenic hormone, ghrelin. We have shown that ghrelin activates the mesoaccumbal dopamine system and that central ghrelin signalling is required for reward from both chemical drugs (eg alcohol) and also from palatable food. Future therapies for problematic over-eating and obesity may include drugs that interfere with incentive motivation, such as ghrelin antagonists.

  16. Coordinated signal control for arterial intersections using fuzzy logic

    Science.gov (United States)

    Kermanian, Davood; Zare, Assef; Balochian, Saeed

    2013-09-01

    Every day growth of the vehicles has become one of the biggest problems of urbanism especially in major cities. This can waste people's time, increase the fuel consumption, air pollution, and increase the density of cars and vehicles. Fuzzy controllers have been widely used in many consumer products and industrial applications with success over the past two decades. This article proposes a comprehensive model of urban traffic network using state space equations and then using Fuzzy Logic Tool Box and SIMULINK Program MATLAB a fuzzy controller in order to optimize and coordinate signal control at two intersections at an arterial road. The fuzzy controller decides to extend, early cut or terminate a signal phase and phase sequence to ensure smooth flow of traffic with minimal waiting time and length of queue. Results show that the performance of the proposed traffic controller at novel fuzzy model is better that of conventional controllers under normal and abnormal traffic conditions.

  17. The Signal Detection and Control Circuit Design for Confocal Auto-Focus System

    OpenAIRE

    Yin Liu; Jin Yu; Zeqiang Mo

    2016-01-01

    Based on the demands of Confocal Auto-Focus system, the implementation method of signal measurement circuit and control circuit is given. Using the high performance instrumental amplifier AD620BN, low noise precision FET Op amplifier AD795JRZ and ultralow offset voltage Op amplifier OP07EP, a signal measurement circuit used to converse the two differential light intensity signal to electric signal is designed. And a control circuit which takes MCU MSP430F149 as core processes the former signa...

  18. Cell proliferation control by Notch signalling during imaginal discs development in Drosophila

    Directory of Open Access Journals (Sweden)

    Carlos Estella

    2015-02-01

    Full Text Available The Notch signalling pathway is evolutionary conserved and participates in numerous developmental processes, including the control of cell proliferation. However, Notch signalling can promote or restrain cell division depending on the developmental context, as has been observed in human cancer where Notch can function as a tumor suppressor or an oncogene. Thus, the outcome of Notch signalling can be influenced by the cross-talk between Notch and other signalling pathways. The use of model organisms such as Drosophila has been proven to be very valuable to understand the developmental role of the Notch pathway in different tissues and its relationship with other signalling pathways during cell proliferation control. Here we review recent studies in Drosophila that shed light in the developmental control of cell proliferation by the Notch pathway in different contexts such as the eye, wing and leg imaginal discs. We also discuss the autonomous and non-autonomous effects of the Notch pathway on cell proliferation and its interactions with different signalling pathways.

  19. Regulator of G-Protein Signaling 7 Regulates Reward Behavior by Controlling Opioid Signaling in the Striatum.

    Science.gov (United States)

    Sutton, Laurie P; Ostrovskaya, Olga; Dao, Maria; Xie, Keqiang; Orlandi, Cesare; Smith, Roy; Wee, Sunmee; Martemyanov, Kirill A

    2016-08-01

    Morphine mediates its euphoric and analgesic effects by acting on the μ-opioid receptor (MOR). MOR belongs to the family of G-protein coupled receptors whose signaling efficiency is controlled by the regulator of G-protein signaling (RGS) proteins. Our understanding of the molecular diversity of RGS proteins that control MOR signaling, their circuit specific actions, and underlying cellular mechanisms is very limited. We used genetic approaches to ablate regulator of G-protein signaling 7 (RGS7) both globally and in specific neuronal populations. We used conditioned place preference and self-administration paradigms to examine reward-related behavior and a battery of tests to assess analgesia, tolerance, and physical dependence to morphine. Electrophysiology approaches were applied to investigate the impact of RGS7 on morphine-induced alterations in neuronal excitability and plasticity of glutamatergic synapses. At least three animals were used for each assessment. Elimination of RGS7 enhanced reward, increased analgesia, delayed tolerance, and heightened withdrawal in response to morphine administration. RGS7 in striatal neurons was selectively responsible for determining the sensitivity of rewarding and reinforcing behaviors to morphine without affecting analgesia, tolerance, and withdrawal. In contrast, deletion of RGS7 in dopaminergic neurons did not influence morphine reward. RGS7 exerted its effects by controlling morphine-induced changes in excitability of medium spiny neurons in nucleus accumbens and gating the compositional plasticity of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid and N-methyl-D-aspartate receptors. This study identifies RGS7 as a novel regulator of MOR signaling by dissecting its circuit specific actions and pinpointing its role in regulating morphine reward by controlling the activity of nucleus accumbens neurons. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  20. Control of stochastic resonance in bistable systems by using periodic signals

    International Nuclear Information System (INIS)

    Min, Lin; Li-Min, Fang; Yong-Jun, Zheng

    2009-01-01

    According to the characteristic structure of double wells in bistable systems, this paper analyses stochastic fluctuations in the single potential well and probability transitions between the two potential wells and proposes a method of controlling stochastic resonance by using a periodic signal. Results of theoretical analysis and numerical simulation show that the phenomenon of stochastic resonance happens when the time scales of the periodic signal and the noise-induced probability transitions between the two potential wells achieve stochastic synchronization. By adding a bistable system with a controllable periodic signal, fluctuations in the single potential well can be effectively controlled, thus affecting the probability transitions between the two potential wells. In this way, an effective control can be achieved which allows one to either enhance or realize stochastic resonance

  1. Target Antigen Density Governs the Efficacy of Anti-CD20-CD28-CD3 zeta Chimeric Antigen Receptor-Modified Effector CD8(+) T Cells

    NARCIS (Netherlands)

    Watanabe, Keisuke; Terakura, Seitaro; Martens, Anton C.; van Meerten, Tom; Uchiyama, Susumu; Imai, Misa; Sakemura, Reona; Goto, Tatsunori; Hanajiri, Ryo; Imahashi, Nobuhiko; Shimada, Kazuyuki; Tomita, Akihiro; Kiyoi, Hitoshi; Nishida, Tetsuya; Naoe, Tomoki; Murata, Makoto

    2015-01-01

    The effectiveness of chimeric Ag receptor (CAR)-transduced T (CAR-T) cells has been attributed to supraphysiological signaling through CARs. Second-and later-generation CARs simultaneously transmit costimulatory signals with CD3 zeta signals upon ligation, but may lead to severe adverse effects

  2. An Adaptive Traffic Signal Control in a Connected Vehicle Environment: A Systematic Review

    Directory of Open Access Journals (Sweden)

    Peng Jing

    2017-08-01

    Full Text Available In the last few years, traffic congestion has become a growing concern due to increasing vehicle ownerships in urban areas. Intersections are one of the major bottlenecks that contribute to urban traffic congestion. Traditional traffic signal control systems cannot adjust the timing pattern depending on road traffic demand. This results in excessive delays for road users. Adaptive traffic signal control in a connected vehicle environment has shown a powerful ability to effectively alleviate urban traffic congestions to achieve desirable objectives (e.g., delay minimization. Connected vehicle technology, as an emerging technology, is a mobile data platform that enables the real-time data exchange among vehicles and between vehicles and infrastructure. Although several reviews about traffic signal control or connected vehicles have been written, a systemic review of adaptive traffic signal control in a connected vehicle environment has not been made. Twenty-six eligible studies searched from six databases constitute the review. A quality evaluation was established based on previous research instruments and applied to the current review. The purpose of this paper is to critically review the existing methods of adaptive traffic signal control in a connected vehicle environment and to compare the advantages or disadvantages of those methods. Further, a systematic framework on connected vehicle based adaptive traffic signal control is summarized to support the future research. Future research is needed to develop more efficient and generic adaptive traffic signal control methods in a connected vehicle environment.

  3. Superoxide dismutases: Dual roles in controlling ROS damage and regulating ROS signaling.

    Science.gov (United States)

    Wang, Ying; Branicky, Robyn; Noë, Alycia; Hekimi, Siegfried

    2018-04-18

    Superoxide dismutases (SODs) are universal enzymes of organisms that live in the presence of oxygen. They catalyze the conversion of superoxide into oxygen and hydrogen peroxide. Superoxide anions are the intended product of dedicated signaling enzymes as well as the byproduct of several metabolic processes including mitochondrial respiration. Through their activity, SOD enzymes control the levels of a variety of reactive oxygen species (ROS) and reactive nitrogen species, thus both limiting the potential toxicity of these molecules and controlling broad aspects of cellular life that are regulated by their signaling functions. All aerobic organisms have multiple SOD proteins targeted to different cellular and subcellular locations, reflecting the slow diffusion and multiple sources of their substrate superoxide. This compartmentalization also points to the need for fine local control of ROS signaling and to the possibility for ROS to signal between compartments. In this review, we discuss studies in model organisms and humans, which reveal the dual roles of SOD enzymes in controlling damage and regulating signaling. © 2018 Wang et al.

  4. 49 CFR 236.205 - Signal control circuits; requirements.

    Science.gov (United States)

    2010-10-01

    ..., INSPECTION, MAINTENANCE, AND REPAIR OF SIGNAL AND TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Automatic... car, (b) When points of a switch are not closed in proper position, (c) When an independently operated...

  5. EMG Versus Torque Control of Human-Machine Systems: Equalizing Control Signal Variability Does not Equalize Error or Uncertainty.

    Science.gov (United States)

    Johnson, Reva E; Kording, Konrad P; Hargrove, Levi J; Sensinger, Jonathon W

    2017-06-01

    In this paper we asked the question: if we artificially raise the variability of torque control signals to match that of EMG, do subjects make similar errors and have similar uncertainty about their movements? We answered this question using two experiments in which subjects used three different control signals: torque, torque+noise, and EMG. First, we measured error on a simple target-hitting task in which subjects received visual feedback only at the end of their movements. We found that even when the signal-to-noise ratio was equal across EMG and torque+noise control signals, EMG resulted in larger errors. Second, we quantified uncertainty by measuring the just-noticeable difference of a visual perturbation. We found that for equal errors, EMG resulted in higher movement uncertainty than both torque and torque+noise. The differences suggest that performance and confidence are influenced by more than just the noisiness of the control signal, and suggest that other factors, such as the user's ability to incorporate feedback and develop accurate internal models, also have significant impacts on the performance and confidence of a person's actions. We theorize that users have difficulty distinguishing between random and systematic errors for EMG control, and future work should examine in more detail the types of errors made with EMG control.

  6. Adaptive Traffic Signal Control: Deep Reinforcement Learning Algorithm with Experience Replay and Target Network

    OpenAIRE

    Gao, Juntao; Shen, Yulong; Liu, Jia; Ito, Minoru; Shiratori, Norio

    2017-01-01

    Adaptive traffic signal control, which adjusts traffic signal timing according to real-time traffic, has been shown to be an effective method to reduce traffic congestion. Available works on adaptive traffic signal control make responsive traffic signal control decisions based on human-crafted features (e.g. vehicle queue length). However, human-crafted features are abstractions of raw traffic data (e.g., position and speed of vehicles), which ignore some useful traffic information and lead t...

  7. Comparison of two different high performance mixed signal controllers for DC/DC converters

    DEFF Research Database (Denmark)

    Jakobsen, Lars Tønnes; Andersen, Michael Andreas E.

    2006-01-01

    This paper describes how mixed signal controllers combining a cheap microcontroller with a simple analogue circuit can offer high performance digital control for DC/DC converters. Mixed signal controllers have the same versatility and performance as DSP based controllers. It is important to have...... an engineer experienced in microcontroller programming write the software algorithms to achieve optimal performance. Two mixed signal controller designs based on the same 8-bit microcontroller are compared both theoretically and experimentally. A 16-bit PID compensator with a sampling frequency of 200 k......Hz implemented in the 16 MIPS, 8-bit ATTiny26 microcontroller is demonstrated....

  8. Digital signal processing in power electronics control circuits

    CERN Document Server

    Sozanski, Krzysztof

    2013-01-01

    Many digital control circuits in current literature are described using analog transmittance. This may not always be acceptable, especially if the sampling frequency and power transistor switching frequencies are close to the band of interest. Therefore, a digital circuit is considered as a digital controller rather than an analog circuit. This helps to avoid errors and instability in high frequency components. Digital Signal Processing in Power Electronics Control Circuits covers problems concerning the design and realization of digital control algorithms for power electronics circuits using

  9. Measuring Workload Weak Resilience Signals at a Rail Control Post

    NARCIS (Netherlands)

    Siegel, A.W.; Schraagen, J.M.C.

    2014-01-01

    OCCUPATIONAL APPLICATIONS This article describes an observational study at a rail control post to measure workload weak resilience signals. A weak resilience signal indicates a possible degradation of a system's resilience, which is defined as the ability of a complex socio-technical system to cope

  10. Identification of the feedforward component in manual control with predictable target signals.

    Science.gov (United States)

    Drop, Frank M; Pool, Daan M; Damveld, Herman J; van Paassen, Marinus M; Mulder, Max

    2013-12-01

    In the manual control of a dynamic system, the human controller (HC) often follows a visible and predictable reference path. Compared with a purely feedback control strategy, performance can be improved by making use of this knowledge of the reference. The operator could effectively introduce feedforward control in conjunction with a feedback path to compensate for errors, as hypothesized in literature. However, feedforward behavior has never been identified from experimental data, nor have the hypothesized models been validated. This paper investigates human control behavior in pursuit tracking of a predictable reference signal while being perturbed by a quasi-random multisine disturbance signal. An experiment was done in which the relative strength of the target and disturbance signals were systematically varied. The anticipated changes in control behavior were studied by means of an ARX model analysis and by fitting three parametric HC models: two different feedback models and a combined feedforward and feedback model. The ARX analysis shows that the experiment participants employed control action on both the error and the target signal. The control action on the target was similar to the inverse of the system dynamics. Model fits show that this behavior can be modeled best by the combined feedforward and feedback model.

  11. Signal Propagation Delay as a Barrier to Control Applications in WAN

    DEFF Research Database (Denmark)

    Knudsen, Thomas Phillip; Patel, A.; Pedersen, Jens Myrup

    With the advent in WAN of delay sensitive technical applications, such as remote control, signal propagation delay becomes a major problem. The extent of the problem is analysed by lower bounding the delay in relation to different transmission media. Requirements for reliability and bandwidth are...... are considered. The consequences of this bounding for communication network planning and provisioning are discussed in relation to mitigating the effects of signal propagation delay as a barrier to the penetration of control applications into WAN......With the advent in WAN of delay sensitive technical applications, such as remote control, signal propagation delay becomes a major problem. The extent of the problem is analysed by lower bounding the delay in relation to different transmission media. Requirements for reliability and bandwidth...

  12. Improving Walkability Through Control Strategies at Signalized Intersections

    Science.gov (United States)

    2017-01-01

    As cities and communities nationwide seek to develop Complete Streets that foster livability and accommodate all modes, signal timing control strategies that include pedestrians in the operational decision process are gaining importance. This researc...

  13. Intelligent Agent Based Traffic Signal Control on Isolated Intersections

    Directory of Open Access Journals (Sweden)

    Daniela Koltovska

    2014-08-01

    Full Text Available The purpose of this paper is to develop an adaptive signal control strategy on isolated urban intersections. An innovative approach to defining the set of states dependent on the actual and primarily observed parameters has been introduced. ?he Q–learning algorithm has been applied. The developed self-learning adaptive signal strategy has been tested on a re?l intersection. The intelligent agent results have been compared to those in cases of fixed-time and actuated control. Regarding the average total delay, the total number of stops and the total throughput, the best results have been obtained for unknown traffic demand and over-capacity.

  14. Digital control card based on digital signal processor

    International Nuclear Information System (INIS)

    Hou Shigang; Yin Zhiguo; Xia Le

    2008-01-01

    A digital control card based on digital signal processor was developed. Two Freescale DSP-56303 processors were utilized to achieve 3 channels proportional- integral-differential regulations. The card offers high flexibility for 100 MeV cyclotron RF system development. It was used as feedback controller in low level radio frequency control prototype, with the feedback gain parameters continuously adjustable. By using high precision analog to digital converter with 500 kHz sampling rate, a regulation bandwidth of 20 kHz was achieved. (authors)

  15. Adaptive control of human action: The role of outcome representations and reward signals

    Directory of Open Access Journals (Sweden)

    Hans eMarien

    2013-09-01

    Full Text Available The present paper aims to advance the understanding of the control of human behavior by integrating two lines of literature that so far have led separate lives. First, one line of literature is concerned with the ideomotor principle of human behavior, according to which actions are represented in terms of their outcomes. The second line of literature mainly considers the role of reward signals in adaptive control. Here, we offer a combined perspective on how outcome representations and reward signals work together to modulate adaptive control processes. We propose that reward signals signify the value of outcome representations and facilitate the recruitment of control resources in situations where behavior needs to be maintained or adapted to attain the represented outcome. We discuss recent research demonstrating how adaptive control of goal-directed behavior may emerge when outcome representations are co-activated with positive reward signals.

  16. Pak2 Controls Acquisition of NKT Cell Fate by Regulating Expression of the Transcription Factors PLZF and Egr2.

    Science.gov (United States)

    O'Hagan, Kyle L; Zhao, Jie; Pryshchep, Olga; Wang, Chyung-Ru; Phee, Hyewon

    2015-12-01

    NKT cells constitute a small population of T cells developed in the thymus that produce large amounts of cytokines and chemokines in response to lipid Ags. Signaling through the Vα14-Jα18 TCR instructs commitment to the NKT cell lineage, but the precise signaling mechanisms that instruct their lineage choice are unclear. In this article, we report that the cytoskeletal remodeling protein, p21-activated kinase 2 (Pak2), was essential for NKT cell development. Loss of Pak2 in T cells reduced stage III NKT cells in the thymus and periphery. Among different NKT cell subsets, Pak2 was necessary for the generation and function of NKT1 and NKT2 cells, but not NKT17 cells. Mechanistically, expression of Egr2 and promyelocytic leukemia zinc finger (PLZF), two key transcription factors for acquiring the NKT cell fate, were markedly diminished in the absence of Pak2. Diminished expression of Egr2 and PLZF were not caused by aberrant TCR signaling, as determined using a Nur77-GFP reporter, but were likely due to impaired induction and maintenance of signaling lymphocyte activation molecule 6 expression, a TCR costimulatory receptor required for NKT cell development. These data suggest that Pak2 controls thymic NKT cell development by providing a signal that links Egr2 to induce PLZF, in part by regulating signaling lymphocyte activation molecule 6 expression. Copyright © 2015 by The American Association of Immunologists, Inc.

  17. From Cellular Attractor Selection to Adaptive Signal Control for Traffic Networks.

    Science.gov (United States)

    Tian, Daxin; Zhou, Jianshan; Sheng, Zhengguo; Wang, Yunpeng; Ma, Jianming

    2016-03-14

    The management of varying traffic flows essentially depends on signal controls at intersections. However, design an optimal control that considers the dynamic nature of a traffic network and coordinates all intersections simultaneously in a centralized manner is computationally challenging. Inspired by the stable gene expressions of Escherichia coli in response to environmental changes, we explore the robustness and adaptability performance of signalized intersections by incorporating a biological mechanism in their control policies, specifically, the evolution of each intersection is induced by the dynamics governing an adaptive attractor selection in cells. We employ a mathematical model to capture such biological attractor selection and derive a generic, adaptive and distributed control algorithm which is capable of dynamically adapting signal operations for the entire dynamical traffic network. We show that the proposed scheme based on attractor selection can not only promote the balance of traffic loads on each link of the network but also allows the global network to accommodate dynamical traffic demands. Our work demonstrates the potential of bio-inspired intelligence emerging from cells and provides a deep understanding of adaptive attractor selection-based control formation that is useful to support the designs of adaptive optimization and control in other domains.

  18. Congestion and flow control in signaling system no. 7: Impacts of intelligent networks and new services

    Science.gov (United States)

    Zepf, Joachim; Rufa, Gerhard

    1994-04-01

    This paper focuses on the transient performance analysis of the congestion and flow control mechanisms in CCITT Signaling System No. 7 (SS7). Special attention is directed to the impacts of the introduction of intelligent services and new applications, e.g., Freephone, credit card services, user-to-user signaling, etc. In particular, we show that signaling traffic characteristics like signaling scenarios or signaling message length as well as end-to-end signaling capabilities have a significant influence on the congestion and flow control and, therefore, on the real-time signaling performance. One important result of our performance studies is that if, e.g., intelligent services are introduced, the SS7 congestion and flow control does not work correctly. To solve this problem, some reinvestigations into these mechanisms would be necessary. Therefore, some approaches, e.g., modification of the Signaling Connection Control Part (SCCP) congestion control, usage of the SCCP relay function, or a redesign of the MTP flow control procedures are discussed in order to guarantee the efficacy of the congestion and flow control mechanisms also in the future.

  19. Wnt/beta-catenin signaling interacts differentially with Ihh signaling in controlling endochondral bone and synovial joint formation.

    Science.gov (United States)

    Mak, Kingston Kinglun; Chen, Miao-Hsueh; Day, Timothy F; Chuang, Pao-Tien; Yang, Yingzi

    2006-09-01

    Both the Wnt/beta-catenin and Ihh signaling pathways play essential roles in crucial aspects of endochondral ossification: osteoblast differentiation, chondrocyte proliferation and hypertrophy. To understand the genetic interaction between these two signaling pathways, we have inactivated the beta-catenin gene and upregulated Ihh signaling simultaneously in the same cells during endochondral skeletal development using beta-catenin and patched 1 floxed alleles. We uncovered previously unexpected roles of Ihh signaling in synovial joint formation and the essential function of Wnt/beta-catenin signaling in regulating chondrocyte survival. More importantly, we found that Wnt and Ihh signaling interact with each other in distinct ways to control osteoblast differentiation, chondrocyte proliferation, hypertrophy, survival and synovial joint formation in the developing endochondral bone. Beta-catenin is required downstream of Ihh signaling and osterix expression for osteoblast differentiation. But in chondrocyte survival, beta-catenin is required upstream of Ihh signaling to inhibit chondrocyte apoptosis. In addition, Ihh signaling can inhibit chondrocyte hypertrophy and synovial joint formation independently of beta-catenin. However, there is a strong synergistic interaction between Wnt/beta-catenin and Ihh signaling in regulating synovial joint formation.

  20. Linear signal noise summer accurately determines and controls S/N ratio

    Science.gov (United States)

    Sundry, J. L.

    1966-01-01

    Linear signal noise summer precisely controls the relative power levels of signal and noise, and mixes them linearly in accurately known ratios. The S/N ratio accuracy and stability are greatly improved by this technique and are attained simultaneously.

  1. Design of human controlled 1 DOF right hand exoskeleton using electromyography signal

    Science.gov (United States)

    Azzam, M.; Wijaya, S. K.; Prawito

    2017-07-01

    Exoskeleton in general is a structure that is anatomically designed to be able to accommodate the physical movement of its user and provide additional strength. The use of EMG signal to control a 1 DOF right arm exoskeleton is evaluated in this research. This research aims to achieve optimum control using EMG signal. EMG signal is a variation of voltage that occurs when muscle contracts hence its strong correlation with the user's intention of movement. The RMS values of each EMG signal that originates from bicep and tricep muscle are calculated and processed to determine the direction and speed of rotation of a DC motor that actuates the exoskeleton. The RMS calculation is conducted at various array length that will theoretically affect its accuracy. The difference between those two RMS values is then calculated and interpreted as the intention of flexion or extension movement that will control the DC motor rotational direction. The absolute value of the RMS difference multiplied with a gain factor is used to regulate the duty cycle of a PWM signal that is used to control the rotational speed of the DC motor. To achieve the smallest settling time, array length and gain factor were varied. The test was conducted in two stages, static and dynamic tests. The test result shows a trend where the settling time decreases when array length is shortened and gain is increased. It shows that optimum control can be achieved by selecting the right array length and gain.

  2. The control of deliberate waiting strategies in a stop-signal task

    Directory of Open Access Journals (Sweden)

    R.P. Sylwan

    2004-06-01

    Full Text Available To inhibit an ongoing flow of thoughts or actions has been largely considered to be a crucial executive function, and the stop-signal paradigm makes inhibitory control measurable. Stop-signal tasks usually combine two concurrent tasks, i.e., manual responses to a primary task (go-task are occasionally countermanded by a stimulus which signals participants to inhibit their response in that trial (stop-task. Participants are always instructed not to wait for the stop-signal, since waiting strategies cause the response times to be unstable, invalidating the data. The aim of the present study was to experimentally control the strategies of waiting deliberately for the stop-signal in a stop-task by means of an algorithm that measured the variation in the reaction times to go-stimuli on-line, and displayed a warning legend urging participants to be faster when their reaction times were more than two standard deviations of the mean. Thirty-four university students performed a stop-task with go- and stop-stimuli, both of which were delivered in the visual modality and were lateralized within the visual field. The participants were divided into two groups (group A, without the algorithm, vs group B, with the algorithm. Group B exhibited lower variability of reaction times to go-stimuli, whereas no significant between-group differences were found in any of the measures of inhibitory control, showing that the algorithm succeeded in controlling the deliberate waiting strategies. Differences between deliberate and unintentional waiting strategies, and anxiety as a probable factor responsible for individual differences in deliberate waiting behavior, are discussed.

  3. Online Traffic Signal Control for Reducing Vehicle Carbon Dioxide Emissions

    Science.gov (United States)

    Oda, Toshihiko; Otokita, Tohru; Niikura, Satoshi

    In Japan, carbon dioxide (CO2) emissions caused by vehicles have been increasing year by year and it is well known that CO2 causes a serious global warming problem. For urban traffic control systems, there is a great demand for realization of signal control measures as soon as possible due to the urgency of the recent environmental situation. This paper describes a new traffic signal control for reducing vehicle CO2 emissions on an arterial road. First, we develop a model for estimating the emissions using the traffic delay and the number of stops a driver makes. Second, to find the optimal control parameters, we introduce a random search method with rapid convergence suitable for an online traffic control. We conduct experiments in Kawasaki to verify the effectiveness of our method. The experiments show that our approach decreases not only the emissions but also congestion and travel time significantly, compared to the method implemented in the real system.

  4. Delays at signalized intersections with exhaustive traffic control

    NARCIS (Netherlands)

    Boon, M.A.A.; Adan, I.J.B.F.; Winands, E.M.M.; Down, D.G.

    2012-01-01

    In this paper, we study a traffic intersection with vehicle-actuated traffic signal control. Traffic lights stay green until all lanes within a group are emptied. Assuming general renewal arrival processes, we derive exact limiting distributions of the delays under heavy traffic (HT) conditions.

  5. Attitude Control of a Satellite by using Digital Signal Processing

    Directory of Open Access Journals (Sweden)

    Adirelle C. Santana

    2012-03-01

    Full Text Available This article has discussed the development of a three-axis attitude digital controller for an artificial satellite using a digital signal processor. The main motivation of this study is the attitude control system of the satellite Multi-Mission Platform, developed by the Brazilian National Institute for Space Research for application in different sort of missions. The controller design was based on the theory of the Linear Quadratic Gaussian Regulator, synthesized from the linearized model of the motion of the satellite, i.e., the kinematics and dynamics of attitude. The attitude actuators considered in this study are pairs of cold gas jets powered by a pulse width/pulse frequency modulator. In the first stage of the project development, a system controller for continuous time was studied with the aim of testing the adequacy of the adopted control. The next steps had included an analysis of discretization techniques, the setting time of sampling rate, and the testing of the digital version of the Linear Quadratic Gaussian Regulator controller in the MATLAB/SIMULINK. To fulfill the study, the controller was implemented in a digital signal processor, specifically the Blackfin BF537 from Analog Devices, along with the pulse width/pulse frequency modulator. The validation tests used a scheme of co-simulation, where the model of the satellite was simulated in MATLAB/SIMULINK, while the controller and modulator were processed in the digital signal processor with a tool called Processor-In-the-Loop, which acted as a data communication link between both environments.function and required time to achieve a given mission accuracy are determined, and results are provided as illustration.

  6. Signal shape registration in the JINR synchrophasotron slowly extracted beam parameter control system

    International Nuclear Information System (INIS)

    Volkov, V.I.; Kulikov, I.I.; Romanov, S.V.

    1982-01-01

    Signal shape registration in the JINR synchrophasotron slowly estracted beam parameter control system on-line with the ES-1010 computer is described. 32 input signals can be connected to the registrator. The maximum measurement rate of signal shape registration is about 38 kHz. The registrator consists of 32-channel analog multiplexer, 10-bit analog-to-digital converter, 1024-word buffer memory and control circuits. For information representation the colour TV monitor is used

  7. Urban Traffic Signal System Control Structural Optimization Based on Network Analysis

    Directory of Open Access Journals (Sweden)

    Li Wang

    2013-01-01

    Full Text Available Advanced urban traffic signal control systems such as SCOOT and SCATS normally coordinate traffic network using multilevel hierarchical control mechanism. In this mechanism, several key intersections will be selected from traffic signal network and the network will be divided into different control subareas. Traditionally, key intersection selection and control subareas division are executed according to dynamic traffic counts and link length between intersections, which largely rely on traffic engineers’ experience. However, it omits important inherent characteristics of traffic network topology. In this paper, we will apply network analysis approach into these two aspects for traffic system control structure optimization. Firstly, the modified C-means clustering algorithm will be proposed to assess the importance of intersections in traffic network and furthermore determine the key intersections based on three indexes instead of merely on traffic counts in traditional methods. Secondly, the improved network community discovery method will be used to give more reasonable evidence in traffic control subarea division. Finally, to test the effectiveness of network analysis approach, a hardware-in-loop simulation environment composed of regional traffic control system, microsimulation software and signal controller hardware, will be built. Both traditional method and proposed approach will be implemented on simulation test bed to evaluate traffic operation performance indexes, for example, travel time, stop times, delay and average vehicle speed. Simulation results show that the proposed network analysis approach can improve the traffic control system operation performance effectively.

  8. Multiobjective Traffic Signal Control Model for Intersection Based on Dynamic Turning Movements Estimation

    Directory of Open Access Journals (Sweden)

    Pengpeng Jiao

    2014-01-01

    Full Text Available The real-time traffic signal control for intersection requires dynamic turning movements as the basic input data. It is impossible to detect dynamic turning movements directly through current traffic surveillance systems, but dynamic origin-destination (O-D estimation can obtain it. However, the combined models of dynamic O-D estimation and real-time traffic signal control are rare in the literature. A framework for the multiobjective traffic signal control model for intersection based on dynamic O-D estimation (MSC-DODE is presented. A state-space model using Kalman filtering is first formulated to estimate the dynamic turning movements; then a revised sequential Kalman filtering algorithm is designed to solve the model, and the root mean square error and mean percentage error are used to evaluate the accuracy of estimated dynamic turning proportions. Furthermore, a multiobjective traffic signal control model is put forward to achieve real-time signal control parameters and evaluation indices. Finally, based on practical survey data, the evaluation indices from MSC-DODE are compared with those from Webster method. The actual and estimated turning movements are further input into MSC-DODE, respectively, and results are also compared. Case studies show that results of MSC-DODE are better than those of Webster method and are very close to unavailable actual values.

  9. Exercise and Glycemic Control: Focus on Redox Homeostasis and Redox-Sensitive Protein Signaling

    Science.gov (United States)

    Parker, Lewan; Shaw, Christopher S.; Stepto, Nigel K.; Levinger, Itamar

    2017-01-01

    Physical inactivity, excess energy consumption, and obesity are associated with elevated systemic oxidative stress and the sustained activation of redox-sensitive stress-activated protein kinase (SAPK) and mitogen-activated protein kinase signaling pathways. Sustained SAPK activation leads to aberrant insulin signaling, impaired glycemic control, and the development and progression of cardiometabolic disease. Paradoxically, acute exercise transiently increases oxidative stress and SAPK signaling, yet postexercise glycemic control and skeletal muscle function are enhanced. Furthermore, regular exercise leads to the upregulation of antioxidant defense, which likely assists in the mitigation of chronic oxidative stress-associated disease. In this review, we explore the complex spatiotemporal interplay between exercise, oxidative stress, and glycemic control, and highlight exercise-induced reactive oxygen species and redox-sensitive protein signaling as important regulators of glucose homeostasis. PMID:28529499

  10. Distinct Signaling of Coreceptors Regulates Specific Metabolism Pathways and Impacts Memory Development in CAR T Cells.

    Science.gov (United States)

    Kawalekar, Omkar U; O'Connor, Roddy S; Fraietta, Joseph A; Guo, Lili; McGettigan, Shannon E; Posey, Avery D; Patel, Prachi R; Guedan, Sonia; Scholler, John; Keith, Brian; Snyder, Nathaniel W; Snyder, Nathaniel; Blair, Ian A; Blair, Ian; Milone, Michael C; June, Carl H

    2016-02-16

    Chimeric antigen receptors (CARs) redirect T cell cytotoxicity against cancer cells, providing a promising approach to cancer immunotherapy. Despite extensive clinical use, the attributes of CAR co-stimulatory domains that impact persistence and resistance to exhaustion of CAR-T cells remain largely undefined. Here, we report the influence of signaling domains of coreceptors CD28 and 4-1BB on the metabolic characteristics of human CAR T cells. Inclusion of 4-1BB in the CAR architecture promoted the outgrowth of CD8(+) central memory T cells that had significantly enhanced respiratory capacity, increased fatty acid oxidation and enhanced mitochondrial biogenesis. In contrast, CAR T cells with CD28 domains yielded effector memory cells with a genetic signature consistent with enhanced glycolysis. These results provide, at least in part, a mechanistic insight into the differential persistence of CAR-T cells expressing 4-1BB or CD28 signaling domains in clinical trials and inform the design of future CAR T cell therapies. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Chemical signal activation of an organocatalyst enables control over soft material formation.

    Science.gov (United States)

    Trausel, Fanny; Maity, Chandan; Poolman, Jos M; Kouwenberg, D S J; Versluis, Frank; van Esch, Jan H; Eelkema, Rienk

    2017-10-12

    Cells can react to their environment by changing the activity of enzymes in response to specific chemical signals. Artificial catalysts capable of being activated by chemical signals are rare, but of interest for creating autonomously responsive materials. We present an organocatalyst that is activated by a chemical signal, enabling temporal control over reaction rates and the formation of materials. Using self-immolative chemistry, we design a deactivated aniline organocatalyst that is activated by the chemical signal hydrogen peroxide and catalyses hydrazone formation. Upon activation of the catalyst, the rate of hydrazone formation increases 10-fold almost instantly. The responsive organocatalyst enables temporal control over the formation of gels featuring hydrazone bonds. The generic design should enable the use of a large range of triggers and organocatalysts, and appears a promising method for the introduction of signal response in materials, constituting a first step towards achieving communication between artificial chemical systems.Enzymes regulated by chemical signals are common in biology, but few such artificial catalysts exist. Here, the authors design an aniline catalyst that, when activated by a chemical trigger, catalyses formation of hydrazone-based gels, demonstrating signal response in a soft material.

  12. Synthesis Study on Transitions in Signal Infrastructure and Control Algorithms for Connected and Automated Transportation

    Energy Technology Data Exchange (ETDEWEB)

    Aziz, H. M. Abdul [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Wang, Hong [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Young, Stan [National Renewable Energy Lab. (NREL), Golden, CO (United States); Sperling, Joshua [National Renewable Energy Lab. (NREL), Golden, CO (United States); Beck, John [Idaho National Lab. (INL), Idaho Falls, ID (United States)

    2017-06-01

    Documenting existing state of practice is an initial step in developing future control infrastructure to be co-deployed for heterogeneous mix of connected and automated vehicles with human drivers while leveraging benefits to safety, congestion, and energy. With advances in information technology and extensive deployment of connected and automated vehicle technology anticipated over the coming decades, cities globally are making efforts to plan and prepare for these transitions. CAVs not only offer opportunities to improve transportation systems through enhanced safety and efficient operations of vehicles. There are also significant needs in terms of exploring how best to leverage vehicle-to-vehicle (V2V) technology, vehicle-to-infrastructure (V2I) technology and vehicle-to-everything (V2X) technology. Both Connected Vehicle (CV) and Connected and Automated Vehicle (CAV) paradigms feature bi-directional connectivity and share similar applications in terms of signal control algorithm and infrastructure implementation. The discussion in our synthesis study assumes the CAV/CV context where connectivity exists with or without automated vehicles. Our synthesis study explores the current state of signal control algorithms and infrastructure, reports the completed and newly proposed CV/CAV deployment studies regarding signal control schemes, reviews the deployment costs for CAV/AV signal infrastructure, and concludes with a discussion on the opportunities such as detector free signal control schemes and dynamic performance management for intersections, and challenges such as dependency on market adaptation and the need to build a fault-tolerant signal system deployment in a CAV/CV environment. The study will serve as an initial critical assessment of existing signal control infrastructure (devices, control instruments, and firmware) and control schemes (actuated, adaptive, and coordinated-green wave). Also, the report will help to identify the future needs for the signal

  13. FireSignal - Data Acquisition and Control System Software

    International Nuclear Information System (INIS)

    Neto, A.; Fernandes, H.; Duarte, A.; Carvalho, B.; Sousa, J.; Valcarcel, D.; Varandas, C.; Hron, M.

    2006-01-01

    Control of fusion devices requires good, non-ambiguous, easy to use user-interfaces to configure hardware devices. To solve this problem a highly generic system for data control and acquisition has been developed. Among the main features it allows remote hardware configuration, shot launching, data sharing between connected users and experiment monitoring. The system is fully distributed: the hardware driver nodes, clients and server are completely independent from each other and might be running in different operating systems and programmed in different languages. All the communication is provided through the Common Object Request Broker Architecture (CORBA) protocol. FireSignal was designed from the beginning to be as independent as possible from any kind of constraints as it's a plugin based system. Database, data viewers and the security system are some examples of what can easily be changed and adapted to the target machine's needs. All hardware is described in eXtendend Markup Language (XML) and from this information the FireSignal client application can build automatically Graphical User Interfaces (GUI) and validate the user's parameter configuration. Any type of hardware can be integrated in the system as long as it is described in XML and the respective driver is developed. Any modern programming language can be used to develop these drivers, and currently we use Python and Java generic drivers. All data storage and indexing is time stamped event-based s. Nodes are responsible for tagging the acquired samples with the absolute time stamps and to react to machine events. FireSignal is currently being used to control the ISTTOK/PT and CASTOR/CZ tokamaks. (author)

  14. Inter-vehicle gap statistics on signal-controlled crossroads

    International Nuclear Information System (INIS)

    Krbalek, Milan

    2008-01-01

    We investigate a microscopical structure in a chain of cars waiting at a red signal on signal-controlled crossroads. A one-dimensional space-continuous thermodynamical model leading to an excellent agreement with the data measured is presented. Moreover, we demonstrate that an inter-vehicle spacing distribution disclosed in relevant traffic data agrees with the thermal-balance distribution of particles in the thermodynamical traffic gas (discussed in [1]) with a high inverse temperature (corresponding to a strong traffic congestion). Therefore, as we affirm, such a system of stationary cars can be understood as a specific state of the traffic sample operating inside a congested traffic stream

  15. Influence factors of human T lymphocyte co-stimulatory effect in vitro

    International Nuclear Information System (INIS)

    Zhou Jianhua; Su Liaoyuan; Tong Jian; Xue Lian

    2000-01-01

    Objective: Effects of CD3 McAb, CD28 McAb, PHA and low-dose γ-ray irradiation on T lymphocytes were investigated to explore factors of influencing T cell signals transduction. Method: Using CD3 McAb and CD28 McAb mimicking as the first and the second signals, and using PHA and low dose γ-rays irradiation as stimulatory factors in T cell activation, the influences of these factors and the two signals on human lymphocyte proliferation response were studied with 3 H-thymidine incorporation. Results: Lymphocyte proliferation response occurred when the two signals were treated co-stimulation or within certain intervals (within 40h). PHA and 10 cGy γ-rays irradiation can also activate lymphocytes to proliferate. However, each of the two signals alone did not activate lymphocytes to proliferate. Conclusion: CD3 McAb, CD28 McAb, PHA and low-dose γ-rays irradiation could stimulate T lymphocyte proliferation, which is an important aspect in cellular immune regulation

  16. c-MPL provides tumor-targeted T-cell receptor-transgenic T cells with costimulation and cytokine signals.

    Science.gov (United States)

    Nishimura, Christopher D; Brenner, Daniel A; Mukherjee, Malini; Hirsch, Rachel A; Ott, Leah; Wu, Meng-Fen; Liu, Hao; Dakhova, Olga; Orange, Jordan S; Brenner, Malcolm K; Lin, Charles Y; Arber, Caroline

    2017-12-21

    Adoptively transferred T-cell receptor (TCR)-engineered T cells depend on host-derived costimulation and cytokine signals for their full and sustained activation. However, in patients with cancer, both signals are frequently impaired. Hence, we developed a novel strategy that combines both essential signals in 1 transgene by expressing the nonlymphoid hematopoietic growth factor receptor c-MPL (myeloproliferative leukemia), the receptor for thrombopoietin (TPO), in T cells. c-MPL signaling activates pathways shared with conventional costimulatory and cytokine receptor signaling. Thus, we hypothesized that host-derived TPO, present in the tumor microenvironment, or pharmacological c-MPL agonists approved by the US Food and Drug Administration could deliver both signals to c-MPL-engineered TCR-transgenic T cells. We found that c-MPL + polyclonal T cells expand and proliferate in response to TPO, and persist longer after adoptive transfer in immunodeficient human TPO-transgenic mice. In TCR-transgenic T cells, c-MPL activation enhances antitumor function, T-cell expansion, and cytokine production and preserves a central memory phenotype. c-MPL signaling also enables sequential tumor cell killing, enhances the formation of effective immune synapses, and improves antileukemic activity in vivo in a leukemia xenograft model. We identify the type 1 interferon pathway as a molecular mechanism by which c-MPL mediates immune stimulation in T cells. In conclusion, we present a novel immunotherapeutic strategy using c-MPL-enhanced transgenic T cells responding to either endogenously produced TPO (a microenvironment factor in hematologic malignancies) or c-MPL-targeted pharmacological agents. © 2017 by The American Society of Hematology.

  17. A Two-Stage Fuzzy Logic Control Method of Traffic Signal Based on Traffic Urgency Degree

    OpenAIRE

    Yan Ge

    2014-01-01

    City intersection traffic signal control is an important method to improve the efficiency of road network and alleviate traffic congestion. This paper researches traffic signal fuzzy control method on a single intersection. A two-stage traffic signal control method based on traffic urgency degree is proposed according to two-stage fuzzy inference on single intersection. At the first stage, calculate traffic urgency degree for all red phases using traffic urgency evaluation module and select t...

  18. Canonical Wnt signaling in differentiated osteoblasts controls osteoclast differentiation.

    NARCIS (Netherlands)

    Glass, D.A.; Bialek, P.; Ahn, J.D.; Starbuck, M.; Patel, M.S.; Clevers, J.C.; Taketo, M.M.; Long, F.; McMahon, A.P.; Lang, R.A.; Karsenty, G.

    2005-01-01

    Inactivation of beta-catenin in mesenchymal progenitors prevents osteoblast differentiation; inactivation of Lrp5, a gene encoding a likely Wnt coreceptor, results in low bone mass (osteopenia) by decreasing bone formation. These observations indicate that Wnt signaling controls osteoblast

  19. Task control signals in pediatric Tourette syndrome show evidence of immature and anomalous functional activity

    Directory of Open Access Journals (Sweden)

    Jessica A Church

    2009-11-01

    Full Text Available Tourette Syndrome (TS is a pediatric movement disorder that may affect control signaling in the brain. Previous work has proposed a dual-networks architecture of control processing involving a task-maintenance network and an adaptive control network (Dosenbach et al., 2008. A prior resting-state functional connectivity MRI (rs-fcMRI analysis in TS has revealed functional immaturity in both putative control networks, with “anomalous” correlations (i.e. correlations outside the typical developmental range limited to the adaptive control network (Church et al., 2009. The present study used functional MRI (fMRI to study brain activity related to adaptive control (by studying start-cues signals, and to task-maintenance (by studying signals sustained across a task set. Two hypotheses from the previous rs-fcMRI results were tested. First, adaptive control (i.e., start-cue activity will be altered in TS, including activity inconsistent with typical development (“anomalous”. Second, group differences found in task maintenance (i.e., sustained activity will be consistent with functional immaturity in TS. We examined regions found through a direct comparison of adolescents with and without TS, as well as regions derived from a previous investigation that showed differences between unaffected children and adults. The TS group showed decreased start-cue signal magnitude in regions where start-cue activity is unchanged over typical development, consistent with anomalous adaptive control. The TS group also had higher magnitude sustained signals in frontal cortex regions that overlapped with regions showing differences over typical development, consistent with immature task maintenance in TS. The results demonstrate task-related fMRI signal differences anticipated by the atypical functional connectivity found previously in adolescents with TS, strengthening the evidence for functional immaturity and anomalous signaling in control networks in adolescents

  20. Performance Analysis of Control Signal Transmission Technique for Cognitive Radios in Dynamic Spectrum Access Networks

    Science.gov (United States)

    Sakata, Ren; Tomioka, Tazuko; Kobayashi, Takahiro

    When cognitive radio (CR) systems dynamically use the frequency band, a control signal is necessary to indicate which carrier frequencies are currently available in the network. In order to keep efficient spectrum utilization, this control signal also should be transmitted based on the channel conditions. If transmitters dynamically select carrier frequencies, receivers have to receive control signals without knowledge of their carrier frequencies. To enable such transmission and reception, this paper proposes a novel scheme called DCPT (Differential Code Parallel Transmission). With DCPT, receivers can receive low-rate information with no knowledge of the carrier frequencies. The transmitter transmits two signals whose carrier frequencies are spaced by a predefined value. The absolute values of the carrier frequencies can be varied. When the receiver acquires the DCPT signal, it multiplies the signal by a frequency-shifted version of the signal; this yields a DC component that represents the data signal which is then demodulated. The performance was evaluated by means of numerical analysis and computer simulation. We confirmed that DCPT operates successfully even under severe interference if its parameters are appropriately configured.

  1. Overload Control in a SIP Signaling Network

    OpenAIRE

    Masataka Ohta

    2007-01-01

    The Internet telephony employs a new type of Internet communication on which a mutual communication is realized by establishing sessions. Session Initiation Protocol (SIP) is used to establish sessions between end-users. For unreliable transmission (UDP), SIP message should be retransmitted when it is lost. The retransmissions increase a load of the SIP signaling network, and sometimes lead to performance degradation when a network is overloaded. The paper proposes an overload control for a S...

  2. The Molecular Interaction of CAR and JAML Recruits the Central Cell Signal Transducer PI3K

    Energy Technology Data Exchange (ETDEWEB)

    Verdino, Petra; Witherden, Deborah A.; Havran, Wendy L.; Wilson, Ian A. (Scripps)

    2010-11-15

    Coxsackie and adenovirus receptor (CAR) is the primary cellular receptor for group B coxsackieviruses and most adenovirus serotypes and plays a crucial role in adenoviral gene therapy. Recent discovery of the interaction between junctional adhesion molecule-like protein (JAML) and CAR uncovered important functional roles in immunity, inflammation, and tissue homeostasis. Crystal structures of JAML ectodomain (2.2 angstroms) and its complex with CAR (2.8 angstroms) reveal an unusual immunoglobulin-domain assembly for JAML and a charged interface that confers high specificity. Biochemical and mutagenesis studies illustrate how CAR-mediated clustering of JAML recruits phosphoinositide 3-kinase (P13K) to a JAML intracellular sequence motif as delineated for the {alpha}{beta} T cell costimulatory receptor CD28. Thus, CAR and JAML are cell signaling receptors of the immune system with implications for asthma, cancer, and chronic nonhealing wounds.

  3. In Vivo Expansion and Antitumor Activity of Coinfused CD28- and 4-1BB-Engineered CAR-T Cells in Patients with B Cell Leukemia.

    Science.gov (United States)

    Cheng, Zhi; Wei, Runhong; Ma, Qiuling; Shi, Lin; He, Feng; Shi, Zixiao; Jin, Tao; Xie, Ronglin; Wei, Baofeng; Chen, Jing; Fang, Hongliang; Han, Xiaolu; Rohrs, Jennifer A; Bryson, Paul; Liu, Yarong; Li, Qi-Jing; Zhu, Bo; Wang, Pin

    2018-04-04

    Several recent clinical trials have successfully incorporated a costimulatory domain derived from either CD28 or 4-1BB with the original CD3ζ T cell activating domain to form second-generation chimeric antigen receptors (CARs) that can increase the responsiveness and survival of CAR-engineered T (CAR-T) cells. However, a rigorous assessment of the individual benefits of these costimulatory components relative to the in vivo performance of infused T cells in patients is still lacking. Therefore, we have designed a study that allows us to investigate and compare the impact of different costimulatory signal domains on CAR-T cells in vivo. Patients with B cell leukemia were infused with a mixture of two types of CD19-specific CAR-T cells, individually bearing CD28 (28ζ) and 4-1BB (BBζ) costimulatory signaling domains. We found that such a clinical procedure was feasible and safe. Complete remission (CR) was observed in five of seven enrolled patients, with two patients exhibiting durable CR lasting more than 15 months. The in vivo expansion pattern of 28ζ and BBζ CAR-T cells varied significantly among individual patients. These results confirm a feasible method of comparing different CAR designs within individual patients, potentially offering objective insights that may facilitate the development of optimal CAR-T cell-based immunotherapies. Copyright © 2018 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

  4. Microscopic Control Delay Modeling at Signalized Arterials Using Bluetooth Technology

    OpenAIRE

    Rajasekhar, Lakshmi

    2011-01-01

    Real-time control delay estimation is an important performance measure for any intersection to improve the signal timing plans dynamically in real-time and hence improve the overall system performance. Control delay estimates helps to determine the level-of-service (LOS) characteristics of various approaches at an intersection and takes into account deceleration delay, stopped delay and acceleration delay. All kinds of traffic delay calculation especially control delay calculation has always ...

  5. sEMG Signal Acquisition Strategy towards Hand FES Control

    Directory of Open Access Journals (Sweden)

    Cinthya Lourdes Toledo-Peral

    2018-01-01

    Full Text Available Due to damage of the nervous system, patients experience impediments in their daily life: severe fatigue, tremor or impaired hand dexterity, hemiparesis, or hemiplegia. Surface electromyography (sEMG signal analysis is used to identify motion; however, standardization of electrode placement and classification of sEMG patterns are major challenges. This paper describes a technique used to acquire sEMG signals for five hand motion patterns from six able-bodied subjects using an array of recording and stimulation electrodes placed on the forearm and its effects over functional electrical stimulation (FES and volitional sEMG combinations, in order to eventually control a sEMG-driven FES neuroprosthesis for upper limb rehabilitation. A two-part protocol was performed. First, personalized templates to place eight sEMG bipolar channels were designed; with these data, a universal template, called forearm electrode set (FELT, was built. Second, volitional and evoked movements were recorded during FES application. 95% classification accuracy was achieved using two sessions per movement. With the FELT, it was possible to perform FES and sEMG recordings simultaneously. Also, it was possible to extract the volitional and evoked sEMG from the raw signal, which is highly important for closed-loop FES control.

  6. A Signal Coordination Control Based on Traversing Empty between Mid-Block Street Crossing and Intersection

    Directory of Open Access Journals (Sweden)

    Changjiang Zheng

    2012-01-01

    Full Text Available To solve the problem in pedestrian Mid-Block street crossing, the method of signal coordination control between mid-block street crossing and intersection is researched in this paper. The paper proposes to use “distance-flow rate-time” graph as the tool for building coordination control system model which is for different situations of traffic control. Through alternating the linear optimization model, the system outputs the distribution of signal timing and system operational factors (delays in vehicles and mid-block street crossing. Finally, taking one section on the Taiping North Road in Nanjing as an example, the signal coordination control is carried out. And the results which are delays in the vehicles and mid-block street crossing are compared to those in the current distribution of signal timing.

  7. Diffusible signal factor-dependent quorum sensing in pathogenic bacteria and its exploitation for disease control.

    Science.gov (United States)

    Dow, J M

    2017-01-01

    Cell-to-cell signals of the diffusible signal factor (DSF) family are cis-2-unsaturated fatty acids of differing chain length and branching pattern. DSF signalling has been described in diverse bacteria to include plant and human pathogens where it acts to regulate functions such as biofilm formation, antibiotic tolerance and the production of virulence factors. DSF family signals can also participate in interspecies signalling with other bacteria and interkingdom signalling such as with the yeast Candida albicans. Interference with DSF signalling may afford new opportunities for the control of bacterial disease. Such strategies will depend in part on detailed knowledge of the molecular mechanisms underlying the processes of signal synthesis, perception and turnover. Here, I review both recent progress in understanding DSF signalling at the molecular level and prospects for translating this knowledge into approaches for disease control. © 2016 The Society for Applied Microbiology.

  8. Reward acts as a signal to control delay-period activity in delayed-response tasks.

    Science.gov (United States)

    Ichihara-Takeda, Satoe; Takeda, Kazuyoshi; Funahashi, Shintaro

    2010-03-31

    Prefrontal delay-period activity represents a neural mechanism for the active maintenance of information and needs to be controlled by some signal to appropriately operate working memory. To examine whether reward-delivery acts as this signal, the effects of delay-period activity in response to unexpected reward-delivery were examined by analyzing single-neuron activity recorded in the primate dorsolateral prefrontal cortex. Among neurons that showed delay-period activity, 34% showed inhibition of this activity in response to unexpected reward-delivery. The delay-period activity of these neurons was affected by the expectation of reward-delivery. The strength of the reward signal in controlling the delay-period activity is related to the strength of the effect of reward information on the delay-period activity. These results indicate that reward-delivery acts as a signal to control delay-period activity.

  9. Fast attainment of computer cursor control with noninvasively acquired brain signals

    Science.gov (United States)

    Bradberry, Trent J.; Gentili, Rodolphe J.; Contreras-Vidal, José L.

    2011-06-01

    Brain-computer interface (BCI) systems are allowing humans and non-human primates to drive prosthetic devices such as computer cursors and artificial arms with just their thoughts. Invasive BCI systems acquire neural signals with intracranial or subdural electrodes, while noninvasive BCI systems typically acquire neural signals with scalp electroencephalography (EEG). Some drawbacks of invasive BCI systems are the inherent risks of surgery and gradual degradation of signal integrity. A limitation of noninvasive BCI systems for two-dimensional control of a cursor, in particular those based on sensorimotor rhythms, is the lengthy training time required by users to achieve satisfactory performance. Here we describe a novel approach to continuously decoding imagined movements from EEG signals in a BCI experiment with reduced training time. We demonstrate that, using our noninvasive BCI system and observational learning, subjects were able to accomplish two-dimensional control of a cursor with performance levels comparable to those of invasive BCI systems. Compared to other studies of noninvasive BCI systems, training time was substantially reduced, requiring only a single session of decoder calibration (~20 min) and subject practice (~20 min). In addition, we used standardized low-resolution brain electromagnetic tomography to reveal that the neural sources that encoded observed cursor movement may implicate a human mirror neuron system. These findings offer the potential to continuously control complex devices such as robotic arms with one's mind without lengthy training or surgery.

  10. Hierarchical Colored Petri Nets for Modeling and Analysis of Transit Signal Priority Control Systems

    Directory of Open Access Journals (Sweden)

    Yisheng An

    2018-01-01

    Full Text Available In this paper, we consider the problem of developing a model for traffic signal control with transit priority using Hierarchical Colored Petri nets (HCPN. Petri nets (PN are useful for state analysis of discrete event systems due to their powerful modeling capability and mathematical formalism. This paper focuses on their use to formalize the transit signal priority (TSP control model. In a four-phase traffic signal control model, the transit detection and two kinds of transit priority strategies are integrated to obtain the HCPN-based TSP control models. One of the advantages to use these models is the clear presentation of traffic light behaviors in terms of conditions and events that cause the detection of a priority request by a transit vehicle. Another advantage of the resulting models is that the correctness and reliability of the proposed strategies are easily analyzed. After their full reachable states are generated, the boundness, liveness, and fairness of the proposed models are verified. Experimental results show that the proposed control model provides transit vehicles with better effectiveness at intersections. This work helps advance the state of the art in the design of signal control models related to the intersection of roadways.

  11. Positive and negative peptide signals control stomatal density.

    Science.gov (United States)

    Shimada, Tomoo; Sugano, Shigeo S; Hara-Nishimura, Ikuko

    2011-06-01

    The stoma is a micro valve found on aerial plant organs that promotes gas exchange between the atmosphere and the plant body. Each stoma is formed by a strict cell lineage during the early stages of leaf development. Molecular genetics research using the model plant Arabidopsis has revealed the genes involved in stomatal differentiation. Cysteine-rich secretory peptides of the EPIDERMAL PATTERNING FACTOR-LIKE (EPFL) family play crucial roles as extracellular signaling factors. Stomatal development is orchestrated by the positive factor STOMAGEN/EPFL9 and the negative factors EPF1, EPF2, and CHALLAH/EPFL6 in combination with multiple receptors. EPF1 and EPF2 are produced in the stomatal lineage cells of the epidermis, whereas STOMAGEN and CHALLAH are derived from the inner tissues. These findings highlight the complex cell-to-cell and intertissue communications that regulate stomatal development. To optimize gas exchange, particularly the balance between the uptake of carbon dioxide (CO(2)) and loss of water, plants control stomatal activity in response to environmental conditions. The CO(2) level and light intensity influence stomatal density. Plants sense environmental cues in mature leaves and adjust the stomatal density of newly forming leaves, indicating the involvement of long-distance systemic signaling. This review summarizes recent research progress in the peptide signaling of stomatal development and discusses the evolutionary model of the signaling machinery.

  12. small signal analysis of load angle governing and excitation control

    African Journals Online (AJOL)

    Dr Obe

    system stabilizers (PSS) or using terminal voltage for control of exciter and speed signal for governor. ... Vfd= generator field voltage. Xd, Xq ... each other in the frequency domain, and therefore ..... angle sensing equipment, relays and.

  13. TGF-β signaling controls FSHR signaling-reduced ovarian granulosa cell apoptosis through the SMAD4/miR-143 axis.

    Science.gov (United States)

    Du, Xing; Zhang, Lifan; Li, Xinyu; Pan, Zengxiang; Liu, Honglin; Li, Qifa

    2016-11-24

    Follicle-stimulating hormone receptor (FSHR) and its intracellular signaling control mammalian follicular development and female infertility. Our previous study showed that FSHR is downregulated during follicular atresia of porcine ovaries. However, its role and regulation in follicular atresia remain unclear. Here, we showed that FSHR knockdown induced porcine granulosa cell (pGC) apoptosis and follicular atresia, and attenuated the levels of intracellular signaling molecules such as PKA, AKT and p-AKT. FSHR was identified as a target of miR-143, a microRNA that was upregulated during porcine follicular atresia. miR-143 enhanced pGC apoptosis by targeting FSHR, and reduced the levels of intracellular signaling molecules. SMAD4, the final molecule in transforming growth factor (TGF)-β signaling, bound to the promoter and induced significant downregulation of miR-143 in vitro and in vivo. Activated TGF-β signaling rescued miR-143-reduced FSHR and intracellular signaling molecules, and miR-143-induced pGC apoptosis. Overall, our findings offer evidence to explain how TGF-β signaling influences and FSHR signaling for regulation of pGC apoptosis and follicular atresia by a specific microRNA, miR-143.

  14. An alternative mode of CD43 signal transduction activates pro-survival pathways of T lymphocytes.

    Science.gov (United States)

    Bravo-Adame, Maria Elena; Vera-Estrella, Rosario; Barkla, Bronwyn J; Martínez-Campos, Cecilia; Flores-Alcantar, Angel; Ocelotl-Oviedo, Jose Pablo; Pedraza-Alva, Gustavo; Rosenstein, Yvonne

    2017-01-01

    CD43 is one of the most abundant co-stimulatory molecules on a T-cell surface; it transduces activation signals through its cytoplasmic domain, contributing to modulation of the outcome of T-cell responses. The aim of this study was to uncover new signalling pathways regulated by this sialomucin. Analysis of changes in protein abundance allowed us to identify pyruvate kinase isozyme M2 (PKM2), an enzyme of the glycolytic pathway, as an element potentially participating in the signalling cascade resulting from the engagement of CD43 and the T-cell receptor (TCR). We found that the glycolytic activity of this enzyme was not significantly increased in response to TCR+CD43 co-stimulation, but that PKM2 was tyrosine phosphorylated, suggesting that it was performing moonlight functions. We report that phosphorylation of both Y 105 of PKM2 and of Y 705 of signal transducer and activator of transcription 3 was induced in response to TCR+CD43 co-stimulation, resulting in activation of the mitogen-activated protein kinase kinase 5/extracellular signal-regulated kinase 5 (MEK5/ERK5) pathway. ERK5 and the cAMP response element binding protein (CREB) were activated, and c-Myc and nuclear factor-κB (p65) nuclear localization, as well as Bad phosphorylation, were augmented. Consistent with this, expression of human CD43 in a murine T-cell hybridoma favoured cell survival. Altogether, our data highlight novel signalling pathways for the CD43 molecule in T lymphocytes, and underscore a role for CD43 in promoting cell survival through non-glycolytic functions of metabolic enzymes. © 2016 John Wiley & Sons Ltd.

  15. A Framework for Diagnosing the Out-of-Control Signals in Multivariate Process Using Optimized Support Vector Machines

    Directory of Open Access Journals (Sweden)

    Tai-fu Li

    2013-01-01

    Full Text Available Multivariate statistical process control is the continuation and development of unitary statistical process control. Most multivariate statistical quality control charts are usually used (in manufacturing and service industries to determine whether a process is performing as intended or if there are some unnatural causes of variation upon an overall statistics. Once the control chart detects out-of-control signals, one difficulty encountered with multivariate control charts is the interpretation of an out-of-control signal. That is, we have to determine whether one or more or a combination of variables is responsible for the abnormal signal. A novel approach for diagnosing the out-of-control signals in the multivariate process is described in this paper. The proposed methodology uses the optimized support vector machines (support vector machine classification based on genetic algorithm to recognize set of subclasses of multivariate abnormal patters, identify the responsible variable(s on the occurrence of abnormal pattern. Multiple sets of experiments are used to verify this model. The performance of the proposed approach demonstrates that this model can accurately classify the source(s of out-of-control signal and even outperforms the conventional multivariate control scheme.

  16. An Adaptive Traffic Signal Control in a Connected Vehicle Environment: A Systematic Review

    OpenAIRE

    Peng Jing; Hao Huang; Long Chen

    2017-01-01

    In the last few years, traffic congestion has become a growing concern due to increasing vehicle ownerships in urban areas. Intersections are one of the major bottlenecks that contribute to urban traffic congestion. Traditional traffic signal control systems cannot adjust the timing pattern depending on road traffic demand. This results in excessive delays for road users. Adaptive traffic signal control in a connected vehicle environment has shown a powerful ability to effectively alleviate u...

  17. Motor Preparation Disrupts Proactive Control in the Stop Signal Task

    Directory of Open Access Journals (Sweden)

    Wuyi Wang

    2018-05-01

    Full Text Available In a study of the stop signal task (SST we employed Bayesian modeling to compute the estimated likelihood of stop signal or P(Stop trial by trial and identified regional processes of conflict anticipation and response slowing. A higher P(Stop is associated with prolonged go trial reaction time (goRT—a form of sequential effect—and reflects proactive control of motor response. However, some individuals do not demonstrate a sequential effect despite similar go and stop success (SS rates. We posited that motor preparation may disrupt proactive control more in certain individuals than others. Specifically, the time interval between trial and go signal onset—the fore-period (FP—varies across trials and a longer FP is associated with a higher level of motor preparation and shorter goRT. Greater motor preparatory activities may disrupt proactive control. To test this hypothesis, we compared brain activations and Granger causal connectivities of 81 adults who demonstrated a sequential effect (SEQ and 35 who did not (nSEQ. SEQ and nSEQ did not differ in regional activations to conflict anticipation, motor preparation, goRT slowing or goRT speeding. In contrast, SEQ and nSEQ demonstrated different patterns of Granger causal connectivities. P(Stop and FP activations shared reciprocal influence in SEQ but FP activities Granger caused P(Stop activities unidirectionally in nSEQ, and FP activities Granger caused goRT speeding activities in nSEQ but not SEQ. These findings support the hypothesis that motor preparation disrupts proactive control in nSEQ and provide direct neural evidence for interactive go and stop processes.

  18. Learning-based traffic signal control algorithms with neighborhood information sharing: An application for sustainable mobility

    Energy Technology Data Exchange (ETDEWEB)

    Aziz, H. M. Abdul [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Zhu, Feng [Purdue University, West Lafayette, IN (United States). Lyles School of Civil Engineering; Ukkusuri, Satish V. [Purdue University, West Lafayette, IN (United States). Lyles School of Civil Engineering

    2017-10-04

    Here, this research applies R-Markov Average Reward Technique based reinforcement learning (RL) algorithm, namely RMART, for vehicular signal control problem leveraging information sharing among signal controllers in connected vehicle environment. We implemented the algorithm in a network of 18 signalized intersections and compare the performance of RMART with fixed, adaptive, and variants of the RL schemes. Results show significant improvement in system performance for RMART algorithm with information sharing over both traditional fixed signal timing plans and real time adaptive control schemes. Additionally, the comparison with reinforcement learning algorithms including Q learning and SARSA indicate that RMART performs better at higher congestion levels. Further, a multi-reward structure is proposed that dynamically adjusts the reward function with varying congestion states at the intersection. Finally, the results from test networks show significant reduction in emissions (CO, CO2, NOx, VOC, PM10) when RL algorithms are implemented compared to fixed signal timings and adaptive schemes.

  19. DFB laser array driver circuit controlled by adjustable signal

    Science.gov (United States)

    Du, Weikang; Du, Yinchao; Guo, Yu; Li, Wei; Wang, Hao

    2018-01-01

    In order to achieve the intelligent controlling of DFB laser array, this paper presents the design of an intelligence and high precision numerical controlling electric circuit. The system takes MCU and FPGA as the main control chip, with compact, high-efficiency, no impact, switching protection characteristics. The output of the DFB laser array can be determined by an external adjustable signal. The system transforms the analog control model into a digital control model, which improves the performance of the driver. The system can monitor the temperature and current of DFB laser array in real time. The output precision of the current can reach ± 0.1mA, which ensures the stable and reliable operation of the DFB laser array. Such a driver can benefit the flexible usage of the DFB laser array.

  20. Rab11-FIP3 Regulation of Lck Endosomal Traffic Controls TCR Signal Transduction.

    Science.gov (United States)

    Bouchet, Jérôme; Del Río-Iñiguez, Iratxe; Vázquez-Chávez, Elena; Lasserre, Rémi; Agüera-González, Sonia; Cuche, Céline; McCaffrey, Mary W; Di Bartolo, Vincenzo; Alcover, Andrés

    2017-04-01

    The role of endosomes in receptor signal transduction is a long-standing question, which remains largely unanswered. The T cell Ag receptor and various components of its proximal signaling machinery are associated with distinct endosomal compartments, but how endosomal traffic affects T cell signaling remains ill-defined. In this article, we demonstrate in human T cells that the subcellular localization and function of the protein tyrosine kinase Lck depends on the Rab11 effector FIP3 (Rab11 family interacting protein-3). FIP3 overexpression or silencing and its ability to interact with Rab11 modify Lck subcellular localization and its delivery to the immunological synapse. Importantly, FIP3-dependent Lck localization controls early TCR signaling events, such as tyrosine phosphorylation of TCRζ, ZAP70, and LAT and intracellular calcium concentration, as well as IL-2 gene expression. Interestingly, FIP3 controls both steady-state and poststimulation phosphotyrosine and calcium levels. Finally, our findings indicate that FIP3 modulates TCR-CD3 cell surface expression via the regulation of steady-state Lck-mediated TCRζ phosphorylation, which in turn controls TCRζ protein levels. This may influence long-term T cell activation in response to TCR-CD3 stimulation. Therefore, our data underscore the importance of finely regulated endosomal traffic in TCR signal transduction and T cell activation leading to IL-2 production. Copyright © 2017 by The American Association of Immunologists, Inc.

  1. POSITION CONTROL OF BRUSHLESS DC MOTOR BASED ON DIGITAL SIGNAL PROCESSING

    Directory of Open Access Journals (Sweden)

    Çetin GENÇER

    2006-01-01

    Full Text Available Brushless DC Motors (BLDC have been used widely high performance control systems which are depended on to development of power electronic and control technology. In these motors to fed commutated supply, the control of position without oscilation has been required. In this study, position control of BLDC with digital signal processing has been implemented by a proportional-derivative (PD controller because of its simple structure. It has been seen that the controller which is proposed from simulation and experimental studies, has a quick dynamic responce with nonoscillation.

  2. State-Space Equations and the First-Phase Algorithm for Signal Control of Single Intersections

    Institute of Scientific and Technical Information of China (English)

    LI Jinyuan; PAN Xin; WANG Xiqin

    2007-01-01

    State-space equations were applied to formulate the queuing and delay of traffic at a single intersection in this paper. The signal control of a single intersection was then modeled as a discrete-time optimal control problem, with consideration of the constraints of stream conflicts, saturation flow rate, minimum green time, and maximum green time. The problem cannot be solved directly due to the nonlinear constraints.However, the results of qualitative analysis were used to develop a first-phase signal control algorithm. Simulation results show that the algorithm substantially reduces the total delay compared to fixed-time control.

  3. Stem cell signaling. An integral program for tissue renewal and regeneration : Wnt signaling and stem cell control

    NARCIS (Netherlands)

    Clevers, Hans; Loh, Kyle M; Nusse, Roel

    2014-01-01

    Stem cells fuel tissue development, renewal, and regeneration, and these activities are controlled by the local stem cell microenvironment, the "niche." Wnt signals emanating from the niche can act as self-renewal factors for stem cells in multiple mammalian tissues. Wnt proteins are lipid-modified,

  4. Chromatic signals control proboscis movements during hovering flight in the hummingbird hawkmoth Macroglossum stellatarum.

    Science.gov (United States)

    Goyret, Joaquín; Kelber, Almut

    2012-01-01

    Most visual systems are more sensitive to luminance than to colour signals. Animals resolve finer spatial detail and temporal changes through achromatic signals than through chromatic ones. Probably, this explains that detection of small, distant, or moving objects is typically mediated through achromatic signals. Macroglossum stellatarum are fast flying nectarivorous hawkmoths that inspect flowers with their long proboscis while hovering. They can visually control this behaviour using floral markings known as nectar guides. Here, we investigate whether this is mediated by chromatic or achromatic cues. We evaluated proboscis placement, foraging efficiency, and inspection learning of naïve moths foraging on flower models with coloured markings that offered either chromatic, achromatic or both contrasts. Hummingbird hawkmoths could use either achromatic or chromatic signals to inspect models while hovering. We identified three, apparently independent, components controlling proboscis placement: After initial contact, 1) moths directed their probing towards the yellow colour irrespectively of luminance signals, suggesting a dominant role of chromatic signals; and 2) moths tended to probe mainly on the brighter areas of models that offered only achromatic signals. 3) During the establishment of the first contact, naïve moths showed a tendency to direct their proboscis towards the small floral marks independent of their colour or luminance. Moths learned to find nectar faster, but their foraging efficiency depended on the flower model they foraged on. Our results imply that M. stellatarum can perceive small patterns through colour vision. We discuss how the different informational contents of chromatic and luminance signals can be significant for the control of flower inspection, and visually guided behaviours in general.

  5. FireSignal-Data acquisition and control system software

    Energy Technology Data Exchange (ETDEWEB)

    Neto, A. [Associacao Euratom/IST, Centro de Fusao Nuclear, Av. Rovisco Pais, P-1049-001 Lisboa (Portugal)], E-mail: andre.neto@cfn.ist.utl.pt; Fernandes, H.; Duarte, A.; Carvalho, B.B.; Sousa, J.; Valcarcel, D.F. [Associacao Euratom/IST, Centro de Fusao Nuclear, Av. Rovisco Pais, P-1049-001 Lisboa (Portugal); Hron, M. [Asociace EURATOM IPP.CR, Prague (Czech Republic); Varandas, C.A.F. [Associacao Euratom/IST, Centro de Fusao Nuclear, Av. Rovisco Pais, P-1049-001 Lisboa (Portugal)

    2007-10-15

    Control of fusion experiments requires non-ambiguous, easy to use, user-interfaces to configure hardware devices. With that aim, a highly generic system for data control and acquisition has been developed. Among the main features it allows remote hardware configuration, shot launching, data sharing between connected users and experiment monitoring. The system is fully distributed: the hardware driver nodes, clients and servers are completely independent from each other and might run in different operating systems and programmed in different languages. All the communication is provided through the Common Object Request Broker Architecture (CORBA) protocol. FireSignal is designed to be as independent as possible from any kind of constraints as it is a plugin based system. Database, data viewers and the security system are some examples of what can easily be changed and adapted to the target machine's needs. In this system, every hardware is described in eXtensible Markup Language (XML) and with this information Graphical User Interfaces (GUI) are automatically built and user's parameter configuration validated. Any type of hardware device can be integrated in the system as long as it is described in XML and the respective driver developed. Any modern programming language can be used to develop these drivers. Currently Python and Java generic drivers are used. Data storage and indexing is time stamp event-based. Nodes are responsible for tagging the acquired samples with the absolute time stamps and to react to machine events. FireSignal is currently being used to control the ISTTOK/PT and CASTOR/CZ tokamaks.

  6. FireSignal-Data acquisition and control system software

    International Nuclear Information System (INIS)

    Neto, A.; Fernandes, H.; Duarte, A.; Carvalho, B.B.; Sousa, J.; Valcarcel, D.F.; Hron, M.; Varandas, C.A.F.

    2007-01-01

    Control of fusion experiments requires non-ambiguous, easy to use, user-interfaces to configure hardware devices. With that aim, a highly generic system for data control and acquisition has been developed. Among the main features it allows remote hardware configuration, shot launching, data sharing between connected users and experiment monitoring. The system is fully distributed: the hardware driver nodes, clients and servers are completely independent from each other and might run in different operating systems and programmed in different languages. All the communication is provided through the Common Object Request Broker Architecture (CORBA) protocol. FireSignal is designed to be as independent as possible from any kind of constraints as it is a plugin based system. Database, data viewers and the security system are some examples of what can easily be changed and adapted to the target machine's needs. In this system, every hardware is described in eXtensible Markup Language (XML) and with this information Graphical User Interfaces (GUI) are automatically built and user's parameter configuration validated. Any type of hardware device can be integrated in the system as long as it is described in XML and the respective driver developed. Any modern programming language can be used to develop these drivers. Currently Python and Java generic drivers are used. Data storage and indexing is time stamp event-based. Nodes are responsible for tagging the acquired samples with the absolute time stamps and to react to machine events. FireSignal is currently being used to control the ISTTOK/PT and CASTOR/CZ tokamaks

  7. Efficient Maturation and Cytokine Production of Neonatal DCs Requires Combined Proinflammatory Signals

    Directory of Open Access Journals (Sweden)

    Doreen Krumbiegel

    2005-01-01

    Full Text Available Specific functional properties of dendritic cells (DCs have been suspected as being responsible for the impaired specific immune responses observed in human neonates. To analyze stimulatory requirements for the critical transition from immature, antigen-processing DCs to mature, antigen-presenting DCs, we investigated the effect of different proinflammatory mediators and antigens on phenotype and cytokine secretion of human neonatal DCs derived from hematopoietic progenitor cells (HPCs. Whereas single proinflammatory mediators were unable to induce the maturation of neonatal DCs, various combinations of IFNγ, CD40L, TNFα, LPS and antigens, induced the maturation of neonatal DCs documented by up-regulation of HLA-DR, CD83 and CD86. Combinations of proinflammatory mediators also increased cytokine secretion by neonatal DCs. Especially combined stimulation with LPS and IFNγ proved to be very efficient in inducing maturation and cytokine synthesis of neonatal DCs. In conclusion, neonatal DCs can be stimulated to express maturation as well as costimulatory surface molecules. However, induction of maturation requires combined stimulation with multiple proinflammatory signals.

  8. Calculation of vehicle delay at signal-controlled intersections with adaptive traffic control algorithm

    Directory of Open Access Journals (Sweden)

    Andronov Roman

    2018-01-01

    Full Text Available By widely introducing information technology tools in the field of traffic control, it is possible to increase the capacity of hubs and reduce vehicle delays. Adaptive traffic light control is one of such tools. Its effectiveness can be assessed through traffic flow simulation. The aim of this study is to create a simulation model of a signal-controlled intersection that can be used to assess the effectiveness of adaptive control in various traffic situations, including the presence or absence of pedestrian traffic through an intersection. The model is based on a numerical experiment conducted using the Monte Carlo method. As a result of the study, vehicle delays, queue length and duration of traffic light cycles are calculated subject to different intensities of incoming traffic flows, and the presence or absence of pedestrian traffic.

  9. HARDWARE ENVIRONMENT FACTOR FOR CONTROL SIGNAL TRANSFER TO A PLANT IN THE SYNTHESIS PROBLEM OF DISCRETE SYSTEMS

    Directory of Open Access Journals (Sweden)

    O. S. Nuyya

    2015-07-01

    Full Text Available The paper attempts to revise certain provisions of the existing theory of discrete systems in the organization of hardware environment control signal transmission to a technical plant. It is known that the formation of a digital signal in discrete control problem of continuous plant is carried out by microcontroller or micro-computer and is represented by a parallel code, which dimension is determined by the hardware used. The parallel code for a digital clock cycle of the designed system is transmitted to the terminal device of a technical continuous plant, where the digital-to-analog conversion takes place. This kind of control signal transmission to the technical plant asserts its implementation by means of parallel buses. It is known that the length of a parallel bus is limited to an amount not exceeding half a meter due to the existing interference environment with modern standards of length. Thus, if the placement of the control signal and control plant is such that their connecting bus length exceeds more than half a meter, there is the inevitable transition from the parallel control signal to an allotted serial. The paper deals with the system factors arising in the transition from the parallel control signal to the serial by modern interfaces. Provisions of the paper are illustrated by an example. This paper is intended for system analytics and channel specialists. The resulting algorithm is applicable for control of plants (electric drive, in particular in the large industrial factories.

  10. A postsynaptic PI3K-cII dependent signaling controller for presynaptic homeostatic plasticity

    Science.gov (United States)

    Hauswirth, Anna G; Ford, Kevin J; Wang, Tingting; Fetter, Richard D; Tong, Amy

    2018-01-01

    Presynaptic homeostatic plasticity stabilizes information transfer at synaptic connections in organisms ranging from insect to human. By analogy with principles of engineering and control theory, the molecular implementation of PHP is thought to require postsynaptic signaling modules that encode homeostatic sensors, a set point, and a controller that regulates transsynaptic negative feedback. The molecular basis for these postsynaptic, homeostatic signaling elements remains unknown. Here, an electrophysiology-based screen of the Drosophila kinome and phosphatome defines a postsynaptic signaling platform that includes a required function for PI3K-cII, PI3K-cIII and the small GTPase Rab11 during the rapid and sustained expression of PHP. We present evidence that PI3K-cII localizes to Golgi-derived, clathrin-positive vesicles and is necessary to generate an endosomal pool of PI(3)P that recruits Rab11 to recycling endosomal membranes. A morphologically distinct subdivision of this platform concentrates postsynaptically where we propose it functions as a homeostatic controller for retrograde, trans-synaptic signaling. PMID:29303480

  11. High signal to noise ratio THz spectroscopy with ASOPS and signal processing schemes for mapping and controlling molecular and bulk relaxation processes

    International Nuclear Information System (INIS)

    Hadjiloucas, S; Walker, G C; Bowen, J W; Becerra, V M; Zafiropoulos, A; Galvao, R K H

    2009-01-01

    Asynchronous Optical Sampling has the potential to improve signal to noise ratio in THz transient sperctrometry. The design of an inexpensive control scheme for synchronising two femtosecond pulse frequency comb generators at an offset frequency of 20 kHz is discussed. The suitability of a range of signal processing schemes adopted from the Systems Identification and Control Theory community for further processing recorded THz transients in the time and frequency domain are outlined. Finally, possibilities for femtosecond pulse shaping using genetic algorithms are mentioned.

  12. High signal to noise ratio THz spectroscopy with ASOPS and signal processing schemes for mapping and controlling molecular and bulk relaxation processes

    Energy Technology Data Exchange (ETDEWEB)

    Hadjiloucas, S; Walker, G C; Bowen, J W; Becerra, V M [Cybernetics, School of Systems Engineering, University of Reading, RG6 6AY (United Kingdom); Zafiropoulos, A [Biosystems Engineering Department, School of Agricultural Technology, Technological Educational Institute of Larissa, 411 10, Larissa (Greece); Galvao, R K H, E-mail: s.hadjiloucas@reading.ac.u [Divisao de Engenharia Eletronica, Instituto Tecnologico de Aeronautica, Sao Jose dos Campos, SP, 12228-900 Brazil (Brazil)

    2009-08-01

    Asynchronous Optical Sampling has the potential to improve signal to noise ratio in THz transient sperctrometry. The design of an inexpensive control scheme for synchronising two femtosecond pulse frequency comb generators at an offset frequency of 20 kHz is discussed. The suitability of a range of signal processing schemes adopted from the Systems Identification and Control Theory community for further processing recorded THz transients in the time and frequency domain are outlined. Finally, possibilities for femtosecond pulse shaping using genetic algorithms are mentioned.

  13. DFIG turbine representation for small signal voltage control studies

    DEFF Research Database (Denmark)

    Garcia, Jorge Martinez; Kjær, Philip Carne; Teodorescu, Remus

    2010-01-01

    This paper addresses the representation of a wind power plant, based on wound rotor asynchronous generators, with a centralized voltage controller, by an equivalent transfer function, valid for small signal voltage control studies. This representation allows to investigate the influence...... introduced recently by several grid codes from around the world, making important to analyze this control when applied to wind power plants. The performance of the equivalent transfer function has been evaluated and compared using an equivalent grid with different short circuit ratios and active power...... of the centralized plant control gain and short circuit ratio on the system stability, for instance, by analyzing the zero-pole placement. Larger percentages of wind power penetration translate to more demanding requirements coming from the grid codes, for example voltage support at the point of connection has been...

  14. Randomness control of vehicular motion through a sequence of traffic signals at irregular intervals

    International Nuclear Information System (INIS)

    Nagatani, Takashi

    2010-01-01

    We study the regularization of irregular motion of a vehicle moving through the sequence of traffic signals with a disordered configuration. Each traffic signal is controlled by both cycle time and phase shift. The cycle time is the same for all signals, while the phase shift varies from signal to signal by synchronizing with intervals between a signal and the next signal. The nonlinear dynamic model of the vehicular motion is presented by the stochastic nonlinear map. The vehicle exhibits the very complex behavior with varying both cycle time and strength of irregular intervals. The irregular motion induced by the disordered configuration is regularized by adjusting the phase shift within the regularization regions.

  15. Foraging Value, Risk Avoidance, and Multiple Control Signals: How the Anterior Cingulate Cortex Controls Value-based Decision-making.

    Science.gov (United States)

    Brown, Joshua W; Alexander, William H

    2017-10-01

    Recent work on the role of the ACC in cognition has focused on choice difficulty, action value, risk avoidance, conflict resolution, and the value of exerting control among other factors. A main underlying question is what are the output signals of ACC, and relatedly, what is their effect on downstream cognitive processes? Here we propose a model of how ACC influences cognitive processing in other brain regions that choose actions. The model builds on the earlier Predicted Response Outcome model and suggests that ACC learns to represent specifically the states in which the potential costs or risks of an action are high, on both short and long timescales. It then uses those cost signals as a basis to bias decisions to minimize losses while maximizing gains. The model simulates both proactive and reactive control signals and accounts for a variety of empirical findings regarding value-based decision-making.

  16. A new traffic control design method for large networks with signalized intersections

    Science.gov (United States)

    Leininger, G. G.; Colony, D. C.; Seldner, K.

    1979-01-01

    The paper presents a traffic control design technique for application to large traffic networks with signalized intersections. It is shown that the design method adopts a macroscopic viewpoint to establish a new traffic modelling procedure in which vehicle platoons are subdivided into main stream queues and turning queues. Optimization of the signal splits minimizes queue lengths in the steady state condition and improves traffic flow conditions, from the viewpoint of the traveling public. Finally, an application of the design method to a traffic network with thirty-three signalized intersections is used to demonstrate the effectiveness of the proposed technique.

  17. Some Aspects of Process Computers Configuration Control in Nuclear Power Plant Krsko - Process Computer Signal Configuration Database (PCSCDB)

    International Nuclear Information System (INIS)

    Mandic, D.; Kocnar, R.; Sucic, B.

    2002-01-01

    During the operation of NEK and other nuclear power plants it has been recognized that certain issues related to the usage of digital equipment and associated software in NPP technological process protection, control and monitoring, is not adequately addressed in the existing programs and procedures. The term and the process of Process Computers Configuration Control joins three 10CFR50 Appendix B quality requirements of Process Computers application in NPP: Design Control, Document Control and Identification and Control of Materials, Parts and Components. This paper describes Process Computer Signal Configuration Database (PCSCDB), that was developed and implemented in order to resolve some aspects of Process Computer Configuration Control related to the signals or database points that exist in the life cycle of different Process Computer Systems (PCS) in Nuclear Power Plant Krsko. PCSCDB is controlled, master database, related to the definition and description of the configurable database points associated with all Process Computer Systems in NEK. PCSCDB holds attributes related to the configuration of addressable and configurable real time database points and attributes related to the signal life cycle references and history data such as: Input/Output signals, Manually Input database points, Program constants, Setpoints, Calculated (by application program or SCADA calculation tools) database points, Control Flags (example: enable / disable certain program feature) Signal acquisition design references to the DCM (Document Control Module Application software for document control within Management Information System - MIS) and MECL (Master Equipment and Component List MIS Application software for identification and configuration control of plant equipment and components) Usage of particular database point in particular application software packages, and in the man-machine interface features (display mimics, printout reports, ...) Signals history (EEAR Engineering

  18. Signalling and the control of skeletal muscle size

    International Nuclear Information System (INIS)

    Otto, Anthony; Patel, Ketan

    2010-01-01

    Skeletal muscle is highly adaptive to environmental stimuli and can alter its mass accordingly. This tissue is almost unique in that it can increase its size through two distinct mechanisms. It can grow through a cellular process mediated by cell fusion, or it can increase its size simply by increasing its protein content. Understanding how these processes are regulated is crucial for the development of potential therapies against debilitating skeletal muscle wasting diseases. Two key signalling molecules, Insulin like Growth Factor (IGF) and GDF-8/myostatin, have emerged in recent years to be potent regulators of skeletal muscle size. In this review we bring together recent data highlighting the important and novel aspects of both molecules and their signalling pathways, culminating in a discussion of the cellular and tissue phenotypic outcomes of their stimulation or antagonism. We emphasise the complex regulatory mechanisms and discuss the temporal and spatial differences that control their action, understanding of which is crucial to further their use as potential therapeutic targets.

  19. Signalling and the control of skeletal muscle size

    Energy Technology Data Exchange (ETDEWEB)

    Otto, Anthony [School of Biological Sciences, Hopkins Building, University of Reading, Whiteknights Campus, Reading, Berkshire, RG6 6UB (United Kingdom); Patel, Ketan, E-mail: ketan.patel@reading.ac.uk [School of Biological Sciences, Hopkins Building, University of Reading, Whiteknights Campus, Reading, Berkshire, RG6 6UB (United Kingdom)

    2010-11-01

    Skeletal muscle is highly adaptive to environmental stimuli and can alter its mass accordingly. This tissue is almost unique in that it can increase its size through two distinct mechanisms. It can grow through a cellular process mediated by cell fusion, or it can increase its size simply by increasing its protein content. Understanding how these processes are regulated is crucial for the development of potential therapies against debilitating skeletal muscle wasting diseases. Two key signalling molecules, Insulin like Growth Factor (IGF) and GDF-8/myostatin, have emerged in recent years to be potent regulators of skeletal muscle size. In this review we bring together recent data highlighting the important and novel aspects of both molecules and their signalling pathways, culminating in a discussion of the cellular and tissue phenotypic outcomes of their stimulation or antagonism. We emphasise the complex regulatory mechanisms and discuss the temporal and spatial differences that control their action, understanding of which is crucial to further their use as potential therapeutic targets.

  20. SH2 and SH3 domains: elements that control interactions of cytoplasmic signaling proteins.

    Science.gov (United States)

    Koch, C A; Anderson, D; Moran, M F; Ellis, C; Pawson, T

    1991-05-03

    Src homology (SH) regions 2 and 3 are noncatalytic domains that are conserved among a series of cytoplasmic signaling proteins regulated by receptor protein-tyrosine kinases, including phospholipase C-gamma, Ras GTPase (guanosine triphosphatase)-activating protein, and Src-like tyrosine kinases. The SH2 domains of these signaling proteins bind tyrosine phosphorylated polypeptides, implicated in normal signaling and cellular transformation. Tyrosine phosphorylation acts as a switch to induce the binding of SH2 domains, thereby mediating the formation of heteromeric protein complexes at or near the plasma membrane. The formation of these complexes is likely to control the activation of signal transduction pathways by tyrosine kinases. The SH3 domain is a distinct motif that, together with SH2, may modulate interactions with the cytoskeleton and membrane. Some signaling and transforming proteins contain SH2 and SH3 domains unattached to any known catalytic element. These noncatalytic proteins may serve as adaptors to link tyrosine kinases to specific target proteins. These observations suggest that SH2 and SH3 domains participate in the control of intracellular responses to growth factor stimulation.

  1. Systemic control of brown fat thermogenesis: integration of peripheral and central signals.

    Science.gov (United States)

    Schulz, Tim J; Tseng, Yu-Hua

    2013-10-01

    Brown adipose tissue (BAT) is of great scientific interest as a potential target to treat obesity. The development of novel strategies to quantify brown fat thermogenesis in adult humans now enables minimally invasive assessment of novel pharmacotherapeutics. Input from the central nervous system via sympathetic efferents is widely regarded as the key controller of BAT-mediated thermogenesis in response to changes in body temperature or nutrient availability. More recently, however, it has become clear that locally secreted signals and endocrine factors originating from multiple organs can control the recruitment of brown adipocytes and, more importantly, induce thermogenesis in brown fat. Thus, they provide an attractive strategy to fine-tune brown fat thermogenesis independent of classical temperature sensing. Here, we summarize recent findings on bone morphogenetic protein signaling as an example of secreted factors in the regulation of brown adipocyte formation and systemic control of energy metabolism. We further highlight endocrine communication routes between the different types of brown adipocytes and other organs that contribute to regulation of thermogenesis. Thus, emerging evidence suggests that the classical mechanisms of central temperature sensing and sympathetic nervous system-driven thermogenesis are complemented by local and endocrine signals to determine systemic energy homeostasis. © 2013 New York Academy of Sciences.

  2. A Distributed Control Strategy for Coordination of an Autonomous LVDC Microgrid Based on Power-Line Signalling

    DEFF Research Database (Denmark)

    Dragicevic, Tomislav; Guerrero, Josep M.; Vasquez, Juan Carlos

    2014-01-01

    In a MG, an energy management control is essential in order to handle the variety of prime movers which may include different types of renewable energy sources (RES) and energy storage systems (ESS). Specifically, the recharging process of secondary battery, the most prominent ESS, should be done...... of sources using power-line signaling (PLS), a distributed control strategy in which the units inject sinusoidal signals of specific frequency into the common bus in order to communicate with each other. The control structure that allows the application of this method is revealed and the optimal range...... of operating PLS frequencies is specified. In order to achieve a zero steady-state error of injected signals in the common bus, primary control of batteries has been extended with dedicated proportional-resonant (PR) controllers that are switched on only during injection period. Finally, a method...

  3. Signalling and obfuscation for congestion control

    Science.gov (United States)

    Mareček, Jakub; Shorten, Robert; Yu, Jia Yuan

    2015-10-01

    We aim to reduce the social cost of congestion in many smart city applications. In our model of congestion, agents interact over limited resources after receiving signals from a central agent that observes the state of congestion in real time. Under natural models of agent populations, we develop new signalling schemes and show that by introducing a non-trivial amount of uncertainty in the signals, we reduce the social cost of congestion, i.e., improve social welfare. The signalling schemes are efficient in terms of both communication and computation, and are consistent with past observations of the congestion. Moreover, the resulting population dynamics converge under reasonable assumptions.

  4. Dual Rate Adaptive Control for an Industrial Heat Supply Process Using Signal Compensation Approach

    Energy Technology Data Exchange (ETDEWEB)

    Chai, Tianyou; Jia, Yao; Wang, Hong; Su, Chun-Yi

    2017-07-09

    The industrial heat supply process (HSP) is a highly nonlinear cascaded process which uses a steam valve opening as its control input, the steam flow-rate as its inner loop output and the supply water temperature as its outer loop output. The relationship between the heat exchange rate and the model parameters, such as steam density, entropy, and fouling correction factor and heat exchange efficiency are unknown and nonlinear. Moreover, these model parameters vary in line with steam pressure, ambient temperature and the residuals caused by the quality variations of the circulation water. When the steam pressure and the ambient temperature are of high values and are subjected to frequent external random disturbances, the supply water temperature and the steam flow-rate would interact with each other and fluctuate a lot. This is also true when the process exhibits unknown characteristic variations of the process dynamics caused by the unexpected changes of the heat exchange residuals. As a result, it is difficult to control the supply water temperature and the rates of changes of steam flow-rate well inside their targeted ranges. In this paper, a novel compensation signal based dual rate adaptive controller is developed by representing the unknown variations of dynamics as unmodeled dynamics. In the proposed controller design, such a compensation signal is constructed and added onto the control signal obtained from the linear deterministic model based feedback control design. Such a compensation signal aims at eliminating the unmodeled dynamics and the rate of changes of the currently sample unmodeled dynamics. A successful industrial application is carried out, where it has been shown that both the supply water temperature and the rate of the changes of the steam flow-rate can be controlled well inside their targeted ranges when the process is subjected to unknown variations of its dynamics.

  5. Viability of Controlling Prosthetic Hand Utilizing Electroencephalograph (EEG) Dataset Signal

    Science.gov (United States)

    Miskon, Azizi; A/L Thanakodi, Suresh; Raihan Mazlan, Mohd; Mohd Haziq Azhar, Satria; Nooraya Mohd Tawil, Siti

    2016-11-01

    This project presents the development of an artificial hand controlled by Electroencephalograph (EEG) signal datasets for the prosthetic application. The EEG signal datasets were used as to improvise the way to control the prosthetic hand compared to the Electromyograph (EMG). The EMG has disadvantages to a person, who has not used the muscle for a long time and also to person with degenerative issues due to age factor. Thus, the EEG datasets found to be an alternative for EMG. The datasets used in this work were taken from Brain Computer Interface (BCI) Project. The datasets were already classified for open, close and combined movement operations. It served the purpose as an input to control the prosthetic hand by using an Interface system between Microsoft Visual Studio and Arduino. The obtained results reveal the prosthetic hand to be more efficient and faster in response to the EEG datasets with an additional LiPo (Lithium Polymer) battery attached to the prosthetic. Some limitations were also identified in terms of the hand movements, weight of the prosthetic, and the suggestions to improve were concluded in this paper. Overall, the objective of this paper were achieved when the prosthetic hand found to be feasible in operation utilizing the EEG datasets.

  6. 1-D Wavelet Signal Analysis of the Actuators Nonlinearities Impact on the Healthy Control Systems Performance

    Directory of Open Access Journals (Sweden)

    Nicolae Tudoroiu

    2017-09-01

    Full Text Available The objective of this paper is to investigate the use of the 1-D wavelet analysis to extract several patterns from signals data sets collected from healthy and faulty input-output signals of control systems as a preliminary step in real-time implementation of fault detection diagnosis and isolation strategies. The 1-D wavelet analysis proved that is an useful tool for signals processing, design and analysis based on wavelet transforms found in a wide range of control systems industrial applications. Based on the fact that in the real life there is a great similitude between the phenomena, we are motivated to extend the applicability of these techniques to solve similar applications from control systems field, such is done in our research work. Their efficiency will be demonstrated on a case study mainly chosen to evaluate the impact of the uncertainties and the nonlinearities of the sensors and actuators on the overall performance of the control systems. The proposed techniques are able to extract in frequency domain some pattern features (signatures of interest directly from the signals data set collected by data acquisition equipment from the control system.

  7. Experimental Study of Low Speed Sensorless Control of PMSM Drive Using High Frequency Signal Injection

    Directory of Open Access Journals (Sweden)

    Jyoti Agrawal

    2016-01-01

    Full Text Available Conventional techniques for sensorless control of permanent magnet synchronous motor drive (PMSM, which requires information on rotor position, are reviewed, and recent developments in this area are introduced in this paper along with their inherent advantages and drawbacks. The paper presents an improved method for sensorless speed control of PMSM drive with emphasis placed on signal injection method. This signal injection method examines the control performance of sensorless PMSM drive by injecting signal externally and thereby sensing the rotor position. The main objective of this drive system is to have speed control at standstill and low speed regions. Several tests are carried out to demonstrate the ability of proposed models at different operating conditions with the help of simulation results in Matlab/Simulink environment. Simulation results confirm that the proposed sensorless control approach of PMSM can achieve high performance at standstill and low speeds but not at very high speeds. An experimental setup is implemented using a 1HP surface mounted (SM PMSM and DsPICDEM^TM MCHV-2 development board, to check the validity of simulation results.

  8. Parametric manipulation of the conflict signal and control-state adaptation.

    Science.gov (United States)

    Forster, Sarah E; Carter, Cameron S; Cohen, Jonathan D; Cho, Raymond Y

    2011-04-01

    Mechanisms by which the brain monitors and modulates performance are an important focus of recent research. The conflict-monitoring hypothesis posits that the ACC detects conflict between competing response pathways which, in turn, signals for enhanced control. The N2, an ERP component that has been localized to ACC, has been observed after high conflict stimuli. As a candidate index of the conflict signal, the N2 would be expected to be sensitive to the degree of response conflict present, a factor that depends on both the features of external stimuli and the internal control state. In the present study, we sought to explore the relationship between N2 amplitude and these variables through use of a modified Eriksen flankers task in which target-distracter compatibility was parametrically varied. We hypothesized that greater target-distracter incompatibility would result in higher levels of response conflict, as indexed by both behavior and the N2 component. Consistent with this prediction, there were parametric degradations in behavioral performance and increases in N2 amplitudes with increasing incompatibility. Further, increasingly incompatible stimuli led to the predicted parametric increases in control on subsequent incompatible trials as evidenced by enhanced performance and reduced N2 amplitudes. These findings suggest that the N2 component and associated behavioral performance are finely sensitive to the degree of response conflict present and to the control adjustments that result from modulations in conflict.

  9. Small-Signal Modeling and Analysis of Grid-Connected Inverter with Power Differential Droop Control

    Directory of Open Access Journals (Sweden)

    Xin Chen

    2016-01-01

    Full Text Available The conventional voltage and frequency droop control strategy in grid-connected inverter suffers a major setback in the presence of disturbance by producing oscillations. Adding a power differential term in droop controller is an effective way to address such drawback. In this paper, grid-connected inverter’s small-signal models of the conventional droop control and the power differential droop control are established. The eigenvalues of the models are then determined by system matrix. The eigenvalues analysis is presented which helps in identifying the relationship between the system stability and controller parameters. It is concluded that the damping ratio of dominant low-frequency eigenvalues increased and the oscillation caused by the disturbance is suppressed when a power differential term is added to the droop control method. The MATLAB/Simulink models of grid-connected inverter with both control strategies are also established to validate the results of small-signal analysis.

  10. Chapter 10 the primary cilium coordinates signaling pathways in cell cycle control and migration during development and tissue repair

    DEFF Research Database (Denmark)

    Christensen, Søren T; Pedersen, Stine F; Satir, Peter

    2008-01-01

    Cell cycle control and migration are critical processes during development and maintenance of tissue functions. Recently, primary cilia were shown to take part in coordination of the signaling pathways that control these cellular processes in human health and disease. In this review, we present...... an overview of the function of primary cilia and the centrosome in the signaling pathways that regulate cell cycle control and migration with focus on ciliary signaling via platelet-derived growth factor receptor alpha (PDGFRalpha). We also consider how the primary cilium and the centrosome interact...... with the extracellular matrix, coordinate Wnt signaling, and modulate cytoskeletal changes that impinge on both cell cycle control and cell migration....

  11. Mechanisms of Wnt signaling and control.

    Science.gov (United States)

    Grainger, Stephanie; Willert, Karl

    2018-03-30

    The Wnt signaling pathway is a highly conserved system that regulates complex biological processes across all metazoan species. At the cellular level, secreted Wnt proteins serve to break symmetry and provide cells with positional information that is critical to the patterning of the entire body plan. At the organismal level, Wnt signals are employed to orchestrate fundamental developmental processes, including the specification of the anterior-posterior body axis, induction of the primitive streak and ensuing gastrulation movements, and the generation of cell and tissue diversity. Wnt functions extend into adulthood where they regulate stem cell behavior, tissue homeostasis, and damage repair. Disruption of Wnt signaling activity during embryonic development or in adults results in a spectrum of abnormalities and diseases, including cancer. The molecular mechanisms that underlie the myriad of Wnt-regulated biological effects have been the subject of intense research for over three decades. This review is intended to summarize our current understanding of how Wnt signals are generated and interpreted. This article is categorized under: Biological Mechanisms > Cell Signaling Developmental Biology > Stem Cell Biology and Regeneration. © 2018 Wiley Periodicals, Inc.

  12. FPGA implementation of a ZigBee wireless network control interface to transmit biomedical signals

    International Nuclear Information System (INIS)

    López, M A Gómez; Goy, C B; Bolognini, P C; Herrera, M C

    2011-01-01

    In recent years, cardiac hemodynamic monitors have incorporated new technologies based on wireless sensor networks which can implement different types of communication protocols. More precisely, a digital conductance catheter system recently developed adds a wireless ZigBee module (IEEE 802.15.4 standards) to transmit cardiac signals (ECG, intraventricular pressure and volume) which would allow the physicians to evaluate the patient's cardiac status in a noninvasively way. The aim of this paper is to describe a control interface, implemented in a FPGA device, to manage a ZigBee wireless network. ZigBee technology is used due to its excellent performance including simplicity, low-power consumption, short-range transmission and low cost. FPGA internal memory stores 8-bit signals with which the control interface prepares the information packets. These data were send to the ZigBee END DEVICE module that receives and transmits wirelessly to the external COORDINATOR module. Using an USB port, the COORDINATOR sends the signals to a personal computer for displaying. Each functional block of control interface was assessed by means of temporal diagrams. Three biological signals, organized in packets and converted to RS232 serial protocol, were successfully transmitted and displayed in a PC screen. For this purpose, a custom-made graphical software was designed using LabView.

  13. FPGA implementation of a ZigBee wireless network control interface to transmit biomedical signals

    Science.gov (United States)

    Gómez López, M. A.; Goy, C. B.; Bolognini, P. C.; Herrera, M. C.

    2011-12-01

    In recent years, cardiac hemodynamic monitors have incorporated new technologies based on wireless sensor networks which can implement different types of communication protocols. More precisely, a digital conductance catheter system recently developed adds a wireless ZigBee module (IEEE 802.15.4 standards) to transmit cardiac signals (ECG, intraventricular pressure and volume) which would allow the physicians to evaluate the patient's cardiac status in a noninvasively way. The aim of this paper is to describe a control interface, implemented in a FPGA device, to manage a ZigBee wireless network. ZigBee technology is used due to its excellent performance including simplicity, low-power consumption, short-range transmission and low cost. FPGA internal memory stores 8-bit signals with which the control interface prepares the information packets. These data were send to the ZigBee END DEVICE module that receives and transmits wirelessly to the external COORDINATOR module. Using an USB port, the COORDINATOR sends the signals to a personal computer for displaying. Each functional block of control interface was assessed by means of temporal diagrams. Three biological signals, organized in packets and converted to RS232 serial protocol, were sucessfully transmitted and displayed in a PC screen. For this purpose, a custom-made graphical software was designed using LabView.

  14. Length sensing and control of a Michelson interferometer with power recycling and twin signal recycling cavities.

    Science.gov (United States)

    Gräf, Christian; Thüring, André; Vahlbruch, Henning; Danzmann, Karsten; Schnabel, Roman

    2013-03-11

    The techniques of power recycling and signal recycling have proven as key concepts to increase the sensitivity of large-scale gravitational wave detectors by independent resonant enhancement of light power and signal sidebands within the interferometer. Developing the latter concept further, twin signal recycling was proposed as an alternative to conventional detuned signal recycling. Twin signal recycling features the narrow-band sensitivity gain of conventional detuned signal recycling but furthermore facilitates the injection of squeezed states of light, increases the detector sensitivity over a wide frequency band and requires a less complex detection scheme for optimal signal readout. These benefits come at the expense of an additional recycling mirror, thus increasing the number of degrees of freedom in the interferometer which need to be controlled.In this article we describe the development of a length sensing and control scheme and its successful application to a tabletop-scale power recycled Michelson interferometer with twin signal recycling. We were able to lock the interferometer in all relevant longitudinal degrees of freedom and thus laid the foundation for further investigations of this interferometer configuration to evaluate its viability for the application in gravitational wave detectors.

  15. Strategies for enhancing adoptive T-cell immunotherapy against solid tumors using engineered cytokine signaling and other modalities.

    Science.gov (United States)

    Shum, Thomas; Kruse, Robert L; Rooney, Cliona M

    2018-05-04

    Cancer therapy has been transformed by the demonstration that tumor-specific T-cells can eliminate tumor cells in a clinical setting with minimal long-term toxicity. However, significant success in the treatment of leukemia and lymphoma with T-cells using native receptors or redirected with chimeric antigen receptors (CARs) has not been recapitulated in the treatment of solid tumors. This lack of success is likely related to the paucity of costimulatory and cytokine signaling available in solid tumors, in addition to a range of inhibitory mechanisms. Areas covered: We summarize the latest developments in engineered T-cell immunotherapy, describe the limitations of these approaches in treating solid tumors, and finally highlight several strategies that may be useful in mediating solid tumor responses in the future, while also ensuring safety of engineered cells. Expert opinion: CAR-T therapies require further engineering to achieve their potential against solid tumors. Facilitating cytokine signaling in CAR T-cells appears to be essential in achieving better responses. However, the engineering of T-cells with potentially unchecked proliferation and potency raises the question of whether the simultaneous combination of enhancements will prove safe, necessitating continued advancements in regulating CAR-T activity at the tumor site and methods to safely switch off these engineered cells.

  16. B7.1 expression on tumor cells circumvents the need of professional antigen presentation for in vitro propagation of cytotoxic T cell lines.

    Science.gov (United States)

    Iezzi, G; Protti, M P; Rugarli, C; Bellone, M

    1996-01-01

    In vitro propagation of tumor-specific CTLs, to be used for identification of tumor antigens (Ag) and/or adoptive immunotherapy, is hampered by the need of large amounts of professional antigen-presenting cells (APC) used for periodical cycles of restimulation. We evaluated whether RMA T lymphoma cells, stably transfected with the cDNA encoding for the B7.1 costimulatory molecule, provided the activation signals to CD8+ T lymphocytes in the absence of professional APC and CD4+ helper cells. We demonstrate here that long-term CD8+ cell lines can be efficiently propagated in vitro by repeated cycles of stimulation with tumor cells stably expressing B7.1. Professional APC and CD4+ helper cells are not required as far as interleukin 2 is exogenously provided. Furthermore, CD8+ blasts needed both signal 1 (Ag in the contest of the MHC molecule) and signal 2 (interaction of costimulatory molecules) for restimulation. T cell blasts in the presence of signal 1 or 2 only still retained their effector potential but did not undergo clonal expansion. These results are very promising for further applications of specific immunotherapies in humans.

  17. Combined analysis of cortical (EEG) and nerve stump signals improves robotic hand control.

    Science.gov (United States)

    Tombini, Mario; Rigosa, Jacopo; Zappasodi, Filippo; Porcaro, Camillo; Citi, Luca; Carpaneto, Jacopo; Rossini, Paolo Maria; Micera, Silvestro

    2012-01-01

    Interfacing an amputee's upper-extremity stump nerves to control a robotic hand requires training of the individual and algorithms to process interactions between cortical and peripheral signals. To evaluate for the first time whether EEG-driven analysis of peripheral neural signals as an amputee practices could improve the classification of motor commands. Four thin-film longitudinal intrafascicular electrodes (tf-LIFEs-4) were implanted in the median and ulnar nerves of the stump in the distal upper arm for 4 weeks. Artificial intelligence classifiers were implemented to analyze LIFE signals recorded while the participant tried to perform 3 different hand and finger movements as pictures representing these tasks were randomly presented on a screen. In the final week, the participant was trained to perform the same movements with a robotic hand prosthesis through modulation of tf-LIFE-4 signals. To improve the classification performance, an event-related desynchronization/synchronization (ERD/ERS) procedure was applied to EEG data to identify the exact timing of each motor command. Real-time control of neural (motor) output was achieved by the participant. By focusing electroneurographic (ENG) signal analysis in an EEG-driven time window, movement classification performance improved. After training, the participant regained normal modulation of background rhythms for movement preparation (α/β band desynchronization) in the sensorimotor area contralateral to the missing limb. Moreover, coherence analysis found a restored α band synchronization of Rolandic area with frontal and parietal ipsilateral regions, similar to that observed in the opposite hemisphere for movement of the intact hand. Of note, phantom limb pain (PLP) resolved for several months. Combining information from both cortical (EEG) and stump nerve (ENG) signals improved the classification performance compared with tf-LIFE signals processing alone; training led to cortical reorganization and

  18. Gröbner bases in control theory and signal processing

    CERN Document Server

    Regensburger, Georg

    2007-01-01

    This volume contains survey and original articles presenting the state of the art on the application of Gröbner bases in control theory and signal processing. The contributions are based on talks delivered at the Special Semester on Gröbner Bases and Related Methods at the Johann Radon Institute of Computational and Applied Mathematics (RICAM), Linz, Austria, in May 2006.

  19. DMPD: The involvement of the interleukin-1 receptor-associated kinases (IRAKs) incellular signaling networks controlling inflammation. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available ncellular signaling networks controlling inflammation. Ringwood L, Li L. Cytokine. 2008 Apr;42(1):1-7. Epub ...ases (IRAKs) incellular signaling networks controlling inflammation. PubmedID 182...49132 Title The involvement of the interleukin-1 receptor-associated kinases (IRAKs) incellular signaling networks controlling

  20. Real-time signal communication between diagnostic and control in ASDEX Upgrade

    International Nuclear Information System (INIS)

    Treutterer, Wolfgang; Neu, Gregor; Raupp, Gerhard; Zehetbauer, Thomas; Zasche, Dieter; Lueddecke, Klaus; Cole, Richard

    2010-01-01

    The ASDEX Upgrade tokamak experiment is equipped with a versatile discharge monitoring and control system. It allows to develop and use advanced control algorithms to investigate plasma physics under well-defined conditions with the objective of optimising plasma performance. The achievable quality depends on the accuracy with which the plasma state can be reconstructed from measurements under real-time conditions. Today's advanced algorithms need physics quantities - scalar entities as well as profiles. These are obtained processing huge numbers of raw measurements with complex diagnostic algorithms. Adequate network communication for the resulting signals is crucial to satisfy real-time requirements, especially when several diagnostic systems cooperate in a feedback control loop. Support for the technology of choice, however, is not easily available for all of the diverse, highly specialised diagnostic systems. We give an overview about the methods that have been explored at ASDEX Upgrade for real-time signal transfer. In particular, we investigated reflective shared memory and Ethernet technologies. Our solution strives to combine their strengths. For fast communication on dedicated computing nodes, reflective shared memory is used. For the majority of diagnostic systems producing large data blocks at moderate rates, Ethernet connections with UDP protocol are employed. Following ASDEX Upgrade's framework concept, a software layer hides the networks used from both diagnostic and control applications.

  1. Real-time signal communication between diagnostic and control in ASDEX Upgrade

    Energy Technology Data Exchange (ETDEWEB)

    Treutterer, Wolfgang, E-mail: Wolfgang.Treutterer@ipp.mpg.d [Max-Planck Institut fuer Plasmaphysik, Garching, EURATOM Association (Germany); Neu, Gregor; Raupp, Gerhard; Zehetbauer, Thomas; Zasche, Dieter [Max-Planck Institut fuer Plasmaphysik, Garching, EURATOM Association (Germany); Lueddecke, Klaus; Cole, Richard [Unlimited Computer Systems, Iffeldorf (Germany)

    2010-07-15

    The ASDEX Upgrade tokamak experiment is equipped with a versatile discharge monitoring and control system. It allows to develop and use advanced control algorithms to investigate plasma physics under well-defined conditions with the objective of optimising plasma performance. The achievable quality depends on the accuracy with which the plasma state can be reconstructed from measurements under real-time conditions. Today's advanced algorithms need physics quantities - scalar entities as well as profiles. These are obtained processing huge numbers of raw measurements with complex diagnostic algorithms. Adequate network communication for the resulting signals is crucial to satisfy real-time requirements, especially when several diagnostic systems cooperate in a feedback control loop. Support for the technology of choice, however, is not easily available for all of the diverse, highly specialised diagnostic systems. We give an overview about the methods that have been explored at ASDEX Upgrade for real-time signal transfer. In particular, we investigated reflective shared memory and Ethernet technologies. Our solution strives to combine their strengths. For fast communication on dedicated computing nodes, reflective shared memory is used. For the majority of diagnostic systems producing large data blocks at moderate rates, Ethernet connections with UDP protocol are employed. Following ASDEX Upgrade's framework concept, a software layer hides the networks used from both diagnostic and control applications.

  2. PULSE REFERENCED CONTROL METHOD FOR ENHANCED POWER AMPLIFICATION OF A PULSE MODULATED SIGNAL

    DEFF Research Database (Denmark)

    1998-01-01

    , by introducing continuous delays on the individual pulse edges on the basis of error information provided by an error processing block. One preferred embodiment of the invention comprises: a Correction Unit with means to control the delays of the individual pulse edges as a function of a control input signal $i...

  3. Controlling low-rate signal path microdischarge for an ultra-low-background proportional counter

    International Nuclear Information System (INIS)

    Mace, E.K.; Aalseth, C.E.; Bonicalzi, R.M.; Day, A.R.; Hoppe, E.W.; Keillor, M.E.; Myers, A.W.; Overman, C.T.; Seifert, A.

    2013-01-01

    Pacific Northwest National Laboratory (PNNL) has developed an ultra-low-background proportional counter (ULBPC) made of high purity copper. These detectors are part of an ultra-low-background counting system (ULBCS) in the newly constructed shallow underground laboratory at PNNL (at a depth of ∼30 m water-equivalent). To control backgrounds, the current preamplifier electronics are located outside the ULBCS shielding. Thus the signal from the detector travels through ∼1 m of cable and is potentially susceptible to high voltage microdischarge and other sources of electronic noise. Based on initial successful tests, commercial cables and connectors were used for this critical signal path. Subsequent testing across different batches of commercial cables and connectors, however, showed unwanted (but still low) rates of microdischarge noise. To control this noise source, two approaches were pursued: first, to carefully validate cables, connectors, and other commercial components in this critical signal path, making modifications where necessary; second, to develop a custom low-noise, low-background preamplifier that can be integrated with the ULBPC and thus remove most commercial components from the critical signal path. This integrated preamplifier approach is based on the Amptek A250 low-noise charge-integrating preamplifier module. The initial microdischarge signals observed are presented and characterized according to the suspected source. Each of the approaches for mitigation is described, and the results from both are compared with each other and with the original performance seen with commercial cables and connectors. (author)

  4. Towards brain-activity-controlled information retrieval: Decoding image relevance from MEG signals.

    Science.gov (United States)

    Kauppi, Jukka-Pekka; Kandemir, Melih; Saarinen, Veli-Matti; Hirvenkari, Lotta; Parkkonen, Lauri; Klami, Arto; Hari, Riitta; Kaski, Samuel

    2015-05-15

    We hypothesize that brain activity can be used to control future information retrieval systems. To this end, we conducted a feasibility study on predicting the relevance of visual objects from brain activity. We analyze both magnetoencephalographic (MEG) and gaze signals from nine subjects who were viewing image collages, a subset of which was relevant to a predetermined task. We report three findings: i) the relevance of an image a subject looks at can be decoded from MEG signals with performance significantly better than chance, ii) fusion of gaze-based and MEG-based classifiers significantly improves the prediction performance compared to using either signal alone, and iii) non-linear classification of the MEG signals using Gaussian process classifiers outperforms linear classification. These findings break new ground for building brain-activity-based interactive image retrieval systems, as well as for systems utilizing feedback both from brain activity and eye movements. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Cell intrinsic modulation of Wnt signaling controls neuroblast migration in C. elegans.

    Science.gov (United States)

    Mentink, Remco A; Middelkoop, Teije C; Rella, Lorenzo; Ji, Ni; Tang, Chung Yin; Betist, Marco C; van Oudenaarden, Alexander; Korswagen, Hendrik C

    2014-10-27

    Members of the Wnt family of secreted signaling proteins are key regulators of cell migration and axon guidance. In the nematode C. elegans, the migration of the QR neuroblast descendants requires multiple Wnt ligands and receptors. We found that the migration of the QR descendants is divided into three sequential phases that are each mediated by a distinct Wnt signaling mechanism. Importantly, the transition from the first to the second phase, which is the main determinant of the final position of the QR descendants along the anteroposterior body axis, is mediated through a cell-autonomous process in which the time-dependent expression of a Wnt receptor turns on the canonical Wnt/β-catenin signaling response that is required to terminate long-range anterior migration. Our results show that, in addition to direct guidance of cell migration by Wnt morphogenic gradients, cell migration can also be controlled indirectly through cell-intrinsic modulation of Wnt signaling responses.

  6. Analysis and software development for controlling RF signal generator proton cyclotron Decy-13 using DDS Technique

    International Nuclear Information System (INIS)

    Prajitno

    2012-01-01

    Analysis and manufacture of computer programs for controlling the signal generator Radio Frequency (RF) proton cyclotron Decy-13 have been done. Signal generator uses a technique Direct Digital Synthesiser (DDS) which settings must be done with software. Signal generator consists of electronic modules which are: DDS, micro controller ATmega16, amplifier RF.dan ± 12 Vdc power supply. Function of the programs that have been made is to set the DDS module, namely: output frequency, step frequency and phase settings and displays the operating parameters of the DDS and the RF amplifier on the monitor screen. Computer programs created with Visual Basic and has been tested to control the RF signal generator to send data serially to the module ATmega16 and receives data to be displayed on the monitor screen. Testing sending and receiving data is done with a baudrate of 1200 bps to 19200 bps with perfect results. Computer programs that have been made equipped with a Human Machine Interface to provide values parameter input on the DDS operations. (author)

  7. Top-Down Control of Visual Alpha Oscillations: Sources of Control Signals and Their Mechanisms of Action

    Science.gov (United States)

    Wang, Chao; Rajagovindan, Rajasimhan; Han, Sahng-Min; Ding, Mingzhou

    2016-01-01

    Alpha oscillations (8–12 Hz) are thought to inversely correlate with cortical excitability. Goal-oriented modulation of alpha has been studied extensively. In visual spatial attention, alpha over the region of visual cortex corresponding to the attended location decreases, signifying increased excitability to facilitate the processing of impending stimuli. In contrast, in retention of verbal working memory, alpha over visual cortex increases, signifying decreased excitability to gate out stimulus input to protect the information held online from sensory interference. According to the prevailing model, this goal-oriented biasing of sensory cortex is effected by top-down control signals from frontal and parietal cortices. The present study tests and substantiates this hypothesis by (a) identifying the signals that mediate the top-down biasing influence, (b) examining whether the cortical areas issuing these signals are task-specific or task-independent, and (c) establishing the possible mechanism of the biasing action. High-density human EEG data were recorded in two experimental paradigms: a trial-by-trial cued visual spatial attention task and a modified Sternberg working memory task. Applying Granger causality to both sensor-level and source-level data we report the following findings. In covert visual spatial attention, the regions exerting top-down control over visual activity are lateralized to the right hemisphere, with the dipoles located at the right frontal eye field (FEF) and the right inferior frontal gyrus (IFG) being the main sources of top-down influences. During retention of verbal working memory, the regions exerting top-down control over visual activity are lateralized to the left hemisphere, with the dipoles located at the left middle frontal gyrus (MFG) being the main source of top-down influences. In both experiments, top-down influences are mediated by alpha oscillations, and the biasing effect is likely achieved via an inhibition

  8. Modeling SMAP Spacecraft Attitude Control Estimation Error Using Signal Generation Model

    Science.gov (United States)

    Rizvi, Farheen

    2016-01-01

    Two ground simulation software are used to model the SMAP spacecraft dynamics. The CAST software uses a higher fidelity model than the ADAMS software. The ADAMS software models the spacecraft plant, controller and actuator models, and assumes a perfect sensor and estimator model. In this simulation study, the spacecraft dynamics results from the ADAMS software are used as CAST software is unavailable. The main source of spacecraft dynamics error in the higher fidelity CAST software is due to the estimation error. A signal generation model is developed to capture the effect of this estimation error in the overall spacecraft dynamics. Then, this signal generation model is included in the ADAMS software spacecraft dynamics estimate such that the results are similar to CAST. This signal generation model has similar characteristics mean, variance and power spectral density as the true CAST estimation error. In this way, ADAMS software can still be used while capturing the higher fidelity spacecraft dynamics modeling from CAST software.

  9. The Drosophila Arf GEF Steppke controls MAPK activation in EGFR signaling.

    Science.gov (United States)

    Hahn, Ines; Fuss, Bernhard; Peters, Annika; Werner, Tamara; Sieberg, Andrea; Gosejacob, Dominic; Hoch, Michael

    2013-06-01

    Guanine nucleotide exchange factors (GEFs) of the cytohesin protein family are regulators of GDP/GTP exchange for members of the ADP ribosylation factor (Arf) of small GTPases. They have been identified as modulators of various receptor tyrosine kinase signaling pathways including the insulin, the vascular epidermal growth factor (VEGF) and the epidermal growth factor (EGF) pathways. These pathways control many cellular functions, including cell proliferation and differentiation, and their misregulation is often associated with cancerogenesis. In vivo studies on cytohesins using genetic loss of function alleles are lacking, however, since knockout mouse models are not available yet. We have recently identified mutants for the single cytohesin Steppke (Step) in Drosophila and we could demonstrate an essential role of Step in the insulin signaling cascade. In the present study, we provide in vivo evidence for a role of Step in EGFR signaling during wing and eye development. By analyzing step mutants, transgenic RNA interference (RNAi) and overexpression lines for tissue specific as well as clonal analysis, we found that Step acts downstream of the EGFR and is required for the activation of mitogen-activated protein kinase (MAPK) and the induction of EGFR target genes. We further demonstrate that step transcription is induced by EGFR signaling whereas it is negatively regulated by insulin signaling. Furthermore, genetic studies and biochemical analysis show that Step interacts with the Connector Enhancer of KSR (CNK). We propose that Step may be part of a larger signaling scaffold coordinating receptor tyrosine kinase-dependent MAPK activation.

  10. Reference-tracking feedforward control design for linear dynamical systems through signal decomposition

    NARCIS (Netherlands)

    Kasemsinsup, Y.; Romagnoli, R.; Heertjes, M.F.; Weiland, S.; Butler, H.

    2017-01-01

    In this work, we study a novel approach towards the reference-tracking feedforward control design for linear dynamical systems. By utilizing the superposition property and exploiting signal decomposition together with a quadratic optimization process, we obtain a feedforward design procedure for

  11. Semaphorin-Plexin Signaling Controls Mitotic Spindle Orientation during Epithelial Morphogenesis and Repair

    DEFF Research Database (Denmark)

    Xia, Jingjing; Swiercz, Jakub M.; Bañón-Rodríguez, Inmaculada

    2015-01-01

    Morphogenesis, homeostasis, and regeneration of epithelial tissues rely on the accurate orientation of cell divisions, which is specified by the mitotic spindle axis. To remain in the epithelial plane, symmetrically dividing epithelial cells align their mitotic spindle axis with the plane. Here, we...... show that this alignment depends on epithelial cell-cell communication via semaphorin-plexin signaling. During kidney morphogenesis and repair, renal tubular epithelial cells lacking the transmembrane receptor Plexin-B2 or its semaphorin ligands fail to correctly orient the mitotic spindle, leading...... to severe defects in epithelial architecture and function. Analyses of a series of transgenic and knockout mice indicate that Plexin-B2 controls the cell division axis by signaling through its GTPase-activating protein (GAP) domain and Cdc42. Our data uncover semaphorin-plexin signaling as a central...

  12. A mechatronics platform to study prosthetic hand control using EMG signals.

    Science.gov (United States)

    Geethanjali, P

    2016-09-01

    In this paper, a low-cost mechatronics platform for the design and development of robotic hands as well as a surface electromyogram (EMG) pattern recognition system is proposed. This paper also explores various EMG classification techniques using a low-cost electronics system in prosthetic hand applications. The proposed platform involves the development of a four channel EMG signal acquisition system; pattern recognition of acquired EMG signals; and development of a digital controller for a robotic hand. Four-channel surface EMG signals, acquired from ten healthy subjects for six different movements of the hand, were used to analyse pattern recognition in prosthetic hand control. Various time domain features were extracted and grouped into five ensembles to compare the influence of features in feature-selective classifiers (SLR) with widely considered non-feature-selective classifiers, such as neural networks (NN), linear discriminant analysis (LDA) and support vector machines (SVM) applied with different kernels. The results divulged that the average classification accuracy of the SVM, with a linear kernel function, outperforms other classifiers with feature ensembles, Hudgin's feature set and auto regression (AR) coefficients. However, the slight improvement in classification accuracy of SVM incurs more processing time and memory space in the low-level controller. The Kruskal-Wallis (KW) test also shows that there is no significant difference in the classification performance of SLR with Hudgin's feature set to that of SVM with Hudgin's features along with AR coefficients. In addition, the KW test shows that SLR was found to be better in respect to computation time and memory space, which is vital in a low-level controller. Similar to SVM, with a linear kernel function, other non-feature selective LDA and NN classifiers also show a slight improvement in performance using twice the features but with the drawback of increased memory space requirement and time

  13. T-cells fighting B-cell lymphoproliferative malignancies: the emerging field of CD19 CAR T-cell therapy

    NARCIS (Netherlands)

    Heijink, D. M.; Kater, A. P.; Hazenberg, M. D.; Hagenbeek, A.; Kersten, M. J.

    2016-01-01

    CAR T-cells are autologous T-cells transduced with a chimeric antigen receptor (CAR). The CAR contains an antigen recognition part (originating from an antibody), a T-cell receptor transmembrane and cytoplasmic signalling part, and one or more co-stimulatory domains. While CAR T-cells can be

  14. Multistaged Nanovaccines Based on Porous Silicon@Acetalated Dextran@Cancer Cell Membrane for Cancer Immunotherapy

    DEFF Research Database (Denmark)

    Fontana, Flavia; Shahbazi, Mohammad Ali; Liu, Dongfei

    2017-01-01

    nanoparticles presented high monodispersity due to the efficient mixing produced in the microfluidic device and were shown to be highly cytocompatible over two human immortalized cell lines, KG1 and BDCM. Moreover, the nanoparticles induced the expression of co-stimulatory signals both in the immortal cell...

  15. Branched-Chain Aminotransferases Control TORC1 Signaling in Saccharomyces cerevisiae.

    Directory of Open Access Journals (Sweden)

    Joanne M Kingsbury

    2015-12-01

    Full Text Available The conserved target of rapamycin complex 1 (TORC1 integrates nutrient signals to orchestrate cell growth and proliferation. Leucine availability is conveyed to control TORC1 activity via the leu-tRNA synthetase/EGOC-GTPase module in yeast and mammals, but the mechanisms sensing leucine remain only partially understood. We show here that both leucine and its α-ketoacid metabolite, α-ketoisocaproate, effectively activate the yeast TORC1 kinase via both EGOC GTPase-dependent and -independent mechanisms. Leucine and α-ketoisocaproate are interconverted by ubiquitous branched-chain aminotransferases (BCAT, which in yeast are represented by the mitochondrial and cytosolic enzymes Bat1 and Bat2, respectively. BCAT yeast mutants exhibit severely compromised TORC1 activity, which is partially restored by expression of Bat1 active site mutants, implicating both catalytic and structural roles of BCATs in TORC1 control. We find that Bat1 interacts with branched-chain amino acid metabolic enzymes and, in a leucine-dependent fashion, with the tricarboxylic acid (TCA-cycle enzyme aconitase. BCAT mutation perturbed TCA-cycle intermediate levels, consistent with a TCA-cycle block, and resulted in low ATP levels, activation of AMPK, and TORC1 inhibition. We propose the biosynthetic capacity of BCAT and its role in forming multicomplex metabolons connecting branched-chain amino acids and TCA-cycle metabolism governs TCA-cycle flux to activate TORC1 signaling. Because mammalian mitochondrial BCAT is known to form a supramolecular branched-chain α-keto acid dehydrogenase enzyme complex that links leucine metabolism to the TCA-cycle, these findings establish a precedent for understanding TORC1 signaling in mammals.

  16. IMPACTS OF GROUP-BASED SIGNAL CONTROL POLICY ON DRIVER BEHAVIOR AND INTERSECTION SAFETY

    Directory of Open Access Journals (Sweden)

    Keshuang TANG

    2008-01-01

    Full Text Available Unlike the typical stage-based policy commonly applied in Japan, the group-based control (often called movement-based in the traffic control industry in Japan refers to such a control pattern that the controller is capable of separately allocating time to each signal group instead of stage based on traffic demand. In order to investigate its applicability at signalized intersections in Japan, an intersection located in Yokkaichi City of Mie Prefecture was selected as an experimental application site by the Japan Universal Traffic Management Society (UTMS. Based on the data collected at the intersection before and after implementing the group-based control policy respectively, this study evaluated the impacts of such a policy on driver behavior and intersection safety. To specify those impacts, a few models utilizing cycle-based data were first developed to interpret the occurrence probability and rate of red-light-running (RLR. Furthermore, analyses were performed on the yellow-entry time (Ye of the last cleared vehicle and post encroachment time (PET during the phase switching. Conclusions supported that the group-based control policy, along with certain other factors, directly or indirectly influenced the RLR behavior of through and right-turn traffics. Meanwhile, it has potential safety benefits as well, indicated by the declined Ye and increased PET values.

  17. Identification of Palmitoleic Acid Controlled by mTOR Signaling as a Biomarker of Polymyositis

    Directory of Open Access Journals (Sweden)

    Geng Yin

    2017-01-01

    Full Text Available Polymyositis (PM is a chronic disease characterized by muscle pain, weakness, and increase in muscle-related enzymes, accompanied with inflammations in lymphocytes. However, it is not well understood how the molecular alternations in lymphocytes contribute to the development of polymyositis. The mechanistic target of rapamycin (mTOR signaling is the central regulator of metabolism and inflammation in mammalian cells. Based on previous studies, we proposed that mTOR signaling may control inflammatory reactions via lipid metabolism. In this study, we aim to figure out the role of mTOR signaling in the development of polymyositis and identify novel biomarkers for the detection and therapy of polymyositis. After screening and validation, we found that palmitoleic acid, a monounsaturated fatty acid, is highly regulated by mTOR signaling. Inhibition of mTORC1 activity decreases palmitoleic acid level. Moreover, mTORC1 regulates the level of palmitoleic acid by controlling its de novo synthesis. Importantly, increased palmitoleic acid has been proven to be a marker of polymyositis. Our work identifies palmitoleic acid in peripheral blood mononuclear cells (PBMC as a biomarker of polymyositis and offers new targets to the clinical therapy.

  18. Evaluation of the skin sensitization potential of chemicals using expression of co-stimulatory molecules, CD54 and CD86, on the naive THP-1 cell line.

    Science.gov (United States)

    Yoshida, Y; Sakaguchi, H; Ito, Y; Okuda, M; Suzuki, H

    2003-04-01

    It has been known that dendritic cells (DCs) including Langerhans cells (LCs) play a critical role in the skin sensitization process. Many attempts have been made to develop in vitro sensitization tests that employ DCs derived from peripheral blood mononuclear cells (PBMC-DC) or CD34+ hematopoietic progenitor cells (CD34+ HPC) purified from cord blood or bone marrow. However, the use of the DCs in in vitro methods has been difficult due to the nature of these cells such as low levels in the source and/or donor-to-donor variability. In our studies, we employed the human monocytic leukemia cell line, THP-1, in order to avoid some of these difficulties. At the start, we examined whether treatment of the cells with various cytokines could produce DCs from THP-1. Treatment of THP-1 cells with cytokines such as GM-CSF, IL-4, TNF-alpha, and/or PMA did induce some phenotypic changes in THP-1 cells that were characteristic of DCs. Subsequently, responses to a known sensitizer, dinitrochlorobenzene (DNCB), and a non-sensitizer, dimethyl sulfoxide (DMSO) or sodium lauryl sulfate (SLS), on the expression of co-stimulatory molecules, CD54 and CD86, were examined between the naive cells and the cytokine-treated cells. Interestingly, the naive THP-1 cells responded only to DNCB and the response to the sensitizer was more distinct than cytokine-treated THP-1 cells. Similar phenomena were also observed in the human myeloid leukemia cell line, KG-1. Furthermore, with treatment of DNCB, naive THP-1 cells showed augmented expression of HLA, CD80 and secretion of IL-1 beta. The response of THP-1 cells to a sensitizer was similar to that of LCs/DCs. Upon demonstrating the differentiation of monocyte cells in our system, we then evaluated a series of chemicals, including known sensitizers and non-sensitizers, for their potential to augment CD54 and CD86 expression on naive THP-1 cells. Indeed, known sensitizers such as PPD and 2-MBT significantly augmented CD54 and CD86 expression in a

  19. Dynamics of response-conflict monitoring and individual differences in response control and behavioral control: an electrophysiological investigation using a stop-signal task.

    Science.gov (United States)

    Stahl, Jutta; Gibbons, Henning

    2007-03-01

    The aim of the present study was to investigate the functional significance of error (related) negativity Ne/ERN and individual differences in human action monitoring. A response-conflict model of Ne/ERN should be tested applying a stop-signal paradigm. After a few modifications of Ne/ERN response-conflict theory (Yeung N, Botvinick MM, Cohen JD. The neural basis of error detection: conflict monitoring and the error-related negativity. Psychological Review 2004:111(4);931-959), strength and time course of response conflict could be modeled as a function of stop-signal delay. In Experiment 1, 35 participants performed a visual two-choice response-time task but tried to withhold the response if an auditory stop signal was presented. Probability of stopping errors was held at 50% using variable delays between visual and auditory stimuli. Experiment 2 (n=10) employed both auditory go and stop signals and confirmed that Ne/ERN effects are due to conflict induced by the auditory stop signal, and not the mere presence or absence of an additional stimulus. As predicted, amplitudes of both the stimulus-locked and response-locked Ne/ERN were largest for non-stopped responses, followed by successfully stopped and go responses. However, independently of response type Ne/ERN also increased with increasing stop-signal delay. Since longer delay invokes stronger response conflict, results specifically support the notion of Ne/ERN reflecting response-conflict monitoring. Furthermore, individual differences related to measures of response control and behavioral control were observed. Both low response control estimated from stop-task performance and high psychometric impulsivity were accompanied by smaller Ne/ERN amplitude on stop trials, suggesting reduced response-conflict monitoring. The present study supported the response-conflict view of Ne/ERN. Furthermore, the observed relationship between impulsivity and Ne/ERN amplitude suggested that individuals with low behavioral

  20. The interaction between glucose and cytokinin signaling in controlling Arabidopsis thaliana seedling root growth and development.

    Science.gov (United States)

    Kushwah, Sunita; Laxmi, Ashverya

    2017-05-04

    Cytokinin (CK) and glucose (GLC) control several common responses in plants. There is an extensive overlap between CK and GLC signal transduction pathways in Arabidopsis. Physiologically, both GLC and CK could regulate root length in light. CK interacts with GLC via HXK1 dependent pathway for root length control. Wild-type (WT) roots cannot elongate in the GLC free medium while CK-receptor mutant ARABIDOPSIS HISTIDINE KINASE4 (ahk4) and type B ARR triple mutant ARABIDOPSIS RESPONSE REGULATOR1, 10,11 (arr1, 10,11) roots could elongate even in the absence of GLC as compared with the WT. The root hair initiation was also found defective in CK signaling mutants ahk4, arr1,10,11 and arr3,4,5,6,8,9 on increasing GLC concentration (up to 3%); and lesser number of root hairs were visible even at 5% GLC as compared with the WT. Out of 941 BAP regulated genes, 103 (11%) genes were involved in root growth and development. Out of these 103 genes, 60 (58%) genes were also regulated by GLC. GLC could regulate 5736 genes, which include 327 (6%) genes involved in root growth and development. Out of these 327 genes, 60 (18%) genes were also regulated by BAP. Both GLC and CK signaling cannot alter root length in light in auxin signaling mutant AUXIN RESPONSE3/INDOLE-3-ACETIC ACID17 (axr3/iaa17) suggesting that they may involve auxin signaling component as a nodal point. Therefore CK- and GLC- signaling are involved in controlling different aspects of root growth and development such as root length, with auxin signaling components working as downstream target.

  1. Drosophila mushroom bodies integrate hunger and satiety signals to control innate food-seeking behavior.

    Science.gov (United States)

    Tsao, Chang-Hui; Chen, Chien-Chun; Lin, Chen-Han; Yang, Hao-Yu; Lin, Suewei

    2018-03-16

    The fruit fly can evaluate its energy state and decide whether to pursue food-related cues. Here, we reveal that the mushroom body (MB) integrates hunger and satiety signals to control food-seeking behavior. We have discovered five pathways in the MB essential for hungry flies to locate and approach food. Blocking the MB-intrinsic Kenyon cells (KCs) and the MB output neurons (MBONs) in these pathways impairs food-seeking behavior. Starvation bi-directionally modulates MBON responses to a food odor, suggesting that hunger and satiety controls occur at the KC-to-MBON synapses. These controls are mediated by six types of dopaminergic neurons (DANs). By manipulating these DANs, we could inhibit food-seeking behavior in hungry flies or promote food seeking in fed flies. Finally, we show that the DANs potentially receive multiple inputs of hunger and satiety signals. This work demonstrates an information-rich central circuit in the fly brain that controls hunger-driven food-seeking behavior. © 2018, Tsao et al.

  2. Visual signal detection in structured backgrounds. II. Effects of contrast gain control, background variations, and white noise

    Science.gov (United States)

    Eckstein, M. P.; Ahumada, A. J. Jr; Watson, A. B.

    1997-01-01

    Studies of visual detection of a signal superimposed on one of two identical backgrounds show performance degradation when the background has high contrast and is similar in spatial frequency and/or orientation to the signal. To account for this finding, models include a contrast gain control mechanism that pools activity across spatial frequency, orientation and space to inhibit (divisively) the response of the receptor sensitive to the signal. In tasks in which the observer has to detect a known signal added to one of M different backgrounds grounds due to added visual noise, the main sources of degradation are the stochastic noise in the image and the suboptimal visual processing. We investigate how these two sources of degradation (contrast gain control and variations in the background) interact in a task in which the signal is embedded in one of M locations in a complex spatially varying background (structured background). We use backgrounds extracted from patient digital medical images. To isolate effects of the fixed deterministic background (the contrast gain control) from the effects of the background variations, we conduct detection experiments with three different background conditions: (1) uniform background, (2) a repeated sample of structured background, and (3) different samples of structured background. Results show that human visual detection degrades from the uniform background condition to the repeated background condition and degrades even further in the different backgrounds condition. These results suggest that both the contrast gain control mechanism and the background random variations degrade human performance in detection of a signal in a complex, spatially varying background. A filter model and added white noise are used to generate estimates of sampling efficiencies, an equivalent internal noise, an equivalent contrast-gain-control-induced noise, and an equivalent noise due to the variations in the structured background.

  3. The Prc and RseP proteases control bacterial cell-surface signalling activity.

    NARCIS (Netherlands)

    Bastiaansen, K.C.J.T.; Ibañez, A.; Ramos, JL; Bitter, W.; Llamas, M.A.

    2014-01-01

    Summary: Extracytoplasmic function (ECF) sigma factors play a key role in the regulation of vital functions in the bacterial response to the environment. In Gram-negative bacteria, activity of these sigma factors is often controlled by cell-surface signalling (CSS), a regulatory system that also

  4. Role of Nuclear Factor (Erythroid-Derived 2-Like 2 Signaling for Effects of Fumaric Acid Esters on Dendritic Cells

    Directory of Open Access Journals (Sweden)

    Anna Hammer

    2017-12-01

    Full Text Available To date, the intracellular signaling pathways involved in dendritic cell (DC function are poorly understood. The antioxidative transcription factor nuclear factor (erythroid-derived 2-like 2 (Nrf2 has been shown to affect maturation, function, and subsequent DC-mediated T cell responses of murine and human DCs. In experimental autoimmune encephalomyelitis (EAE, as prototype animal model for a T helper cell-mediated autoimmune disease, antigen presentation, cytokine production, and costimulation by DCs play a major role. We explore the role of Nrf2 in DC function, and DC-mediated T cell responses during T cell-mediated autoimmunity of the central nervous system using genetic ablation and pharmacological activation in mice and men to corroborate our data in a translational setting. In murine and human DCs, monomethyl fumarate induced Nrf2 signaling inhibits DC maturation and DC-mediated T cell proliferation by reducing inflammatory cytokine production and expression of costimulatory molecules. In contrast, Nrf2-deficient DCs generate more activated T helper cells (Th1/Th17 but fewer regulatory T cells and foster T cell proliferation. Transfer of DCs with Nrf2 activation during active EAE reduces disease severity and T cell infiltration. Our data demonstrate that Nrf2 signaling modulates autoimmunity in murine and human systems via inhibiting DC maturation and function thus shedding further light on the mechanism of action of antioxidative stress pathways in antigen-presenting cells.

  5. A digital signal processor based rf control system for the TRIUMF ISAC RFQ prototype

    International Nuclear Information System (INIS)

    Fong, K.; Fang, S.; Laverty, M.

    1996-01-01

    A stand alone digital signal processor is used to control the RFQ prototype in the TRIUMF ISAC development program. The advantage of a digital control system over the traditional analogue system is that it offers the higher degree of flexibility necessary for a development system. For this application the system is designed to have the outward appearance of an analogue system, and uses dials, knobs, and switches as the operator interface. The digital signal processor is used as a feedback controller during CW rf operation, with the feedback gain parameters continually adjustable. It is also able to perform the same regulation during pulsed operation, with additional feedforward compensation for initial pulse on duration. Using a low cost analogue-to-digital converter with a sample rate of 100 kHz, a regulation bandwidth of 10 kHz is achieved. (author)

  6. How salicylic acid takes transcriptional control over jasmonic acid signaling

    Directory of Open Access Journals (Sweden)

    Lotte eCaarls

    2015-03-01

    Full Text Available Transcriptional regulation is a central process in plant immunity. The induction or repression of defense genes is orchestrated by signaling networks that are directed by plant hormones of which salicylic acid (SA and jasmonic acid (JA are the major players. Extensive cross-communication between the hormone signaling pathways allows for fine tuning of transcriptional programs, determining resistance to invaders and trade-offs with plant development. Here, we give an overview of how SA can control transcriptional reprogramming of JA-induced genes in Arabidopsis thaliana. SA can influence activity and/or localization of transcriptional regulators by post-translational modifications of transcription factors and co-regulators. SA-induced redox changes, mediated by thioredoxins and glutaredoxins, modify transcriptional regulators that are involved in suppression of JA-dependent genes, such as NPR1 and TGA transcription factors, which affects their localization or DNA binding activity. Furthermore, SA can mediate sequestering of JA-responsive transcription factors away from their target genes by stalling them in the cytosol or in complexes with repressor proteins in the nucleus. SA also affects JA-induced transcription by inducing degradation of transcription factors with an activating role in JA signaling, as was shown for the ERF transcription factor ORA59. Additionally, SA can induce negative regulators, among which WRKY transcription factors, that can directly or indirectly inhibit JA-responsive gene expression. Finally, at the DNA level, modification of histones by SA-dependent factors can result in repression of JA-responsive genes. These diverse and complex regulatory mechanisms affect important signaling hubs in the integration of hormone signaling networks. Some pathogens have evolved effectors that highjack hormone crosstalk mechanisms for their own good, which are described in this review as well.

  7. Impact of Leishmania mexicana infection on dendritic cell signaling and functions.

    Directory of Open Access Journals (Sweden)

    Irazú Contreras

    2014-09-01

    Full Text Available Leishmania parasites have the ability to modify macrophage signaling pathways in order to survive and multiply within its mammalian host. They are also known to invade other cells including neutrophils, fibroblasts and dendritic cells (DCs. DCs have an important role in immunity as the link between innate and adaptive immunity, necessary for the development of an effective response; however, the impact of Leishmania mexicana infection on DCs has been poorly studied. Herein, we report that Leishmania infection rapidly induced DC protein tyrosine phosphatases activity, leading to MAP kinases inactivation. In line with this, L. mexicana was found to decrease the nuclear translocation of transcription factors such as AP-1 and NF-κB. Concomitantly, L. mexicana-infected DCs showed reduced expression of several surface antigen-presenting and co-stimulatory molecules upon LPS stimulation. Leishmania-induced interference on DC maturation was further reflected by their reduced capacity to present OVA antigen to OVA-specific T cells, as shown by abrogation of IL-2 production by the T cells. Collectively, our data revealed that DC infection by L. mexicana appears to affect the cellular and immunological mechanisms necessary for the development of an effective and protective immune response, therefore favouring the survival and propagation of the parasite within its host.

  8. Small-Signal Analysis of the Microgrid Secondary Control Considering a Communication Time Delay

    DEFF Research Database (Denmark)

    Coelho, Ernane Antônio Alves; Wu, Dan; Guerrero, Josep M.

    2016-01-01

    This paper presents a small-signal analysis of an islanded microgrid composed of two or more voltage-source inverters connected in parallel. The primary control of each inverter is integrated through an internal current and voltage loops using proportional resonant compensators, a virtual impedance......, and an external power controller based on frequency and voltage droops. The frequency restoration function is implemented at the secondary control level, which executes a consensus algorithm that consists of a load-frequency control and a single time delay communication network. The consensus network consists...... the behavior of the system considering control parameters and time delay variation....

  9. CHAM: weak signals detection through a new multivariate algorithm for process control

    Science.gov (United States)

    Bergeret, François; Soual, Carole; Le Gratiet, B.

    2016-10-01

    Derivatives technologies based on core CMOS processes are significantly aggressive in term of design rules and process control requirements. Process control plan is a derived from Process Assumption (PA) calculations which result in a design rule based on known process variability capabilities, taking into account enough margin to be safe not only for yield but especially for reliability. Even though process assumptions are calculated with a 4 sigma known process capability margin, efficient and competitive designs are challenging the process especially for derivatives technologies in 40 and 28nm nodes. For wafer fab process control, PA are declined in monovariate (layer1 CD, layer2 CD, layer2 to layer1 overlay, layer3 CD etc….) control charts with appropriated specifications and control limits which all together are securing the silicon. This is so far working fine but such system is not really sensitive to weak signals coming from interactions of multiple key parameters (high layer2 CD combined with high layer3 CD as an example). CHAM is a software using an advanced statistical algorithm specifically designed to detect small signals, especially when there are many parameters to control and when the parameters can interact to create yield issues. In this presentation we will first present the CHAM algorithm, then the case-study on critical dimensions, with the results, and we will conclude on future work. This partnership between Ippon and STM is part of E450LMDAP, European project dedicated to metrology and lithography development for future technology nodes, especially 10nm.

  10. FireSignal application Node for subsystem control

    Czech Academy of Sciences Publication Activity Database

    Duarte, A.S.; Santos, B.; Pereira, T.; Carvalho, B.B.; Fernandes, H.; Neto, A.; Janky, Filip; Cahyna, Pavel; Písačka, Jan; Hron, Martin

    2010-01-01

    Roč. 85, 3-4 (2010), s. 496-499 ISSN 0920-3796. [IAEA Technical Meeting on Control , Data Acquisition and Remote Participation for Fusion Research/7th./. Aix – en – Provence, 15.06.2009-19.06.2009] Institutional research plan: CEZ:AV0Z20430508 Keywords : Subsystems * CODAC * FireSignal * Java * Remote operation Subject RIV: BL - Plasma and Gas Discharge Physics Impact factor: 1.143, year: 2010 http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6V3C-4YYGPR8-4&_user=6542793&_coverDate=07%2F31%2F2010&_rdoc=1&_fmt=high&_orig=search&_origin=search&_sort=d&_docanchor=&view=c&_acct=C000070123&_version=1&_urlVersion=0&_userid=6542793&md5=899631b6e2f4d05b21b04bde3cfb8e65&searchtype=a

  11. Signal processing and control challenges for smart vehicles

    Science.gov (United States)

    Zhang, Hui; Braun, Simon G.

    2017-03-01

    Smart phones have changed not only the mobile phone market but also our society during the past few years. Could the next potential intelligent device may be the vehicle? Judging by the visibility, in all media, of the numerous attempts to develop autonomous vehicles, this is certainly one of the logical outcomes. Smart vehicles would be equipped with an advanced operating system such that the vehicles could communicate with others, optimize the operation to reduce fuel consumption and emissions, enhance safety, or even become self-driving. These combined new features of vehicles require instrumentation and hardware developments, fast signal processing/fusion, decision making and online optimization. Meanwhile, the inevitable increasing system complexity would certainly challenges the control unit design.

  12. A soft sensor for bioprocess control based on sequential filtering of metabolic heat signals.

    Science.gov (United States)

    Paulsson, Dan; Gustavsson, Robert; Mandenius, Carl-Fredrik

    2014-09-26

    Soft sensors are the combination of robust on-line sensor signals with mathematical models for deriving additional process information. Here, we apply this principle to a microbial recombinant protein production process in a bioreactor by exploiting bio-calorimetric methodology. Temperature sensor signals from the cooling system of the bioreactor were used for estimating the metabolic heat of the microbial culture and from that the specific growth rate and active biomass concentration were derived. By applying sequential digital signal filtering, the soft sensor was made more robust for industrial practice with cultures generating low metabolic heat in environments with high noise level. The estimated specific growth rate signal obtained from the three stage sequential filter allowed controlled feeding of substrate during the fed-batch phase of the production process. The biomass and growth rate estimates from the soft sensor were also compared with an alternative sensor probe and a capacitance on-line sensor, for the same variables. The comparison showed similar or better sensitivity and lower variability for the metabolic heat soft sensor suggesting that using permanent temperature sensors of a bioreactor is a realistic and inexpensive alternative for monitoring and control. However, both alternatives are easy to implement in a soft sensor, alone or in parallel.

  13. A Soft Sensor for Bioprocess Control Based on Sequential Filtering of Metabolic Heat Signals

    Directory of Open Access Journals (Sweden)

    Dan Paulsson

    2014-09-01

    Full Text Available Soft sensors are the combination of robust on-line sensor signals with mathematical models for deriving additional process information. Here, we apply this principle to a microbial recombinant protein production process in a bioreactor by exploiting bio-calorimetric methodology. Temperature sensor signals from the cooling system of the bioreactor were used for estimating the metabolic heat of the microbial culture and from that the specific growth rate and active biomass concentration were derived. By applying sequential digital signal filtering, the soft sensor was made more robust for industrial practice with cultures generating low metabolic heat in environments with high noise level. The estimated specific growth rate signal obtained from the three stage sequential filter allowed controlled feeding of substrate during the fed-batch phase of the production process. The biomass and growth rate estimates from the soft sensor were also compared with an alternative sensor probe and a capacitance on-line sensor, for the same variables. The comparison showed similar or better sensitivity and lower variability for the metabolic heat soft sensor suggesting that using permanent temperature sensors of a bioreactor is a realistic and inexpensive alternative for monitoring and control. However, both alternatives are easy to implement in a soft sensor, alone or in parallel.

  14. Molecular mechanism and function of CD40/CD40L engagement in the immune system.

    Science.gov (United States)

    Elgueta, Raul; Benson, Micah J; de Vries, Victor C; Wasiuk, Anna; Guo, Yanxia; Noelle, Randolph J

    2009-05-01

    During the generation of a successful adaptive immune response, multiple molecular signals are required. A primary signal is the binding of cognate antigen to an antigen receptor expressed by T and B lymphocytes. Multiple secondary signals involve the engagement of costimulatory molecules expressed by T and B lymphocytes with their respective ligands. Because of its essential role in immunity, one of the best characterized of the costimulatory molecules is the receptor CD40. This receptor, a member of the tumor necrosis factor receptor family, is expressed by B cells, professional antigen-presenting cells, as well as non-immune cells and tumors. CD40 binds its ligand CD40L, which is transiently expressed on T cells and other non-immune cells under inflammatory conditions. A wide spectrum of molecular and cellular processes is regulated by CD40 engagement including the initiation and progression of cellular and humoral adaptive immunity. In this review, we describe the downstream signaling pathways initiated by CD40 and overview how CD40 engagement or antagonism modulates humoral and cellular immunity. Lastly, we discuss the role of CD40 as a target in harnessing anti-tumor immunity. This review underscores the essential role CD40 plays in adaptive immunity.

  15. On the electric signal direction indicator for teh control of road traffic ...

    African Journals Online (AJOL)

    An electronic signal direction indicator (ESDI) for the control of road traffic has been designed, constructed and studied. The construction was done using 555 timer IC, a transistor-transistor logic compatible device that can operate in several modes as the major active element. The ESDI system circuit is reliable, satisfactorily ...

  16. 49 CFR 236.401 - Automatic block signal system and interlocking standards applicable to traffic control systems.

    Science.gov (United States)

    2010-10-01

    ... TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Traffic Control Systems Standards § 236.401 Automatic... 49 Transportation 4 2010-10-01 2010-10-01 false Automatic block signal system and interlocking standards applicable to traffic control systems. 236.401 Section 236.401 Transportation Other Regulations...

  17. ICOS regulates the pool of group 2 innate lymphoid cells under homeostatic and inflammatory conditions in mice.

    Science.gov (United States)

    Paclik, Daniela; Stehle, Christina; Lahmann, Annette; Hutloff, Andreas; Romagnani, Chiara

    2015-10-01

    Group 2 innate lymphoid cells (ILC2s) are innate effectors playing an important role in the defense against helminthic infections and in the pathogenesis of allergic inflammation. Cytokines have been identified as the major stimuli driving ILC2 activation and expansion. Conversely, it is unclear whether costimulatory molecules contribute to regulation of ILC2 functions. ILC2s display high expression of inducible T-cell costimulator (ICOS), which belongs to the CD28 superfamily, and which has been shown to control late effector T-cell functions, and is of utmost importance for the humoral immune response. However, the biological function of ICOS expression on ILC2s is unknown. Here, we show that ICOS signaling in mice regulates ILC2 homeostasis independently of T cells and B cells, by promoting proliferation and accumulation of mature ILC2s in lung and intestine. In a model of IL-33-induced airway inflammation, ICOS controls ILC2 activation and eosinophil infiltration in the lung. Our data identify a role of ICOS in innate immunity and indicate that not only cytokines, but also costimulatory pathways such as those involving ICOS, can contribute to regulate the ILC2 pool. Thus, ICOS costimulation blockade, which is currently under clinical evaluation for inhibiting the humoral immune response, could also target innate inflammatory circuits. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. An adaptive synchronization strategy based on active control for demodulating message hidden in chaotic signals

    International Nuclear Information System (INIS)

    Tang Fang

    2008-01-01

    In the field of secure communication, it is very important to demodulate the message hidden in chaotic signals. In this paper, an adaptive synchronization strategy based on active control is proposed, which is used to design an active controller and an appropriate adaptive demodulator at the receiver to recover the transmitted message hidden in chaotic signals of a drive system. Based on Lyapunov stability theory, it is shown that the transmitted message can be theoretically recovered by using the proposed strategy. Numerical simulations based on the Chua's circuit are also presented to verify the effectiveness of the proposed strategy. In addition, it is shown via simulations that, by increasing the gain of the active controller the message error caused by the external noise and the discontinuous property of the message can be reduced

  19. Signal transduction profile of chemical sensitisers in dendritic cells: An endpoint to be included in a cell-based in vitro alternative approach to hazard identification?

    International Nuclear Information System (INIS)

    Neves, Bruno Miguel; Goncalo, Margarida; Figueiredo, Americo; Duarte, Carlos B.; Lopes, Maria Celeste; Cruz, Maria Teresa

    2011-01-01

    The development of non-animal testing methods for the assessment of skin sensitisation potential is an urgent challenge within the framework of existing and forthcoming legislation. Efforts have been made to replace current animal tests, but so far no alternative methods have been developed. It is widely recognised that alternatives to animal testing cannot be accomplished with a single approach, but rather will require the integration of results obtained from different in vitro and in silico assays. The argument subjacent to the development of in vitro dendritic cell (DC)-based assays is that sensitiser-induced changes in the DC phenotype can be differentiated from those induced by irritants. This assumption is derived from the unique capacity of DC to convert environmental signals encountered at the skin into a receptor expression pattern (MHC class II molecules, co-stimulatory molecules, chemokine receptors) and a soluble mediator release profile that will stimulate T lymphocytes. Since signal transduction cascades precede changes in surface marker expression and cytokine/chemokine secretion, these phenotypic modifications are a consequence of a signal transduction profile that is specifically triggered by sensitisers and not by irritants. A limited number of studies have addressed this subject and the present review attempts to summarise and highlight all of the signalling pathways modulated by skin sensitisers and irritants. Furthermore, we conclude this review by focusing on the most promising strategies suitable for inclusion into a cell-based in vitro alternative approach to hazard identification.

  20. Complex motion of a vehicle through a series of signals controlled by power-law phase

    Science.gov (United States)

    Nagatani, Takashi

    2017-07-01

    We study the dynamic motion of a vehicle moving through the series of traffic signals controlled by the position-dependent phase of power law. All signals are controlled by both cycle time and position-dependent phase. The dynamic model of the vehicular motion is described in terms of the nonlinear map. The vehicular motion varies in a complex manner by varying cycle time for various values of the power of the position-dependent phase. The vehicle displays the periodic motion with a long cycle for the integer power of the phase, while the vehicular motion exhibits the very complex behavior for the non-integer power of the phase.

  1. Use of frontal lobe hemodynamics as reinforcement signals to an adaptive controller.

    Directory of Open Access Journals (Sweden)

    Marcello M DiStasio

    Full Text Available Decision-making ability in the frontal lobe (among other brain structures relies on the assignment of value to states of the animal and its environment. Then higher valued states can be pursued and lower (or negative valued states avoided. The same principle forms the basis for computational reinforcement learning controllers, which have been fruitfully applied both as models of value estimation in the brain, and as artificial controllers in their own right. This work shows how state desirability signals decoded from frontal lobe hemodynamics, as measured with near-infrared spectroscopy (NIRS, can be applied as reinforcers to an adaptable artificial learning agent in order to guide its acquisition of skills. A set of experiments carried out on an alert macaque demonstrate that both oxy- and deoxyhemoglobin concentrations in the frontal lobe show differences in response to both primarily and secondarily desirable (versus undesirable stimuli. This difference allows a NIRS signal classifier to serve successfully as a reinforcer for an adaptive controller performing a virtual tool-retrieval task. The agent's adaptability allows its performance to exceed the limits of the NIRS classifier decoding accuracy. We also show that decoding state desirabilities is more accurate when using relative concentrations of both oxyhemoglobin and deoxyhemoglobin, rather than either species alone.

  2. Signal sciences workshop proceedings

    Energy Technology Data Exchange (ETDEWEB)

    Candy, J.V.

    1997-05-01

    This meeting is aimed primarily at signal processing and controls. The technical program for the 1997 Workshop includes a variety of efforts in the Signal Sciences with applications in the Microtechnology Area a new program at LLNL and a future area of application for both Signal/Image Sciences. Special sessions organized by various individuals in Seismic and Optical Signal Processing as well as Micro-Impulse Radar Processing highlight the program, while the speakers at the Signal Processing Applications session discuss various applications of signal processing/control to real world problems. For the more theoretical, a session on Signal Processing Algorithms was organized as well as for the more pragmatic, featuring a session on Real-Time Signal Processing.

  3. Signal sciences workshop. Proceedings

    International Nuclear Information System (INIS)

    Candy, J.V.

    1997-01-01

    This meeting is aimed primarily at signal processing and controls. The technical program for the 1997 Workshop includes a variety of efforts in the Signal Sciences with applications in the Microtechnology Area a new program at LLNL and a future area of application for both Signal/Image Sciences. Special sessions organized by various individuals in Seismic and Optical Signal Processing as well as Micro-Impulse Radar Processing highlight the program, while the speakers at the Signal Processing Applications session discuss various applications of signal processing/control to real world problems. For the more theoretical, a session on Signal Processing Algorithms was organized as well as for the more pragmatic, featuring a session on Real-Time Signal Processing

  4. Molecular and Cellular Signaling

    CERN Document Server

    Beckerman, Martin

    2005-01-01

    A small number of signaling pathways, no more than a dozen or so, form a control layer that is responsible for all signaling in and between cells of the human body. The signaling proteins belonging to the control layer determine what kinds of cells are made during development and how they function during adult life. Malfunctions in the proteins belonging to the control layer are responsible for a host of human diseases ranging from neurological disorders to cancers. Most drugs target components in the control layer, and difficulties in drug design are intimately related to the architecture of the control layer. Molecular and Cellular Signaling provides an introduction to molecular and cellular signaling in biological systems with an emphasis on the underlying physical principles. The text is aimed at upper-level undergraduates, graduate students and individuals in medicine and pharmacology interested in broadening their understanding of how cells regulate and coordinate their core activities and how diseases ...

  5. On the role of exchange of power and information signals in control and stability of the human-robot interaction

    Science.gov (United States)

    Kazerooni, H.

    1991-01-01

    A human's ability to perform physical tasks is limited, not only by his intelligence, but by his physical strength. If, in an appropriate environment, a machine's mechanical power is closely integrated with a human arm's mechanical power under the control of the human intellect, the resulting system will be superior to a loosely integrated combination of a human and a fully automated robot. Therefore, we must develop a fundamental solution to the problem of 'extending' human mechanical power. The work presented here defines 'extenders' as a class of robot manipulators worn by humans to increase human mechanical strength, while the wearer's intellect remains the central control system for manipulating the extender. The human, in physical contact with the extender, exchanges power and information signals with the extender. The aim is to determine the fundamental building blocks of an intelligent controller, a controller which allows interaction between humans and a broad class of computer-controlled machines via simultaneous exchange of both power and information signals. The prevalent trend in automation has been to physically separate the human from the machine so the human must always send information signals via an intermediary device (e.g., joystick, pushbutton, light switch). Extenders, however are perfect examples of self-powered machines that are built and controlled for the optimal exchange of power and information signals with humans. The human wearing the extender is in physical contact with the machine, so power transfer is unavoidable and information signals from the human help to control the machine. Commands are transferred to the extender via the contact forces and the EMG signals between the wearer and the extender. The extender augments human motor ability without accepting any explicit commands: it accepts the EMG signals and the contact force between the person's arm and the extender, and the extender 'translates' them into a desired position. In

  6. Controlling microwave signals by means of slow and fast light effects in SOA-EA structures

    DEFF Research Database (Denmark)

    Sales, Salvador; Öhman, Filip; Capmany, José

    2007-01-01

    We present a novel scheme for the control of microwave signals in the optical domain. We propose the use of alternating amplifying and absorbing sections to implement phase control by using fast and slow light effects in semiconductors. The potential benefits from the proposed semiconductor optic...

  7. The other side of cardiac Ca2+ signaling: transcriptional control

    Directory of Open Access Journals (Sweden)

    Alejandro eDomínguez-Rodríquez

    2012-11-01

    Full Text Available Ca2+ is probably the most versatile signal transduction element used by all cell types. In the heart, it is essential to activate cellular contraction in each heartbeat. Nevertheless Ca2+ is not only a key element in excitation-contraction coupling (EC coupling, but it is also a pivotal second messenger in cardiac signal transduction, being able to control processes such as excitability, metabolism, and transcriptional regulation. Regarding the latter, Ca2+ activates Ca2+-dependent transcription factors by a process called excitation-transcription coupling (ET coupling. ET coupling is an integrated process by which the common signaling pathways that regulate EC coupling activate transcription factors. Although ET coupling has been extensively studied in neurons and other cell types, less is known in cardiac muscle. Some hints have been found in studies on the development of cardiac hypertrophy, where two Ca2+-dependent enzymes are key actors: Ca2+/Calmodulin kinase II (CaMKII and phosphatase calcineurin, both of which are activated by the complex Ca2+/ /Calmodulin. The question now is how ET coupling occurs in cardiomyocytes, where intracellular Ca2+ is continuously oscillating. In this focused review, we will draw attention to location of Ca2+ signaling: intranuclear ([Ca2+]n or cytoplasmic ([Ca2+]c, and the specific ionic channels involved in the activation of cardiac ET coupling. Specifically, we will highlight the role of the 1,4,5 inositol triphosphate receptors (IP3Rs in the elevation of [Ca2+]n levels, which are important to locally activate CaMKII, and the role of transient receptor potential channels canonical (TRPCs in [Ca2+]c, needed to activate calcineurin.

  8. ERECTA signaling controls Arabidopsis inflorescence architecture through chromatin-mediated activation of PRE1 expression.

    Science.gov (United States)

    Cai, Hanyang; Zhao, Lihua; Wang, Lulu; Zhang, Man; Su, Zhenxia; Cheng, Yan; Zhao, Heming; Qin, Yuan

    2017-06-01

    Flowering plants display a remarkable diversity in inflorescence architecture, and pedicel length is one of the key contributors to this diversity. In Arabidopsis thaliana, the receptor-like kinase ERECTA (ER) mediated signaling pathway plays important roles in regulating inflorescence architecture by promoting cell proliferation. However, the regulating mechanism remains elusive in the pedicel. Genetic interactions between ERECTA signaling and the chromatin remodeling complex SWR1 in the control of inflorescence architecture were studied. Comparative transcriptome analysis was applied to identify downstream components. Chromatin immunoprecipitation and nucleosome occupancy was further investigated. The results indicated that the chromatin remodeler SWR1 coordinates with ERECTA signaling in regulating inflorescence architecture by activating the expression of PRE1 family genes and promoting pedicel elongation. It was found that SWR1 is required for the incorporation of the H2A.Z histone variant into nucleosomes of the whole PRE1 gene family and the ERECTA controlled expression of PRE1 gene family through regulating nucleosome dynamics. We propose that utilization of a chromatin remodeling complex to regulate gene expression is a common theme in developmental control across kingdoms. These findings shed light on the mechanisms through which chromatin remodelers orchestrate complex transcriptional regulation of gene expression in coordination with a developmental cue. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

  9. Piezoelectric self-sensing actuator for active vibration control of motorized spindle based on adaptive signal separation

    Science.gov (United States)

    He, Ye; Chen, Xiaoan; Liu, Zhi; Qin, Yi

    2018-06-01

    The motorized spindle is the core component of CNC machine tools, and the vibration of it reduces the machining precision and service life of the machine tools. Owing to the fast response, large output force, and displacement of the piezoelectric stack, it is often used as the actuator in the active vibration control of the spindle. A piezoelectric self-sensing actuator (SSA) can reduce the cost of the active vibration control system and simplify the structure by eliminating the use of a sensor, because a SSA can have both actuating and sensing functions at the same time. The signal separation method of a SSA based on a bridge circuit is widely applied because of its simple principle and easy implementation. However, it is difficult to maintain dynamic balance of the circuit. Prior research has used adaptive algorithm to balance of the bridge circuit on the flexible beam dynamically, but those algorithms need no correlation between sensing and control voltage, which limit the applications of SSA in the vibration control of the rotor-bearing system. Here, the electromechanical coupling model of the piezoelectric stack is established, followed by establishment of the dynamic model of the spindle system. Next, a new adaptive signal separation method based on the bridge circuit is proposed, which can separate relative small sensing voltage from related mixed voltage adaptively. The experimental results show that when the self-sensing signal obtained from the proposed method is used as a displacement signal, the vibration of the motorized spindle can be suppressed effectively through a linear quadratic Gaussian (LQG) algorithm.

  10. Signal-Noise Ratio Control Subsystem of Digital Equipment for Transmission of "Strela" Relay Protection Commands

    Directory of Open Access Journals (Sweden)

    I. I. Zabenkov

    2012-01-01

    Full Text Available Continuous measurement function of relative noise and interference level in the information transmission channel is considered as an important one for controlling parameters of high-frequency signal. The present paper simulates an algorithm for measuring signal-noise ratio in the transmission channel of high-voltage lines which is used in the digital equipment for transmission of relay protection and emergency automation commands of "Strela" complex.

  11. A new paradigm: innate immune sensing of viruses via the Unfolded Protein Response

    Directory of Open Access Journals (Sweden)

    Judith A Smith

    2014-05-01

    Full Text Available The immune system depends upon combinations of signals to mount appropriate responses: pathogen specific signals in the context of co-stimulatory danger signals drive immune strength and accuracy. Viral infections trigger anti-viral type I interferon (IFN responses by stimulating endosomal and cytosolic pattern recognition receptors (PRRs. However, viruses have also evolved many strategies to counteract IFN responses. Are there intracellular danger signals that enhance immune responses to viruses? During infection, viruses place a heavy demand on the protein folding machinery of the host endoplasmic reticulum (ER. To survive ER stress, host cells mount an Unfolded Protein Response (UPR to decrease ER protein load and enhance protein-folding capacity. Viruses also directly elicit the UPR to enhance their replication. Increasing evidence supports an intersection between the host UPR and inflammation, in particular the production of pro-inflammatory cytokines and type I IFN. The UPR directly activates pro-inflammatory cytokine transcription factors and dramatically enhances cytokine production in response to viral PRR engagement. Additionally, viral PRR engagement may stimulate specific pathways within the UPR to enhance cytokine production. Through these mechanisms, viral detection via the UPR and inflammatory cytokine production are intertwined. Consequently, the UPR response is perfectly poised to act as an infection-triggered danger signal. The UPR may serve as an internal co-stimulatory signal that 1 provides specificity and 2 critically augments responses to overcome viral subterfuge. Further work is needed to test this hypothesis during viral infections.

  12. Hippo/Yap signaling controls epithelial progenitor cell proliferation and differentiation in the embryonic and adult lung

    Science.gov (United States)

    Lange, Alexander W.; Sridharan, Anusha; Xu, Yan; Stripp, Barry R.; Perl, Anne-Karina; Whitsett, Jeffrey A.

    2015-01-01

    The Hippo/Yap pathway is a well-conserved signaling cascade that regulates cell proliferation and differentiation to control organ size and stem/progenitor cell behavior. Following airway injury, Yap was dynamically regulated in regenerating airway epithelial cells. To determine the role of Hippo signaling in the lung, the mammalian Hippo kinases, Mst1 and Mst2, were deleted in epithelial cells of the embryonic and mature mouse lung. Mst1/2 deletion in the fetal lung enhanced proliferation and inhibited sacculation and epithelial cell differentiation. The transcriptional inhibition of cell proliferation and activation of differentiation during normal perinatal lung maturation were inversely regulated following embryonic Mst1/2 deletion. Ablation of Mst1/2 from bronchiolar epithelial cells in the adult lung caused airway hyperplasia and altered differentiation. Inhibitory Yap phosphorylation was decreased and Yap nuclear localization and transcriptional targets were increased after Mst1/2 deletion, consistent with canonical Hippo/Yap signaling. YAP potentiated cell proliferation and inhibited differentiation of human bronchial epithelial cells in vitro. Loss of Mst1/2 and expression of YAP regulated transcriptional targets controlling cell proliferation and differentiation, including Ajuba LIM protein. Ajuba was required for the effects of YAP on cell proliferation in vitro. Hippo/Yap signaling regulates Ajuba and controls proliferation and differentiation of lung epithelial progenitor cells. PMID:25480985

  13. Aging and insulin signaling differentially control normal and tumorous germline stem cells.

    Science.gov (United States)

    Kao, Shih-Han; Tseng, Chen-Yuan; Wan, Chih-Ling; Su, Yu-Han; Hsieh, Chang-Che; Pi, Haiwei; Hsu, Hwei-Jan

    2015-02-01

    Aging influences stem cells, but the processes involved remain unclear. Insulin signaling, which controls cellular nutrient sensing and organismal aging, regulates the G2 phase of Drosophila female germ line stem cell (GSC) division cycle in response to diet; furthermore, this signaling pathway is attenuated with age. The role of insulin signaling in GSCs as organisms age, however, is also unclear. Here, we report that aging results in the accumulation of tumorous GSCs, accompanied by a decline in GSC number and proliferation rate. Intriguingly, GSC loss with age is hastened by either accelerating (through eliminating expression of Myt1, a cell cycle inhibitory regulator) or delaying (through mutation of insulin receptor (dinR) GSC division, implying that disrupted cell cycle progression and insulin signaling contribute to age-dependent GSC loss. As flies age, DNA damage accumulates in GSCs, and the S phase of the GSC cell cycle is prolonged. In addition, GSC tumors (which escape the normal stem cell regulatory microenvironment, known as the niche) still respond to aging in a similar manner to normal GSCs, suggesting that niche signals are not required for GSCs to sense or respond to aging. Finally, we show that GSCs from mated and unmated females behave similarly, indicating that female GSC-male communication does not affect GSCs with age. Our results indicate the differential effects of aging and diet mediated by insulin signaling on the stem cell division cycle, highlight the complexity of the regulation of stem cell aging, and describe a link between ovarian cancer and aging. © 2014 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  14. Controlling a human-computer interface system with a novel classification method that uses electrooculography signals.

    Science.gov (United States)

    Wu, Shang-Lin; Liao, Lun-De; Lu, Shao-Wei; Jiang, Wei-Ling; Chen, Shi-An; Lin, Chin-Teng

    2013-08-01

    Electrooculography (EOG) signals can be used to control human-computer interface (HCI) systems, if properly classified. The ability to measure and process these signals may help HCI users to overcome many of the physical limitations and inconveniences in daily life. However, there are currently no effective multidirectional classification methods for monitoring eye movements. Here, we describe a classification method used in a wireless EOG-based HCI device for detecting eye movements in eight directions. This device includes wireless EOG signal acquisition components, wet electrodes and an EOG signal classification algorithm. The EOG classification algorithm is based on extracting features from the electrical signals corresponding to eight directions of eye movement (up, down, left, right, up-left, down-left, up-right, and down-right) and blinking. The recognition and processing of these eight different features were achieved in real-life conditions, demonstrating that this device can reliably measure the features of EOG signals. This system and its classification procedure provide an effective method for identifying eye movements. Additionally, it may be applied to study eye functions in real-life conditions in the near future.

  15. Suppression of Langerhans cell activation is conserved amongst human papillomavirus α and β genotypes, but not a µ genotype.

    Science.gov (United States)

    Da Silva, Diane M; Movius, Carly A; Raff, Adam B; Brand, Heike E; Skeate, Joseph G; Wong, Michael K; Kast, W Martin

    2014-03-01

    Human papillomavirus (HPV) has evolved mechanisms that allow it to evade the human immune system. Studies have shown HPV-mediated suppression of activation of Langerhans cells (LC) is a key mechanism through which HPV16 evades initial immune surveillance. However, it has not been established whether high- and low-risk mucosal and cutaneous HPV genotypes share a common mechanism of immune suppression. Here, we demonstrate that LC exposed to capsids of HPV types 18, 31, 45, 11, (alpha-papillomaviruses) and HPV5 (beta-papillomavirus) similarly suppress LC activation, including lack of costimulatory molecule expression, lack of cytokine and chemokine secretion, lack of migration, and deregulated cellular signaling. In contrast, HPV1 (mu-papillomavirus) induced costimulatory molecule and cytokine upregulation, but LC migration and cellular signaling was suppressed. These results suggest that alpha and beta HPV genotypes, and partially a mu genotype, share a conserved mechanism of immune escape that enables these viruses to remain undetected in the absence of other inflammatory events. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. An Active Capacitor with Self-Power and Internal Feedback Control Signals

    DEFF Research Database (Denmark)

    Wang, Haoran; Wang, Huai

    2017-01-01

    This paper proposes a concept of two-terminal active capacitor implemented by power semiconductor switches and passive elements. The active capacitor has the same level of convenience as a passive one with two power terminals only. A control strategy that does not require any external feedback...... signal is proposed and a self-power scheme for gate drivers and the controller is applied to achieve the two-terminal active capacitor. The concept, control method, self-power scheme, efficiency, and impedance characteristics of the active capacitor are presented. A case study of the proposed active...... capacitor for a capacitive DC-link application is discussed. The results reveal a significantly lower overall energy storage of passive elements and a reduced cost to fulfill a specific reliability target, compared to a passive capacitor solution. Proof-of-concept experimental results are given to verify...

  17. Small-Signal Modeling of the PVR-Based AD Scheme and Controller Design for Three-Phase Standalone DG System

    DEFF Research Database (Denmark)

    Shen, Pan; Han, Yang; Lu, Chang

    2016-01-01

    This paper presents the small-signal state-space modeling and a new multifunctional multi-loop control strategy for three-phase inverter-based islanded DG systems under unbalanced and/or nonlinear load conditions. The proposed control methodology utilizes the parallel virtual resistance (PVR...... controllers are based on an enhanced proportional resonant (PR) structure to achieve zero steady-state error, and multi-resonant harmonic compensator (MRHC) plus PR controller to prevent low-order load current harmonics to distort the output voltage. The proposed small-signal model of the islanded DG system...... with multi-loop control strategy in the stationary reference frame is presented. Moreover, an enhanced delay compensation (EDC) scheme based on two integrators of the discrete PR controller is presented to improve stability margins with a higher accuracy compared with the existing methods. Then, a detailed...

  18. The TOR Signaling Pathway in Spatial and Temporal Control of Cell Size and Growth

    Directory of Open Access Journals (Sweden)

    Suam Gonzalez

    2017-06-01

    Full Text Available Cell size is amenable by genetic and environmental factors. The highly conserved nutrient-responsive Target of Rapamycin (TOR signaling pathway regulates cellular metabolic status and growth in response to numerous inputs. Timing and duration of TOR pathway activity is pivotal for both cell mass built up as well as cell cycle progression and is controlled and fine-tuned by the abundance and quality of nutrients, hormonal signals, growth factors, stress, and oxygen. TOR kinases function within two functionally and structurally discrete multiprotein complexes, TORC1 and TORC2, that are implicated in temporal and spatial control of cell size and growth respectively; however, recent data indicate that such functional distinctions are much more complex. Here, we briefly review roles of the two complexes in cellular growth and cytoarchitecture in various experimental model systems.

  19. Regulation of T Cell Homeostasis and Responses by Pten

    Directory of Open Access Journals (Sweden)

    Ryan H. Newton

    2012-06-01

    Full Text Available The generation of lipid products catalyzed by PI3K is critical for normal T cell homeostasis and a productive immune response. PI3K can be activated in response to antigen receptor, costimulatory, cytokine and chemokine signals. Moreover, dysregulation of this pathway frequently occurs in T cell lymphomas and is implicated in lymphoproliferative autoimmune disease. Akt acts as a central mediator of PI3K signals, downstream of which is the mTOR pathway, controlling cell growth and metabolism. Members of the Foxo family of transcription factors are also regulated by Akt, thus linking control over homing and migration of T cells, as well cell cycle entry, apoptosis, and DNA damage and oxidative stress responses, to PI3K signaling. PTEN, first identified as a tumor suppressor gene, encodes a lipid phosphatase that, by catalyzing the reverse of the PI3K reaction, directly opposes PI3K signaling. However, PTEN may have other functions as well, and recent reports have suggested roles for PTEN as a tumor suppressor independent of its effects on PI3K signaling. Through the use of models in which Pten is deleted specifically in T cells, it is becoming increasingly clear that control over autoimmunity and lymphomagenesis by PTEN involves multi-faceted functions of this molecule at multiple stages of T cell development.

  20. Traffic Efficiency Evaluation of Elliptical Roundabout Compared with Modern and Turbo Roundabouts Considering Traffic Signal Control

    Directory of Open Access Journals (Sweden)

    Hadi Hatami

    2017-02-01

    Full Text Available This paper compared the performance of elliptical roundabout with turbo and modern roundabouts. It considers the effects of increasing the central island radius and speed limit on delay and capacity. Three types of roundabouts (modern, turbo and elliptical roundabouts with different numbers of lanes (single lane, two-lane and three-lane were designed. Unsignalized and signalized controls were applied for these roundabouts. The robustness of the designed roundabouts was investigated for saturated and unsaturated flow conditions. Based on the obtained results, increasing the central island radius had both positive and negative effects on delay and capacity. However, a positive effect on these variables was observed in all roundabouts when increasing the speed limit. In unsignalized and signalized control under unsaturated flow conditions, a modern roundabout had lower delay time than an elliptical roundabout. Moreover, in saturated flow, the elliptical roundabout had the best performance in terms of delay. Overall, in comparison with the turbo roundabouts, modern and elliptical roundabouts had the highest capacities in unsignalized and signalized controls. This study can provide useful information for engineers who decide to design a roundabout.

  1. Generating Human-Like Velocity-Adapted Jumping Gait from sEMG Signals for Bionic Leg’s Control

    Directory of Open Access Journals (Sweden)

    Weiwei Yu

    2017-01-01

    Full Text Available In the case of dynamic motion such as jumping, an important fact in sEMG (surface Electromyogram signal based control on exoskeletons, myoelectric prostheses, and rehabilitation gait is that multichannel sEMG signals contain mass data and vary greatly with time, which makes it difficult to generate compliant gait. Inspired by the fact that muscle synergies leading to dimensionality reduction may simplify motor control and learning, this paper proposes a new approach to generate flexible gait based on muscle synergies extracted from sEMG signal. Two questions were discussed and solved, the first one concerning whether the same set of muscle synergies can explain the different phases of hopping movement with various velocities. The second one is about how to generate self-adapted gait with muscle synergies while alleviating model sensitivity to sEMG transient changes. From the experimental results, the proposed method shows good performance both in accuracy and in robustness for producing velocity-adapted vertical jumping gait. The method discussed in this paper provides a valuable reference for the sEMG-based control of bionic robot leg to generate human-like dynamic gait.

  2. Self-organized neural network for the quality control of 12-lead ECG signals

    International Nuclear Information System (INIS)

    Chen, Yun; Yang, Hui

    2012-01-01

    Telemedicine is very important for the timely delivery of health care to cardiovascular patients, especially those who live in the rural areas of developing countries. However, there are a number of uncertainty factors inherent to the mobile-phone-based recording of electrocardiogram (ECG) signals such as personnel with minimal training and other extraneous noises. PhysioNet organized a challenge in 2011 to develop efficient algorithms that can assess the ECG signal quality in telemedicine settings. This paper presents our efforts in this challenge to integrate multiscale recurrence analysis with a self-organizing map for controlling the ECG signal quality. As opposed to directly evaluating the 12-lead ECG, we utilize an information-preserving transform, i.e. Dower transform, to derive the 3-lead vectorcardiogram (VCG) from the 12-lead ECG in the first place. Secondly, we delineate the nonlinear and nonstationary characteristics underlying the 3-lead VCG signals into multiple time-frequency scales. Furthermore, a self-organizing map is trained, in both supervised and unsupervised ways, to identify the correlations between signal quality and multiscale recurrence features. The efficacy and robustness of this approach are validated using real-world ECG recordings available from PhysioNet. The average performance was demonstrated to be 95.25% for the training dataset and 90.0% for the independent test dataset with unknown labels. (paper)

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

    Science.gov (United States)

    Arkun, Yaman; Yasemi, Mohammadreza

    2018-01-01

    Cell signaling is the process by which extracellular information is transmitted into the cell to perform useful biological functions. The ERK (extracellular-signal-regulated kinase) signaling controls several cellular processes such as cell growth, proliferation, differentiation and apoptosis. The ERK signaling pathway considered in this work starts with an extracellular stimulus and ends with activated (double phosphorylated) ERK which gets translocated into the nucleus. We model and analyze this complex pathway by decomposing it into three functional subsystems. The first subsystem spans the initial part of the pathway from the extracellular growth factor to the formation of the SOS complex, ShC-Grb2-SOS. The second subsystem includes the activation of Ras which is mediated by the SOS complex. This is followed by the MAPK subsystem (or the Raf-MEK-ERK pathway) which produces the double phosphorylated ERK upon being activated by Ras. Although separate models exist in the literature at the subsystems level, a comprehensive model for the complete system including the important regulatory feedback loops is missing. Our dynamic model combines the existing subsystem models and studies their steady-state and dynamic interactions under feedback. We establish conditions under which bistability and oscillations exist for this important pathway. In particular, we show how the negative and positive feedback loops affect the dynamic characteristics that determine the cellular outcome.

  4. Abatacept til behandling af reumatoid artritis

    DEFF Research Database (Denmark)

    Nielsen, Henrik; Hansen, Annette

    2009-01-01

    Abatacept (CTLA4Ig) is a human fusion protein which consists of a cytotoxic lymphocytic-associated type 4 antigen which is bound to the Fc part of the IgG1. Abatacept binds to CD80/CD86 on antigen-presenting cells thus blocking the co-stimulatory signal to the naïve T cells and interfering with a...

  5. A real-time traffic control method for the intersection with pre-signals under the phase swap sorting strategy.

    Directory of Open Access Journals (Sweden)

    Yiming Bie

    Full Text Available To deal with the conflicts between left-turn and through traffic streams and increase the discharge capacity, this paper addresses the pre-signal which is implemented at a signalized intersection. Such an intersection with pre-signal is termed as a tandem intersection. For the tandem intersection, phase swap sorting strategy is deemed as the most effective phasing scheme in view of some exclusive merits, such as easier compliance of drivers, and shorter sorting area. However, a major limitation of the phase swap sorting strategy is not considered in previous studies: if one or more vehicle is left at the sorting area after the signal light turns to red, the capacity of the approach would be dramatically dropped. Besides, previous signal control studies deal with a fixed timing plan that is not adaptive with the fluctuation of traffic flows. Therefore, to cope with these two gaps, this paper firstly takes an in-depth analysis of the traffic flow operations at the tandem intersection. Secondly, three groups of loop detectors are placed to obtain the real-time vehicle information for adaptive signalization. The lane selection behavior in the sorting area is considered to set the green time for intersection signals. With the objective of minimizing the vehicle delay, the signal control parameters are then optimized based on a dynamic programming method. Finally, numerical experiments show that average vehicle delay and maximum queue length can be reduced under all scenarios.

  6. A real-time traffic control method for the intersection with pre-signals under the phase swap sorting strategy.

    Science.gov (United States)

    Bie, Yiming; Liu, Zhiyuan; Wang, Yinhai

    2017-01-01

    To deal with the conflicts between left-turn and through traffic streams and increase the discharge capacity, this paper addresses the pre-signal which is implemented at a signalized intersection. Such an intersection with pre-signal is termed as a tandem intersection. For the tandem intersection, phase swap sorting strategy is deemed as the most effective phasing scheme in view of some exclusive merits, such as easier compliance of drivers, and shorter sorting area. However, a major limitation of the phase swap sorting strategy is not considered in previous studies: if one or more vehicle is left at the sorting area after the signal light turns to red, the capacity of the approach would be dramatically dropped. Besides, previous signal control studies deal with a fixed timing plan that is not adaptive with the fluctuation of traffic flows. Therefore, to cope with these two gaps, this paper firstly takes an in-depth analysis of the traffic flow operations at the tandem intersection. Secondly, three groups of loop detectors are placed to obtain the real-time vehicle information for adaptive signalization. The lane selection behavior in the sorting area is considered to set the green time for intersection signals. With the objective of minimizing the vehicle delay, the signal control parameters are then optimized based on a dynamic programming method. Finally, numerical experiments show that average vehicle delay and maximum queue length can be reduced under all scenarios.

  7. Canine Distemper Virus Infection Leads to an Inhibitory Phenotype of Monocyte-Derived Dendritic Cells In Vitro with Reduced Expression of Co-Stimulatory Molecules and Increased Interleukin-10 Transcription

    Science.gov (United States)

    Herder, Vanessa; Stein, Veronika M.; Tipold, Andrea; Urhausen, Carola; Günzel-Apel, Anne-Rose; Rohn, Karl; Baumgärtner, Wolfgang; Beineke, Andreas

    2014-01-01

    Canine distemper virus (CDV) exhibits a profound lymphotropism that causes immunosuppression and increased susceptibility of affected dogs to opportunistic infections. Similar to human measles virus, CDV is supposed to inhibit terminal differentiation of dendritic cells (DCs), responsible for disturbed repopulation of lymphoid tissues and diminished antigen presenting function in dogs. In order to testify the hypothesis that CDV-infection leads to an impairment of professional antigen presenting cells, canine DCs have been generated from peripheral blood monocytes in vitro and infected with CDV. Virus infection was confirmed and quantified by transmission electron microscopy, CDV-specific immunofluorescence, and virus titration. Flow cytometric analyses revealed a significant down-regulation of the major histocompatibility complex class II and co-stimulatory molecules CD80 and CD86 in CDV-infected DCs, indicative of disturbed antigen presenting capacity. Molecular analyses revealed an increased expression of the immune inhibitory cytokine interleukin-10 in DCs following infection. Results of the present study demonstrate that CDV causes phenotypical changes and altered cytokine expression of DCs, which represent potential mechanisms to evade host immune responses and might contribute to immune dysfunction and virus persistence in canine distemper. PMID:24769532

  8. Canine distemper virus infection leads to an inhibitory phenotype of monocyte-derived dendritic cells in vitro with reduced expression of co-stimulatory molecules and increased interleukin-10 transcription.

    Directory of Open Access Journals (Sweden)

    Visar Qeska

    Full Text Available Canine distemper virus (CDV exhibits a profound lymphotropism that causes immunosuppression and increased susceptibility of affected dogs to opportunistic infections. Similar to human measles virus, CDV is supposed to inhibit terminal differentiation of dendritic cells (DCs, responsible for disturbed repopulation of lymphoid tissues and diminished antigen presenting function in dogs. In order to testify the hypothesis that CDV-infection leads to an impairment of professional antigen presenting cells, canine DCs have been generated from peripheral blood monocytes in vitro and infected with CDV. Virus infection was confirmed and quantified by transmission electron microscopy, CDV-specific immunofluorescence, and virus titration. Flow cytometric analyses revealed a significant down-regulation of the major histocompatibility complex class II and co-stimulatory molecules CD80 and CD86 in CDV-infected DCs, indicative of disturbed antigen presenting capacity. Molecular analyses revealed an increased expression of the immune inhibitory cytokine interleukin-10 in DCs following infection. Results of the present study demonstrate that CDV causes phenotypical changes and altered cytokine expression of DCs, which represent potential mechanisms to evade host immune responses and might contribute to immune dysfunction and virus persistence in canine distemper.

  9. Canine distemper virus infection leads to an inhibitory phenotype of monocyte-derived dendritic cells in vitro with reduced expression of co-stimulatory molecules and increased interleukin-10 transcription.

    Science.gov (United States)

    Qeska, Visar; Barthel, Yvonne; Herder, Vanessa; Stein, Veronika M; Tipold, Andrea; Urhausen, Carola; Günzel-Apel, Anne-Rose; Rohn, Karl; Baumgärtner, Wolfgang; Beineke, Andreas

    2014-01-01

    Canine distemper virus (CDV) exhibits a profound lymphotropism that causes immunosuppression and increased susceptibility of affected dogs to opportunistic infections. Similar to human measles virus, CDV is supposed to inhibit terminal differentiation of dendritic cells (DCs), responsible for disturbed repopulation of lymphoid tissues and diminished antigen presenting function in dogs. In order to testify the hypothesis that CDV-infection leads to an impairment of professional antigen presenting cells, canine DCs have been generated from peripheral blood monocytes in vitro and infected with CDV. Virus infection was confirmed and quantified by transmission electron microscopy, CDV-specific immunofluorescence, and virus titration. Flow cytometric analyses revealed a significant down-regulation of the major histocompatibility complex class II and co-stimulatory molecules CD80 and CD86 in CDV-infected DCs, indicative of disturbed antigen presenting capacity. Molecular analyses revealed an increased expression of the immune inhibitory cytokine interleukin-10 in DCs following infection. Results of the present study demonstrate that CDV causes phenotypical changes and altered cytokine expression of DCs, which represent potential mechanisms to evade host immune responses and might contribute to immune dysfunction and virus persistence in canine distemper.

  10. Development of Hand Grip Assistive Device Control System for Old People through Electromyography (EMG Signal Acquisitions

    Directory of Open Access Journals (Sweden)

    Khamis Herman

    2017-01-01

    Full Text Available The hand grip assistive device is a glove to assist old people who suffer from hand weakness in their daily life activities. The device earlier control system only use simple on and off switch. This required old people to use both hand to activate the device. The new control system of the hand grip assistive device was developed to allow single hand operation for old people. New control system take advantages of electromyography (EMG and flex sensor which was implemented to the device. It was programmed into active and semi-active mode operation. EMG sensors were placed on the forearm to capture EMG signal of Flexor Digitorum Profundus muscle to activate the device. Flex sensor was used to indicate the finger position and placed on top of the finger. The signal from both sensors then used to control the device. The new control system allowed single hand operation and designed to prevent user from over depended on the device by activating it through moving their fingers.

  11. NOD1 cooperates with TLR2 to enhance T cell receptor-mediated activation in CD8 T cells.

    Directory of Open Access Journals (Sweden)

    Blandine C Mercier

    Full Text Available Pattern recognition receptors (PRR, like Toll-like receptors (TLR and NOD-like receptors (NLR, are involved in the detection of microbial infections and tissue damage by cells of the innate immune system. Recently, we and others have demonstrated that TLR2 can additionally function as a costimulatory receptor on CD8 T cells. Here, we establish that the intracytosolic receptor NOD1 is expressed and functional in CD8 T cells. We show that C12-iEDAP, a synthetic ligand for NOD1, has a direct impact on both murine and human CD8 T cells, increasing proliferation and effector functions of cells activated via their T cell receptor (TCR. This effect is dependent on the adaptor molecule RIP2 and is associated with an increased activation of the NF-κB, JNK and p38 signaling pathways. Furthermore, we demonstrate that NOD1 stimulation can cooperate with TLR2 engagement on CD8 T cells to enhance TCR-mediated activation. Altogether our results indicate that NOD1 might function as an alternative costimulatory receptor in CD8 T cells. Our study provides new insights into the function of NLR in T cells and extends to NOD1 the recent concept that PRR stimulation can directly control T cell functions.

  12. Multiobjective Reinforcement Learning for Traffic Signal Control Using Vehicular Ad Hoc Network

    Directory of Open Access Journals (Sweden)

    Houli Duan

    2010-01-01

    Full Text Available We propose a new multiobjective control algorithm based on reinforcement learning for urban traffic signal control, named multi-RL. A multiagent structure is used to describe the traffic system. A vehicular ad hoc network is used for the data exchange among agents. A reinforcement learning algorithm is applied to predict the overall value of the optimization objective given vehicles' states. The policy which minimizes the cumulative value of the optimization objective is regarded as the optimal one. In order to make the method adaptive to various traffic conditions, we also introduce a multiobjective control scheme in which the optimization objective is selected adaptively to real-time traffic states. The optimization objectives include the vehicle stops, the average waiting time, and the maximum queue length of the next intersection. In addition, we also accommodate a priority control to the buses and the emergency vehicles through our model. The simulation results indicated that our algorithm could perform more efficiently than traditional traffic light control methods.

  13. Markers of glutamate signaling in cerebrospinal fluid and serum from patients with bipolar disorder and healthy controls.

    Science.gov (United States)

    Pålsson, Erik; Jakobsson, Joel; Södersten, Kristoffer; Fujita, Yuko; Sellgren, Carl; Ekman, Carl-Johan; Ågren, Hans; Hashimoto, Kenji; Landén, Mikael

    2015-01-01

    Glutamate is the major excitatory neurotransmitter in the brain. Aberrations in glutamate signaling have been linked to the pathophysiology of mood disorders. Increased plasma levels of glutamate as well as higher glutamine+glutamate levels in the brain have been demonstrated in patients with bipolar disorder as compared to healthy controls. In this study, we explored the glutamate hypothesis of bipolar disorder by examining peripheral and central levels of amino acids related to glutamate signaling. A total of 215 patients with bipolar disorder and 112 healthy controls from the Swedish St. Göran bipolar project were included in this study. Glutamate, glutamine, glycine, L-serine and D-serine levels were determined in serum and in cerebrospinal fluid using high performance liquid chromatography with fluorescence detection. Serum levels of glutamine, glycine and D-serine were significantly higher whereas L-serine levels were lower in patients with bipolar disorder as compared to controls. No differences between the patient and control group in amino acid levels were observed in cerebrospinal fluid. The observed differences in serum amino acid levels may be interpreted as a systemic aberration in amino acid metabolism that affects several amino acids related to glutamate signaling. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

  14. An RFID-Based Intelligent Vehicle Speed Controller Using Active Traffic Signals

    Directory of Open Access Journals (Sweden)

    Joshué Pérez

    2010-06-01

    Full Text Available These days, mass-produced vehicles benefit from research on Intelligent Transportation System (ITS. One prime example of ITS is vehicle Cruise Control (CC, which allows it to maintain a pre-defined reference speed, to economize on fuel or energy consumption, to avoid speeding fines, or to focus all of the driver’s attention on the steering of the vehicle. However, achieving efficient Cruise Control is not easy in roads or urban streets where sudden changes of the speed limit can happen, due to the presence of unexpected obstacles or maintenance work, causing, in inattentive drivers, traffic accidents. In this communication we present a new Infrastructure to Vehicles (I2V communication and control system for intelligent speed control, which is based upon Radio Frequency Identification (RFID technology for identification of traffic signals on the road, and high accuracy vehicle speed measurement with a Hall effect-based sensor. A fuzzy logic controller, based on sensor fusion of the information provided by the I2V infrastructure, allows the efficient adaptation of the speed of the vehicle to the circumstances of the road. The performance of the system is checked empirically, with promising results.

  15. An RFID-Based Intelligent Vehicle Speed Controller Using Active Traffic Signals

    Science.gov (United States)

    Pérez, Joshué; Seco, Fernando; Milanés, Vicente; Jiménez, Antonio; Díaz, Julio C.; de Pedro, Teresa

    2010-01-01

    These days, mass-produced vehicles benefit from research on Intelligent Transportation System (ITS). One prime example of ITS is vehicle Cruise Control (CC), which allows it to maintain a pre-defined reference speed, to economize on fuel or energy consumption, to avoid speeding fines, or to focus all of the driver’s attention on the steering of the vehicle. However, achieving efficient Cruise Control is not easy in roads or urban streets where sudden changes of the speed limit can happen, due to the presence of unexpected obstacles or maintenance work, causing, in inattentive drivers, traffic accidents. In this communication we present a new Infrastructure to Vehicles (I2V) communication and control system for intelligent speed control, which is based upon Radio Frequency Identification (RFID) technology for identification of traffic signals on the road, and high accuracy vehicle speed measurement with a Hall effect-based sensor. A fuzzy logic controller, based on sensor fusion of the information provided by the I2V infrastructure, allows the efficient adaptation of the speed of the vehicle to the circumstances of the road. The performance of the system is checked empirically, with promising results. PMID:22219692

  16. An RFID-based intelligent vehicle speed controller using active traffic signals.

    Science.gov (United States)

    Pérez, Joshué; Seco, Fernando; Milanés, Vicente; Jiménez, Antonio; Díaz, Julio C; de Pedro, Teresa

    2010-01-01

    These days, mass-produced vehicles benefit from research on Intelligent Transportation System (ITS). One prime example of ITS is vehicle Cruise Control (CC), which allows it to maintain a pre-defined reference speed, to economize on fuel or energy consumption, to avoid speeding fines, or to focus all of the driver's attention on the steering of the vehicle. However, achieving efficient Cruise Control is not easy in roads or urban streets where sudden changes of the speed limit can happen, due to the presence of unexpected obstacles or maintenance work, causing, in inattentive drivers, traffic accidents. In this communication we present a new Infrastructure to Vehicles (I2V) communication and control system for intelligent speed control, which is based upon Radio Frequency Identification (RFID) technology for identification of traffic signals on the road, and high accuracy vehicle speed measurement with a Hall effect-based sensor. A fuzzy logic controller, based on sensor fusion of the information provided by the I2V infrastructure, allows the efficient adaptation of the speed of the vehicle to the circumstances of the road. The performance of the system is checked empirically, with promising results.

  17. Influence of Wind Plant Ancillary Voltage Control on System Small Signal Stability

    DEFF Research Database (Denmark)

    Su, Chi; Chen, Zhe

    2012-01-01

    As a common tendency, large-scale wind farms are increasingly connected to the transmission system of modern power grids. This introduces some new challenges to the connected power systems, and the transmission system operators (TSOs) have to put some new requirements as part of the grid codes...... on the integration of wind farms. One common requirement to wind farms is the function of system voltage control which can be implemented in the grid-side convertor controller of a variable speed wind turbine. This ancillary voltage control provided by wind farms could have some influence on the system small signal...... stability. This paper implements an ancillary voltage control strategy on a direct-drive-full-convertor-based wind farm and studies its influence on the damping ratio values of the dominant oscillation mode within the connected power system. All the calculations and simulations are conducted in DIg...

  18. Design of LQG Controller for Active Suspension without Considering Road Input Signals

    Directory of Open Access Journals (Sweden)

    Hui Pang

    2017-01-01

    Full Text Available As the road conditions are completely unknown in the design of a suspension controller, an improved linear quadratic and Gaussian distributed (LQG controller is proposed for active suspension system without considering road input signals. The main purpose is to optimize the vehicle body acceleration, pitching angular acceleration, displacement of suspension system, and tire dynamic deflection comprehensively. Meanwhile, it will extend the applicability of the LQG controller. Firstly, the half-vehicle and road input mathematical models of an active suspension system are established, with the weight coefficients of each evaluating indicator optimized by using genetic algorithm (GA. Then, a simulation model is built in Matlab/Simulink environment. Finally, a comparison of simulation is conducted to illustrate that the proposed LQG controller can obtain the better comprehensive performance of vehicle suspension system and improve riding comfort and handling safety compared to the conventional one.

  19. Control mechanism to prevent correlated message arrivals from degrading signaling no. 7 network performance

    Science.gov (United States)

    Kosal, Haluk; Skoog, Ronald A.

    1994-04-01

    Signaling System No. 7 (SS7) is designed to provide a connection-less transfer of signaling messages of reasonable length. Customers having access to user signaling bearer capabilities as specified in the ANSI T1.623 and CCITT Q.931 standards can send bursts of correlated messages (e.g., by doing a file transfer that results in the segmentation of a block of data into a number of consecutive signaling messages) through SS7 networks. These message bursts with short interarrival times could have an adverse impact on the delay performance of the SS7 networks. A control mechanism, Credit Manager, is investigated in this paper to regulate incoming traffic to the SS7 network by imposing appropriate time separation between messages when the incoming stream is too bursty. The credit manager has a credit bank where credits accrue at a fixed rate up to a prespecified credit bank capacity. When a message arrives, the number of octets in that message is compared to the number of credits in the bank. If the number of credits is greater than or equal to the number of octets, then the message is accepted for transmission and the number of credits in the bank is decremented by the number of octets. If the number of credits is less than the number of octets, then the message is delayed until enough credits are accumulated. This paper presents simulation results showing delay performance of the SS7 ISUP and TCAP message traffic with a range of correlated message traffic, and control parameters of the credit manager (i.e., credit generation rate and bank capacity) are determined that ensure the traffic entering the SS7 network is acceptable. The results show that control parameters can be set so that for any incoming traffic stream there is no detrimental impact on the SS7 ISUP and TCAP message delay, and the credit manager accepts a wide range of traffic patterns without causing significant delay.

  20. Protein kinase C alpha controls erythropoietin receptor signaling.

    NARCIS (Netherlands)

    M.M. von Lindern (Marieke); M. Parren-Van Amelsvoort (Martine); T.B. van Dijk (Thamar); E. Deiner; B. Löwenberg (Bob); E. van den Akker (Emile); S. van Emst-de Vries (Sjenet); P.J. Willems (Patrick); H. Beug (Hartmut)

    2000-01-01

    textabstractProtein kinase C (PKC) is implied in the activation of multiple targets of erythropoietin (Epo) signaling, but its exact role in Epo receptor (EpoR) signal transduction and in the regulation of erythroid proliferation and differentiation remained elusive. We

  1. Enhancing Raman signals with an interferometrically controlled AFM tip

    International Nuclear Information System (INIS)

    Oron-Carl, Matti; Krupke, Ralph

    2013-01-01

    We demonstrate the upgrade of a commercial confocal Raman microscope into a tip-enhanced Raman microscope/spectroscopy system (TERS) by integrating an interferometrically controlled atomic force microscope into the base of an existing upright microscope to provide near-field detection and thus signal enhancement. The feasibility of the system is demonstrated by measuring the Raman near-field enhancement on thin PEDOT:PSS films and on carbon nanotubes within a device geometry. An enhancement factor of 2–3 and of 5–6 is observed, respectively. Moreover, on a nanotube device we show local conductivity measurement and its correlation to Raman and topography recordings. Upgrading an existing upright confocal Raman microscope in the demonstrated way is significantly cheaper than purchasing a complete commercial TERS system. (paper)

  2. Diverse FGF receptor signaling controls astrocyte specification and proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Kyungjun [School of Life Sciences, Gwangju Institute of Science and Technology, Oryong-dong, Buk-gu, Gwangju 500-712 (Korea, Republic of); Song, Mi-Ryoung, E-mail: msong@gist.ac.kr [School of Life Sciences, Gwangju Institute of Science and Technology, Oryong-dong, Buk-gu, Gwangju 500-712 (Korea, Republic of); Bioimaging Research Center and Cell Dynamics Research Center, Gwangju Institute of Science and Technology, Oryong-dong, Buk-gu, Gwangju 500-712 (Korea, Republic of)

    2010-05-07

    During CNS development, pluripotency neuronal progenitor cells give rise in succession to neurons and glia. Fibroblast growth factor-2 (FGF-2), a major signal that maintains neural progenitors in the undifferentiated state, is also thought to influence the transition from neurogenesis to gliogenesis. Here we present evidence that FGF receptors and underlying signaling pathways transmit the FGF-2 signals that regulate astrocyte specification aside from its mitogenic activity. Application of FGF-2 to cortical progenitors suppressed neurogenesis whereas treatment with an FGFR antagonist in vitro promoted neurogenesis. Introduction of chimeric FGFRs with mutated tyrosine residues into cortical progenitors and drug treatments to specifically block individual downstream signaling pathways revealed that the overall activity of FGFR rather than individual autophosphorylation sites is important for delivering signals for glial specification. In contrast, a signal for cell proliferation by FGFR was mainly delivered by MAPK pathway. Together our findings indicate that FGFR activity promotes astrocyte specification in the developing CNS.

  3. Diverse FGF receptor signaling controls astrocyte specification and proliferation

    International Nuclear Information System (INIS)

    Kang, Kyungjun; Song, Mi-Ryoung

    2010-01-01

    During CNS development, pluripotency neuronal progenitor cells give rise in succession to neurons and glia. Fibroblast growth factor-2 (FGF-2), a major signal that maintains neural progenitors in the undifferentiated state, is also thought to influence the transition from neurogenesis to gliogenesis. Here we present evidence that FGF receptors and underlying signaling pathways transmit the FGF-2 signals that regulate astrocyte specification aside from its mitogenic activity. Application of FGF-2 to cortical progenitors suppressed neurogenesis whereas treatment with an FGFR antagonist in vitro promoted neurogenesis. Introduction of chimeric FGFRs with mutated tyrosine residues into cortical progenitors and drug treatments to specifically block individual downstream signaling pathways revealed that the overall activity of FGFR rather than individual autophosphorylation sites is important for delivering signals for glial specification. In contrast, a signal for cell proliferation by FGFR was mainly delivered by MAPK pathway. Together our findings indicate that FGFR activity promotes astrocyte specification in the developing CNS.

  4. Type III Interferon-Mediated Signaling Is Critical for Controlling Live Attenuated Yellow Fever Virus Infection In Vivo

    Directory of Open Access Journals (Sweden)

    Florian Douam

    2017-08-01

    Full Text Available Yellow fever virus (YFV is an arthropod-borne flavivirus, infecting ~200,000 people worldwide annually and causing about 30,000 deaths. The live attenuated vaccine strain, YFV-17D, has significantly contributed in controlling the global burden of yellow fever worldwide. However, the viral and host contributions to YFV-17D attenuation remain elusive. Type I interferon (IFN-α/β signaling and type II interferon (IFN-γ signaling have been shown to be mutually supportive in controlling YFV-17D infection despite distinct mechanisms of action in viral infection. However, it remains unclear how type III IFN (IFN-λ integrates into this antiviral system. Here, we report that while wild-type (WT and IFN-λ receptor knockout (λR−/− mice were largely resistant to YFV-17D, deficiency in type I IFN signaling resulted in robust infection. Although IFN-α/β receptor knockout (α/βR−/− mice survived the infection, mice with combined deficiencies in both type I signaling and type III IFN signaling were hypersusceptible to YFV-17D and succumbed to the infection. Mortality was associated with viral neuroinvasion and increased permeability of the blood-brain barrier (BBB. α/βR−/− λR−/− mice also exhibited distinct changes in the frequencies of multiple immune cell lineages, impaired T-cell activation, and severe perturbation of the proinflammatory cytokine balance. Taken together, our data highlight that type III IFN has critical immunomodulatory and neuroprotective functions that prevent viral neuroinvasion during active YFV-17D replication. Type III IFN thus likely represents a safeguard mechanism crucial for controlling YFV-17D infection and contributing to shaping vaccine immunogenicity.

  5. Xenopus Zic3 controls notochord and organizer development through suppression of the Wnt/β-catenin signaling pathway.

    Science.gov (United States)

    Fujimi, Takahiko J; Hatayama, Minoru; Aruga, Jun

    2012-01-15

    Zic3 controls neuroectodermal differentiation and left-right patterning in Xenopus laevis embryos. Here we demonstrate that Zic3 can suppress Wnt/β-catenin signaling and control development of the notochord and Spemann's organizer. When we overexpressed Zic3 by injecting its RNA into the dorsal marginal zone of 2-cell-stage embryos, the embryos lost mesodermal dorsal midline structures and showed reduced expression of organizer markers (Siamois and Goosecoid) and a notochord marker (Xnot). Co-injection of Siamois RNA partially rescued the reduction of Xnot expression caused by Zic3 overexpression. Because the expression of Siamois in the organizer region is controlled by Wnt/β-catenin signaling, we subsequently examined the functional interaction between Zic3 and Wnt signaling. Co-injection of Xenopus Zic RNAs and β-catenin RNA with a reporter responsive to the Wnt/β-catenin cascade indicated that Zic1, Zic2, Zic3, Zic4, and Zic5 can all suppress β-catenin-mediated transcriptional activation. In addition, co-injection of Zic3 RNA inhibited the secondary axis formation caused by ventral-side injection of β-catenin RNA in Xenopus embryos. Zic3-mediated Wnt/β-catenin signal suppression required the nuclear localization of Zic3, and involved the reduction of β-catenin nuclear transport and enhancement of β-catenin degradation. Furthermore, Zic3 co-precipitated with Tcf1 (a β-catenin co-factor) and XIC (I-mfa domain containing factor required for dorsoanterior development). The findings in this report produce a novel system for fine-tuning of Wnt/β-catenin signaling. Copyright © 2011. Published by Elsevier Inc.

  6. Endogenous Glucagon-like Peptide-1 Receptor Signaling in the Nucleus Tractus Solitarius is Required for Food Intake Control.

    Science.gov (United States)

    Alhadeff, Amber L; Mergler, Blake D; Zimmer, Derek J; Turner, Christopher A; Reiner, David J; Schmidt, Heath D; Grill, Harvey J; Hayes, Matthew R

    2017-06-01

    Alhough the glucagon-like peptide-1 (GLP-1) system is critical to energy balance control and is a target for obesity pharmacotherapies, the receptor-population-mediating effects of endogenous GLP-1 signaling are not fully understood. To address this, we developed a novel adeno-associated virus (AAV-GLP-1R) that utilizes short hairpin RNA to chronically knock down GLP-1 receptors (GLP-1R) in rats. As pharmacological studies highlight the hindbrain nucleus tractus solitarius (NTS) as a brain region important for GLP-1R-mediated effects on energy balance, AAV-GLP-1R was injected into the NTS to examine the role of endogenous NTS GLP-1R signaling in energy balance control. Chow intake and meal size were significantly increased following chronic NTS GLP-1R knockdown. In addition, NTS GLP-1R knockdown significantly increased self-administration of palatable food under both fixed and progressive ratio schedules of reinforcement. Collectively, these data demonstrate that endogenous NTS GLP-1R signaling is required for the control of food intake and motivation to feed, and provide a new strategy to investigate the importance of distinct GLP-1R populations in the control of a variety of functions.

  7. Signal multiplexing scheme for LINAC

    International Nuclear Information System (INIS)

    Sujo, C.I.; Mohan, Shyam; Joshi, Gopal; Singh, S.K.; Karande, Jitendra

    2004-01-01

    For the proper operation of the LINAC some signals, RF (radio frequency) as well as LF (low frequency) have to be available at the Master Control Station (MCS). These signals are needed to control, calibrate and characterize the RF fields in the resonators. This can be achieved by proper multiplexing of various signals locally and then routing the selected signals to the MCS. A multiplexing scheme has been designed and implemented, which will allow the signals from the selected cavity to the MCS. High isolation between channels and low insertion loss for a given signal are important issues while selecting the multiplexing scheme. (author)

  8. Evaluation of anticipatory signal to steam generator pressure control program for 700 MWe Indian pressurized heavy water reactor

    International Nuclear Information System (INIS)

    Pahari, S.; Hajela, S.; Rammohan, H. P.; Malhotra, P. K.; Ghadge, S. G.

    2012-01-01

    700 MWe Indian Pressurized Heavy Water Reactor (IPHWR) is horizontal channel type reactor with partial boiling at channel outlet. Due to boiling, it has a large volume of vapor present in the primary loops. It has two primary loops connected with the help of pressurizer surge line. The pressurizer has a large capacity and is partly filled by liquid and partly by vapor. Large vapor volume improves compressibility of the system. During turbine trip or load rejection, pressure builds up in Steam Generator (SG). This leads to pressurization of Primary Heat Transport System (PHTS). To control pressurization of SG and PHTS, around 70% of the steam generated in SG is dumped into the condenser by opening Condenser Steam Dump Valves (CSDVs) and rest of the steam is released to the atmosphere by opening Atmospheric Steam Discharge Valves (ASDVs) immediately after sensing the event. This is accomplished by adding anticipatory signal to the output of SG pressure controller. Anticipatory signal is proportional to the thermal power of reactor and the proportionality constant is set so that SG pressure controller's output jacks up to ASDV opening range when operating at 100% FP. To simulate this behavior for 700 MWe IPHWR, Primary and secondary heat transport system is modeled. SG pressure control and other process control program have also been modeled to capture overall plant dynamics. Analysis has been carried out with 3-D neutron kinetics coupled thermal hydraulic computer code ATMIKA.T to evaluate the effect of the anticipatory signal on PHT pressure and over all plant dynamics during turbine trip in 700 MWe IPHWR. This paper brings out the results of the analysis with and without considering anticipatory signal in SG pressure control program during turbine trip. (authors)

  9. Protein kinase C alpha controls erythropoietin receptor signaling

    NARCIS (Netherlands)

    von Lindern, M.; Parren-van Amelsvoort, M.; van Dijk, T.; Deiner, E.; van den Akker, E.; van Emst-de Vries, S.; Willems, P.; Beug, H.; Löwenberg, B.

    2000-01-01

    Protein kinase C (PKC) is implied in the activation of multiple targets of erythropoietin (Epo) signaling, but its exact role in Epo receptor (EpoR) signal transduction and in the regulation of erythroid proliferation and differentiation remained elusive. We analyzed the effect of PKC inhibitors

  10. Saturation flow versus green time at two-stage signal controlled intersections

    Directory of Open Access Journals (Sweden)

    A. Boumediene

    2009-12-01

    Full Text Available Intersections are the key components of road networks considerably affecting capacity. As flow levels and experience have increased over the years, methods and means have been developed to cope with growing demand for traffic at road junctions. Among various traffic control devices and techniques developed to cope with conflicting movements, traffic signals create artificial gaps to accommodate the impeded traffic streams. The majority of parameters that govern signalised intersection control and operations such as a degree of saturation, delays, queue lengths, the level of service etc. are very sensitive to saturation flow. Therefore, it is essential to reliably evaluate saturation flow for correctly setting traffic signals to avoid unnecessary delays and conflicts. Generally, almost all guidelines support the constancy of saturation flow irrespective of green time duration. This paper presents the results of field studies carried out to enable the performance of signalised intersections to be compared at different green time durations. It was found that saturation flow decreased slightly with growing green time. Reduction corresponded to between 2 and 5 pcus/gh per second of green time. However, the analyses of the discharge rate during the successive time intervals of 6-seconds showed a substantial reduction of 10% to 13% in saturation flow levels after 36 seconds of green time compared to those relating to 6–36 seconds range. No reduction in saturation flow levels was detected at the sites where only green periods of 44 seconds or less were implemented.

  11. Generation of synthetic surface electromyography signals under fatigue conditions for varying force inputs using feedback control algorithm.

    Science.gov (United States)

    Venugopal, G; Deepak, P; Ghosh, Diptasree M; Ramakrishnan, S

    2017-11-01

    Surface electromyography is a non-invasive technique used for recording the electrical activity of neuromuscular systems. These signals are random, complex and multi-component. There are several techniques to extract information about the force exerted by muscles during any activity. This work attempts to generate surface electromyography signals for various magnitudes of force under isometric non-fatigue and fatigue conditions using a feedback model. The model is based on existing current distribution, volume conductor relations, the feedback control algorithm for rate coding and generation of firing pattern. The result shows that synthetic surface electromyography signals are highly complex in both non-fatigue and fatigue conditions. Furthermore, surface electromyography signals have higher amplitude and lower frequency under fatigue condition. This model can be used to study the influence of various signal parameters under fatigue and non-fatigue conditions.

  12. Langerhans cells from human oral epithelium are more effective at stimulating allogeneic T cells in vitro than Langerhans cells from skin.

    Science.gov (United States)

    Hasséus, B; Jontell, M; Bergenholtz, G; Dahlgren, U I

    2004-06-01

    This report is focused on the functional capacity of Langerhans cells (LC) in the epithelium of skin and oral mucosa, which both meet different antigenic challenges. The capacity of LC from human oral and skin epithelium to provide co-stimulatory signals to T cells in vitro was compared. LC in a crude suspension of oral epithelial cells had a significantly enhanced T cell co-stimulatory capacity compared to skin epithelial cells. This applied both to cultures with concanavalin A (con-A)-stimulated syngeneic T cells and to a mixed epithelial cell lymphocyte reaction involving allogeneic T cells. The co-stimulatory capacity of oral and skin epithelial cells was reduced by >70% if monoclonal antibodies against HLA-DR, -DP and -DQ were added to the cultures with allogeneic T cells, indicating the involvement of HLA class II expressing LC. Immunohistochemistry revealed that 6% of the epithelial cells were CD1a + LC in sections from both oral and skin epithelium. Interleukin (IL)-8 production was higher in cultures of oral epithelial cells and con-A stimulated T cells than in corresponding cultures with skin epithelial cells as accessory cells. The results suggest that LC in human oral epithelium are more efficient at stimulating T cells than those of skin.

  13. Research on the Method of Setting Waiting Area for Non-motor Vehicle at Signal Control Intersection

    Directory of Open Access Journals (Sweden)

    Wang Yun Xia

    2018-01-01

    Full Text Available Electric bicycle has become an indispensable important component of the transportation system. The fact is that traffic organization and channelizing design of signal control intersection is not intensive, which cannot adapt to the current traffic demand of non-motor vehicle, such as unclear traffic rules and poor visibility, thus the traffic safety of non-motor vehicle is not optimistic. Therefore, it is necessary to study on traffic organization method based on the demand of non-motor vehicle, which can provide certain theoretical basis for traffic administrative department to make policy and traffic design. This article focuses on the method of setting waiting area for non-motor vehicle at signal control intersection, including the advantages, disadvantages and the applicable conditions.

  14. Increasing the ex vivo antigen-specific IFN-γ production in subpopulations of T cells and NKp46+ cells by anti-CD28, anti-CD49d and recombinant IL-12 costimulation in cattle vaccinated with recombinant proteins from Mycobacterium avium subspecies paratuberculosis

    DEFF Research Database (Denmark)

    Thakur, Aneesh; Riber, Ulla; Davis, William C.

    2013-01-01

    -γ secretion by CD4, CD8, γδ T cells and NK cells. Age matched male jersey calves, experimentally infected with Mycobacterium avium subsp. paratuberculosis (MAP), were vaccinated with a cocktail of recombinant MAP proteins or left unvaccinated. Vaccine induced ex vivo recall responses were measured through Ag......T cells, which encounter specific antigen (Ag), require additional signals to mount a functional immune response. Here, we demonstrate activation of signal 2, by anti-CD28 mAb (aCD28) and other costimulatory molecules (aCD49d, aCD5), and signal 3, by recombinant IL-12, enhance Ag-specific IFN...

  15. The activation of the adaptive immune system: cross-talk between antigen-presenting cells, T cells and B cells.

    Science.gov (United States)

    den Haan, Joke M M; Arens, Ramon; van Zelm, Menno C

    2014-12-01

    The adaptive immune system consists of T and B cells that express clonally distributed antigen receptors. To achieve functional adaptive immune responses, antigen-specific T cell populations are stimulated by professional antigen-presenting cells like dendritic cells (DCs), which provide crucial stimulatory signals for efficient expansion and development of effector functions. Antigen-specific B cells receive costimulatory signals from helper T cells to stimulate affinity maturation and isotype switching. Here we elaborate on the interactions between DCs, T cells and B cells, and on the important signals for efficient induction of adaptive immune responses. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Electrical system for pulse-width modulated control of a power inverter using phase-shifted carrier signals and related operating methods

    Science.gov (United States)

    Welchko, Brian A [Torrance, CA

    2012-02-14

    Systems and methods are provided for pulse-width modulated control of power inverter using phase-shifted carrier signals. An electrical system comprises an energy source and a motor. The motor has a first set of windings and a second set of windings, which are electrically isolated from each other. An inverter module is coupled between the energy source and the motor and comprises a first set of phase legs coupled to the first set of windings and a second set of phase legs coupled to the second set of windings. A controller is coupled to the inverter module and is configured to achieve a desired power flow between the energy source and the motor by modulating the first set of phase legs using a first carrier signal and modulating the second set of phase legs using a second carrier signal. The second carrier signal is phase-shifted relative to the first carrier signal.

  17. Chronic recording of hand prosthesis control signals via a regenerative peripheral nerve interface in a rhesus macaque

    Science.gov (United States)

    Irwin, Z. T.; Schroeder, K. E.; Vu, P. P.; Tat, D. M.; Bullard, A. J.; Woo, S. L.; Sando, I. C.; Urbanchek, M. G.; Cederna, P. S.; Chestek, C. A.

    2016-08-01

    Objective. Loss of even part of the upper limb is a devastating injury. In order to fully restore natural function when lacking sufficient residual musculature, it is necessary to record directly from peripheral nerves. However, current approaches must make trade-offs between signal quality and longevity which limit their clinical potential. To address this issue, we have developed the regenerative peripheral nerve interface (RPNI) and tested its use in non-human primates. Approach. The RPNI consists of a small, autologous partial muscle graft reinnervated by a transected peripheral nerve branch. After reinnervation, the graft acts as a bioamplifier for descending motor commands in the nerve, enabling long-term recording of high signal-to-noise ratio (SNR), functionally-specific electromyographic (EMG) signals. We implanted nine RPNIs on separate branches of the median and radial nerves in two rhesus macaques who were trained to perform cued finger movements. Main results. No adverse events were noted in either monkey, and we recorded normal EMG with high SNR (>8) from the RPNIs for up to 20 months post-implantation. Using RPNI signals recorded during the behavioral task, we were able to classify each monkey’s finger movements as flexion, extension, or rest with >96% accuracy. RPNI signals also enabled functional prosthetic control, allowing the monkeys to perform the same behavioral task equally well with either physical finger movements or RPNI-based movement classifications. Significance. The RPNI signal strength, stability, and longevity demonstrated here represents a promising method for controlling advanced prosthetic limbs and fully restoring natural movement.

  18. Control of electrochemical signals from quantum dots conjugated to organic materials by using DNA structure in an analog logic gate.

    Science.gov (United States)

    Chen, Qi; Yoo, Si-Youl; Chung, Yong-Ho; Lee, Ji-Young; Min, Junhong; Choi, Jeong-Woo

    2016-10-01

    Various bio-logic gates have been studied intensively to overcome the rigidity of single-function silicon-based logic devices arising from combinations of various gates. Here, a simple control tool using electrochemical signals from quantum dots (QDs) was constructed using DNA and organic materials for multiple logic functions. The electrochemical redox current generated from QDs was controlled by the DNA structure. DNA structure, in turn, was dependent on the components (organic materials) and the input signal (pH). Independent electrochemical signals from two different logic units containing QDs were merged into a single analog-type logic gate, which was controlled by two inputs. We applied this electrochemical biodevice to a simple logic system and achieved various logic functions from the controlled pH input sets. This could be further improved by choosing QDs, ionic conditions, or DNA sequences. This research provides a feasible method for fabricating an artificial intelligence system. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Control of deviations and prediction of surface roughness from micro machining of THz waveguides using acoustic emission signals

    Science.gov (United States)

    Griffin, James M.; Diaz, Fernanda; Geerling, Edgar; Clasing, Matias; Ponce, Vicente; Taylor, Chris; Turner, Sam; Michael, Ernest A.; Patricio Mena, F.; Bronfman, Leonardo

    2017-02-01

    By using acoustic emission (AE) it is possible to control deviations and surface quality during micro milling operations. The method of micro milling is used to manufacture a submillimetre waveguide where micro machining is employed to achieve the required superior finish and geometrical tolerances. Submillimetre waveguide technology is used in deep space signal retrieval where highest detection efficiencies are needed and therefore every possible signal loss in the receiver has to be avoided and stringent tolerances achieved. With a sub-standard surface finish the signals travelling along the waveguides dissipate away faster than with perfect surfaces where the residual roughness becomes comparable with the electromagnetic skin depth. Therefore, the higher the radio frequency the more critical this becomes. The method of time-frequency analysis (STFT) is used to transfer raw AE into more meaningful salient signal features (SF). This information was then correlated against the measured geometrical deviations and, the onset of catastrophic tool wear. Such deviations can be offset from different AE signals (different deviations from subsequent tests) and feedback for a final spring cut ensuring the geometrical accuracies are met. Geometrical differences can impact on the required transfer of AE signals (change in cut off frequencies and diminished SNR at the interface) and therefore errors have to be minimised to within 1 μm. Rules based on both Classification and Regression Trees (CART) and Neural Networks (NN) were used to implement a simulation displaying how such a control regime could be used as a real time controller, be it corrective measures (via spring cuts) over several initial machining passes or, with a micron cut introducing a level plain measure for allowing setup corrective measures (similar to a spirit level).

  20. A reverse signaling pathway downstream of Sema4A controls cell migration via Scrib.

    Science.gov (United States)

    Sun, Tianliang; Yang, Lida; Kaur, Harmandeep; Pestel, Jenny; Looso, Mario; Nolte, Hendrik; Krasel, Cornelius; Heil, Daniel; Krishnan, Ramesh K; Santoni, Marie-Josée; Borg, Jean-Paul; Bünemann, Moritz; Offermanns, Stefan; Swiercz, Jakub M; Worzfeld, Thomas

    2017-01-02

    Semaphorins comprise a large family of ligands that regulate key cellular functions through their receptors, plexins. In this study, we show that the transmembrane semaphorin 4A (Sema4A) can also function as a receptor, rather than a ligand, and transduce signals triggered by the binding of Plexin-B1 through reverse signaling. Functionally, reverse Sema4A signaling regulates the migration of various cancer cells as well as dendritic cells. By combining mass spectrometry analysis with small interfering RNA screening, we identify the polarity protein Scrib as a downstream effector of Sema4A. We further show that binding of Plexin-B1 to Sema4A promotes the interaction of Sema4A with Scrib, thereby removing Scrib from its complex with the Rac/Cdc42 exchange factor βPIX and decreasing the activity of the small guanosine triphosphatase Rac1 and Cdc42. Our data unravel a role for Plexin-B1 as a ligand and Sema4A as a receptor and characterize a reverse signaling pathway downstream of Sema4A, which controls cell migration. © 2017 Sun et al.

  1. Signal validation with control-room information-processing computers

    International Nuclear Information System (INIS)

    Belblidia, L.A.; Carlson, R.W.; Russell, J.L. Jr.

    1985-01-01

    One of the 'lessons learned' from the Three Mile Island accident focuses upon the need for a validated source of plant-status information in the control room. The utilization of computer-generated graphics to display the readings of the major plant instrumentation has introduced the capability of validating signals prior to their presentation to the reactor operations staff. The current operations philosophies allow the operator a quick look at the gauges to form an impression of the fraction of full scale as the basis for knowledge of the current plant conditions. After the introduction of a computer-based information-display system such as the Safety Parameter Display System (SPDS), operational decisions can be based upon precise knowledge of the parameters that define the operation of the reactor and auxiliary systems. The principal impact of this system on the operator will be to remove the continuing concern for the validity of the instruments which provide the information that governs the operator's decisions. (author)

  2. Luminance and chromatic signals interact differently with melanopsin activation to control the pupil light response.

    Science.gov (United States)

    Barrionuevo, Pablo A; Cao, Dingcai

    2016-09-01

    Intrinsically photosensitive retinal ganglion cells (ipRGCs) express the photopigment melanopsin. These cells receive afferent inputs from rods and cones, which provide inputs to the postreceptoral visual pathways. It is unknown, however, how melanopsin activation is integrated with postreceptoral signals to control the pupillary light reflex. This study reports human flicker pupillary responses measured using stimuli generated with a five-primary photostimulator that selectively modulated melanopsin, rod, S-, M-, and L-cone excitations in isolation, or in combination to produce postreceptoral signals. We first analyzed the light adaptation behavior of melanopsin activation and rod and cones signals. Second, we determined how melanopsin is integrated with postreceptoral signals by testing with cone luminance, chromatic blue-yellow, and chromatic red-green stimuli that were processed by magnocellular (MC), koniocellular (KC), and parvocellular (PC) pathways, respectively. A combined rod and melanopsin response was also measured. The relative phase of the postreceptoral signals was varied with respect to the melanopsin phase. The results showed that light adaptation behavior for all conditions was weaker than typical Weber adaptation. Melanopsin activation combined linearly with luminance, S-cone, and rod inputs, suggesting the locus of integration with MC and KC signals was retinal. The melanopsin contribution to phasic pupil responses was lower than luminance contributions, but much higher than S-cone contributions. Chromatic red-green modulation interacted with melanopsin activation nonlinearly as described by a "winner-takes-all" process, suggesting the integration with PC signals might be mediated by a postretinal site.

  3. A single amino acid residue controls Ca2+ signaling by an octopamine receptor from Drosophila melanogaster.

    Science.gov (United States)

    Hoff, Max; Balfanz, Sabine; Ehling, Petra; Gensch, Thomas; Baumann, Arnd

    2011-07-01

    Rhythmic activity of cells and cellular networks plays an important role in physiology. In the nervous system oscillations of electrical activity and/or second messenger concentrations are important to synchronize neuronal activity. At the molecular level, rhythmic activity can be initiated by different routes. We have recently shown that an octopamine-activated G-protein-coupled receptor (GPCR; DmOctα1Rb, CG3856) from Drosophila initiates Ca(2+) oscillations. Here, we have unraveled the molecular basis of cellular Ca(2+) signaling controlled by the DmOctα1Rb receptor using a combination of pharmacological intervention, site-directed mutagenesis, and functional cellular Ca(2+) imaging on heterologously expressed receptors. Phosphorylation of a single amino acid residue in the third intracellular loop of the GPCR by PKC is necessary and sufficient to desensitize the receptor. From its desensitized state, DmOctα1Rb is resensitized by dephosphorylation, and a new Ca(2+) signal occurs on octopamine stimulation. Our findings show that transient changes of the receptor's surface profile have a strong effect on its physiological signaling properties. We expect that the detailed knowledge of DmOctα1Rb-dependent signal transduction fosters the identification of specific drugs that can be used for GPCR-mediated pest control, since octopamine serves important physiological and behavioral functions in arthropods.

  4. Type III Interferon-Mediated Signaling Is Critical for Controlling Live Attenuated Yellow Fever Virus Infection In Vivo.

    Science.gov (United States)

    Douam, Florian; Soto Albrecht, Yentli E; Hrebikova, Gabriela; Sadimin, Evita; Davidson, Christian; Kotenko, Sergei V; Ploss, Alexander

    2017-08-15

    Yellow fever virus (YFV) is an arthropod-borne flavivirus, infecting ~200,000 people worldwide annually and causing about 30,000 deaths. The live attenuated vaccine strain, YFV-17D, has significantly contributed in controlling the global burden of yellow fever worldwide. However, the viral and host contributions to YFV-17D attenuation remain elusive. Type I interferon (IFN-α/β) signaling and type II interferon (IFN-γ) signaling have been shown to be mutually supportive in controlling YFV-17D infection despite distinct mechanisms of action in viral infection. However, it remains unclear how type III IFN (IFN-λ) integrates into this antiviral system. Here, we report that while wild-type (WT) and IFN-λ receptor knockout (λR -/- ) mice were largely resistant to YFV-17D, deficiency in type I IFN signaling resulted in robust infection. Although IFN-α/β receptor knockout (α/βR -/- ) mice survived the infection, mice with combined deficiencies in both type I signaling and type III IFN signaling were hypersusceptible to YFV-17D and succumbed to the infection. Mortality was associated with viral neuroinvasion and increased permeability of the blood-brain barrier (BBB). α/βR -/- λR -/- mice also exhibited distinct changes in the frequencies of multiple immune cell lineages, impaired T-cell activation, and severe perturbation of the proinflammatory cytokine balance. Taken together, our data highlight that type III IFN has critical immunomodulatory and neuroprotective functions that prevent viral neuroinvasion during active YFV-17D replication. Type III IFN thus likely represents a safeguard mechanism crucial for controlling YFV-17D infection and contributing to shaping vaccine immunogenicity. IMPORTANCE YFV-17D is a live attenuated flavivirus vaccine strain recognized as one of the most effective vaccines ever developed. However, the host and viral determinants governing YFV-17D attenuation and its potent immunogenicity are still unknown. Here, we analyzed the

  5. Automatic analysis of signals during Eddy currents controls

    International Nuclear Information System (INIS)

    Chiron, D.

    1983-06-01

    A method and the corresponding instrument have been developed for automatic analysis of Eddy currents testing signals. This apparatus enables at the same time the analysis, every 2 milliseconds, of two signals at two different frequencies. It can be used either on line with an Eddy Current testing instrument or with a magnetic tape recorder [fr

  6. Measurand transient signal suppressor

    Science.gov (United States)

    Bozeman, Richard J., Jr. (Inventor)

    1994-01-01

    A transient signal suppressor for use in a controls system which is adapted to respond to a change in a physical parameter whenever it crosses a predetermined threshold value in a selected direction of increasing or decreasing values with respect to the threshold value and is sustained for a selected discrete time interval is presented. The suppressor includes a sensor transducer for sensing the physical parameter and generating an electrical input signal whenever the sensed physical parameter crosses the threshold level in the selected direction. A manually operated switch is provided for adapting the suppressor to produce an output drive signal whenever the physical parameter crosses the threshold value in the selected direction of increasing or decreasing values. A time delay circuit is selectively adjustable for suppressing the transducer input signal for a preselected one of a plurality of available discrete suppression time and producing an output signal only if the input signal is sustained for a time greater than the selected suppression time. An electronic gate is coupled to receive the transducer input signal and the timer output signal and produce an output drive signal for energizing a control relay whenever the transducer input is a non-transient signal which is sustained beyond the selected time interval.

  7. Buck-Boost DC-DC Converter Control by Using the Extracted Model from Signal Flow Graph Method

    OpenAIRE

    Mohammadian, Leila; Babaei, Ebrahim; Bannae Sharifian, Mohammad Bagher

    2015-01-01

    In this paper, the signal flow graph technique and Mason gain formula are applied for extracting the model and transfer functions from control to output and from input to output of a buck-boost converter. In order to investigate a controller necessity for the converter of assumed parameters, the frequency and time domain analysis are done and the open loop system characteristics are verified and the needed closed loop controlled system specifications are determined. Finally designing a contro...

  8. Multivariate control charts based on net analyte signal (NAS) and Raman spectroscopy for quality control of carbamazepine

    Energy Technology Data Exchange (ETDEWEB)

    Rocha, Werickson Fortunato de Carvalho [Institute of Chemistry, University of Campinas - UNICAMP, P.O. Box 6154, 13083-970 Campinas, SP (Brazil); National Institute of Metrology, Standardization and Industrial Quality, Inmetro, Dimci/Dquim - Directorate of Metrology, Science and Industry/Division of Chemical Metrology, Av. Nossa Senhora das Gracas 50, Building 6, 25250-020, Xerem, Duque de Caxias, RJ (Brazil); Poppi, Ronei Jesus, E-mail: ronei@iqm.unicamp.br [Institute of Chemistry, University of Campinas - UNICAMP, P.O. Box 6154, 13083-970 Campinas, SP (Brazil); National Institute of Science and Technology (INCT) for Bioanalytics, 13083-970 Campinas, SP (Brazil)

    2011-10-31

    Raman spectroscopy and control charts based on the net analyte signal (NAS) were applied to polymorphic characterization of carbamazepine. Carbamazepine presents four polymorphic forms: I-IV (dihydrate). X-ray powder diffraction was used as a reference technique. The control charts were built generating three charts: the NAS chart that corresponds to the analyte of interest (form III in this case), the interference chart that corresponds to the contribution of other compounds in the sample and the residual chart that corresponds to nonsystematic variations. For each chart, statistical limits were developed using samples within the quality specifications. It was possible to identify the different polymorphic forms of carbamazepine present in pharmaceutical formulations. Thus, an alternative method for the quality monitoring of the carbamazepine polymorphic forms after the crystallization process is presented.

  9. Multivariate control charts based on net analyte signal (NAS) and Raman spectroscopy for quality control of carbamazepine

    International Nuclear Information System (INIS)

    Rocha, Werickson Fortunato de Carvalho; Poppi, Ronei Jesus

    2011-01-01

    Raman spectroscopy and control charts based on the net analyte signal (NAS) were applied to polymorphic characterization of carbamazepine. Carbamazepine presents four polymorphic forms: I-IV (dihydrate). X-ray powder diffraction was used as a reference technique. The control charts were built generating three charts: the NAS chart that corresponds to the analyte of interest (form III in this case), the interference chart that corresponds to the contribution of other compounds in the sample and the residual chart that corresponds to nonsystematic variations. For each chart, statistical limits were developed using samples within the quality specifications. It was possible to identify the different polymorphic forms of carbamazepine present in pharmaceutical formulations. Thus, an alternative method for the quality monitoring of the carbamazepine polymorphic forms after the crystallization process is presented.

  10. crm-1 facilitates BMP signaling to control body size in Caenorhabditis elegans.

    Science.gov (United States)

    Fung, Wong Yan; Fat, Ko Frankie Chi; Eng, Cheah Kathryn Song; Lau, Chow King

    2007-11-01

    We have identified in Caenorhabditis elegans a homologue of the vertebrate Crim1, crm-1, which encodes a putative transmembrane protein with multiple cysteine-rich (CR) domains known to have bone morphogenetic proteins (BMPs) binding activity. Using the body morphology of C. elegans as an indicator, we showed that attenuation of crm-1 activity leads to a small body phenotype reminiscent of that of BMP pathway mutants. We showed that the crm-1 loss-of-function phenotype can be rescued by constitutive supply of sma-4 activity. crm-1 can enhance BMP signaling and this activity is dependent on the presence of the DBL-1 ligand and its receptors. crm-1 is expressed in neurons at the ventral nerve cord, where the DBL-1 ligand is produced. However, ectopic expression experiments reveal that crm-1 gene products act outside the DBL-1 producing cells and function non-autonomously to facilitate dbl/sma pathway signaling to control body size.

  11. Cathepsin B in antigen-presenting cells controls mediators of the Th1 immune response during Leishmania major infection.

    Directory of Open Access Journals (Sweden)

    Iris J Gonzalez-Leal

    2014-09-01

    Full Text Available Resistance and susceptibility to Leishmania major infection in the murine model is determined by the capacity of the host to mount either a protective Th1 response or a Th2 response associated with disease progression. Previous reports involving the use of cysteine cathepsin inhibitors indicated that cathepsins B (Ctsb and L (Ctsl play important roles in Th1/Th2 polarization during L. major infection in both susceptible and resistant mouse strains. Although it was hypothesized that these effects are a consequence of differential patterns of antigen processing, the mechanisms underlying these differences were not further investigated. Given the pivotal roles that dendritic cells and macrophages play during Leishmania infection, we generated bone-marrow derived dendritic cells (BMDC and macrophages (BMM from Ctsb-/- and Ctsl-/- mice, and studied the effects of Ctsb and Ctsl deficiency on the survival of L. major in infected cells. Furthermore, the signals used by dendritic cells to instruct Th cell polarization were addressed: the expression of MHC class II and co-stimulatory molecules, and cytokine production. We found that Ctsb-/- BMDC express higher levels of MHC class II molecules than wild-type (WT and Ctsl-/- BMDC, while there were no significant differences in the expression of co-stimulatory molecules between cathepsin-deficient and WT cells. Moreover, both BMDC and BMM from Ctsb-/- mice significantly up-regulated the levels of interleukin 12 (IL-12 expression, a key Th1-inducing cytokine. These findings indicate that Ctsb-/- BMDC display more pro-Th1 properties than their WT and Ctsl-/- counterparts, and therefore suggest that Ctsb down-regulates the Th1 response to L. major. Moreover, they propose a novel role for Ctsb as a regulator of cytokine expression.

  12. Detection of combustion start in the controlled auto ignition engine by wavelet transform of the engine block vibration signal

    International Nuclear Information System (INIS)

    Kim, Seonguk; Min, Kyoungdoug

    2008-01-01

    The CAI (controlled auto ignition) engine ignites fuel and air mixture by trapping high temperature burnt gas using a negative valve overlap. Due to auto ignition in CAI combustion, efficiency improvements and low level NO x emission can be obtained. Meanwhile, the CAI combustion regime is restricted and control parameters are limited. The start of combustion data in the compressed ignition engine are most critical for controlling the overall combustion. In this research, the engine block vibration signal is transformed by the Meyer wavelet to analyze CAI combustion more easily and accurately. Signal acquisition of the engine block vibration is a more suitable method for practical use than measurement of in-cylinder pressure. A new method for detecting combustion start in CAI engines through wavelet transformation of the engine block vibration signal was developed and results indicate that it is accurate enough to analyze the start of combustion. Experimental results show that wavelet transformation of engine block vibration can track the start of combustion in each cycle. From this newly developed method, the start of combustion data in CAI engines can be detected more easily and used as input data for controlling CAI combustion

  13. Signal Control for Reducing Vehicle NOx and CO2 Emissions Based on Prediction of Arrival Traffic Flows at Intersections

    Science.gov (United States)

    Oda, Toshihiko

    Nitrogen oxide (NOx) and carbon dioxide (CO2) emissions from vehicles have been increasing every year because of the growing number of vehicles, and they cause serious environmental problems such as air pollution and global warming. To alleviate these problems, this paper proposes a new traffic signal control method for reducing vehicle NOx and CO2 emissions on arterial roads. To this end, we first model the amount of vehicle emissions as a function of the traffic delay and the number of stops at intersections. This step is necessary because it is difficult to obtain the amount of emissions directly using traffic control systems. Second, we introduce a signal control model in which the control parameters are continuously updated on the basis of predictions of arrival traffic flows at intersections. The signal timings are calculated in such a manner so as to minimize the weighted sum of the two emissions, which depend on the traffic flow. To evaluate the validity of this method, simulation experiments are carried out on an arterial road. The experiments show that the proposed method significantly outperforms existing methods in reducing both the emissions and travel time.

  14. Detection of combustion start in the controlled auto ignition engine by wavelet transform of the engine block vibration signal

    Science.gov (United States)

    Kim, Seonguk; Min, Kyoungdoug

    2008-08-01

    The CAI (controlled auto ignition) engine ignites fuel and air mixture by trapping high temperature burnt gas using a negative valve overlap. Due to auto ignition in CAI combustion, efficiency improvements and low level NOx emission can be obtained. Meanwhile, the CAI combustion regime is restricted and control parameters are limited. The start of combustion data in the compressed ignition engine are most critical for controlling the overall combustion. In this research, the engine block vibration signal is transformed by the Meyer wavelet to analyze CAI combustion more easily and accurately. Signal acquisition of the engine block vibration is a more suitable method for practical use than measurement of in-cylinder pressure. A new method for detecting combustion start in CAI engines through wavelet transformation of the engine block vibration signal was developed and results indicate that it is accurate enough to analyze the start of combustion. Experimental results show that wavelet transformation of engine block vibration can track the start of combustion in each cycle. From this newly developed method, the start of combustion data in CAI engines can be detected more easily and used as input data for controlling CAI combustion.

  15. Adaptive synchronization of fractional Lorenz systems using a reduced number of control signals and parameters

    International Nuclear Information System (INIS)

    Aguila-Camacho, Norelys; Duarte-Mermoud, Manuel A.; Delgado-Aguilera, Efredy

    2016-01-01

    This paper analyzes the synchronization of two fractional Lorenz systems in two cases: the first one considering fractional Lorenz systems with unknown parameters, and the second one considering known upper bounds on some of the fractional Lorenz systems parameters. The proposed control strategies use a reduced number of control signals and control parameters, employing mild assumptions. The stability of the synchronization errors is analytically demonstrated in all cases, and the convergence to zero of the synchronization errors is analytically proved in the case when the upper bounds on some system parameters are assumed to be known. Simulation studies are presented, which allows verifying the effectiveness of the proposed control strategies.

  16. Coordinated Primary and Secondary Control with Frequency-Bus-Signaling for Distributed Generation and Storage in Islanded Microgrids

    DEFF Research Database (Denmark)

    Wu, Dan; Tang, Fen; Dragicevic, Tomislav

    2013-01-01

    In this paper, a distributed coordinated control scheme based on frequency-bus-signaling (FBS) method for a low-voltage AC three phase microgrid is proposed. The control scheme is composed by two levels. Firstly a primary local control which is different for the DGs and the ESS is proposed. The ESS...... control is implemented to restore the frequency deviation produced by the primary ESS controller while preserving the coordinated control performance. Real-time simulation results show the feasibility of the proposed approach by showing the operation of the microgrid in different scenarios....

  17. Star-PAP Control of BIK Expression and Apoptosis Is Regulated by Nuclear PIPKIα and PKCδ Signaling

    Science.gov (United States)

    Li, Weimin; Laishram, Rakesh S.; Ji, Zhe; Barlow, Christy A.; Tian, Bin; Anderson, Richard A.

    2012-01-01

    SUMMARY BIK protein is an initiator of mitochondrial apoptosis and BIK expression is induced by pro-apoptotic signals including DNA damage. Here we demonstrate that 3′-end processing and expression of BIK mRNA are controlled by the nuclear PI4,5P2-regulated poly(A) polymerase Star-PAP downstream of DNA damage. Nuclear PKCδ is a key mediator of apoptosis and DNA damage stimulates PKCδ association with the Star-PAP complex where PKCδ is required for Star-PAP-dependent BIK expression. PKCδ binds the PI4,5P2-generating enzyme PIPKIα, which is essential for PKCδ interaction with the Star-PAP complex and PKCδ activity is directly stimulated by PI4,5P2. Features in the BIK 3′-UTR uniquely define Star-PAP specificity and may block canonical PAP activity toward BIK mRNA. This reveals a nuclear phosphoinositide signaling nexus where PIPKIα, PI4,5P2 and PKCδ regulate Star-PAP control of BIK expression and induction of apoptosis. This pathway is distinct from the Star-PAP-mediated oxidative stress pathway indicating signal-specific regulation of mRNA 3′-end processing. PMID:22244330

  18. Signal detection

    International Nuclear Information System (INIS)

    Tholomier, M.

    1985-01-01

    In a scanning electron microscope, whatever is the measured signal, the same set is found: incident beam, sample, signal detection, signal amplification. The resulting signal is used to control the spot luminosity with the observer cathodoscope. This is synchronized with the beam scanning on the sample; on the cathodoscope, the image in secondary electrons, backscattered electrons,... of the sample surface is reconstituted. The best compromise must be found between a register time low enough to remove eventual variations (under the incident beam) of the nature of the observed phenomenon, and a good spatial resolution of the image and a signal-to-noise ratio high enough. The noise is one of the basic limitations of the scanning electron microscope performance. The whose measurement line must be optimized to reduce it [fr

  19. The role of CD40L, IL-10 and IL-17 in radioprotection

    International Nuclear Information System (INIS)

    Li Ting

    2003-01-01

    CD40L/CD40 interaction is central to the control of thymus-dependent humoral immunity and cell mediated immune responses. IL-17 has been shown to induce the production of IL-6 and G-CSF, which can induce proliferation and differentiation of CD34 + hematopoietic progenitors. IL-10 can interfere with up-regulation of costimulatory molecules, thus suppressing the production of costimulatory cytokines, such as IL-12. IL-10 has been implicated as an essential mediator in the induction of systemic immune suppression following ultraviolet (UV) exposure. Treating UV-irradiated mice with anti-IL-10 blocks the induction of immune suppression

  20. Surface topography regulates wnt signaling through control of primary cilia structure in mesenchymal stem cells

    Science.gov (United States)

    McMurray, R. J.; Wann, A. K. T.; Thompson, C. L.; Connelly, J. T.; Knight, M. M.

    2013-01-01

    The primary cilium regulates cellular signalling including influencing wnt sensitivity by sequestering β-catenin within the ciliary compartment. Topographic regulation of intracellular actin-myosin tension can control stem cell fate of which wnt is an important mediator. We hypothesized that topography influences mesenchymal stem cell (MSC) wnt signaling through the regulation of primary cilia structure and function. MSCs cultured on grooves expressed elongated primary cilia, through reduced actin organization. siRNA inhibition of anterograde intraflagellar transport (IFT88) reduced cilia length and increased active nuclear β-catenin. Conversely, increased primary cilia assembly in MSCs cultured on the grooves was associated with decreased levels of nuclear active β-catenin, axin-2 induction and proliferation, in response to wnt3a. This negative regulation, on grooved topography, was reversed by siRNA to IFT88. This indicates that subtle regulation of IFT and associated cilia structure, tunes the wnt response controlling stem cell differentiation. PMID:24346024

  1. Bovine lactoferrin counteracts Toll-like receptor mediated activation signals in antigen presenting cells.

    Directory of Open Access Journals (Sweden)

    Patrizia Puddu

    Full Text Available Lactoferrin (LF, a key element in mammalian immune system, plays pivotal roles in host defence against infection and excessive inflammation. Its protective effects range from direct antimicrobial activities against a large panel of microbes, including bacteria, viruses, fungi and parasites, to antinflammatory and anticancer activities. In this study, we show that monocyte-derived dendritic cells (MD-DCs generated in the presence of bovine LF (bLF fail to undergo activation by up-modulating CD83, co-stimulatory and major histocompatibility complex molecules, and cytokine/chemokine secretion. Moreover, these cells are weak activators of T cell proliferation and retain antigen uptake activity. Consistent with an impaired maturation, bLF-MD-DC primed T lymphocytes exhibit a functional unresponsiveness characterized by reduced expression of CD154 and impaired expression of IFN-γ and IL-2. The observed imunosuppressive effects correlate with an increased expression of molecules with negative regulatory functions (i.e. immunoglobulin-like transcript 3 and programmed death ligand 1, indoleamine 2,3-dioxygenase, and suppressor of cytokine signaling-3. Interestingly, bLF-MD-DCs produce IL-6 and exhibit constitutive signal transducer and activator of transcription 3 activation. Conversely, bLF exposure of already differentiated MD-DCs completely fails to induce IL-6, and partially inhibits Toll-like receptor (TLR agonist-induced activation. Cell-specific differences in bLF internalization likely account for the distinct response elicited by bLF in monocytes versus immature DCs, providing a mechanistic base for its multiple effects. These results indicate that bLF exerts a potent anti-inflammatory activity by skewing monocyte differentiation into DCs with impaired capacity to undergo activation and to promote Th1 responses. Overall, these bLF-mediated effects may represent a strategy to block excessive DC activation upon TLR-induced inflammation, adding

  2. Optogenetic control of chemokine receptor signal and T-cell migration

    Science.gov (United States)

    Xu, Yuexin; Hyun, Young-Min; Lim, Kihong; Lee, Hyunwook; Cummings, Ryan J.; Gerber, Scott A.; Bae, Seyeon; Cho, Thomas Yoonsang; Lord, Edith M.; Kim, Minsoo

    2014-01-01

    Adoptive cell transfer of ex vivo-generated immune-promoting or tolerogenic T cells to either enhance immunity or promote tolerance in patients has been used with some success. However, effective trafficking of the transferred cells to the target tissue sites is the main barrier to achieving successful clinical outcomes. Here we developed a strategy for optically controlling T-cell trafficking using a photoactivatable (PA) chemokine receptor. Photoactivatable-chemokine C-X-C motif receptor 4 (PA-CXCR4) transmitted intracellular CXCR4 signals in response to 505-nm light. Localized activation of PA-CXCR4 induced T-cell polarization and directional migration (phototaxis) both in vitro and in vivo. Directing light onto the melanoma was sufficient to recruit PA-CXCR4–expressing tumor-targeting cytotoxic T cells and improved the efficacy of adoptive T-cell transfer immunotherapy, with a significant reduction in tumor growth in mice. These findings suggest that the use of photoactivatable chemokine receptors allows remotely controlled leukocyte trafficking with outstanding spatial resolution in tissues and may be feasible in other cell transfer therapies. PMID:24733886

  3. Bang-bang control of feeding: role of hypothalamic and satiety signals.

    Directory of Open Access Journals (Sweden)

    B Silvano Zanutto

    2007-05-01

    Full Text Available Rats, people, and many other omnivores eat in meals rather than continuously. We show by experimental test that eating in meals is regulated by a simple bang-bang control system, an idea foreshadowed by Le Magnen and many others, shown by us to account for a wide range of behavioral data, but never explicitly tested or tied to neurophysiological facts. The hypothesis is simply that the tendency to eat rises with time at a rate determined by satiety signals. When these signals fall below a set point, eating begins, in on-off fashion. The delayed sequelae of eating increment the satiety signals, which eventually turn eating off. Thus, under free conditions, the organism eats in bouts separated by noneating activities. We report an experiment with rats to test novel predictions about meal patterns that are not explained by existing homeostatic approaches. Access to food was systematically but unpredictably interrupted just as the animal tried to start a new meal. A simple bang-bang model fits the resulting meal-pattern data well, and its elements can be identified with neurophysiological processes. Hypothalamic inputs can provide the set point for longer-term regulation carried out by a comparator in the hindbrain. Delayed gustatory and gastrointestinal aftereffects of eating act via the nucleus of the solitary tract and other hindbrain regions as neural feedback governing short-term regulation. In this way, the model forges real links between a functioning feedback mechanism, neuro-hormonal data, and both short-term (meals and long-term (eating-rate regulation behavioral data.

  4. ICOS gene polymorphisms are associated with sporadic breast cancer: a case-control study

    International Nuclear Information System (INIS)

    Xu, Fengyan; Li, Dalin; Zhang, Qiujin; Fu, Zhenkun; Zhang, Jie; Yuan, Weiguang; Chen, Shuang; Pang, Da; Li, Dianjun

    2011-01-01

    Inducible costimulator (ICOS), a costimulatory molecular of the CD28 family, provides positive signal to enhance T cell proliferation. Its abnormal expression can disturb the immune response and entail an increased risk of cancer. To investigate whether single nucleotide polymorphisms (SNPs) in the ICOS gene are associated with sporadic breast cancer susceptibility and progression in Chinese women, a case-control study was conducted. In the study cohort, we genotyped five SNPs (rs11889031, rs10932029, rs4675374, rs10183087 and rs10932037) in ICOS gene among 609 breast cancer patients and 665 age-matched healthy controls. Furthermore, the positive results were replicated in an independent validation cohort of 619 patients and 682 age-matched healthy controls. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to determine the genotypes. In rs10932029, compared with TT genotype and T allele, the CT genotype and C allele showed a significantly increased risk of breast cancer (P = 0.030, OR = 1.467, 95% CI 1.037-2.077; P = 0.017, OR = 1.481, 95% CI 1.070-2.049, respectively), and the associations were also significant in the validation cohort (P = 0.002, OR = 1.693, 95% CI 1.211-2.357; P = 0.003, OR = 1.607, 95% CI 1.171-2.204, respectively). Haplotype analysis showed that CTCAC haplotype containing rs10932029 T allele had a lower frequency in cases than in controls (P = 0.015), whereas haplotype CCCAC containing rs10932029 C allele was more common in cases than in controls (P = 0.013). In the analysis of clinicopathologic features, rs11889031 CT genotype and T allele were associated with progesterone receptor (PR) status and lymph node metastasis, which were further supported by our validation cohort. Moreover, some haplotypes were associated with estrogen receptor (ER) and PR statuses. These results indicate that ICOS gene polymorphisms may affect the risk of breast cancer and show that some SNPs are associated with breast cancer

  5. Antioxidant and signal modulation properties of plant polyphenols in controlling vascular inflammation.

    Science.gov (United States)

    Kostyuk, Vladimir A; Potapovich, Alla I; Suhan, Tatyana O; de Luca, Chiara; Korkina, Liudmila G

    2011-05-11

    Oxidized low-density lipoproteins (oxLDL) play a critical role in the initiation of atherosclerosis through activation of inflammatory signaling. In the present work we investigated the role of antioxidant and signal modulation properties of plant polyphenols in controlling vascular inflammation. Significant decrease in intracellular NO level and superoxide overproduction was found in human umbilical vein endothelial cells (HUVEC) treated with oxLDL, but not with LDL. The redox imbalance was prevented by the addition of quercetin or resveratrol. Expression analysis of 14 genes associated with oxidative stress and inflammation revealed oxLDL-mediated up-regulation of genes specifically involved in leukocyte recruitment and adhesion. This up-regulation could be partially avoided by the addition of verbascoside or resveratrol, while treatment with quercetin resulted in a further increase in the expression of these genes. Lipopolysaccharide (LPS)-treated HUVEC were also used for the evaluation of anti-inflammatory potency of plant polyphenols. Significant differences between HUVEC treaded with oxLDL and LPS were found in both the expression pattern of inflammation-related genes and the effects of plant polyphenols on cellular responses. The present data indicate that plant polyphenols may affect vascular inflammation not only as antioxidants but also as modulators of inflammatory redox signaling pathways. Crown Copyright © 2011. Published by Elsevier B.V. All rights reserved.

  6. Bootstrap Signal-to-Noise Confidence Intervals: An Objective Method for Subject Exclusion and Quality Control in ERP Studies

    Science.gov (United States)

    Parks, Nathan A.; Gannon, Matthew A.; Long, Stephanie M.; Young, Madeleine E.

    2016-01-01

    Analysis of event-related potential (ERP) data includes several steps to ensure that ERPs meet an appropriate level of signal quality. One such step, subject exclusion, rejects subject data if ERP waveforms fail to meet an appropriate level of signal quality. Subject exclusion is an important quality control step in the ERP analysis pipeline as it ensures that statistical inference is based only upon those subjects exhibiting clear evoked brain responses. This critical quality control step is most often performed simply through visual inspection of subject-level ERPs by investigators. Such an approach is qualitative, subjective, and susceptible to investigator bias, as there are no standards as to what constitutes an ERP of sufficient signal quality. Here, we describe a standardized and objective method for quantifying waveform quality in individual subjects and establishing criteria for subject exclusion. The approach uses bootstrap resampling of ERP waveforms (from a pool of all available trials) to compute a signal-to-noise ratio confidence interval (SNR-CI) for individual subject waveforms. The lower bound of this SNR-CI (SNRLB) yields an effective and objective measure of signal quality as it ensures that ERP waveforms statistically exceed a desired signal-to-noise criterion. SNRLB provides a quantifiable metric of individual subject ERP quality and eliminates the need for subjective evaluation of waveform quality by the investigator. We detail the SNR-CI methodology, establish the efficacy of employing this approach with Monte Carlo simulations, and demonstrate its utility in practice when applied to ERP datasets. PMID:26903849

  7. Long-range gap junctional signaling controls oncogene-mediated tumorigenesis in Xenopus laevis embryos

    Directory of Open Access Journals (Sweden)

    Brook T Chernet

    2015-01-01

    Full Text Available In addition to the immediate microenvironment, long-range signaling may be an important component of cancer. Molecular-genetic analyses have implicated gap junctions – key mediators of cell-cell communication – in carcinogenesis. We recently showed that the resting voltage potential of distant cell groups is a key determinant of metastatic transformation and tumor induction. Here, we show in the Xenopus laevis model that gap junctional communication (GJC is a modulator of the long-range bioelectric signaling that regulates tumor formation. Genetic disruption of GJC taking place within tumors, within remote host tissues, or between the host and tumors – significantly lowers the incidence of tumors induced by KRAS mutations. The most pronounced suppression of tumor incidence was observed upon GJC disruption taking place farther away from oncogene-expressing cells, revealing a role for GJC in distant cells in the control of tumor growth. In contrast, enhanced GJC communication through the overexpression of wild-type connexin Cx26 increased tumor incidence. Our data confirm a role for GJC in tumorigenesis, and reveal that this effect is non-local. Based on these results and on published data on movement of ions through GJs, we present a quantitative model linking the GJC coupling and bioelectrical state of cells to the ability of oncogenes to initiate tumorigenesis. When integrated with data on endogenous bioelectric signaling during left-right patterning, the model predicts differential tumor incidence outcomes depending on the spatial configurations of gap junction paths relative to tumor location and major anatomical body axes. Testing these predictions, we found that the strongest influence of GJ modulation on tumor suppression by hyperpolarization occurred along the embryonic left-right axis. Together, these data reveal new, long-range aspects of cancer control by the host’s physiological parameters.

  8. Original article Impulsive antisociality and executive control problems: evidence from go/no-go and stop-signal tasks

    Directory of Open Access Journals (Sweden)

    Jarosław M. Michałowski

    2015-03-01

    Full Text Available Background People with impulsive-antisocial traits may engage in unplanned behaviors that reduce their efficiency and may even result in harm to self and others. The present study aimed to investigate the relationship between executive control functions and impulsive antisociality, as assessed with the Psychopathic Personality Inventory (PPI. Using go/no-go and stop-signal paradigms, we examined whether healthy participants with high impulsive-antisocial traits would show delayed response inhibition and error monitoring deficits when compared to those reporting low levels of impulsive antisociality. Participants and procedure A total of 26 participants were recruited from different Warsaw universities based on the Impulsive Antisociality subscale scores of the PPI. Subjects scoring in the first quartile were assigned to the low and those with a score in the fourth quartile were selected for the high impulsivity group. All participants were tested with go/no-go and stop-signal tasks that were executed in a random order. Results Higher levels of impulsive-antisocial traits were associated with poorer executive control. In particular, high impulsive-antisocial individuals demonstrated reduced post-error slowing in response to go stimuli following an error and took longer to respond to the stop signal than the control group. The two groups did not differ in their performance accuracy. Conclusions The study extends previous findings regarding the relationship between impulsivity and executive control showing that non-clinical impulsive antisociality results in decreased conflict detection ability and delayed response inhibition. These problems may result in reduced executive effectiveness in everyday life situations.

  9. Real-time measurement and control at JET signal processing and physics analysis for diagnostics

    International Nuclear Information System (INIS)

    Felton, R.; Joffrin, E.; Murari, A.

    2005-01-01

    To meet the requirements of the scientific programme, the EFDA JET real-time measurement and control project has developed an integrated set of real-time plasma measurements, experiment control and communication facilities. Traditional experiments collected instrument data during the plasma pulse and calculated physics data after the pulse. The challenge for continuous tokamak operation is to calculate the physics data in real-time, keeping up with the evolution of the plasma. In JET, many plasma diagnostics have been augmented with extra data acquisition and signal-processing systems so that they can both capture instrument data for conventional post-pulse analysis and calculate calibrated, validated physics results in real-time. During the pulse, the systems send sampled data sets into a network, which distributes the data to several destinations. The receiving systems may do further analysis, integrating data from several measurements, or may control the plasma scenario by heating or fuelling. The simplest real-time diagnostic systems apply scale factors to the signals, as with the electron cyclotron emission (ECE) diagnostic's 96 tuned radiometer channels, giving the electron temperature profile. In various spectroscopy diagnostics, spectral features are least-squares-fitted to measure spectra from several lines of sight, within 50 ms. Ion temperatures and rotation speed can be calculated from the line widths and shifts. For diagnostics using modulation techniques, the systems implement digital-signal processing phase trackers, lock-in amplifiers and filters, e.g., the far infrared (FIR) interferometer samples 15 channels at 400 kHz for 30 s, i.e., six million samples per second. Diagnostics have specific lines of sight, spatial channels, and various sampling rates. The heating/fuelling systems have relatively coarse spatial localisation. Analysis systems have been developed to integrate the basic physics data into smaller sets of controllable parameters on a

  10. NADPH Oxidase 1 Modulates WNT and NOTCH1 Signaling To Control the Fate of Proliferative Progenitor Cells in the Colon▿

    Science.gov (United States)

    Coant, Nicolas; Ben Mkaddem, Sanae; Pedruzzi, Eric; Guichard, Cécile; Tréton, Xavier; Ducroc, Robert; Freund, Jean-Noel; Cazals-Hatem, Dominique; Bouhnik, Yoram; Woerther, Paul-Louis; Skurnik, David; Grodet, Alain; Fay, Michèle; Biard, Denis; Lesuffleur, Thécla; Deffert, Christine; Moreau, Richard; Groyer, André; Krause, Karl-Heinz; Daniel, Fanny; Ogier-Denis, Eric

    2010-01-01

    The homeostatic self-renewal of the colonic epithelium requires coordinated regulation of the canonical Wnt/β-catenin and Notch signaling pathways to control proliferation and lineage commitment of multipotent stem cells. However, the molecular mechanisms by which the Wnt/β-catenin and Notch1 pathways interplay in controlling cell proliferation and fate in the colon are poorly understood. Here we show that NADPH oxidase 1 (NOX1), a reactive oxygen species (ROS)-producing oxidase that is highly expressed in colonic epithelial cells, is a pivotal determinant of cell proliferation and fate that integrates Wnt/β-catenin and Notch1 signals. NOX1-deficient mice reveal a massive conversion of progenitor cells into postmitotic goblet cells at the cost of colonocytes due to the concerted repression of phosphatidylinositol 3-kinase (PI3K)/AKT/Wnt/β-catenin and Notch1 signaling. This conversion correlates with the following: (i) the redox-dependent activation of the dual phosphatase PTEN, causing the inactivation of the Wnt pathway effector β-catenin, and (ii) the downregulation of Notch1 signaling that provokes derepression of mouse atonal homolog 1 (Math1) expression. We conclude that NOX1 controls the balance between goblet and absorptive cell types in the colon by coordinately modulating PI3K/AKT/Wnt/β-catenin and Notch1 signaling. This finding provides the molecular basis for the role of NOX1 in cell proliferation and postmitotic differentiation. PMID:20351171

  11. Using a digital signal processor as a data stream controller for digital subtraction angiography

    International Nuclear Information System (INIS)

    Meng, J.D.; Katz, J.E.

    1991-10-01

    High speed, flexibility, and good arithmetic abilities make digital signal processors (DSP) a good choice as input/output controllers for real time applications. The DSP can be made to pre-process data in real time to reduce data volume, to open early windows on what is being acquired and to implement local servo loops. We present an example of a DSP as an input/output controller for a digital subtraction angiographic imaging system. The DSP pre-processes the raw data, reducing data volume by a factor of two, and is potentially capable of producing real-time subtracted images for immediate display

  12. Control rod position control device

    International Nuclear Information System (INIS)

    Ubukata, Shinji.

    1997-01-01

    The present invention provides a control rod position control device which stores data such as of position signals and driving control rod instruction before and after occurrence of abnormality in control for the control rod position for controlling reactor power and utilized the data effectively for investigating the cause of abnormality. Namely, a plurality of individual control devices have an operation mismatching detection circuit for outputting signals when difference is caused between a driving instruction given to the control rod position control device and the control rod driving means and signals from a detection means for detecting an actual moving amount. A general control device collectively controls the individual control devices. In addition, there is also disposed a position storing circuit for storing position signals at least before and after the occurrence of the control rod operation mismatching. With such procedures, the cause of the abnormality can be determined based on the position signals before and after the occurrence of control rod mismatching operation stored in the position storing circuit. Accordingly, the abnormality cause can be determined to conduct restoration in an early stage. (I.S.)

  13. COUP-TFII controls mouse pancreatic β-cell mass through GLP-1-β-catenin signaling pathways.

    Directory of Open Access Journals (Sweden)

    Marie Boutant

    Full Text Available The control of the functional pancreatic β-cell mass serves the key homeostatic function of releasing the right amount of insulin to keep blood sugar in the normal range. It is not fully understood though how β-cell mass is determined.Conditional chicken ovalbumin upstream promoter transcription factor II (COUP-TFII-deficient mice were generated and crossed with mice expressing Cre under the control of pancreatic duodenal homeobox 1 (pdx1 gene promoter. Ablation of COUP-TFII in pancreas resulted in glucose intolerance. Beta-cell number was reduced at 1 day and 3 weeks postnatal. Together with a reduced number of insulin-containing cells in the ductal epithelium and normal β-cell proliferation and apoptosis, this suggests decreased β-cell differentiation in the neonatal period. By testing islets isolated from these mice and cultured β-cells with loss and gain of COUP-TFII function, we found that COUP-TFII induces the expression of the β-catenin gene and its target genes such as cyclin D1 and axin 2. Moreover, induction of these genes by glucagon-like peptide 1 (GLP-1 via β-catenin was impaired in absence of COUP-TFII. The expression of two other target genes of GLP-1 signaling, GLP-1R and PDX-1 was significantly lower in mutant islets compared to control islets, possibly contributing to reduced β-cell mass. Finally, we demonstrated that COUP-TFII expression was activated by the Wnt signaling-associated transcription factor TCF7L2 (T-cell factor 7-like 2 in human islets and rat β-cells providing a feedback loop.Our findings show that COUP-TFII is a novel component of the GLP-1 signaling cascade that increases β-cell number during the neonatal period. COUP-TFII is required for GLP-1 activation of the β-catenin-dependent pathway and its expression is under the control of TCF7L2.

  14. Traffic Congestion Evaluation and Signal Control Optimization Based on Wireless Sensor Networks: Model and Algorithms

    Directory of Open Access Journals (Sweden)

    Wei Zhang

    2012-01-01

    Full Text Available This paper presents the model and algorithms for traffic flow data monitoring and optimal traffic light control based on wireless sensor networks. Given the scenario that sensor nodes are sparsely deployed along the segments between signalized intersections, an analytical model is built using continuum traffic equation and develops the method to estimate traffic parameter with the scattered sensor data. Based on the traffic data and principle of traffic congestion formation, we introduce the congestion factor which can be used to evaluate the real-time traffic congestion status along the segment and to predict the subcritical state of traffic jams. The result is expected to support the timing phase optimization of traffic light control for the purpose of avoiding traffic congestion before its formation. We simulate the traffic monitoring based on the Mobile Century dataset and analyze the performance of traffic light control on VISSIM platform when congestion factor is introduced into the signal timing optimization model. The simulation result shows that this method can improve the spatial-temporal resolution of traffic data monitoring and evaluate traffic congestion status with high precision. It is helpful to remarkably alleviate urban traffic congestion and decrease the average traffic delays and maximum queue length.

  15. High signal-to-noise ratio sensing with Shack–Hartmann wavefront sensor based on auto gain control of electron multiplying CCD

    International Nuclear Information System (INIS)

    Zhu Zhao-Yi; Li Da-Yu; Hu Li-Fa; Mu Quan-Quan; Yang Cheng-Liang; Cao Zhao-Liang; Xuan Li

    2016-01-01

    High signal-to-noise ratio can be achieved with the electron multiplying charge-coupled-device (EMCCD) applied in the Shack–Hartmann wavefront sensor (S–H WFS) in adaptive optics (AO). However, when the brightness of the target changes in a large scale, the fixed electron multiplying (EM) gain will not be suited to the sensing limitation. Therefore an auto-gain-control method based on the brightness of light-spots array in S–H WFS is proposed in this paper. The control value is the average of the maximum signals of every light spot in an array, which has been demonstrated to be kept stable even under the influence of some noise and turbulence, and sensitive enough to the change of target brightness. A goal value is needed in the control process and it is predetermined based on the characters of EMCCD. Simulations and experiments have demonstrated that this auto-gain-control method is valid and robust, the sensing SNR reaches the maximum for the corresponding signal level, and especially is greatly improved for those dim targets from 6 to 4 magnitude in the visual band. (special topic)

  16. Unified Digital Periodic Signal Filters for Power Converter Systems

    DEFF Research Database (Denmark)

    Yang, Yongheng; Xin, Zhen; Zhou, Keliang

    2017-01-01

    Periodic signal controllers like repetitive and resonant controllers have demonstrated much potential in the control of power electronic converters, where periodic signals (e.g., ac voltages and currents) can be precisely regulated to follow references. Beyond the control of periodic signals, ac...... signal processing (e.g., in synchronization and pre-filtering) is also very important for power converter systems. Hence, this paper serves to unify digital periodic signal filters so as to maximize their roles in power converter systems (e.g., enhance the control of ac signals). The unified digital...... periodic signal filters behave like a comb filter, but it can also be configured to selectively filter out the harmonics of interest (e.g., the odd-order harmonics in single-phase power converter systems). Moreover, a virtual variable-sampling-frequency unit delay that enables frequency adaptive periodic...

  17. SignalGuru: Leveraging mobile phones for collaborative traffic signal schedule advisory

    OpenAIRE

    Koukoumidis, Emmanouil; Peh, Li-Shiuan; Martonosi, Margaret

    2011-01-01

    While traffic signals are necessary to safely control competing flows of traffic, they inevitably enforce a stop-and-go movement pattern that increases fuel consumption, reduces traffic flow and causes traffic jams. These side effects can be alleviated by providing drivers and their onboard computational devices (e.g., vehicle computer, smartphone) with information about the schedule of the traffic signals ahead. Based on when the signal ahead will turn green, drivers can then adjust speed so...

  18. Romantic love is associated with enhanced inhibitory control in an emotional stop-signal task

    Directory of Open Access Journals (Sweden)

    Sensen Song

    2016-10-01

    Full Text Available Purpose: This study explored whether romantic lovers differ in emotion-related inhibitory control capacity from those who are single. Methods: 88 healthy undergraduate college students participated in the study. Half were currently in love and in a romantic relationship (love group, LG, and half were single and had never been in a romantic relationship (single group, SG. Based on duration of romantic relationship (i.e., love duration, the LG were further divided into two subgroups: early stage love and longer periods of love. All participants completed an emotional Stop Signal Task (eSST, which consisted of a variety of human face stimuli representing sadness (a negative emotion, as well as neutral emotions. Results: Results found that relative to SG, lovers showed greater inhibitory control [shorter stop-signal reaction time (SSRT] during negative emotion condition trials. Furthermore, in early stages of love, SSRT for negative emotion condition trials was significantly shorter compared to that in longer periods of love or SG individuals, with no significant differences between the latter two groups. Conclusions: Compared with individuals who were single, early-stage lovers showed greater capacity for inhibiting action during presentation of negative emotional stimuli. Within a greater social context, greater inhibitory control capacity during early stages of love may be related to the successful formation of romantic relationships, particularly to the ability to persevere in goal-directed action despite negative emotional contexts such as that of sadness.

  19. Romantic Love Is Associated with Enhanced Inhibitory Control in an Emotional Stop-Signal Task

    Science.gov (United States)

    Song, Sensen; Zou, Zhiling; Song, Hongwen; Wang, Yongming; d’Oleire Uquillas, Federico; Wang, Huijun; Chen, Hong

    2016-01-01

    Purpose: This study explored whether romantic lovers differ in emotion-related inhibitory control capacity from those who are single. Methods: 88 healthy undergraduate college students participated in the study. Half were currently in love and in a romantic relationship (love group, LG), and half were single and had never been in a romantic relationship (single group, SG). Based on duration of romantic relationship (i.e., love duration), the LG were further divided into two subgroups: “early stage love” and “longer periods of love”. All participants completed an emotional Stop Signal Task, consisting of a variety of human face stimuli displaying either sad or neutral affect. Results: Results found that relative to SG, lovers showed greater inhibitory control [shorter stop-signal reaction time (SSRT)] during negative emotion condition trials. Furthermore, in early stages of love, SSRT for negative emotion condition trials was significantly shorter compared to that in “longer periods of love” or SG individuals, with no significant differences between the two latter groups. Conclusion: Compared with individuals who were single, early stage lovers showed greater capacity for inhibiting action during presentation of negative emotional stimuli. Within a greater social context, greater inhibitory control capacity during early stages of love may be related to the successful formation of romantic relationships, particularly to the ability to persevere in goal-directed action despite negative emotional contexts such as that of sadness. PMID:27826260

  20. A PtdIns(4)P-driven electrostatic field controls cell membrane identity and signalling in plants.

    Science.gov (United States)

    Simon, Mathilde Laetitia Audrey; Platre, Matthieu Pierre; Marquès-Bueno, Maria Mar; Armengot, Laia; Stanislas, Thomas; Bayle, Vincent; Caillaud, Marie-Cécile; Jaillais, Yvon

    2016-06-20

    Many signalling proteins permanently or transiently localize to specific organelles. It is well established that certain lipids act as biochemical landmarks to specify compartment identity. However, they also influence membrane biophysical properties, which emerge as important features in specifying cellular territories. Such parameters include the membrane inner surface potential, which varies according to the lipid composition of each organelle. Here, we found that the plant plasma membrane (PM) and the cell plate of dividing cells have a unique electrostatic signature controlled by phosphatidylinositol-4-phosphate (PtdIns(4)P). Our results further reveal that, contrarily to other eukaryotes, PtdIns(4)P massively accumulates at the PM, establishing it as a critical hallmark of this membrane in plants. Membrane surface charges control the PM localization and function of the polar auxin transport regulator PINOID as well as proteins from the BRI1 KINASE INHIBITOR1 (BKI1)/MEMBRANE ASSOCIATED KINASE REGULATOR (MAKR) family, which are involved in brassinosteroid and receptor-like kinase signalling. We anticipate that this PtdIns(4)P-driven physical membrane property will control the localization and function of many proteins involved in development, reproduction, immunity and nutrition.

  1. Evidence implicating the Ras pathway in multiple CD28 costimulatory functions in CD4+ T cells.

    Directory of Open Access Journals (Sweden)

    Sujit V Janardhan

    Full Text Available CD28 costimulation is a critical event in the full activation of CD4(+ T cells that augments cytokine gene transcription, promotes cytokine mRNA stability, prevents induction of anergy, increases cellular metabolism, and increases cell survival. However, despite extensive biochemical analysis of the signaling events downstream of CD28, molecular pathways sufficient to functionally replace the diverse aspects of CD28-mediated costimulation in normal T cells have not been identified. Ras/MAPK signaling is a critical pathway downstream of T cell receptor stimulation, but its role in CD28-mediated costimulation has been controversial. We observed that physiologic CD28 costimulation caused a relocalization of the RasGEF RasGRP to the T cell-APC interface by confocal microscopy. In whole cell biochemical analysis, CD28 cross-linking with either anti-CD28 antibody or B7.1-Ig augmented TCR-induced Ras activation. To determine whether Ras signaling was sufficient to functionally mimic CD28 costimulation, we utilized an adenoviral vector encoding constitutively active H-Ras (61L to transduce normal, Coxsackie-Adenovirus Receptor (CAR transgenic CD4(+ T cells. Like costimulation via CD28, active Ras induced AKT, JNK and ERK phosphorylation. In addition, constitutive Ras signaling mimicked the ability of CD28 to costimulate IL-2 protein secretion, prevent anergy induction, increase glucose uptake, and promote cell survival. Importantly, we also found that active Ras mimicked the mechanism by which CD28 costimulates IL-2 production: by increasing IL-2 gene transcription, and promoting IL-2 mRNA stability. Finally, active Ras was able to induce IL-2 production when combined with ionomycin stimulation in a MEK-1-dependent fashion. Our results are consistent with a central role for Ras signaling in CD28-mediated costimulation.

  2. The Essential Role of Epstein-Barr Virus in the Pathogenesis of Multiple Sclerosis

    Science.gov (United States)

    Pender, Michael P.

    2011-01-01

    There is increasing evidence that infection with the Epstein-Barr virus (EBV) plays a role in the development of multiple sclerosis (MS), a chronic inflammatory demyelinating disease of the CNS. This article provides a four-tier hypothesis proposing (1) EBV infection is essential for the development of MS; (2) EBV causes MS in genetically susceptible individuals by infecting autoreactive B cells, which seed the CNS where they produce pathogenic autoantibodies and provide costimulatory survival signals to autoreactive T cells that would otherwise die in the CNS by apoptosis; (3) the susceptibility to develop MS after EBV infection is dependent on a genetically determined quantitative deficiency of the cytotoxic CD8+ T cells that normally keep EBV infection under tight control; and (4) sunlight and vitamin D protect against MS by increasing the number of CD8+ T cells available to control EBV infection. The hypothesis makes predictions that can be tested, including the prevention and successful treatment of MS by controlling EBV infection. PMID:21075971

  3. Functional Neuromuscular Stimulation Controlled by Surface Electromyographic Signals Produced by Volitional Activation of the Same Muscle

    DEFF Research Database (Denmark)

    Sennels, Søren; Biering-Sørensen, Fin; Andersen, Ole Trier

    1997-01-01

    In order to use the volitional electromyography (EMG) as a control signal for the stimulation of the same muscle, it is necessary to eliminate the stimulation artifacts and the muscle responses caused by the stimulation. The stimulation artifacts, caused by the electric field in skin and tissue...

  4. Probabilistic interpretation of command and control signals: Bayesian updating of the probability of nuclear attack

    International Nuclear Information System (INIS)

    Pate-Cornell, M.Elisabeth; Fischbeck, Paul S.

    1995-01-01

    A warning system such as the Command, Control, Communication, and Intelligence system (C 3 I) for the United States nuclear forces operates on the basis of various sources of information among which are signals from sensors. A fundamental problem in the use of such signals is that these sensors provide only imperfect information. Bayesian probability, defined as a degree of belief in the possibility of each event, is therefore a key concept in the logical treatment of the signals. However, the base of evidence for estimation of these probabilities may be small and, therefore, the results of the updating (posterior probabilities of attack) may also be uncertain. In this paper, we examine the case where uncertainties hinge upon the existence of several possible underlying hypotheses (or models), and where the decision-maker attributes a different probability of attack to each of these fundamental hypotheses. We present a two-stage Bayesian updating process, first of the probabilities of the fundamental hypotheses, then of the probabilities of attack conditional on each hypothesis, given a positive signal from the C 3 I. We illustrate the method in the discrete case where there are only two possible fundamental hypotheses, and in the case of a continuous set of hypotheses. We discuss briefly the implications of the results for decision-making. The method can be generalized to other warning systems with imperfect signals, when the prior probability of the event of interest is uncertain

  5. Identification of motion from multi-channel EMG signals for control of prosthetic hand

    International Nuclear Information System (INIS)

    Geethanjali, P.; Ray, K.K.

    2011-01-01

    Full text: The authors in this paper propose an effective and efficient pattern recognition technique from four channel electromyogram (EMG) signals for control of multifunction prosthetic hand. Time domain features such as mean absolute value, number of zero crossings, number of slope sign changes and waveform length are considered for pattern recognition. The patterns are classified using simple logistic regression (SLR) technique and decision tree (DT) using J48 algorithm. In this study six specific hand and wrist motions are identified from the EMG signals obtained from ten different able-bodied. By considering relevant dominant features for pattern recognition, the processing time as well as memory space of the SLR and DT classifiers is found to be less in comparison with neural network (NN), k-nearest neighbour model 1 (kNN Model-1), k-nearest neighbour model 2 (kNN-Model-2) and linear discriminant analysis. The classification accuracy of SLR classifier is found to be 91 ± 1.9%. (author)

  6. A computerized traffic control algorithm to determine optimal traffic signal settings. Ph.D. Thesis - Toledo Univ.

    Science.gov (United States)

    Seldner, K.

    1977-01-01

    An algorithm was developed to optimally control the traffic signals at each intersection using a discrete time traffic model applicable to heavy or peak traffic. Off line optimization procedures were applied to compute the cycle splits required to minimize the lengths of the vehicle queues and delay at each intersection. The method was applied to an extensive traffic network in Toledo, Ohio. Results obtained with the derived optimal settings are compared with the control settings presently in use.

  7. Statistical process control: separating signal from noise in emergency department operations.

    Science.gov (United States)

    Pimentel, Laura; Barrueto, Fermin

    2015-05-01

    Statistical process control (SPC) is a visually appealing and statistically rigorous methodology very suitable to the analysis of emergency department (ED) operations. We demonstrate that the control chart is the primary tool of SPC; it is constructed by plotting data measuring the key quality indicators of operational processes in rationally ordered subgroups such as units of time. Control limits are calculated using formulas reflecting the variation in the data points from one another and from the mean. SPC allows managers to determine whether operational processes are controlled and predictable. We review why the moving range chart is most appropriate for use in the complex ED milieu, how to apply SPC to ED operations, and how to determine when performance improvement is needed. SPC is an excellent tool for operational analysis and quality improvement for these reasons: 1) control charts make large data sets intuitively coherent by integrating statistical and visual descriptions; 2) SPC provides analysis of process stability and capability rather than simple comparison with a benchmark; 3) SPC allows distinction between special cause variation (signal), indicating an unstable process requiring action, and common cause variation (noise), reflecting a stable process; and 4) SPC keeps the focus of quality improvement on process rather than individual performance. Because data have no meaning apart from their context, and every process generates information that can be used to improve it, we contend that SPC should be seriously considered for driving quality improvement in emergency medicine. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Thyroid hormone and adrenergic signaling interact to control pineal expression of the dopamine receptor D4 gene (Drd4)

    DEFF Research Database (Denmark)

    Kim, Jong-So; Bailey, Michael J; Weller, Joan L

    2009-01-01

    is circadian in nature and under photoneural control. Whereas most rhythmically expressed genes in the pineal are controlled by adrenergic/cAMP signaling, Drd4 expression also requires thyroid hormone. This advance raises the questions of whether Drd4 expression is regulated by this mechanism in other systems...

  9. A common control signal and a ballistic stage can explain the control of coordinated eye-hand movements.

    Science.gov (United States)

    Gopal, Atul; Murthy, Aditya

    2016-06-01

    Voluntary control has been extensively studied in the context of eye and hand movements made in isolation, yet little is known about the nature of control during eye-hand coordination. We probed this with a redirect task. Here subjects had to make reaching/pointing movements accompanied by coordinated eye movements but had to change their plans when the target occasionally changed its position during some trials. Using a race model framework, we found that separate effector-specific mechanisms may be recruited to control eye and hand movements when executed in isolation but when the same effectors are coordinated a unitary mechanism to control coordinated eye-hand movements is employed. Specifically, we found that performance curves were distinct for the eye and hand when these movements were executed in isolation but were comparable when they were executed together. Second, the time to switch motor plans, called the target step reaction time, was different in the eye-alone and hand-alone conditions but was similar in the coordinated condition under assumption of a ballistic stage of ∼40 ms, on average. Interestingly, the existence of this ballistic stage could predict the extent of eye-hand dissociations seen in individual subjects. Finally, when subjects were explicitly instructed to control specifically a single effector (eye or hand), redirecting one effector had a strong effect on the performance of the other effector. Taken together, these results suggest that a common control signal and a ballistic stage are recruited when coordinated eye-hand movement plans require alteration. Copyright © 2016 the American Physiological Society.

  10. Sprouty2 controls proliferation of palate mesenchymal cells via fibroblast growth factor signaling

    International Nuclear Information System (INIS)

    Matsumura, Kaori; Taketomi, Takaharu; Yoshizaki, Keigo; Arai, Shinsaku; Sanui, Terukazu; Yoshiga, Daigo; Yoshimura, Akihiko; Nakamura, Seiji

    2011-01-01

    Research highlights: → Sprouty2-deficient mice exhibit cleft palate as a result of failure of palatal shelf elevation. → We examined palate cell proliferation in Sprouty2-deficient mice. → Palate mesenchymal cell proliferation was increased in Sprouty2 KO mice. → Sprouty2 plays roles in murine palatogenesis by regulating cell proliferation. -- Abstract: Cleft palate is one of the most common craniofacial deformities. The fibroblast growth factor (FGF) plays a central role in reciprocal interactions between adjacent tissues during palatal development, and the FGF signaling pathway has been shown to be inhibited by members of the Sprouty protein family. In this study, we report the incidence of cleft palate, possibly caused by failure of palatal shelf elevation, in Sprouty2-deficient (KO) mice. Sprouty2-deficient palates fused completely in palatal organ culture. However, palate mesenchymal cell proliferation estimated by Ki-67 staining was increased in Sprouty2 KO mice compared with WT mice. Sprouty2-null palates expressed higher levels of FGF target genes, such as Msx1, Etv5, and Ptx1 than WT controls. Furthermore, proliferation and the extracellular signal-regulated kinase (Erk) activation in response to FGF was enhanced in palate mesenchymal cells transfected with Sprouty2 small interfering RNA. These results suggest that Sprouty2 regulates palate mesenchymal cell proliferation via FGF signaling and is involved in palatal shelf elevation.

  11. Sprouty2 controls proliferation of palate mesenchymal cells via fibroblast growth factor signaling

    Energy Technology Data Exchange (ETDEWEB)

    Matsumura, Kaori [Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Taketomi, Takaharu, E-mail: taketomi@dent.kyushu-u.ac.jp [Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Yoshizaki, Keigo [Section of Orthodontics, Division of Oral Health, Growth and Development, Faculty of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Arai, Shinsaku [Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Sanui, Terukazu [Section of Periodontology, Division of Oral Rehabilitation, Faculty of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Yoshiga, Daigo [Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Yoshimura, Akihiko [Department of Microbiology and Immunology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582 (Japan); Japan Science and Technology Agency (JST), CREST, Chiyoda-ku, Tokyo 102-0075 (Japan); Nakamura, Seiji [Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan)

    2011-01-28

    Research highlights: {yields} Sprouty2-deficient mice exhibit cleft palate as a result of failure of palatal shelf elevation. {yields} We examined palate cell proliferation in Sprouty2-deficient mice. {yields} Palate mesenchymal cell proliferation was increased in Sprouty2 KO mice. {yields} Sprouty2 plays roles in murine palatogenesis by regulating cell proliferation. -- Abstract: Cleft palate is one of the most common craniofacial deformities. The fibroblast growth factor (FGF) plays a central role in reciprocal interactions between adjacent tissues during palatal development, and the FGF signaling pathway has been shown to be inhibited by members of the Sprouty protein family. In this study, we report the incidence of cleft palate, possibly caused by failure of palatal shelf elevation, in Sprouty2-deficient (KO) mice. Sprouty2-deficient palates fused completely in palatal organ culture. However, palate mesenchymal cell proliferation estimated by Ki-67 staining was increased in Sprouty2 KO mice compared with WT mice. Sprouty2-null palates expressed higher levels of FGF target genes, such as Msx1, Etv5, and Ptx1 than WT controls. Furthermore, proliferation and the extracellular signal-regulated kinase (Erk) activation in response to FGF was enhanced in palate mesenchymal cells transfected with Sprouty2 small interfering RNA. These results suggest that Sprouty2 regulates palate mesenchymal cell proliferation via FGF signaling and is involved in palatal shelf elevation.

  12. Gfi1b controls integrin signaling-dependent cytoskeleton dynamics and organization in megakaryocytes.

    Science.gov (United States)

    Beauchemin, Hugues; Shooshtarizadeh, Peiman; Vadnais, Charles; Vassen, Lothar; Pastore, Yves D; Möröy, Tarik

    2017-03-01

    Mutations in GFI1B are associated with inherited bleeding disorders called GFI1B -related thrombocytopenias. We show here that mice with a megakaryocyte-specific Gfi1b deletion exhibit a macrothrombocytopenic phenotype along a megakaryocytic dysplasia reminiscent of GFI1B -related thrombocytopenia. GFI1B deficiency increases megakaryocyte proliferation and affects their ploidy, but also abrogates their responsiveness towards integrin signaling and their ability to spread and reorganize their cytoskeleton. Gfi1b -null megakaryocytes are also unable to form proplatelets, a process independent of integrin signaling. GFI1B-deficient megakaryocytes exhibit aberrant expression of several components of both the actin and microtubule cytoskeleton, with a dramatic reduction of α-tubulin. Inhibition of FAK or ROCK, both important for actin cytoskeleton organization and integrin signaling, only partially restored their response to integrin ligands, but the inhibition of PAK, a regulator of the actin cytoskeleton, completely rescued the responsiveness of Gfi1b -null megakaryocytes to ligands, but not their ability to form proplatelets. We conclude that Gfi1b controls major functions of megakaryocytes such as integrin-dependent cytoskeleton organization, spreading and migration through the regulation of PAK activity whereas the proplatelet formation defect in GFI1B-deficient megakaryocytes is due, at least partially, to an insufficient α-tubulin content. Copyright© Ferrata Storti Foundation.

  13. Model-based control of the temporal patterns of intracellular signaling in silico

    Science.gov (United States)

    Murakami, Yohei; Koyama, Masanori; Oba, Shigeyuki; Kuroda, Shinya; Ishii, Shin

    2017-01-01

    The functions of intracellular signal transduction systems are determined by the temporal behavior of intracellular molecules and their interactions. Of the many dynamical properties of the system, the relationship between the dynamics of upstream molecules and downstream molecules is particularly important. A useful tool in understanding this relationship is a methodology to control the dynamics of intracellular molecules with an extracellular stimulus. However, this is a difficult task because the relationship between the levels of upstream molecules and those of downstream molecules is often not only stochastic, but also time-inhomogeneous, nonlinear, and not one-to-one. In this paper, we present an easy-to-implement model-based control method that makes the target downstream molecule to trace a desired time course by changing the concentration of a controllable upstream molecule. Our method uses predictions from Monte Carlo simulations of the model to decide the strength of the stimulus, while using a particle-based approach to make inferences regarding unobservable states. We applied our method to in silico control problems of insulin-dependent AKT pathway model and EGF-dependent Akt pathway model with system noise. We show that our method can robustly control the dynamics of the intracellular molecules against unknown system noise of various strengths, even in the absence of complete knowledge of the true model of the target system. PMID:28275530

  14. Light-Triggered Soft Artificial Muscles: Molecular-Level Amplification of Actuation Control Signals.

    Science.gov (United States)

    Dicker, Michael P M; Baker, Anna B; Iredale, Robert J; Naficy, Sina; Bond, Ian P; Faul, Charl F J; Rossiter, Jonathan M; Spinks, Geoffrey M; Weaver, Paul M

    2017-08-23

    The principle of control signal amplification is found in all actuation systems, from engineered devices through to the operation of biological muscles. However, current engineering approaches require the use of hard and bulky external switches or valves, incompatible with both the properties of emerging soft artificial muscle technology and those of the bioinspired robotic systems they enable. To address this deficiency a biomimetic molecular-level approach is developed that employs light, with its excellent spatial and temporal control properties, to actuate soft, pH-responsive hydrogel artificial muscles. Although this actuation is triggered by light, it is largely powered by the resulting excitation and runaway chemical reaction of a light-sensitive acid autocatalytic solution in which the actuator is immersed. This process produces actuation strains of up to 45% and a three-fold chemical amplification of the controlling light-trigger, realising a new strategy for the creation of highly functional soft actuating systems.

  15. R-spondin1 Controls Muscle Cell Fusion through Dual Regulation of Antagonistic Wnt Signaling Pathways

    Directory of Open Access Journals (Sweden)

    Floriane Lacour

    2017-03-01

    Full Text Available Wnt-mediated signals are involved in many important steps in mammalian regeneration. In multiple cell types, the R-spondin (Rspo family of secreted proteins potently activates the canonical Wnt/β-catenin pathway. Here, we identify Rspo1 as a mediator of skeletal muscle tissue repair. First, we show that deletion of Rspo1 results in global alteration of muscle regeneration kinetics following acute injury. We find that muscle progenitor cells lacking Rspo1 show delayed differentiation due to reduced activation of Wnt/β-catenin target genes. Furthermore, muscle cells lacking Rspo1 have a fusion phenotype leading to larger myotubes containing supernumerary nuclei both in vitro and in vivo. The increase in muscle fusion was dependent on downregulation of Wnt/β-catenin and upregulation of non-canonical Wnt7a/Fzd7/Rac1 signaling. We conclude that reciprocal control of antagonistic Wnt signaling pathways by Rspo1 in muscle stem cell progeny is a key step ensuring normal tissue architecture restoration following acute damage.

  16. Interactive Teaching of Adaptive Signal Processing

    OpenAIRE

    Stewart, R W; Harteneck, M; Weiss, S

    2000-01-01

    Over the last 30 years adaptive digital signal processing has progressed from being a strictly graduate level advanced class in signal processing theory to a topic that is part of the core curriculum for many undergraduate signal processing classes. The key reason is the continued advance of communications technology, with its need for echo control and equalisation, and the widespread use of adaptive filters in audio, biomedical, and control applications. In this paper we will review the basi...

  17. Biomedical signals and systems

    CERN Document Server

    Tranquillo, Joseph V

    2013-01-01

    Biomedical Signals and Systems is meant to accompany a one-semester undergraduate signals and systems course. It may also serve as a quick-start for graduate students or faculty interested in how signals and systems techniques can be applied to living systems. The biological nature of the examples allows for systems thinking to be applied to electrical, mechanical, fluid, chemical, thermal and even optical systems. Each chapter focuses on a topic from classic signals and systems theory: System block diagrams, mathematical models, transforms, stability, feedback, system response, control, time

  18. Evaluation of Adaptive Signal Control Technology—Volume 2 : Comparison of Base Condition to the First Year After Implementation

    Science.gov (United States)

    2018-05-01

    Field evaluation of adaptive signal control technologies (ASCT) is very important in understanding the systems contribution to safety and operational efficiency. Data were collected at six intersections along the Neil Street corridor in Champaign,...

  19. Neural processing of auditory signals and modular neural control for sound tropism of walking machines

    DEFF Research Database (Denmark)

    Manoonpong, Poramate; Pasemann, Frank; Fischer, Joern

    2005-01-01

    and a neural preprocessing system together with a modular neural controller are used to generate a sound tropism of a four-legged walking machine. The neural preprocessing network is acting as a low-pass filter and it is followed by a network which discerns between signals coming from the left or the right....... The parameters of these networks are optimized by an evolutionary algorithm. In addition, a simple modular neural controller then generates the desired different walking patterns such that the machine walks straight, then turns towards a switched-on sound source, and then stops near to it....

  20. Wnt signaling in cancer

    Science.gov (United States)

    Zhan, T; Rindtorff, N; Boutros, M

    2017-01-01

    Wnt signaling is one of the key cascades regulating development and stemness, and has also been tightly associated with cancer. The role of Wnt signaling in carcinogenesis has most prominently been described for colorectal cancer, but aberrant Wnt signaling is observed in many more cancer entities. Here, we review current insights into novel components of Wnt pathways and describe their impact on cancer development. Furthermore, we highlight expanding functions of Wnt signaling for both solid and liquid tumors. We also describe current findings how Wnt signaling affects maintenance of cancer stem cells, metastasis and immune control. Finally, we provide an overview of current strategies to antagonize Wnt signaling in cancer and challenges that are associated with such approaches. PMID:27617575

  1. LIN28 phosphorylation by MAPK/ERK couples signaling to the post-transcriptional control of pluripotency

    Science.gov (United States)

    Tsanov, Kaloyan M.; Pearson, Daniel S.; Wu, Zhaoting; Han, Areum; Triboulet, Robinson; Seligson, Marc T.; Powers, John T.; Osborne, Jihan K.; Kane, Susan; Gygi, Steven P.; Gregory, Richard I.; Daley, George Q.

    2016-01-01

    Signaling and post-transcriptional gene control are both critical for the regulation of pluripotency1,2, yet how they are integrated to influence cell identity remains poorly understood. LIN28 (also known as LIN28A), a highly conserved RNA-binding protein (RBP), has emerged as a central post-transcriptional regulator of cell fate through blockade of let-7 microRNA (miRNA) biogenesis and direct modulation of mRNA translation3. Here we show that LIN28 is phosphorylated by MAPK/ERK in pluripotent stem cells (PSCs), which increases its levels via post-translational stabilization. LIN28 phosphorylation had little impact on let-7 but enhanced LIN28’s effect on its direct mRNA targets, revealing a mechanism that uncouples LIN28’s let-7-dependent and independent activities. We have linked this mechanism to the induction of pluripotency by somatic cell reprogramming and the transition from naïve to primed pluripotency. Collectively, our findings indicate that MAPK/ERK directly impacts LIN28, defining an axis that connects signaling, post-transcriptional gene control, and cell fate regulation. PMID:27992407

  2. Staphylococcal enterotoxin-A directly stimulates signal transduction and interferon-gamma production in psoriatic T-cell lines

    DEFF Research Database (Denmark)

    Nielsen, M B; Odum, N; Gerwien, J

    1998-01-01

    class II. Here we address the question of whether SEA can directly activate psoriatic T cells in the absence of professional antigen-presenting cells. We show that SEA induces i) tyrosine phosphorylation of several proteins, ii) downregulation of the T-cell receptor (TCR), and iii) production......-mediated proliferation. In contrast, SEA with a mutation in the MHC class II alpha-binding site induces IFN-gamma and a qualitatively changed tyrosine phosphorylation profile. Both mutations delete the co-stimulatory effect on cytokine-mediated proliferation. This suggests that both MHC class II binding sites...

  3. Exposure to lateral collision in signalized intersections with protected left turn under different traffic control strategies.

    Science.gov (United States)

    Midenet, Sophie; Saunier, Nicolas; Boillot, Florence

    2011-11-01

    This paper proposes an original definition of the exposure to lateral collision in signalized intersections and discusses the results of a real world experiment. This exposure is defined as the duration of situations where the stream that is given the right-of-way goes through the conflict zone while road users are waiting in the cross-traffic approach. This measure, obtained from video sensors, makes it possible to compare different operating conditions such as different traffic signal strategies. The data from a real world experiment is used, where the adaptive real-time strategy CRONOS (ContRol Of Networks by Optimization of Switchovers) and a time-plan strategy with vehicle-actuated ranges alternately controlled an isolated intersection near Paris. Hourly samples with similar traffic volumes are compared and the exposure to lateral collision is different in various areas of the intersection and various traffic conditions for the two strategies. The total exposure under peak hour traffic conditions drops by roughly 5 min/h with the CRONOS strategy compared to the time-plan strategy, which occurs mostly on entry streams. The results are analyzed through the decomposition of cycles in phase sequences and recommendations are made for traffic control strategies. Copyright © 2011 Elsevier Ltd. All rights reserved.

  4. Small-Signal Modeling, Analysis and Testing of Parallel Three-Phase-Inverters with A Novel Autonomous Current Sharing Controller

    DEFF Research Database (Denmark)

    Guan, Yajuan; Quintero, Juan Carlos Vasquez; Guerrero, Josep M.

    2015-01-01

    A novel simple and effective autonomous currentsharing controller for parallel three-phase inverters is employed in this paper. The novel controller is able to endow to the system high speed response and precision in contrast to the conventional droop control as it does not require calculating any...... active or reactive power, instead it uses a virtual impedance loop and a SFR phase-locked loop. The small-signal model of the system was developed for the autonomous operation of inverter-based microgrid with the proposed controller. The developed model shows large stability margin and fast transient...

  5. Fuzzy control of optical PPM CDMA with M-ary orthogonal signaling

    Science.gov (United States)

    Cui, K.; Leeson, M. S.; Hines, E. L.

    2008-06-01

    This paper introduces an incorporated spectral-amplitude coding (SAC) optical code-division multiple-access (OCDMA) scheme. One novel class of optical signature codes based on combinatorial designs is employed with M-ary pulse-position modulation (PPM) signaling to improve the system performance beyond the interference limit. A union upper bound on the bit error rate (BER) is derived and the performance characteristics are then discussed with a variety of system parameters. Furthermore, fuzzy logic (FL) control is proposed to provide tolerance of different degrees of reliability in multirate transmission and to achieve distinct service differentiation for multimedia applications. It is shown that the proposed system can effectively suppress noise effects and offer improved adaptation capabilities for multi-quality network requirements in comparison with systems without optimization.

  6. A Novel Method for Control Performance Assessment with Fractional Order Signal Processing and Its Application to Semiconductor Manufacturing

    Directory of Open Access Journals (Sweden)

    Kai Liu

    2018-06-01

    Full Text Available The significant task for control performance assessment (CPA is to review and evaluate the performance of the control system. The control system in the semiconductor industry exhibits a complex dynamic behavior, which is hard to analyze. This paper investigates the interesting crossover properties of Hurst exponent estimations and proposes a novel method for feature extraction of the nonlinear multi-input multi-output (MIMO systems. At first, coupled data from real industry are analyzed by multifractal detrended fluctuation analysis (MFDFA and the resultant multifractal spectrum is obtained. Secondly, the crossover points with spline fit in the scale-law curve are located and then employed to segment the entire scale-law curve into several different scaling regions, in which a single Hurst exponent can be estimated. Thirdly, to further ascertain the origin of the multifractality of control signals, the generalized Hurst exponents of the original series are compared with shuffled data. At last, non-Gaussian statistical properties, multifractal properties and Hurst exponents of the process control variables are derived and compared with different sets of tuning parameters. The results have shown that CPA of the MIMO system can be better employed with the help of fractional order signal processing (FOSP.

  7. Y2 receptor signalling in NPY neurons controls bone formation and fasting induced feeding but not spontaneous feeding.

    Science.gov (United States)

    Qi, Yue; Fu, Melissa; Herzog, Herbert

    2016-02-01

    Y2 receptors have been implicated in the development of obesity and are a potential target for obesity treatment due to their known role of inhibiting neuropeptide Y (NPY) induced feeding responses. However, the precise neuronal population on which Y2 receptors act to fulfil this role is less clear. Here we utilise a novel inducible, postnatal onset NPY neurons specific deletion model to investigate the functional consequences of loss of Y2 signalling in this population of neurons on feeding and energy homeostasis regulation. While the consequences of lack of Y2 signalling in NPY neurons are confirmed in terms of the uncoupling of suppression/increasing of NPY and pro-opiomelanocortin (POMC) mRNA expression in the arcuate nuclei (Arc), respectively, this lack of Y2 signalling surprisingly does not have any significant effect on spontaneous food intake. Fasting induced food intake, however, is strongly increased but only in the first 1h after re-feeding. Consequently no significant changes in body weight are being observed although body weight gain is increased in male mice after postnatal onset Y2 deletion. Importantly, another known function of central Y2 receptor signalling, the suppression of bone formation is conserved in this conditional model with whole body bone mineral content being decreased. Taken together this model confirms the critical role of Y2 signalling to control NPY and associated POMC expression in the Arc, but also highlights the possibility that others, non-NPY neuronal Y2 receptors, are also involved in controlling feeding and energy homeostasis regulation. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Agonistic anti-TIGIT treatment inhibits T cell responses in LDLr deficient mice without affecting atherosclerotic lesion development.

    Directory of Open Access Journals (Sweden)

    Amanda C Foks

    Full Text Available OBJECTIVE: Co-stimulatory and co-inhibitory molecules are mainly expressed on T cells and antigen presenting cells and strongly orchestrate adaptive immune responses. Whereas co-stimulatory molecules enhance immune responses, signaling via co-inhibitory molecules dampens the immune system, thereby showing great therapeutic potential to prevent cardiovascular diseases. Signaling via co-inhibitory T cell immunoglobulin and ITIM domain (TIGIT directly inhibits T cell activation and proliferation, and therefore represents a novel therapeutic candidate to specifically dampen pro-atherogenic T cell reactivity. In the present study, we used an agonistic anti-TIGIT antibody to determine the effect of excessive TIGIT-signaling on atherosclerosis. METHODS AND RESULTS: TIGIT was upregulated on CD4(+ T cells isolated from mice fed a Western-type diet in comparison with mice fed a chow diet. Agonistic anti-TIGIT suppressed T cell activation and proliferation both in vitro and in vivo. However, agonistic anti-TIGIT treatment of LDLr(-/- mice fed a Western-type diet for 4 or 8 weeks did not affect atherosclerotic lesion development in comparison with PBS and Armenian Hamster IgG treatment. Furthermore, elevated percentages of dendritic cells were observed in the blood and spleen of agonistic anti-TIGIT-treated mice. Additionally, these cells showed an increased activation status but decreased IL-10 production. CONCLUSIONS: Despite the inhibition of splenic T cell responses, agonistic anti-TIGIT treatment does not affect initial atherosclerosis development, possibly due to increased activity of dendritic cells.

  9. Randomized, controlled clinical trial evaluating the efficacy of pulsed signal therapy in dogs with osteoarthritis.

    Science.gov (United States)

    Sullivan, Meghan O; Gordon-Evans, Wanda J; Knap, Kim E; Evans, Richard B

    2013-04-01

    To evaluate the efficacy of pulsed signal therapy (PST) in reducing pain and increasing function in dogs with osteoarthritis (OA) using a randomized, blinded, controlled clinical trial. Randomized, controlled, blinded clinical trial. Adult dogs (n = 60) with moderate-to-severe clinical signs of OA. Dogs were randomized by age into 2 groups: dogs ≥ 9 years and dogs Goniometry and gait analysis were performed, and the Canine Brief Pain Inventory (CBPI) questionnaire was given to the owners to fill out without supervision. Outcome measures were repeated at the end of treatment (Day 11) and 6 weeks after beginning treatment (Day 42). The PST group performed significantly better than the control group as measured by the CBPI Severity and Interference scores (P Veterinary Surgeons.

  10. Functional Neuromuscular Stimulation Controlled by Surface Electromyographic Signals Produced by the Volitional Activation of the Same Muscle:

    DEFF Research Database (Denmark)

    Sennels, Søren; Fin, Biering-Sørensen; Andersen, Ole Trier

    1997-01-01

    Using the voluntary EMG as a control signal for the stimulation of the same muscle necessitates elimination of stimulus artifacts and the muscle response caused by the stimulation. The stimulus artifacts are easily eliminated by shutting down the amplifier during stimulation. The muscle response ...

  11. Control of single-phase islanded PV/battery minigrids based on power-line signaling

    DEFF Research Database (Denmark)

    Quintana, Pablo; Guerrero, Josep M.; Dragicevic, Tomislav

    2014-01-01

    should be utilized as efficiently as possible. This paper proposes a coordinated control strategy based on power-line signaling (PLS), instead of common communications, for a single-phase minigrid in which each unit can operate in different operation modes taking into account the resource limitation...... types of renewable energy sources (RES) and energy storage systems (ESS). Specifically, the recharging process of secondary battery, the most prominent ESS, should be done in a specific manner to preserve its life-time, microgrid line voltage must be kept within the bounds and the energy offered by RES...

  12. Synthesis of railway-signaling plans using reachability games

    DEFF Research Database (Denmark)

    Kasting, Patrick Frederik Soelmark; Hansen, Michael Reichhardt; Vester, Steen

    2016-01-01

    (the control system) controls signals and points and the universal player (the antagonistic environment) controls movement of trains. A winning strategy for the existential player provides a signaling plan that will safely guide trains through the network. The concepts from the railway network model......In this work, we show the feasibility of using functional programming (more specifically F#) in connection with gamebased methods for synthesis of correct-by-construction controllers (also called signaling plans) for railway networks. This is a massively resource-demanding application. A model...

  13. Mitofusin 2 as a driver that controls energy metabolism and insulin signaling.

    Science.gov (United States)

    Zorzano, Antonio; Hernández-Alvarez, María Isabel; Sebastián, David; Muñoz, Juan Pablo

    2015-04-20

    Mitochondrial dynamics is a complex process that impacts on mitochondrial biology. Recent evidence indicates that proteins participating in mitochondrial dynamics have additional cellular roles. Mitofusin 2 (Mfn2) is a potent modulator of mitochondrial metabolism with an impact on energy metabolism in muscle, liver, and hypothalamic neurons. In addition, Mfn2 is subjected to tight regulation. Hence, factors such as proinflammatory cytokines, lipid availability, or glucocorticoids block its expression, whereas exercise and increased energy expenditure promote its upregulation. Importantly, Mfn2 controls cell metabolism and insulin signaling by limiting reactive oxygen species production and by modulation of endoplasmic reticulum stress. In this connection, it is critical to understand precisely the molecular mechanisms involved in the global actions of Mfn2. Future directions should concentrate into the analysis of those mechanisms, and to fully demonstrate that Mfn2 represents a cellular hub that senses the metabolic and hormonal milieu and drives the control of metabolic homeostasis.

  14. Evaluating lane-by-lane gap-out based signal control for isolated intersection under stop-line, single and multiple advance detection systems

    Directory of Open Access Journals (Sweden)

    Chandan Keerthi Kancharla

    2016-12-01

    Full Text Available In isolated intersection’s actuated signal control, inductive loop detector layout plays a crucial role in providingthe vehicle information to the signal controller. Based on vehicle actuations at the detector, the green time is extended till a pre-defined threshold gap-out occurs. The Federal Highway Administration (FHWA proposed various guidelines for detec-tor layouts on low-speed and high-speed approaches. This paper proposes single and multiple advance detection schemes for low-speed traffic movements, that utilizes vehicle actuations from advance detectors located upstream of the stop-line, which are able to detect spill-back queues. The proposed detection schemes operate with actuated signal control based on lane-by-lane gap-out criteria. The performance of the proposed schemes is compared with FHWA’s stop-line and single advance detection schemes in the VISSIM simulation tool. Results have shown that the proposed single advance detection schemes showed improved performance in reducing travel time delay and average number of stops per vehicle under low volumes while the multiple advance detection scheme performed well under high volumes.

  15. E-Textile Embroidered Metamaterial Transmission Line for Signal Propagation Control

    Directory of Open Access Journals (Sweden)

    Bahareh Moradi

    2018-06-01

    Full Text Available In this paper, the utilization of common fabrics for the manufacturing of e-textile metamaterial transmission lines is investigated. In order to filter and control the signal propagation in the ultra-high frequency (UHF range along the e-textile, a conventional metamaterial transmission line was compared with embroidered metamaterial particles. The proposed design was based on a transmission line loaded with one or several split-ring resonators (SRR on a felt substrate. To explore the relations between physical parameters and filter performance characteristics, theoretical models based on transmission matrices’ description of the filter constituent components were proposed. Excellent agreement between theoretical prediction, electromagnetic simulations, and measurement were found. Experimental results showed stop-band levels higher than −30 dB for compact embroidered metamaterial e-textiles. The validated results confirmed embroidery as a useful technique to obtain customized electromagnetic properties, such as filtering, on wearable applications.

  16. E-Textile Embroidered Metamaterial Transmission Line for Signal Propagation Control.

    Science.gov (United States)

    Moradi, Bahareh; Fernández-García, Raul; Gil, Ignacio

    2018-06-05

    In this paper, the utilization of common fabrics for the manufacturing of e-textile metamaterial transmission lines is investigated. In order to filter and control the signal propagation in the ultra-high frequency (UHF) range along the e-textile, a conventional metamaterial transmission line was compared with embroidered metamaterial particles. The proposed design was based on a transmission line loaded with one or several split-ring resonators (SRR) on a felt substrate. To explore the relations between physical parameters and filter performance characteristics, theoretical models based on transmission matrices' description of the filter constituent components were proposed. Excellent agreement between theoretical prediction, electromagnetic simulations, and measurement were found. Experimental results showed stop-band levels higher than -30 dB for compact embroidered metamaterial e-textiles. The validated results confirmed embroidery as a useful technique to obtain customized electromagnetic properties, such as filtering, on wearable applications.

  17. A cascade of morphogenic signaling initiated by the meninges controls corpus callosum formation.

    Science.gov (United States)

    Choe, Youngshik; Siegenthaler, Julie A; Pleasure, Samuel J

    2012-02-23

    The corpus callosum is the most prominent commissural connection between the cortical hemispheres, and numerous neurodevelopmental disorders are associated with callosal agenesis. By using mice either with meningeal overgrowth or selective loss of meninges, we have identified a cascade of morphogenic signals initiated by the meninges that regulates corpus callosum development. The meninges produce BMP7, an inhibitor of callosal axon outgrowth. This activity is overcome by the induction of expression of Wnt3 by the callosal pathfinding neurons, which antagonize the inhibitory effects of BMP7. Wnt3 expression in the cingulate callosal pathfinding axons is developmentally regulated by another BMP family member, GDF5, which is produced by the adjacent Cajal-Retzius neurons and turns on before outgrowth of the callosal axons. The effects of GDF5 are in turn under the control of a soluble GDF5 inhibitor, Dan, made by the meninges. Thus, the meninges and medial neocortex use a cascade of signals to regulate corpus callosum development. Copyright © 2012 Elsevier Inc. All rights reserved.

  18. An equilibrium-point model of electromyographic patterns during single-joint movements based on experimentally reconstructed control signals.

    Science.gov (United States)

    Latash, M L; Goodman, S R

    1994-01-01

    The purpose of this work has been to develop a model of electromyographic (EMG) patterns during single-joint movements based on a version of the equilibrium-point hypothesis, a method for experimental reconstruction of the joint compliant characteristics, the dual-strategy hypothesis, and a kinematic model of movement trajectory. EMG patterns are considered emergent properties of hypothetical control patterns that are equally affected by the control signals and peripheral feedback reflecting actual movement trajectory. A computer model generated the EMG patterns based on simulated movement kinematics and hypothetical control signals derived from the reconstructed joint compliant characteristics. The model predictions have been compared to published recordings of movement kinematics and EMG patterns in a variety of movement conditions, including movements over different distances, at different speeds, against different-known inertial loads, and in conditions of possible unexpected decrease in the inertial load. Changes in task parameters within the model led to simulated EMG patterns qualitatively similar to the experimentally recorded EMG patterns. The model's predictive power compares it favourably to the existing models of the EMG patterns. Copyright © 1994. Published by Elsevier Ltd.

  19. Experiment and practice on signal processing

    International Nuclear Information System (INIS)

    2002-11-01

    The contents of this book contains basic practice of CEM Tool, discrete time signal and experiment and practice of system, experiment and practice of discrete time signal sampling, practice of frequency analysis, experiment of digital filter design, application of digital signal processing, project related voice, basic principle of signal processing, the technique of basic image signal processing, biology astronomy and Robot soccer with apply of image signal processing technique, control video signal and project related image. It also has an introduction of CEM Linker I. O in the end.

  20. Experiment and practice on signal processing

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2002-11-15

    The contents of this book contains basic practice of CEM Tool, discrete time signal and experiment and practice of system, experiment and practice of discrete time signal sampling, practice of frequency analysis, experiment of digital filter design, application of digital signal processing, project related voice, basic principle of signal processing, the technique of basic image signal processing, biology astronomy and Robot soccer with apply of image signal processing technique, control video signal and project related image. It also has an introduction of CEM Linker I. O in the end.

  1. Small-signal stability analysis for two-area interconnected power system with load frequency controller in coordination with FACTS and energy storage device

    Directory of Open Access Journals (Sweden)

    Ravi Shankar

    2016-06-01

    Full Text Available This paper deals with the modelling and small signal stability analysis for the two areas interconnected power system using a load frequency controller. The eigenvalues and the participation factor analysis are used to examine the small signal stability and contribution of different states in a particular eigenvalue of the system, respectively. A load frequency controller is designed to stabilize the frequency deviations which occur due to the small perturbation in the system. In this paper, the proposed control scheme consists of an integral controller in coordination with the Redox Flow Energy Storage System (RFESS and the Static Synchronous Series Compensator (SSSC. The dynamic responses of the overall system have been improved by the proposed controller, which is also verified with the help of eigenvalue and participation factor analysis. This analysis shows that overall system oscillation has been reduced through a proposed controller.

  2. MUSCLE OR MOTIVATION? A STOP SIGNAL STUDY ON THE EFFECTS OF SEQUENTIAL COGNITIVE CONTROL

    Directory of Open Access Journals (Sweden)

    Hilde M. Huizenga

    2012-05-01

    Full Text Available Performance in cognitive control tasks deteriorates when these tasks are performed together with other tasks that also require cognitive control, that is, if simultaneous cognitive control is required. Surprisingly, this decrease in performance is also observed if tasks are preceded by other cognitive control tasks, that is, if sequential cognitive control is required. The common explanation for the latter finding is that previous acts of cognitive control deplete a common resource, just like a muscle becomes fatigued after repeated use. An alternative explanation however has also been put forward, namely that repeated acts of cognitive control reduce the motivation to match allocated resources to required resources. In this paper we formalize these two accounts, the muscle and the motivation account, and show that they yield differential predictions on the interaction between simultaneous and sequential cognitive control. Such an interaction is not predicted by the muscle account, whereas it is predicted by the motivation account.These predictions were tested in a paradigm where participants had to perform a series of stop-signal tasks, these tasks varied both in their demands on simultaneous control and in their demands on sequential control. This paradigm, combined with a multilevel analysis, offered the possibility to test the differential predictions directly. Results of two studies indicate that an interaction between simultaneous and sequential cognitive control is present. Therefore it is concluded that effects of sequential cognitive control are best explained by the motivation account.

  3. The Toll-like receptor 1/2 agonists Pam(3) CSK(4) and human β-defensin-3 differentially induce interleukin-10 and nuclear factor-κB signalling patterns in human monocytes.

    Science.gov (United States)

    Funderburg, Nicholas T; Jadlowsky, Julie K; Lederman, Michael M; Feng, Zhimin; Weinberg, Aaron; Sieg, Scott F

    2011-10-01

    Human β-defensin 3 (hBD-3) activates antigen-presenting cells through Toll-like receptors (TLRs) 1/2. Several TLR1/2 agonists have been identified but little is known about how they might differentially affect cellular activation. We compared the effects of hBD-3 with those of another TLR1/2 agonist, Pam(3) CSK(4) , in human monocytes. Monocytes incubated with hBD-3 or Pam(3) CSK(4) produced interleukin-6 (IL-6), IL-8 and IL-1β, but only Pam(3) CSK(4) induced IL-10. The IL-10 induction by Pam(3) CSK(4) caused down-modulation of the co-stimulatory molecule, CD86, whereas CD86 expression was increased in monocytes exposed to hBD-3. Assessment of signalling pathways linked to IL-10 induction indicated that mitogen-activated protein kinases were activated similarly by hBD-3 or Pam(3) CSK(4) , whereas the non-canonical nuclear factor-κB pathway was only induced by Pam(3) CSK(4) . Our data suggest that the lack of non-canonical nuclear factor-κB signalling by hBD-3 could contribute to the failure of this TLR agonist to induce production of the anti-inflammatory cytokine, IL-10, in human monocytes. © 2011 The Authors. Immunology © 2011 Blackwell Publishing Ltd.

  4. Orphan Nuclear Receptor ERRα Controls Macrophage Metabolic Signaling and A20 Expression to Negatively Regulate TLR-Induced Inflammation.

    Science.gov (United States)

    Yuk, Jae-Min; Kim, Tae Sung; Kim, Soo Yeon; Lee, Hye-Mi; Han, Jeongsu; Dufour, Catherine Rosa; Kim, Jin Kyung; Jin, Hyo Sun; Yang, Chul-Su; Park, Ki-Sun; Lee, Chul-Ho; Kim, Jin-Man; Kweon, Gi Ryang; Choi, Hueng-Sik; Vanacker, Jean-Marc; Moore, David D; Giguère, Vincent; Jo, Eun-Kyeong

    2015-07-21

    The orphan nuclear receptor estrogen-related receptor α (ERRα; NR3B1) is a key metabolic regulator, but its function in regulating inflammation remains largely unknown. Here, we demonstrate that ERRα negatively regulates Toll-like receptor (TLR)-induced inflammation by promoting Tnfaip3 transcription and fine-tuning of metabolic reprogramming in macrophages. ERRα-deficient (Esrra(-/-)) mice showed increased susceptibility to endotoxin-induced septic shock, leading to more severe pro-inflammatory responses than control mice. ERRα regulated macrophage inflammatory responses by directly binding the promoter region of Tnfaip3, a deubiquitinating enzyme in TLR signaling. In addition, Esrra(-/-) macrophages showed an increased glycolysis, but impaired mitochondrial respiratory function and biogenesis. Further, ERRα was required for the regulation of NF-κB signaling by controlling p65 acetylation via maintenance of NAD(+) levels and sirtuin 1 activation. These findings unravel a previously unappreciated role for ERRα as a negative regulator of TLR-induced inflammatory responses through inducing Tnfaip3 transcription and controlling the metabolic reprogramming. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. An Optimization Model of Multi-Intersection Signal Control for Trunk Road under Collaborative Information

    Directory of Open Access Journals (Sweden)

    Xun Li

    2017-01-01

    Full Text Available We proposed a signal control optimization model for urban main trunk line intersections. Four-phase intersection was analyzed and modeled based on the Cell Transmission Model (CTM. CTM and signal control model in our study had both been improved for multi-intersections by three-phase theory and information-exchanging. To achieve a real-time application, an improved genetic algorithm (GA was proposed finally, the DISCO traffic simulation software was used for numerical simulation experiment, and comparisons with the standard GA and CTM were reported in this paper. Experimental results indicate that our searching time is less than that of SGA by 38%, and our method needs only 1/3 iteration time of SGA. According to our DISCO traffic simulation processing, compared with SGA, if the input traffic flow is changed from free phase to synchronized phase, for example, less than 900 vel/h, the delay time can reduce to 87.99% by our method, and the minimum delay time is 77.76% of existing method. Furthermore, if input traffic volume is increased to 1200 vel/h or more at the synchronized phase, the summary and minimum values of average delay time are reduced to 81.16% and 75.83%, respectively, and the average delay time is reduced to 17.72 seconds.

  6. On the use of peripheral autonomic signals for binary control of body–machine interfaces

    International Nuclear Information System (INIS)

    Falk, Tiago H; Guirgis, Mirna; Power, Sarah; Blain, Stefanie; Chau, Tom

    2010-01-01

    In this work, the potential of using peripheral autonomic (PA) responses as control signals for body–machine interfaces that require no physical movement was investigated. Electrodermal activity, skin temperature, heart rate and respiration rate were collected from six participants and hidden Markov models (HMMs) were used to automatically detect when a subject was performing music imagery as opposed to being at rest. Experiments were performed under controlled silent conditions as well as in the presence of continuous and startle (e.g. door slamming) ambient noise. By developing subject-specific HMMs, music imagery was detected under silent conditions with the average sensitivity and specificity of 94.2% and 93.3%, respectively. In the presence of startle noise stimuli, the system sensitivity and specificity levels of 78.8% and 80.2% were attained, respectively. In environments corrupted by continuous ambient and startle noise, the system specificity further decreased to 75.9%. To improve the system robustness against environmental noise, a startle noise detection and compensation strategy were proposed. Once in place, performance levels were shown to be comparable to those observed in silence. The obtained results suggest that PA signals, combined with HMMs, can be useful tools for the development of body–machine interfaces that allow individuals with severe motor impairments to communicate and/or to interact with their environment

  7. Light Controls Cytokinin Signaling via Transcriptional Regulation of Constitutively Active Sensor Histidine Kinase CKI1.

    Science.gov (United States)

    Dobisova, Tereza; Hrdinova, Vendula; Cuesta, Candela; Michlickova, Sarka; Urbankova, Ivana; Hejatkova, Romana; Zadnikova, Petra; Pernisova, Marketa; Benkova, Eva; Hejatko, Jan

    2017-05-01

    In plants, the multistep phosphorelay (MSP) pathway mediates a range of regulatory processes, including those activated by cytokinins. The cross talk between cytokinin response and light has been known for a long time. However, the molecular mechanism underlying the interaction between light and cytokinin signaling remains elusive. In the screen for upstream regulators we identified a LONG PALE HYPOCOTYL ( LPH ) gene whose activity is indispensable for spatiotemporally correct expression of CYTOKININ INDEPENDENT1 ( CKI1 ), encoding the constitutively active sensor His kinase that activates MSP signaling. lph is a new allele of HEME OXYGENASE1 ( HY1 ) that encodes the key protein in the biosynthesis of phytochromobilin, a cofactor of photoconvertible phytochromes. Our analysis confirmed the light-dependent regulation of the CKI1 expression pattern. We show that CKI1 expression is under the control of phytochrome A (phyA), functioning as a dual (both positive and negative) regulator of CKI1 expression, presumably via the phyA-regulated transcription factors (TF) PHYTOCHROME INTERACTING FACTOR3 and CIRCADIAN CLOCK ASSOCIATED1. Changes in CKI1 expression observed in lph / hy1 - 7 and phy mutants correlate with misregulation of MSP signaling, changed cytokinin sensitivity, and developmental aberrations that were previously shown to be associated with cytokinin and/or CKI1 action. Besides that, we demonstrate a novel role of phyA-dependent CKI1 expression in the hypocotyl elongation and hook development during skotomorphogenesis. Based on these results, we propose that the light-dependent regulation of CKI1 provides a plausible mechanistic link underlying the well-known interaction between light- and cytokinin-controlled plant development. © 2017 American Society of Plant Biologists. All Rights Reserved.

  8. Signaling equilibria in sensorimotor interactions.

    Science.gov (United States)

    Leibfried, Felix; Grau-Moya, Jordi; Braun, Daniel A

    2015-08-01

    Although complex forms of communication like human language are often assumed to have evolved out of more simple forms of sensorimotor signaling, less attention has been devoted to investigate the latter. Here, we study communicative sensorimotor behavior of humans in a two-person joint motor task where each player controls one dimension of a planar motion. We designed this joint task as a game where one player (the sender) possesses private information about a hidden target the other player (the receiver) wants to know about, and where the sender's actions are costly signals that influence the receiver's control strategy. We developed a game-theoretic model within the framework of signaling games to investigate whether subjects' behavior could be adequately described by the corresponding equilibrium solutions. The model predicts both separating and pooling equilibria, in which signaling does and does not occur respectively. We observed both kinds of equilibria in subjects and found that, in line with model predictions, the propensity of signaling decreased with increasing signaling costs and decreasing uncertainty on the part of the receiver. Our study demonstrates that signaling games, which have previously been applied to economic decision-making and animal communication, provide a framework for human signaling behavior arising during sensorimotor interactions in continuous and dynamic environments. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Developmental maturation of dynamic causal control signals in higher-order cognition: a neurocognitive network model.

    Directory of Open Access Journals (Sweden)

    Kaustubh Supekar

    2012-02-01

    Full Text Available Cognitive skills undergo protracted developmental changes resulting in proficiencies that are a hallmark of human cognition. One skill that develops over time is the ability to problem solve, which in turn relies on cognitive control and attention abilities. Here we use a novel multimodal neurocognitive network-based approach combining task-related fMRI, resting-state fMRI and diffusion tensor imaging (DTI to investigate the maturation of control processes underlying problem solving skills in 7-9 year-old children. Our analysis focused on two key neurocognitive networks implicated in a wide range of cognitive tasks including control: the insula-cingulate salience network, anchored in anterior insula (AI, ventrolateral prefrontal cortex and anterior cingulate cortex, and the fronto-parietal central executive network, anchored in dorsolateral prefrontal cortex and posterior parietal cortex (PPC. We found that, by age 9, the AI node of the salience network is a major causal hub initiating control signals during problem solving. Critically, despite stronger AI activation, the strength of causal regulatory influences from AI to the PPC node of the central executive network was significantly weaker and contributed to lower levels of behavioral performance in children compared to adults. These results were validated using two different analytic methods for estimating causal interactions in fMRI data. In parallel, DTI-based tractography revealed weaker AI-PPC structural connectivity in children. Our findings point to a crucial role of AI connectivity, and its causal cross-network influences, in the maturation of dynamic top-down control signals underlying cognitive development. Overall, our study demonstrates how a unified neurocognitive network model when combined with multimodal imaging enhances our ability to generalize beyond individual task-activated foci and provides a common framework for elucidating key features of brain and cognitive

  10. Redox signaling in plants.

    Science.gov (United States)

    Foyer, Christine H; Noctor, Graham

    2013-06-01

    Our aim is to deliver an authoritative and challenging perspective of current concepts in plant redox signaling, focusing particularly on the complex interface between the redox and hormone-signaling pathways that allow precise control of plant growth and defense in response to metabolic triggers and environmental constraints and cues. Plants produce significant amounts of singlet oxygen and other reactive oxygen species (ROS) as a result of photosynthetic electron transport and metabolism. Such pathways contribute to the compartment-specific redox-regulated signaling systems in plant cells that convey information to the nucleus to regulate gene expression. Like the chloroplasts and mitochondria, the apoplast-cell wall compartment makes a significant contribution to the redox signaling network, but unlike these organelles, the apoplast has a low antioxidant-buffering capacity. The respective roles of ROS, low-molecular antioxidants, redox-active proteins, and antioxidant enzymes are considered in relation to the functions of plant hormones such as salicylic acid, jasmonic acid, and auxin, in the composite control of plant growth and defense. Regulation of redox gradients between key compartments in plant cells such as those across the plasma membrane facilitates flexible and multiple faceted opportunities for redox signaling that spans the intracellular and extracellular environments. In conclusion, plants are recognized as masters of the art of redox regulation that use oxidants and antioxidants as flexible integrators of signals from metabolism and the environment.

  11. Wnt signaling in limb organogenesis

    OpenAIRE

    Geetha-Loganathan, Poongodi; Nimmagadda, Suresh; Scaal, Martin

    2008-01-01

    Secreted signaling molecules of the Wnt family have been found to play a central role in controlling embryonic development of a wide range of taxa from Hydra to humans. The most extensively studied Wnt signaling pathway is the canonical Wnt pathway, which controls gene expression by stabilizing β-catenin, and regulates a multitude of developmental processes. More recently, noncanonical Wnt pathways, which are β-catenin-independent, have been found to be important developmental regulators. Und...

  12. Improvement of density control by feedback on Langmuir probe signals in Tore Supra

    International Nuclear Information System (INIS)

    Gunn, J.; Bucalossi, J.; Costanzo, L.; Grisolia, C.; Ghendrih, Ph.; Grosman, A.; Loarer, T.; Martin, G.; Monier-Garbet, P.; Moulin, D.; Pascal, J.Y.; Saint-Laurent, F.

    1999-12-01

    Real time control of deuterium or helium gas injection by feedback on Langmuir probe signals is implemented in Tore Supra ergodic divertor discharges. The feedback schemes are based on the robust experimental observation that the density limit coincides with edge temperature T e ∼ 10 eV. Three control algorithms are used: (1) proportional feedback on the central line-averaged density with real-time attenuation of the system gain and security cut-off of the gas injection if the edge temperature becomes too low; (2) proportional feedback on the central line-averaged density with security cut-off controlled by the degree of detachment (DoD); (3) proportional feedback on edge temperature with security cut-off on the DoD. The DoD is defined for deuterium discharges, but not for helium since those do not detach. All three feedback modes permit operation close to the density limit and have been successfully applied for plasma currents 0.4 p p =1.4 MA with up to 4 MW of ICRH power. (author)

  13. Transcription factor TLX1 controls retinoic acid signaling to ensure spleen development

    Science.gov (United States)

    Lenti, Elisa; Farinello, Diego; Penkov, Dmitry; Castagnaro, Laura; Lavorgna, Giovanni; Wuputra, Kenly; Tjaden, Naomi E. Butler; Bernassola, Francesca; Caridi, Nicoletta; Wagner, Michael; Kozinc, Katja; Niederreither, Karen; Blasi, Francesco; Pasini, Diego; Trainor, Paul A.

    2016-01-01

    The molecular mechanisms that underlie spleen development and congenital asplenia, a condition linked to increased risk of overwhelming infections, remain largely unknown. The transcription factor TLX1 controls cell fate specification and organ expansion during spleen development, and Tlx1 deletion causes asplenia in mice. Deregulation of TLX1 expression has recently been proposed in the pathogenesis of congenital asplenia in patients carrying mutations of the gene-encoding transcription factor SF-1. Herein, we have shown that TLX1-dependent regulation of retinoic acid (RA) metabolism is critical for spleen organogenesis. In a murine model, loss of Tlx1 during formation of the splenic anlage increased RA signaling by regulating several genes involved in RA metabolism. Uncontrolled RA activity resulted in premature differentiation of mesenchymal cells and reduced vasculogenesis of the splenic primordium. Pharmacological inhibition of RA signaling in Tlx1-deficient animals partially rescued the spleen defect. Finally, spleen growth was impaired in mice lacking either cytochrome P450 26B1 (Cyp26b1), which results in excess RA, or retinol dehydrogenase 10 (Rdh10), which results in RA deficiency. Together, these findings establish TLX1 as a critical regulator of RA metabolism and provide mechanistic insights into the molecular determinants of human congenital asplenia. PMID:27214556

  14. The timing of control signals underlying fast point-to-point arm movements.

    Science.gov (United States)

    Ghafouri, M; Feldman, A G

    2001-04-01

    on the handle, or computed with equations of motion. In some trials, an electromagnetic brake prevented movements. In such movements, the hand force and joint torques reached a steady state after a time that was much smaller than the movement duration in unobstructed movements and was approximately equal to the time to peak velocity (mean difference hypothesis that, in unobstructed movements, the IC shifts and resulting shifts in the EP end approximately at peak velocity. In other words, during the latter part of the movement, the control signals responsible for the equilibrium shift remained constant, and the movement was driven by the arm inertial, viscous and elastic forces produced by the muscle-reflex system. Fast movements may thus be completed without continuous control guidance. As a consequence, central corrections and sequential commands may be issued rapidly, without waiting for the end of kinematic responses to each command, which may be important for many motor behaviours including typing, piano playing and speech. Our study also illustrates that the timing of the control signals may be substantially different from that of the resulting motor output and that the same control pattern may produce different motor outputs depending on external conditions.

  15. Mycobacterium tuberculosis Controls Phagosomal Acidification by Targeting CISH-Mediated Signaling

    Directory of Open Access Journals (Sweden)

    Christophe J. Queval

    2017-09-01

    Full Text Available Pathogens have evolved a range of mechanisms to counteract host defenses, notably to survive harsh acidic conditions in phagosomes. In the case of Mycobacterium tuberculosis, it has been shown that regulation of phagosome acidification could be achieved by interfering with the retention of the V-ATPase complexes at the vacuole. Here, we present evidence that M. tuberculosis resorts to yet another strategy to control phagosomal acidification, interfering with host suppressor of cytokine signaling (SOCS protein functions. More precisely, we show that infection of macrophages with M. tuberculosis leads to granulocyte-macrophage colony-stimulating factor (GM-CSF secretion, inducing STAT5-mediated expression of cytokine-inducible SH2-containing protein (CISH, which selectively targets the V-ATPase catalytic subunit A for ubiquitination and degradation by the proteasome. Consistently, we show that inhibition of CISH expression leads to reduced replication of M. tuberculosis in macrophages. Our findings further broaden the molecular understanding of mechanisms deployed by bacteria to survive.

  16. Test signal generation for analog circuits

    Directory of Open Access Journals (Sweden)

    B. Burdiek

    2003-01-01

    Full Text Available In this paper a new test signal generation approach for general analog circuits based on the variational calculus and modern control theory methods is presented. The computed transient test signals also called test stimuli are optimal with respect to the detection of a given fault set by means of a predefined merit functional representing a fault detection criterion. The test signal generation problem of finding optimal test stimuli detecting all faults form the fault set is formulated as an optimal control problem. The solution of the optimal control problem representing the test stimuli is computed using an optimization procedure. The optimization procedure is based on the necessary conditions for optimality like the maximum principle of Pontryagin and adjoint circuit equations.

  17. Socs36E Controls Niche Competition by Repressing MAPK Signaling in the Drosophila Testis.

    Directory of Open Access Journals (Sweden)

    Marc Amoyel

    2016-01-01

    Full Text Available The Drosophila testis is a well-established system for studying stem cell self-renewal and competition. In this tissue, the niche supports two stem cell populations, germ line stem cells (GSCs, which give rise to sperm, and somatic stem cells called cyst stem cells (CySCs, which support GSCs and their descendants. It has been established that CySCs compete with each other and with GSCs for niche access, and mutations have been identified that confer increased competitiveness to CySCs, resulting in the mutant stem cell and its descendants outcompeting wild type resident stem cells. Socs36E, which encodes a negative feedback inhibitor of the JAK/STAT pathway, was the first identified regulator of niche competition. The competitive behavior of Socs36E mutant CySCs was attributed to increased JAK/STAT signaling. Here we show that competitive behavior of Socs36E mutant CySCs is due in large part to unbridled Mitogen-Activated Protein Kinase (MAPK signaling. In Socs36E mutant clones, MAPK activity is elevated. Furthermore, we find that clonal upregulation of MAPK in CySCs leads to their outcompetition of wild type CySCs and of GSCs, recapitulating the Socs36E mutant phenotype. Indeed, when MAPK activity is removed from Socs36E mutant clones, they lose their competitiveness but maintain self-renewal, presumably due to increased JAK/STAT signaling in these cells. Consistently, loss of JAK/STAT activity in Socs36E mutant clones severely impairs their self-renewal. Thus, our results enable the genetic separation of two essential processes that occur in stem cells. While some niche signals specify the intrinsic property of self-renewal, which is absolutely required in all stem cells for niche residence, additional signals control the ability of stem cells to compete with their neighbors. Socs36E is node through which these processes are linked, demonstrating that negative feedback inhibition integrates multiple aspects of stem cell behavior.

  18. Thermal resonance in signal transmission

    International Nuclear Information System (INIS)

    Reigada, Ramon; Sarmiento, Antonio; Lindenberg, Katja

    2001-01-01

    We use temperature tuning to control signal propagation in simple one-dimensional arrays of masses connected by hard anharmonic springs and with no local potentials. In our numerical model a sustained signal is applied at one site of a chain immersed in a thermal environment and the signal-to-noise ratio is measured at each oscillator. We show that raising the temperature can lead to enhanced signal propagation along the chain, resulting in thermal resonance effects akin to the resonance observed in arrays of bistable systems

  19. Thermal resonance in signal transmission

    Energy Technology Data Exchange (ETDEWEB)

    Reigada, Ramon; Sarmiento, Antonio; Lindenberg, Katja

    2001-06-01

    We use temperature tuning to control signal propagation in simple one-dimensional arrays of masses connected by hard anharmonic springs and with no local potentials. In our numerical model a sustained signal is applied at one site of a chain immersed in a thermal environment and the signal-to-noise ratio is measured at each oscillator. We show that raising the temperature can lead to enhanced signal propagation along the chain, resulting in thermal resonance effects akin to the resonance observed in arrays of bistable systems.

  20. T helper-independent activation of human CD8+ cells: the role of CD28 costimulation.

    Science.gov (United States)

    Van Gool, S W; Zhang, Y; Kasran, A; de Boer, M; Ceuppens, J L

    1996-07-01

    The concept that activation of MHC class I-restricted CD8+ cells entirely depends on help from MHC class II-restricted CD4+ T cells has recently been supplemented with an alternative model in which CD8+ cells can directly be activated by MHC class I-expressing professional antigen-presenting cells (APC), which are able to deliver an accessory signal. The authors analysed the role of CD28-mediated costimulation for T helper cell-independent activation of purified human CD8+ T cells in two different in vitro models. Freshly isolated CD8+ cells could be activated (proliferation, IL-2 production and cytotoxic activity) by anti-CD3-presenting Fc gamma R+ mouse cells transfected with the human CD28 ligand, CD80, as the only accessory signal. On the other hand, activation of CD8+ cells by allogeneic MHC class I on EBV-transformed B cells, which express two different CD28 ligands, CD80 and CD86, also proceeded very efficiently (proliferation, cytotoxic activity and CD25 expression), but was either not, or only partially, blocked by anti-CD80 and anti-CD86 MoAb or CTLA-4Ig. This indicates that other costimulatory signals are also effective, and that CD28 triggering is not absolutely required for initial T-cell activation. CsA and CD80/CD86-blocking agents were synergistic in completely inhibiting activation of CD8+ cells in the MLR with allogeneic B-cell lines. This combination also induced non-responsiveness of CD8+ cells upon restimulation in the absence of blocking agents. Therefore, although professional APC can apparently provide multiple costimulatory signals for direct activation of CD8+ T cells, the signal derived from CD80/CD86 is unique in providing CsA-resistance.

  1. Compensation of the AKT signaling by ERK signaling in transgenic mice hearts overexpressing TRIM72

    Energy Technology Data Exchange (ETDEWEB)

    Ham, Young-Mi, E-mail: youngmi_ham@hms.harvard.edu [College of Life Science and Biotechnology, Korea University, Seoul (Korea, Republic of); Department of Cell Biology, Harvard Medical School, Boston, MA 02115 (United States); Mahoney, Sarah Jane [Department of Cell Biology, Harvard Medical School, Boston, MA 02115 (United States)

    2013-06-10

    The AKT and ERK signaling pathways are known to be involved in cell hypertrophy, proliferation, survival and differentiation. Although there is evidence for crosstalk between these two signaling pathways in cellulo, there is less evidence for cross talk in vivo. Here, we show that crosstalk between AKT and ERK signaling in the hearts of TRIM72-overexpressing transgenic mice (TRIM72-Tg) with alpha-MHC promoter regulates and maintains their heart size. TRIM72, a heart- and skeletal muscle-specific protein, downregulates AKT-mTOR signaling via IRS-1 degradation and reduces the size of rat cardiomyocytes and the size of postnatal TRIM72-Tg hearts. TRIM72 expression was upregulated by hypertrophic inducers in cardiomyocytes, while IRS-1 was downregulated by IGF-1. TRIM72 specifically regulated IGF-1-dependent AKT-mTOR signaling, resulting in a reduction of the size of cardiomyocytes. Postnatal TRIM72-Tg hearts were smaller than control-treated hearts with inhibition of AKT-mTOR signaling. However, adult TRIM72-Tg hearts were larger than of control despite the suppression of AKT-mTOR signaling. Activation of ERK, PKC-α, and JNK were observed to be elevated in adult TRIM72-Tg, and these signals were mediated by ET-1 via the ET receptors A and B. Altogether, these results suggest that AKT signaling regulates cardiac hypertrophy in physiological conditions, and ERK signaling compensates for the absence of AKT signaling during TRIM72 overexpression, leading to pathological hypertrophy. -- Highlights: • TRIM72 inhibits AKT signaling through ubiquitination of IRS-1 in cardiac cells. • TRIM72 regulates the size of cardiac cells. • TRIM72 regulates size of postnatal TRIM72-overexpressing transgenic mice hearts. • Adult TRIM72-overexpressing transgenic mice hearts showed cardiac dysfunction. • Adult TRIM72 transgenic mice hearts showed higher expression of endothelin receptors.

  2. Compensation of the AKT signaling by ERK signaling in transgenic mice hearts overexpressing TRIM72

    International Nuclear Information System (INIS)

    Ham, Young-Mi; Mahoney, Sarah Jane

    2013-01-01

    The AKT and ERK signaling pathways are known to be involved in cell hypertrophy, proliferation, survival and differentiation. Although there is evidence for crosstalk between these two signaling pathways in cellulo, there is less evidence for cross talk in vivo. Here, we show that crosstalk between AKT and ERK signaling in the hearts of TRIM72-overexpressing transgenic mice (TRIM72-Tg) with alpha-MHC promoter regulates and maintains their heart size. TRIM72, a heart- and skeletal muscle-specific protein, downregulates AKT-mTOR signaling via IRS-1 degradation and reduces the size of rat cardiomyocytes and the size of postnatal TRIM72-Tg hearts. TRIM72 expression was upregulated by hypertrophic inducers in cardiomyocytes, while IRS-1 was downregulated by IGF-1. TRIM72 specifically regulated IGF-1-dependent AKT-mTOR signaling, resulting in a reduction of the size of cardiomyocytes. Postnatal TRIM72-Tg hearts were smaller than control-treated hearts with inhibition of AKT-mTOR signaling. However, adult TRIM72-Tg hearts were larger than of control despite the suppression of AKT-mTOR signaling. Activation of ERK, PKC-α, and JNK were observed to be elevated in adult TRIM72-Tg, and these signals were mediated by ET-1 via the ET receptors A and B. Altogether, these results suggest that AKT signaling regulates cardiac hypertrophy in physiological conditions, and ERK signaling compensates for the absence of AKT signaling during TRIM72 overexpression, leading to pathological hypertrophy. -- Highlights: • TRIM72 inhibits AKT signaling through ubiquitination of IRS-1 in cardiac cells. • TRIM72 regulates the size of cardiac cells. • TRIM72 regulates size of postnatal TRIM72-overexpressing transgenic mice hearts. • Adult TRIM72-overexpressing transgenic mice hearts showed cardiac dysfunction. • Adult TRIM72 transgenic mice hearts showed higher expression of endothelin receptors

  3. Phase dynamics of complex-valued neural networks and its application to traffic signal control.

    Science.gov (United States)

    Nishikawa, Ikuko; Iritani, Takeshi; Sakakibara, Kazutoshi; Kuroe, Yasuaki

    2005-01-01

    Complex-valued Hopfield networks which possess the energy function are analyzed. The dynamics of the network with certain forms of an activation function is de-composable into the dynamics of the amplitude and phase of each neuron. Then the phase dynamics is described as a coupled system of phase oscillators with a pair-wise sinusoidal interaction. Therefore its phase synchronization mechanism is useful for the area-wide offset control of the traffic signals. The computer simulations show the effectiveness under the various traffic conditions.

  4. Positional information generated by spatially distributed signaling cascades.

    Directory of Open Access Journals (Sweden)

    Javier Muñoz-García

    2009-03-01

    Full Text Available The temporal and stationary behavior of protein modification cascades has been extensively studied, yet little is known about the spatial aspects of signal propagation. We have previously shown that the spatial separation of opposing enzymes, such as a kinase and a phosphatase, creates signaling activity gradients. Here we show under what conditions signals stall in the space or robustly propagate through spatially distributed signaling cascades. Robust signal propagation results in activity gradients with long plateaus, which abruptly decay at successive spatial locations. We derive an approximate analytical solution that relates the maximal amplitude and propagation length of each activation profile with the cascade level, protein diffusivity, and the ratio of the opposing enzyme activities. The control of the spatial signal propagation appears to be very different from the control of transient temporal responses for spatially homogenous cascades. For spatially distributed cascades where activating and deactivating enzymes operate far from saturation, the ratio of the opposing enzyme activities is shown to be a key parameter controlling signal propagation. The signaling gradients characteristic for robust signal propagation exemplify a pattern formation mechanism that generates precise spatial guidance for multiple cellular processes and conveys information about the cell size to the nucleus.

  5. Neural signal processing and closed-loop control algorithm design for an implanted neural recording and stimulation system.

    Science.gov (United States)

    Hamilton, Lei; McConley, Marc; Angermueller, Kai; Goldberg, David; Corba, Massimiliano; Kim, Louis; Moran, James; Parks, Philip D; Sang Chin; Widge, Alik S; Dougherty, Darin D; Eskandar, Emad N

    2015-08-01

    A fully autonomous intracranial device is built to continually record neural activities in different parts of the brain, process these sampled signals, decode features that correlate to behaviors and neuropsychiatric states, and use these features to deliver brain stimulation in a closed-loop fashion. In this paper, we describe the sampling and stimulation aspects of such a device. We first describe the signal processing algorithms of two unsupervised spike sorting methods. Next, we describe the LFP time-frequency analysis and feature derivation from the two spike sorting methods. Spike sorting includes a novel approach to constructing a dictionary learning algorithm in a Compressed Sensing (CS) framework. We present a joint prediction scheme to determine the class of neural spikes in the dictionary learning framework; and, the second approach is a modified OSort algorithm which is implemented in a distributed system optimized for power efficiency. Furthermore, sorted spikes and time-frequency analysis of LFP signals can be used to generate derived features (including cross-frequency coupling, spike-field coupling). We then show how these derived features can be used in the design and development of novel decode and closed-loop control algorithms that are optimized to apply deep brain stimulation based on a patient's neuropsychiatric state. For the control algorithm, we define the state vector as representative of a patient's impulsivity, avoidance, inhibition, etc. Controller parameters are optimized to apply stimulation based on the state vector's current state as well as its historical values. The overall algorithm and software design for our implantable neural recording and stimulation system uses an innovative, adaptable, and reprogrammable architecture that enables advancement of the state-of-the-art in closed-loop neural control while also meeting the challenges of system power constraints and concurrent development with ongoing scientific research designed

  6. Performance and Usability of Various Robotic Arm Control Modes from Human Force Signals

    Directory of Open Access Journals (Sweden)

    Sébastien Mick

    2017-10-01

    Full Text Available Elaborating an efficient and usable mapping between input commands and output movements is still a key challenge for the design of robotic arm prostheses. In order to address this issue, we present and compare three different control modes, by assessing them in terms of performance as well as general usability. Using an isometric force transducer as the command device, these modes convert the force input signal into either a position or a velocity vector, whose magnitude is linearly or quadratically related to force input magnitude. With the robotic arm from the open source 3D-printed Poppy Humanoid platform simulating a mobile prosthesis, an experiment was carried out with eighteen able-bodied subjects performing a 3-D target-reaching task using each of the three modes. The subjects were given questionnaires to evaluate the quality of their experience with each mode, providing an assessment of their global usability in the context of the task. According to performance metrics and questionnaire results, velocity control modes were found to perform better than position control mode in terms of accuracy and quality of control as well as user satisfaction and comfort. Subjects also seemed to favor quadratic velocity control over linear (proportional velocity control, even if these two modes did not clearly distinguish from one another when it comes to performance and usability assessment. These results highlight the need to take into account user experience as one of the key criteria for the design of control modes intended to operate limb prostheses.

  7. PTEN and PI-3 kinase inhibitors control LPS signaling and the lymphoproliferative response in the CD19+ B cell compartment

    International Nuclear Information System (INIS)

    Singh, Alok R.; Peirce, Susan K.; Joshi, Shweta; Durden, Donald L.

    2014-01-01

    Pattern recognition receptors (PRRs), e.g. toll receptors (TLRs) that bind ligands within the microbiome have been implicated in the pathogenesis of cancer. LPS is a ligand for two TLR family members, TLR4 and RP105 which mediate LPS signaling in B cell proliferation and migration. Although LPS/TLR/RP105 signaling is well-studied; our understanding of the underlying molecular mechanisms controlling these PRR signaling pathways remains incomplete. Previous studies have demonstrated a role for PTEN/PI-3K signaling in B cell selection and survival, however a role for PTEN/PI-3K in TLR4/RP105/LPS signaling in the B cell compartment has not been reported. Herein, we crossed a CD19cre and PTEN fl/fl mouse to generate a conditional PTEN knockout mouse in the CD19+ B cell compartment. These mice were further crossed with an IL-14α transgenic mouse to study the combined effect of PTEN deletion, PI-3K inhibition and expression of IL-14α (a cytokine originally identified as a B cell growth factor) in CD19+ B cell lymphoproliferation and response to LPS stimulation. Targeted deletion of PTEN and directed expression of IL-14α in the CD19+ B cell compartment (IL-14+PTEN-/-) lead to marked splenomegaly and altered spleen morphology at baseline due to expansion of marginal zone B cells, a phenotype that was exaggerated by treatment with the B cell mitogen and TLR4/RP105 ligand, LPS. Moreover, LPS stimulation of CD19+ cells isolated from these mice display increased proliferation, augmented AKT and NFκB activation as well as increased expression of c-myc and cyclinD1. Interestingly, treatment of LPS treated IL-14+PTEN-/- mice with a pan PI-3K inhibitor, SF1126, reduced splenomegaly, cell proliferation, c-myc and cyclin D1 expression in the CD19+ B cell compartment and normalized the splenic histopathologic architecture. These findings provide the direct evidence that PTEN and PI-3K inhibitors control TLR4/RP105/LPS signaling in the CD19+ B cell compartment and that pan PI-3

  8. PTEN and PI-3 kinase inhibitors control LPS signaling and the lymphoproliferative response in the CD19+ B cell compartment

    Energy Technology Data Exchange (ETDEWEB)

    Singh, Alok R. [UCSD Department of Pediatrics, Moores UCSD Cancer Center, University of California School of Medicine, San Diego, CA 92093 (United States); Peirce, Susan K. [Department of Pediatrics, Emory University School of Medicine, Atlanta, GA (United States); Joshi, Shweta [UCSD Department of Pediatrics, Moores UCSD Cancer Center, University of California School of Medicine, San Diego, CA 92093 (United States); Durden, Donald L., E-mail: ddurden@ucsd.edu [UCSD Department of Pediatrics, Moores UCSD Cancer Center, University of California School of Medicine, San Diego, CA 92093 (United States); Division of Pediatric Hematology-Oncology, UCSD Rady Children' s Hospital, La Jolla, CA (United States)

    2014-09-10

    Pattern recognition receptors (PRRs), e.g. toll receptors (TLRs) that bind ligands within the microbiome have been implicated in the pathogenesis of cancer. LPS is a ligand for two TLR family members, TLR4 and RP105 which mediate LPS signaling in B cell proliferation and migration. Although LPS/TLR/RP105 signaling is well-studied; our understanding of the underlying molecular mechanisms controlling these PRR signaling pathways remains incomplete. Previous studies have demonstrated a role for PTEN/PI-3K signaling in B cell selection and survival, however a role for PTEN/PI-3K in TLR4/RP105/LPS signaling in the B cell compartment has not been reported. Herein, we crossed a CD19cre and PTEN{sup fl/fl} mouse to generate a conditional PTEN knockout mouse in the CD19+ B cell compartment. These mice were further crossed with an IL-14α transgenic mouse to study the combined effect of PTEN deletion, PI-3K inhibition and expression of IL-14α (a cytokine originally identified as a B cell growth factor) in CD19+ B cell lymphoproliferation and response to LPS stimulation. Targeted deletion of PTEN and directed expression of IL-14α in the CD19+ B cell compartment (IL-14+PTEN-/-) lead to marked splenomegaly and altered spleen morphology at baseline due to expansion of marginal zone B cells, a phenotype that was exaggerated by treatment with the B cell mitogen and TLR4/RP105 ligand, LPS. Moreover, LPS stimulation of CD19+ cells isolated from these mice display increased proliferation, augmented AKT and NFκB activation as well as increased expression of c-myc and cyclinD1. Interestingly, treatment of LPS treated IL-14+PTEN-/- mice with a pan PI-3K inhibitor, SF1126, reduced splenomegaly, cell proliferation, c-myc and cyclin D1 expression in the CD19+ B cell compartment and normalized the splenic histopathologic architecture. These findings provide the direct evidence that PTEN and PI-3K inhibitors control TLR4/RP105/LPS signaling in the CD19+ B cell compartment and that pan PI

  9. Traffic flow model at fixed control signals with discrete service time distribution

    Directory of Open Access Journals (Sweden)

    Lucky I. Igbinosun

    2016-04-01

    Full Text Available Most of the models of road traffic flow at fixed-cycle controlled intersection assume stationary distributions and provide steady state results. The assumption that a constant number of vehicles can leave the system during the green phase is unrealistic in real life situations. A discrete time queuing model was developed to describe the operation of traffic flow at a road intersection with fixed-cycle signalized control and to account for the randomness in the number of vehicles that can leave the system. The results show the expected queue size in the system when the traffic is light and for a busy period, respectively. For the light period, when the traffic intensity is less than one, it takes a shorter green cycle time for vehicles to clear up than during high traffic intensity (the road junction is saturated. Increasing the number of cars that can leave the junction at the turn of the green phase reduces the number of cycle times before the queue is cleared.

  10. Realization of Flight Control System in Virtual Reality Environment with Biological Signals

    OpenAIRE

    ALTIN, Cemil; ER, Orhan

    2018-01-01

    In this study, anunmanned aerial vehicle was flown on a virtual reality gaming platform with thehelp of commands processed by signal processing methods of biological signals. In thedeveloped application, Matlab signal processing environment and Unity 3Denvironment which is a virtual reality software platform are integrated witheach other and made to work. The biological signals obtained from the EEG ve EMGsensors are processed in Matlab environment and then converted to commands andtransferre...

  11. A new cellular automaton for signal controlled traffic flow based on driving behaviors

    Science.gov (United States)

    Wang, Yang; Chen, Yan-Yan

    2015-03-01

    The complexity of signal controlled traffic largely stems from the various driving behaviors developed in response to the traffic signal. However, the existing models take a few driving behaviors into account and consequently the traffic dynamics has not been completely explored. Therefore, a new cellular automaton model, which incorporates the driving behaviors typically manifesting during the different stages when the vehicles are moving toward a traffic light, is proposed in this paper. Numerical simulations have demonstrated that the proposed model can produce the spontaneous traffic breakdown and the dissolution of the over-saturated traffic phenomena. Furthermore, the simulation results indicate that the slow-to-start behavior and the inch-forward behavior can foster the traffic breakdown. Particularly, it has been discovered that the over-saturated traffic can be revised to be an under-saturated state when the slow-down behavior is activated after the spontaneous breakdown. Finally, the contributions of the driving behaviors on the traffic breakdown have been examined. Project supported by the National Basic Research Program of China (Grand No. 2012CB723303) and the Beijing Committee of Science and Technology, China (Grand No. Z1211000003120100).

  12. Guidelines for Vehicle Robbery Prevention using Remote Blocking Signals

    Directory of Open Access Journals (Sweden)

    Narong Sangwaranatee

    2016-01-01

    Full Text Available In this paper, the radio signal remote sensing device was used to control the vehicle door switching control, which was the field trials experiment. The switching "On" and "Off" of the switching signals were used to control the vehicle door and investigated. In application, the blocking signal from the commit the remote vehicle crime in the venerable place can be protected. The results obtained have shown that the signal blocking by using another remote control over 5 meters, 10 meters and 15 meters could be achieved. The proposed models and tested results have shown that the Vehicle Brand A Model No. 1 could be blocked by 83.33 percent, while Brand A Model No.2 by 83.33 percent, Brand B Model No.1 by 40 percent, Brand B Model No.2 by 60 percent, Brand C Model No. 1 by 83.33 percent, Brand C Model No. 2 by 83.33 percent, meanwhile, the remote control for general vehicle are used radio waves with frequency 315 and 433 MHz, where the criminal will use the interference signals to form the blocking (jamming signals, the vehicle can be robbed.

  13. Improvement of small-signal stability of power system by controlling doubly fed induction generators of a large-capacity wind farm

    Directory of Open Access Journals (Sweden)

    Tomohiro Adachi

    2016-01-01

    Full Text Available Many wind turbine generations have been installed into power systems around the world, where in recent years doubly fed induction generator (DFIG attracts a lot of attentions because of its efficiency and controllability. However, the DFIG is connected to the power system through inverters and originally does not have an ability to release the kinetic energy of the rotor or resorb the surplus power of the power system as the kinetic energy. Therefore, it has not been made clear how the DFIGs have an influence on small-signal stability in power systems. In this paper, we propose a control scheme of the DFIG and analyse its effect on the small-signal stability of the power system by eigenvalue calculations and time-domain simulations.

  14. Controlling a nuclear reactor with dropped control rods

    International Nuclear Information System (INIS)

    Mc Atee, K.R.; Alsop, B.H.

    1987-01-01

    A control system is described for a nuclear power plant including a reactor with a core having an upper portion and a lower portion and control rods which are inserted into and withdrawn from the core of the reactor vertically to control reactivity in the core. The system comprises: means to measure neutron flux separately in the upper portion and the lower portion of the reactor and to generate from such measurements a signal representative of axial distribution of power between the upper and lower portions of the reactor core; means to detect a dropped control rod in the reactor and to generate a dropped rod signal in response thereto; means to generate an axial power distribution limit signal representative of a critical axial power distribution for a dropped rod condition; means to compare the axial power distribution signal to the axial power distribution limit signal and to generate an axial power distribution out of limits signal when the axial power distribution signal exceeds the axial power distribution limit signal; and means responsive only to the presence of both the dropped rod signal and the axial power distribution out of limits signal to generate a signal for shutting the reactor down

  15. Exponential signaling gain at the receptor level enhances signal-to-noise ratio in bacterial chemotaxis.

    Directory of Open Access Journals (Sweden)

    Silke Neumann

    Full Text Available Cellular signaling systems show astonishing precision in their response to external stimuli despite strong fluctuations in the molecular components that determine pathway activity. To control the effects of noise on signaling most efficiently, living cells employ compensatory mechanisms that reach from simple negative feedback loops to robustly designed signaling architectures. Here, we report on a novel control mechanism that allows living cells to keep precision in their signaling characteristics - stationary pathway output, response amplitude, and relaxation time - in the presence of strong intracellular perturbations. The concept relies on the surprising fact that for systems showing perfect adaptation an exponential signal amplification at the receptor level suffices to eliminate slowly varying multiplicative noise. To show this mechanism at work in living systems, we quantified the response dynamics of the E. coli chemotaxis network after genetically perturbing the information flux between upstream and downstream signaling components. We give strong evidence that this signaling system results in dynamic invariance of the activated response regulator against multiplicative intracellular noise. We further demonstrate that for environmental conditions, for which precision in chemosensing is crucial, the invariant response behavior results in highest chemotactic efficiency. Our results resolve several puzzling features of the chemotaxis pathway that are widely conserved across prokaryotes but so far could not be attributed any functional role.

  16. Utilization of excitation signal harmonics for control of nonlinear systems

    DEFF Research Database (Denmark)

    Vinther, Kasper; Rasmussen, Henrik; Izadi-Zamanabadi, Roozbeh

    2012-01-01

    signal together with Fourier analysis to generate a feedback signal and simulations have shown that different system gains and time constants does not change the global equilibrium/operating point. An evaporator in a refrigeration system was used as example in the simulations, however, it is anticipated...... that the method is applicable in a wide variety of systems satisfying the sigmoid function properties....

  17. Position control device for a control rod

    International Nuclear Information System (INIS)

    Ono, Takehiko; Kusaka, Shuji.

    1976-01-01

    Purpose: To reliably prevent dangerous operation in the control of the position of the control rod by checking for abnormal pulse motor coil excitation voltage and, at the time of occurrence of abnormality, immediately holding the control rod stationary lest it should be moved to an unsafe position, this being accomplished excitation from a compensating excitation system. Constitution: In an FBR reactor, a circuit for memorizing the correct output states of individual drive signals at arbitrary instants and consequtively producing the memorized results is provided, and the output of the circuit and the actual drive signal are compared at all times to discriminate whether the drive signal being compared is normal or not. When the actual drive signal is abnormal, a series signal varying after a predetermined pattern is shifted to enable replacement of the actual drive signal, so that irrespective of whether the problem drive signal is ''on'' or ''off'', a drive signal of the correct pattern may be supplied to the pulse motor to hold the control rod and prevent it from being moved toward the dangerous side due to its own weight or other causes. (Horiuchi, T.)

  18. Histone deacetylase 3 supports endochondral bone formation by controlling cytokine signaling and matrix remodeling

    Science.gov (United States)

    Carpio, Lomeli R.; Bradley, Elizabeth W.; McGee-Lawrence, Meghan E.; Weivoda, Megan M.; Poston, Daniel D.; Dudakovic, Amel; Xu, Ming; Tchkonia, Tamar; Kirkland, James L.; van Wijnen, Andre J.; Oursler, Merry Jo; Westendorf, Jennifer J.

    2017-01-01

    Histone deacetylase (HDAC) inhibitors are efficacious epigenetic-based therapies for some cancers and neurological disorders; however, each of these drugs inhibits multiple HDACs and has detrimental effects on the skeleton. To better understand how HDAC inhibitors affect endochondral bone formation, we conditionally deleted one of their targets, Hdac3, pre- and postnatally in type II collagen α1 (Col2α1)–expressing chondrocytes. Embryonic deletion was lethal, but postnatal deletion of Hdac3 delayed secondary ossification center formation, altered maturation of growth plate chondrocytes, and increased osteoclast activity in the primary spongiosa. HDAC3-deficient chondrocytes exhibited increased expression of cytokine and matrix-degrading genes (Il-6, Mmp3, Mmp13, and Saa3) and a reduced abundance of genes related to extracellular matrix production, bone development, and ossification (Acan, Col2a1, Ihh, and Col10a1). Histone acetylation increased at and near genes that had increased expression. The acetylation and activation of nuclear factor κB (NF-κB) were also increased in HDAC3-deficient chondrocytes. Increased cytokine signaling promoted autocrine activation of Janus kinase (JAK)–signal transducer and activator of transcription (STAT) and NF-κB pathways to suppress chondrocyte maturation, as well as paracrine activation of osteoclasts and bone resorption. Blockade of interleukin-6 (IL-6)–JAK–STAT signaling, NF-κB signaling, and bromodomain extraterminal proteins, which recognize acetylated lysines and promote transcriptional elongation, significantly reduced Il-6 and Mmp13 expression in HDAC3-deficient chondrocytes and secondary activation in osteoclasts. The JAK inhibitor ruxolitinib also reduced osteoclast activity in Hdac3 conditional knockout mice. Thus, HDAC3 controls the temporal and spatial expression of tissue-remodeling genes and inflammatory responses in chondrocytes to ensure proper endochondral ossification during development. PMID

  19. BMP signaling inhibits intestinal stem cell self-renewal through suppression of Wnt-beta-catenin signaling.

    Science.gov (United States)

    He, Xi C; Zhang, Jiwang; Tong, Wei-Gang; Tawfik, Ossama; Ross, Jason; Scoville, David H; Tian, Qiang; Zeng, Xin; He, Xi; Wiedemann, Leanne M; Mishina, Yuji; Li, Linheng

    2004-10-01

    In humans, mutations in BMPR1A, SMAD4 and PTEN are responsible for juvenile polyposis syndrome, juvenile intestinal polyposis and Cowden disease, respectively. The development of polyposis is a common feature of these diseases, suggesting that there is an association between BMP and PTEN pathways. The mechanistic link between BMP and PTEN pathways and the related etiology of juvenile polyposis is unresolved. Here we show that conditional inactivation of Bmpr1a in mice disturbs homeostasis of intestinal epithelial regeneration with an expansion of the stem and progenitor cell populations, eventually leading to intestinal polyposis resembling human juvenile polyposis syndrome. We show that BMP signaling suppresses Wnt signaling to ensure a balanced control of stem cell self-renewal. Mechanistically, PTEN, through phosphatidylinosital-3 kinase-Akt, mediates the convergence of the BMP and Wnt pathways on control of beta-catenin. Thus, BMP signaling may control the duplication of intestinal stem cells, thereby preventing crypt fission and the subsequent increase in crypt number.

  20. Multiple signalling systems controlling expression of luminescence in Vibrio harveyi: sequence and function of genes encoding a second sensory pathway.

    Science.gov (United States)

    Bassler, B L; Wright, M; Silverman, M R

    1994-07-01

    Density-dependent expression of luminescence in Vibrio harveyi is regulated by the concentration of extracellular signal molecules (autoinducers) in the culture medium. One signal-response system is encoded by the luxL,M,N locus. The luxL and luxM genes are required for the production of an autoinducer (probably beta-hydroxybutyl homoserine lactone), and the luxN gene is required for the response to that autoinducer. Analysis of the phenotypes of LuxL,M and N mutants indicated that an additional signal-response system also controls density sensing. We report here the identification, cloning and analysis of luxP and luxQ, which encode functions required for a second density-sensing system. Mutants with defects in luxP and luxQ are defective in response to a second autoinducer substance. LuxQ, like LuxN, is similar to members of the family of two-component, signal transduction proteins and contains both a histidine protein kinase and a response regulator domain. Analysis of signalling mutant phenotypes indicates that there are at least two separate signal-response pathways which converge to regulate expression of luminescence in V. harveyi.

  1. Reduced frequency of T lymphocytes expressing CTLA-4 in frontotemporal dementia compared to Alzheimer's disease.

    Science.gov (United States)

    Santos, Rodrigo Ribeiro; Torres, Karen C; Lima, Giselle S; Fiamoncini, Carolina M; Mapa, Filipe C; Pereira, Patricia A; Rezende, Vitor B; Martins, Luiza C; Bicalho, Maria A; Moraes, Edgar N; Reis, Helton J; Teixeira, Antonio L; Romano-Silva, Marco A

    2014-01-03

    Studies suggest that inflammation is involved in the neurodegenerative cascade of dementias. Immunological mechanisms may be part of the pathophysiological process in frontotemporal dementia (FTD), but up till now only vague evidence of such mechanisms has been presented. The B7- CD28/CTLA-4 pathway is an important immunological signaling pathway involved in modulation of T cell activation. The aim of this study was to compare the expression of molecules associated with co-stimulatory signaling in peripheral blood mononuclear cells (PBMC) of FTD to Alzheimer disease (AD) and control groups. Our results confirm the previous demonstrated increased expression of CD80 in CD14+ Alzheimer patients T cells but show, for the first time, a reduction in the expression of CTLA-4 in CD4+ FTD cells. As CTLA-4 is the most potent negative regulators of T-cell activation we speculated that peripheral T lymphocytes in FTD are more activated and this could be involved in the neurodegeneration observed in this dementia. © 2013 Elsevier Inc. All rights reserved.

  2. Signals and systems with MATLAB

    CERN Document Server

    Yang, Won Young; Song, Ik H; Cho, Yong S

    2009-01-01

    Covers some of the theoretical foundations and mathematical derivations that can be used in higher-level related subjects such as signal processing, communication, and control, minimizing the mathematical difficulty and computational burden. This book illustrates the usage of MATLAB and Simulink for signal and system analysis and design.

  3. Controlled branched-chain amino acids auxotrophy in Listeria monocytogenes allows isoleucine to serve as a host signal and virulence effector.

    Science.gov (United States)

    Brenner, Moran; Lobel, Lior; Borovok, Ilya; Sigal, Nadejda; Herskovits, Anat A

    2018-03-01

    Listeria monocytogenes (Lm) is a saprophyte and intracellular pathogen. Transition to the pathogenic state relies on sensing of host-derived metabolites, yet it remains unclear how these are recognized and how they mediate virulence gene regulation. We previously found that low availability of isoleucine signals Lm to activate the virulent state. This response is dependent on CodY, a global regulator and isoleucine sensor. Isoleucine-bound CodY represses metabolic pathways including branched-chain amino acids (BCAA) biosynthesis, however under BCAA depletion, as occurs during infection, BCAA biosynthesis is upregulated and isoleucine-unbound CodY activates virulence genes. While isoleucine was revealed as an important input signal, it was not identified how internal levels are controlled during infection. Here we show that Lm regulates BCAA biosynthesis via CodY and via a riboregulator located upstream to the BCAA biosynthesis genes, named Rli60. rli60 is transcribed when BCAA levels drop, forming a ribosome-mediated attenuator that cis-regulates the downstream genes according to BCAA supply. Notably, we found that Rli60 restricts BCAA production, essentially starving Lm, a mechanism that is directly linked to virulence, as it controls the internal isoleucine pool and thereby CodY activity. This controlled BCAA auxotrophy likely evolved to enable isoleucine to serve as a host signal and virulence effector.

  4. Controlled branched-chain amino acids auxotrophy in Listeria monocytogenes allows isoleucine to serve as a host signal and virulence effector.

    Directory of Open Access Journals (Sweden)

    Moran Brenner

    2018-03-01

    Full Text Available Listeria monocytogenes (Lm is a saprophyte and intracellular pathogen. Transition to the pathogenic state relies on sensing of host-derived metabolites, yet it remains unclear how these are recognized and how they mediate virulence gene regulation. We previously found that low availability of isoleucine signals Lm to activate the virulent state. This response is dependent on CodY, a global regulator and isoleucine sensor. Isoleucine-bound CodY represses metabolic pathways including branched-chain amino acids (BCAA biosynthesis, however under BCAA depletion, as occurs during infection, BCAA biosynthesis is upregulated and isoleucine-unbound CodY activates virulence genes. While isoleucine was revealed as an important input signal, it was not identified how internal levels are controlled during infection. Here we show that Lm regulates BCAA biosynthesis via CodY and via a riboregulator located upstream to the BCAA biosynthesis genes, named Rli60. rli60 is transcribed when BCAA levels drop, forming a ribosome-mediated attenuator that cis-regulates the downstream genes according to BCAA supply. Notably, we found that Rli60 restricts BCAA production, essentially starving Lm, a mechanism that is directly linked to virulence, as it controls the internal isoleucine pool and thereby CodY activity. This controlled BCAA auxotrophy likely evolved to enable isoleucine to serve as a host signal and virulence effector.

  5. Molecular pathway profiling of T lymphocyte signal transduction pathways; Th1 and Th2 genomic fingerprints are defined by TCR and CD28-mediated signaling

    Directory of Open Access Journals (Sweden)

    Smeets Ruben L

    2012-03-01

    Full Text Available Abstract Background T lymphocytes are orchestrators of adaptive immunity. Naïve T cells may differentiate into Th1, Th2, Th17 or iTreg phenotypes, depending on environmental co-stimulatory signals. To identify genes and pathways involved in differentiation of Jurkat T cells towards Th1 and Th2 subtypes we performed comprehensive transcriptome analyses of Jurkat T cells stimulated with various stimuli and pathway inhibitors. Results from these experiments were validated in a human experimental setting using whole blood and purified CD4+ Tcells. Results Calcium-dependent activation of T cells using CD3/CD28 and PMA/CD3 stimulation induced a Th1 expression profile reflected by increased expression of T-bet, RUNX3, IL-2, and IFNγ, whereas calcium-independent activation via PMA/CD28 induced a Th2 expression profile which included GATA3, RXRA, CCL1 and Itk. Knock down with siRNA and gene expression profiling in the presence of selective kinase inhibitors showed that proximal kinases Lck and PKCθ are crucial signaling hubs during T helper cell activation, revealing a clear role for Lck in Th1 development and for PKCθ in both Th1 and Th2 development. Medial signaling via MAPkinases appeared to be less important in these pathways, since specific inhibitors of these kinases displayed a minor effect on gene expression. Translation towards a primary, whole blood setting and purified human CD4+ T cells revealed that PMA/CD3 stimulation induced a more pronounced Th1 specific, Lck and PKCθ dependent IFNγ production, whereas PMA/CD28 induced Th2 specific IL-5 and IL-13 production, independent of Lck activation. PMA/CD3-mediated skewing towards a Th1 phenotype was also reflected in mRNA expression of the master transcription factor Tbet, whereas PMA/CD28-mediated stimulation enhanced GATA3 mRNA expression in primary human CD4+ Tcells. Conclusions This study identifies stimulatory pathways and gene expression profiles for in vitro skewing of T helper cell

  6. Id1 expression promotes peripheral CD4{sup +} T cell proliferation and survival upon TCR activation without co-stimulation

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Chen; Jin, Rong [Department of Immunology, Peking University Health Science Center, Beijing (China); Wang, Hong-Cheng [Oklahoma Medical Research Foundation, Oklahoma City, OK (United States); Tang, Hui; Liu, Yuan-Feng; Qian, Xiao-Ping; Sun, Xiu-Yuan; Ge, Qing [Department of Immunology, Peking University Health Science Center, Beijing (China); Sun, Xiao-Hong, E-mail: sunx@omrf.org [Oklahoma Medical Research Foundation, Oklahoma City, OK (United States); Zhang, Yu, E-mail: zhangyu007@bjmu.edu.cn [Department of Immunology, Peking University Health Science Center, Beijing (China)

    2013-06-21

    Highlights: •Id1 expression enables naïve T cell proliferation without anti-CD28 co-stimulation. •Id1 expression facilitates T cells survival when stimulated with anti-CD3. •Elevation of IL-2 production by Id1 contributes increased proliferation and survival. •Id1 potentiates NF-κB activation by anti-CD3 stimulation. -- Abstract: Although the role of E proteins in the thymocyte development is well documented, much less is known about their function in peripheral T cells. Here we demonstrated that CD4 promoter-driven transgenic expression of Id1, a naturally occurring dominant-negative inhibitor of E proteins, can substitute for the co-stimulatory signal delivered by CD28 to facilitate the proliferation and survival of naïve CD4{sup +} cells upon anti-CD3 stimulation. We next discovered that IL-2 production and NF-κB activity after anti-CD3 stimulation were significantly elevated in Id1-expressing cells, which may be, at least in part, responsible for the augmentation of their proliferation and survival. Taken together, results from this study suggest an important role of E and Id proteins in peripheral T cell activation. The ability of Id proteins to by-pass co-stimulatory signals to enable T cell activation has significant implications in regulating T cell immunity.

  7. Structural, mutational and biophysical studies reveal a canonical mode of molecular recognition between immune receptor TIGIT and nectin-2

    Energy Technology Data Exchange (ETDEWEB)

    Samanta, Dibyendu; Guo, Haisu; Rubinstein, Rotem; Ramagopal, Udupi A.; Almo, Steven C.

    2017-01-01

    In addition to antigen-specific stimulation of T cell receptor (TCR) by a peptide-MHC complex, the functional outcome of TCR engagement is regulated by antigen-independent costimulatory signals. Costimulatory signals are provided by an array of interactions involving activating and inhibitory receptors expressed on T cells and their cognate ligands on antigen presenting cells. T cell immunoglobulin and ITIM domain (TIGIT), a recently identified immune receptor expressed on T and NK cells, upon interaction with either of its two ligands, nectin-2 or poliovirus receptor (PVR), inhibits activation of T and NK cells. Here we report the crystal structure of the human TIGIT ectodomain, which exhibits the classic two-layer β-sandwich topology observed in other immunoglobulin super family (IgSF) members. Biophysical studies indicate that TIGIT is monomeric in solution but can form a dimer at high concentrations, consistent with the observation of a canonical immunoglobulin-like dimer interface in the crystalline state. Based on existing structural data, we present a model of the TIGIT:nectin-2 complex and utilized complementary biochemical studies to map the nectin-binding interface on TIGIT. Our data provide important structural and biochemical determinants responsible for the recognition of nectin-2 by TIGIT. Defining the TIGIT:nectin-2 binding interface provides the basis for rational manipulation of this molecular interaction for the development of immunotherapeutic reagents in autoimmunity and cancer.

  8. Treatment of acute lymphoblastic leukaemia with the second generation of CD19 CAR-T containing either CD28 or 4-1BB.

    Science.gov (United States)

    Li, Shiqi; Zhang, Jiasi; Wang, Meiling; Fu, Gang; Li, Yunyan; Pei, Li; Xiong, Zhouxing; Qin, Dabing; Zhang, Rui; Tian, Xiaobo; Wei, Zhihao; Chen, Run; Chen, Xuejiao; Wan, Jia; Chen, Jun; Wei, Xia; Xu, Yanmin; Zhang, Pei; Wang, Ping; Peng, Xi; Yang, Sainan; Shen, Junjie; Yang, Zhi; Chen, Jieping; Qian, Cheng

    2018-04-10

    T cells modified with anti-CD19 chimeric antigen receptor (CAR) containing either CD28 or 4-1BB (also termed TNFRSF9, CD137) costimulatory signalling have shown great potential in the treatment of acute lymphoblastic leukaemia (ALL). However, the difference between CD28 and 4-1BB costimulatory signalling in CAR-T treatment has not been well elucidated in clinical trials. In this study, we treated 10 relapsed or refractory ALL patients with the second generation CD19 CAR-T. The first 5 patients were treated with CD28-CAR and the other 5 patients were treated with 4-1BB CAR-T. All the 10 patients were response-evaluable. Three patients achieved complete remission and 1 patient with extramedullary disease achieved partial response after CD28-CAR-T treatment. In the 4-1BB CAR-T treatment group, 3 patients achieved complete remission. Furthermore, FLT-3 ligand (FLT3LG) was highly correlated with response time and may serve as a prognosis factor. No severe adverse events were observed in these 10 treated patients. Our study showed that both CD28 CAR-T and 4-1BB CAR-T both worked for response but they differed in response pattern (peak reaction time, reaction lasting time and reaction degree), adverse events, cytokine secretion and immune-suppressive factor level. © 2018 John Wiley & Sons Ltd.

  9. Signal one and two blockade are both critical for non-myeloablative murine HSCT across a major histocompatibility complex barrier.

    Directory of Open Access Journals (Sweden)

    Kia J Langford-Smith

    Full Text Available Non-myeloablative allogeneic haematopoietic stem cell transplantation (HSCT is rarely achievable clinically, except where donor cells have selective advantages. Murine non-myeloablative conditioning regimens have limited clinical success, partly through use of clinically unachievable cell doses or strain combinations permitting allograft acceptance using immunosuppression alone. We found that reducing busulfan conditioning in murine syngeneic HSCT, increases bone marrow (BM:blood SDF-1 ratio and total donor cells homing to BM, but reduces the proportion of donor cells engrafting. Despite this, syngeneic engraftment is achievable with non-myeloablative busulfan (25 mg/kg and higher cell doses induce increased chimerism. Therefore we investigated regimens promoting initial donor cell engraftment in the major histocompatibility complex barrier mismatched CBA to C57BL/6 allo-transplant model. This requires full myeloablation and immunosuppression with non-depleting anti-CD4/CD8 blocking antibodies to achieve engraftment of low cell doses, and rejects with reduced intensity conditioning (≤75 mg/kg busulfan. We compared increased antibody treatment, G-CSF, niche disruption and high cell dose, using reduced intensity busulfan and CD4/8 blockade in this model. Most treatments increased initial donor engraftment, but only addition of co-stimulatory blockade permitted long-term engraftment with reduced intensity or non-myeloablative conditioning, suggesting that signal 1 and 2 T-cell blockade is more important than early BM niche engraftment for transplant success.

  10. Signal one and two blockade are both critical for non-myeloablative murine HSCT across a major histocompatibility complex barrier.

    Science.gov (United States)

    Langford-Smith, Kia J; Sandiford, Zara; Langford-Smith, Alex; Wilkinson, Fiona L; Jones, Simon A; Wraith, J Ed; Wynn, Robert F; Bigger, Brian W

    2013-01-01

    Non-myeloablative allogeneic haematopoietic stem cell transplantation (HSCT) is rarely achievable clinically, except where donor cells have selective advantages. Murine non-myeloablative conditioning regimens have limited clinical success, partly through use of clinically unachievable cell doses or strain combinations permitting allograft acceptance using immunosuppression alone. We found that reducing busulfan conditioning in murine syngeneic HSCT, increases bone marrow (BM):blood SDF-1 ratio and total donor cells homing to BM, but reduces the proportion of donor cells engrafting. Despite this, syngeneic engraftment is achievable with non-myeloablative busulfan (25 mg/kg) and higher cell doses induce increased chimerism. Therefore we investigated regimens promoting initial donor cell engraftment in the major histocompatibility complex barrier mismatched CBA to C57BL/6 allo-transplant model. This requires full myeloablation and immunosuppression with non-depleting anti-CD4/CD8 blocking antibodies to achieve engraftment of low cell doses, and rejects with reduced intensity conditioning (≤75 mg/kg busulfan). We compared increased antibody treatment, G-CSF, niche disruption and high cell dose, using reduced intensity busulfan and CD4/8 blockade in this model. Most treatments increased initial donor engraftment, but only addition of co-stimulatory blockade permitted long-term engraftment with reduced intensity or non-myeloablative conditioning, suggesting that signal 1 and 2 T-cell blockade is more important than early BM niche engraftment for transplant success.

  11. Source of seismic signals

    Energy Technology Data Exchange (ETDEWEB)

    Frankovskii, B.A.; Khor' yakov, K.A.

    1980-08-30

    Patented is a source of seismic signals consisting of a shock generator with a basic low-voltage and auxillary high-voltage stator coils, a capacitive transformer and control switches. To increase the amplitude of signal excitation a condensor battery and auxillary commutator are introduced into the device, which are connected in parallel and serially into the circuit of the main low-voltage stator coil.

  12. Differences In Early T-Cell Signaling In Cultures Grown In a Rotating Clinostat vs. Static Controls

    Science.gov (United States)

    Alexamder. M.; Nelman-Gonzales, M.; Penkala, J.; Sams, C.

    1999-01-01

    Altered gravity has previously been demonstrated to be a stress that can influence components of the immune system. Specifically, T-cell activation has been shown to be affected by changes in gravity, exhibiting a decrease in proliferative response to in vitro stimulation in microgravity. Subsequent ground based studies utilizing a rotating clinostat to model some of the effects of microgravity have been consistent with earlier flight based experiments. These ground and flight experiments have examined T-cell activation by measuring various responses including production of cytokines, DNA synthesis and the production of various cell surface activation markers. These indicators of T-cell activation were measured anywhere from 4 to 72 hours after stimulation. Prior to the work described here, the initial signaling events in T-cell activation had not been directly examined. The goal of this project was to determine how the process of early signal transduction was affected by growth in a rotating clinostat. Here we directly show a defect in signaling from TCR to MAPK in purified peripheral T-cells activated in the clinostat by OKT3/antiCD28 coated microbeads as compared to static controls.

  13. Mechanical control of cyclic AMP signalling and gene transcription through integrins

    Science.gov (United States)

    Meyer, C. J.; Alenghat, F. J.; Rim, P.; Fong, J. H.; Fabry, B.; Ingber, D. E.

    2000-01-01

    This study was carried out to discriminate between two alternative hypotheses as to how cells sense mechanical forces and transduce them into changes in gene transcription. Do cells sense mechanical signals through generalized membrane distortion or through specific transmembrane receptors, such as integrins? Here we show that mechanical stresses applied to the cell surface alter the cyclic AMP signalling cascade and downstream gene transcription by modulating local release of signals generated by activated integrin receptors in a G-protein-dependent manner, whereas distortion of integrins in the absence of receptor occupancy has no effect.

  14. Ultrahigh bandwidth signal processing

    DEFF Research Database (Denmark)

    Oxenløwe, Leif Katsuo

    2016-01-01

    Optical time lenses have proven to be very versatile for advanced optical signal processing. Based on a controlled interplay between dispersion and phase-modulation by e.g. four-wave mixing, the processing is phase-preserving, an hence useful for all types of data signals including coherent multi......-level modulation founats. This has enabled processing of phase-modulated spectrally efficient data signals, such as orthogonal frequency division multiplexed (OFDM) signa In that case, a spectral telescope system was used, using two time lenses with different focal lengths (chirp rates), yielding a spectral...... regeneratio These operations require a broad bandwidth nonlinear platform, and novel photonic integrated nonlinear platform like aluminum gallium arsenide nano-waveguides used for 1.28 Tbaud optical signal processing will be described....

  15. Targeting CD28, CTLA-4 and PD-L1 costimulation differentially controls immune synapses and function of human regulatory and conventional T-cells.

    Directory of Open Access Journals (Sweden)

    Nahzli Dilek

    Full Text Available CD28, CTLA-4 and PD-L1, the three identified ligands for CD80/86, are pivotal positive and negative costimulatory molecules that, among other functions, control T cell motility and formation of immune synapse between T cells and antigen-presenting cells (APCs. What remains incompletely understood is how CD28 leads to the activation of effector T cells (Teff but inhibition of suppression by regulatory T cells (Tregs, while CTLA-4 and PD-L1 inhibit Teff function but are crucial for the suppressive function of Tregs. Using alloreactive human T cells and blocking antibodies, we show here by live cell dynamic microscopy that CD28, CTLA-4, and PD-L1 differentially control velocity, motility and immune synapse formation in activated Teff versus Tregs. Selectively antagonizing CD28 costimulation increased Treg dwell time with APCs and induced calcium mobilization which translated in increased Treg suppressive activity, in contrast with the dampening effect on Teff responses. The increase in Treg suppressive activity after CD28 blockade was also confirmed with polyclonal Tregs. Whereas CTLA-4 played a critical role in Teff by reversing TCR-induced STOP signals, it failed to affect motility in Tregs but was essential for formation of the Treg immune synapse. Furthermore, we identified a novel role for PD-L1-CD80 interactions in suppressing motility specifically in Tregs. Thus, our findings reveal that the three identified ligands of CD80/86, CD28, CTLA-4 and PD-L1, differentially control immune synapse formation and function of the human Teff and Treg cells analyzed here. Individually targeting CD28, CTLA-4 and PD-L1 might therefore represent a valuable therapeutic strategy to treat immune disorders where effector and regulatory T cell functions need to be differentially targeted.

  16. Mycobacterium tuberculosis Controls Phagosomal Acidification by Targeting CISH-Mediated Signaling.

    Science.gov (United States)

    Queval, Christophe J; Song, Ok-Ryul; Carralot, Jean-Philippe; Saliou, Jean-Michel; Bongiovanni, Antonino; Deloison, Gaspard; Deboosère, Nathalie; Jouny, Samuel; Iantomasi, Raffaella; Delorme, Vincent; Debrie, Anne-Sophie; Park, Sei-Jin; Gouveia, Joana Costa; Tomavo, Stanislas; Brosch, Roland; Yoshimura, Akihiko; Yeramian, Edouard; Brodin, Priscille

    2017-09-26

    Pathogens have evolved a range of mechanisms to counteract host defenses, notably to survive harsh acidic conditions in phagosomes. In the case of Mycobacterium tuberculosis, it has been shown that regulation of phagosome acidification could be achieved by interfering with the retention of the V-ATPase complexes at the vacuole. Here, we present evidence that M. tuberculosis resorts to yet another strategy to control phagosomal acidification, interfering with host suppressor of cytokine signaling (SOCS) protein functions. More precisely, we show that infection of macrophages with M. tuberculosis leads to granulocyte-macrophage colony-stimulating factor (GM-CSF) secretion, inducing STAT5-mediated expression of cytokine-inducible SH2-containing protein (CISH), which selectively targets the V-ATPase catalytic subunit A for ubiquitination and degradation by the proteasome. Consistently, we show that inhibition of CISH expression leads to reduced replication of M. tuberculosis in macrophages. Our findings further broaden the molecular understanding of mechanisms deployed by bacteria to survive. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  17. Adaptive traffic signal control with actor-critic methods in a real-world traffic network with different traffic disruption events

    NARCIS (Netherlands)

    Aslani, Mohammad; Mesgari, Mohammad Saadi; Wiering, Marco

    2017-01-01

    The transportation demand is rapidly growing in metropolises, resulting in chronic traffic con-gestions in dense downtown areas. Adaptive traffic signal control as the principle part of in-telligent transportation systems has a primary role to effectively reduce traffic congestion by making a

  18. Differences in time-domain and spectral indexes of skin-surface laser-Doppler signals between controls and breast-cancer subjects.

    Science.gov (United States)

    Hsiu, Hsin; Chen, Chao-Tsung; Hung, Shuo-Hui; Chen, Guan-Zhang; Huang, Yu-Ling

    2018-04-13

    There is an urgent need to improve the early diagnosis of breast cancer. The present study applied spectral and beat-to-beat analyses to laser-Doppler (LDF) data sequences measured on the skin surface on the back of the right hands, with the aim of comparing the different peripheral microcirculatory-blood-flow (MBF) perfusion condition between breast-cancer and control subjects. ECG and LDF signals were obtained simultaneously and noninvasively from 23 breast-cancer patients and 23 age-matched control subjects. Time-domain beat-to-beat indexes and their variability parameters were calculated. Spectral indexes were calculated using the Morlet wavelet transform. The beat-to-beat LDF pulse width and its variability were significantly smaller in cancer patients than in the controls. The energy contributions of endothelial-, neural-, and myogenic-related frequency bands were also significantly smaller in cancer patients. The present study has revealed significant differences in the beat-to-beat and spectral indexes of skin-surface-acquired LDF signals between control subjects and breast-cancer patients. This illustrates that LDF indexes may be useful for monitoring the changes in the MBF perfusion condition induced by breast cancer. Since the breast-cancer patients were at TNM stages 0- 2, the present findings may aid the development of indexes for detecting breast cancer.

  19. Control of word processing environment using myoelectric signals

    Czech Academy of Sciences Publication Activity Database

    Pošusta, Antonín; Sporka, A. J.; Poláček, O.; Rudolf, Š.; Otáhal, Jakub

    2015-01-01

    Roč. 9, č. 4 (2015), s. 299-311 ISSN 1783-7677 R&D Projects: GA ČR(CZ) GBP304/12/G069 Institutional support: RVO:67985823 Keywords : assistive technology * text input * myoelectric signals * user study Subject RIV: FH - Neurology Impact factor: 1.017, year: 2015

  20. Induced disease resistance signaling in plants

    NARCIS (Netherlands)

    Verhagen, B.W.M.; Loon, L.C. van; Pieterse, C.M.J.

    2006-01-01

    To protect themselves from disease, plants have evolved sophisticated inducible defense mechanisms in which the signal molecules salicylic acid, jasmonic acid and ethylene often play crucial roles. Elucidation of signaling pathways controlling induced disease resistance is a major objective in

  1. Msx homeobox genes critically regulate embryo implantation by controlling paracrine signaling between uterine stroma and epithelium.

    Science.gov (United States)

    Nallasamy, Shanmugasundaram; Li, Quanxi; Bagchi, Milan K; Bagchi, Indrani C

    2012-01-01

    The mammalian Msx homeobox genes, Msx1 and Msx2, encode transcription factors that control organogenesis and tissue interactions during embryonic development. We observed overlapping expression of these factors in uterine epithelial and stromal compartments of pregnant mice prior to embryo implantation. Conditional ablation of both Msx1 and Msx2 in the uterus resulted in female infertility due to a failure in implantation. In these mutant mice (Msx1/2(d/d)), the uterine epithelium exhibited persistent proliferative activity and failed to attach to the embryos. Gene expression profiling of uterine epithelium and stroma of Msx1/2(d/d) mice revealed an elevated expression of several members of the Wnt gene family in the preimplantation uterus. Increased canonical Wnt signaling in the stromal cells activated β-catenin, stimulating the production of a subset of fibroblast growth factors (FGFs) in these cells. The secreted FGFs acted in a paracrine manner via the FGF receptors in the epithelium to promote epithelial proliferation, thereby preventing differentiation of this tissue and creating a non-receptive uterus refractory to implantation. Collectively, these findings delineate a unique signaling network, involving Msx1/2, Wnts, and FGFs, which operate in the uterus at the time of implantation to control the mesenchymal-epithelial dialogue critical for successful establishment of pregnancy.

  2. The advantages of PD1 activating chimeric receptor (PD1-ACR) engineered lymphocytes for PDL1(+) cancer therapy.

    Science.gov (United States)

    Tang, Xiaolong; Li, Qingguo; Zhu, Yongqiang; Zheng, Donghui; Dai, Jingjing; Ni, Wenxuan; Wei, Jia; Xue, Yubao; Chen, Ke; Hou, Wei; Zhang, Chao; Feng, Xiaojun; Liang, Yong

    2015-01-01

    Tumors exploit immunoregulatory checkpoints to attenuate T cell responses as a means of circumventing immunologic rejection. By activating the inhibitory costimulatory pathway of Programmed Death 1 (PD1)/PDL1 which provides tumor cells an escape mechanism from immune surveillance, Programmed Death Ligand1 (PDL1)(+) tumors hamper activated tumor-specific T cell functions and render them functionally exhausted. To overcome the inhibitory costimulatory effects of PDL1 on the adoptively transferred T cells, we sought to convert PD1 to a T cell costimulatory receptor by exchanging its transmembrane and cytoplasmic tail with CD28 and 4-1BB signaling domains (PD1-CD28-4-1BB, PD1-ACR), anticipating the genetically modified effector T lymphocytes expressing PD1-ACR would exhibit enhanced functional attributes. And the results showed that PD1-ACR expressed T cells retained the ability to bind PDL1, resulting in T cell activation as evidenced by the elevated activity of phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt), the augmentation of cytokine secretion and the increased proliferative capacity. Moreover, when systemically administered in the mouse model of glioblastoma metastases, PD1-ACR T cells localized at the area of U87 invasive tumor, which results in suppressed tumor growth and enhanced survival of mice with established U87 glioblastoma. Together, these data demonstrated that PD1-ACR has a high potential to serve as a novel strategy to overcome PDL1 mediated immunosuppression of T cells for cancer therapy.

  3. Parallel feedback active noise control of MRI acoustic noise with signal decomposition using hybrid RLS-NLMS adaptive algorithms.

    Science.gov (United States)

    Ganguly, Anshuman; Krishna Vemuri, Sri Hari; Panahi, Issa

    2014-01-01

    This paper presents a cost-effective adaptive feedback Active Noise Control (FANC) method for controlling functional Magnetic Resonance Imaging (fMRI) acoustic noise by decomposing it into dominant periodic components and residual random components. Periodicity of fMRI acoustic noise is exploited by using linear prediction (LP) filtering to achieve signal decomposition. A hybrid combination of adaptive filters-Recursive Least Squares (RLS) and Normalized Least Mean Squares (NLMS) are then used to effectively control each component separately. Performance of the proposed FANC system is analyzed and Noise attenuation levels (NAL) up to 32.27 dB obtained by simulation are presented which confirm the effectiveness of the proposed FANC method.

  4. A functional screen reveals an extensive layer of transcriptional and splicing control underlying RAS/MAPK signaling in Drosophila.

    Directory of Open Access Journals (Sweden)

    Dariel Ashton-Beaucage

    2014-03-01

    Full Text Available The small GTPase RAS is among the most prevalent oncogenes. The evolutionarily conserved RAF-MEK-MAPK module that lies downstream of RAS is one of the main conduits through which RAS transmits proliferative signals in normal and cancer cells. Genetic and biochemical studies conducted over the last two decades uncovered a small set of factors regulating RAS/MAPK signaling. Interestingly, most of these were found to control RAF activation, thus suggesting a central regulatory role for this event. Whether additional factors are required at this level or further downstream remains an open question. To obtain a comprehensive view of the elements functionally linked to the RAS/MAPK cascade, we used a quantitative assay in Drosophila S2 cells to conduct a genome-wide RNAi screen for factors impacting RAS-mediated MAPK activation. The screen led to the identification of 101 validated hits, including most of the previously known factors associated to this pathway. Epistasis experiments were then carried out on individual candidates to determine their position relative to core pathway components. While this revealed several new factors acting at different steps along the pathway--including a new protein complex modulating RAF activation--we found that most hits unexpectedly work downstream of MEK and specifically influence MAPK expression. These hits mainly consist of constitutive splicing factors and thereby suggest that splicing plays a specific role in establishing MAPK levels. We further characterized two representative members of this group and surprisingly found that they act by regulating mapk alternative splicing. This study provides an unprecedented assessment of the factors modulating RAS/MAPK signaling in Drosophila. In addition, it suggests that pathway output does not solely rely on classical signaling events, such as those controlling RAF activation, but also on the regulation of MAPK levels. Finally, it indicates that core splicing

  5. Water pressure control device for control rod drive

    International Nuclear Information System (INIS)

    Sato, Hideyuki.

    1981-01-01

    Purpose: To minimize the fluctuations in the reactor water level upon occurrence of abnormality by inputting the level signal of the reactor to an arithmetic unit for controlling the pressure of control rod drive water to thereby enable effective reactor level control. Constitution: Signal from a flow rate transmitter is inputted into an arithmetic unit to perform constant flow rate control upon normal operation. While on the other hand, if abnormality occurs such as feedwater pump trips, the arithmetic unit is switched from the constant flow rate control to the reactor water level control. Reactor water level signal is inputted into the arithmetic unit and the control valve is most suitably controlled, whereby water is fed from CST to the reactor by way of control rod drive water system to secure the reactor water level if feedwater to the reactor is interrupted by loss of coolants on the feedwater system. Since this enables to minimize the fluctuations in the reactor water level upon abnormality, the reactor water level can be controlled most suitably by the reactor water level signal. (Moriyama, K.)

  6. Proteolytic degradation of regulator of G protein signaling 2 facilitates temporal regulation of Gq/11 signaling and vascular contraction.

    Science.gov (United States)

    Kanai, Stanley M; Edwards, Alethia J; Rurik, Joel G; Osei-Owusu, Patrick; Blumer, Kendall J

    2017-11-24

    Regulator of G protein signaling 2 (RGS2) controls signaling by receptors coupled to the G q/11 class heterotrimeric G proteins. RGS2 deficiency causes several phenotypes in mice and occurs in several diseases, including hypertension in which a proteolytically unstable RGS2 mutant has been reported. However, the mechanisms and functions of RGS2 proteolysis remain poorly understood. Here we addressed these questions by identifying degradation signals in RGS2, and studying dynamic regulation of G q/11 -evoked Ca 2+ signaling and vascular contraction. We identified a novel bipartite degradation signal in the N-terminal domain of RGS2. Mutations disrupting this signal blunted proteolytic degradation downstream of E3 ubiquitin ligase binding to RGS2. Analysis of RGS2 mutants proteolyzed at various rates and the effects of proteasome inhibition indicated that proteolytic degradation controls agonist efficacy by setting RGS2 protein expression levels, and affecting the rate at which cells regain agonist responsiveness as synthesis of RGS2 stops. Analyzing contraction of mesenteric resistance arteries supported the biological relevance of this mechanism. Because RGS2 mRNA expression often is strikingly and transiently up-regulated and then down-regulated upon cell stimulation, our findings indicate that proteolytic degradation tightly couples RGS2 transcription, protein levels, and function. Together these mechanisms provide tight temporal control of G q/11 -coupled receptor signaling in the cardiovascular, immune, and nervous systems. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  7. Chlamydia abortus Pmp18.1 Induces IL-1β Secretion by TLR4 Activation through the MyD88, NF-κB, and Caspase-1 Signaling Pathways.

    Science.gov (United States)

    Pan, Qing; Zhang, Qiang; Chu, Jun; Pais, Roshan; Liu, Shanshan; He, Cheng; Eko, Francis O

    2017-01-01

    The polymorphic membrane protein D (Pmp18D) is a 160-kDa outer membrane protein that is conserved and plays an important role in Chlamydia abortus pathogenesis. We have identified an N-terminal fragment of Pmp18D (designated Pmp18.1) as a possible subunit vaccine antigen. In this study, we evaluated the vaccine potential of Pmp18.1 by investigating its ability to induce innate immune responses in dendritic cells and the signaling pathway(s) involved in rPmp18.1-induced IL-1β secretion. We next investigated the immunomodulatory impact of VCG, in comparison with the more established Th1-promoting adjuvants, CpG and FL, on rPmp18.1-mediated innate immune activation. Finally, the effect of siRNA targeting TLR4, MyD88, NF-κB p50, and Caspase-1 mRNA in DCs on IL-1β cytokine secretion was also investigated. Bone marrow-derived dendritic cells (BMDCs) were stimulated with rPmp18.1 in the presence or absence of VCG or CpG or FL and the magnitude of cytokines produced was assessed using a multiplex cytokine ELISA assay. Expression of costimulatory molecules and Toll-like receptors (TLRs) was analyzed by flow cytometry. Quantitation of intracellular levels of myeloid differentiation factor 88 (MyD88), nuclear factor kappa beta (NF-κB p50/p65), and Caspase-1 was evaluated by Western immunoblotting analysis while NF-κB p65 nuclear translocation was assessed by confocal microscopy. The results showed DC stimulation with rPmp18.1 provoked the secretion of proinflammatory cytokines and upregulated expression of TLRs and co-stimulatory molecules associated with DC maturation. These responses were significantly ( p ≤ 0.001) enhanced by VCG but not CpG or FL. In addition, rPmp18.1 activated the expression of MyD88, NF-κB p50, and Caspase-1 as well as the nuclear expression of NF-κB p65 in treated DCs. Furthermore, targeting TLR4, MyD88, NF-κB p50, and Caspase-1 mRNA in BMDCs with siRNA significantly reduced their expression levels, resulting in decreased IL-1β cytokine

  8. Chlamydia abortus Pmp18.1 Induces IL-1β Secretion by TLR4 Activation through the MyD88, NF-κB, and Caspase-1 Signaling Pathways

    Directory of Open Access Journals (Sweden)

    Qing Pan

    2017-12-01

    Full Text Available The polymorphic membrane protein D (Pmp18D is a 160-kDa outer membrane protein that is conserved and plays an important role in Chlamydia abortus pathogenesis. We have identified an N-terminal fragment of Pmp18D (designated Pmp18.1 as a possible subunit vaccine antigen. In this study, we evaluated the vaccine potential of Pmp18.1 by investigating its ability to induce innate immune responses in dendritic cells and the signaling pathway(s involved in rPmp18.1-induced IL-1β secretion. We next investigated the immunomodulatory impact of VCG, in comparison with the more established Th1-promoting adjuvants, CpG and FL, on rPmp18.1-mediated innate immune activation. Finally, the effect of siRNA targeting TLR4, MyD88, NF-κB p50, and Caspase-1 mRNA in DCs on IL-1β cytokine secretion was also investigated. Bone marrow-derived dendritic cells (BMDCs were stimulated with rPmp18.1 in the presence or absence of VCG or CpG or FL and the magnitude of cytokines produced was assessed using a multiplex cytokine ELISA assay. Expression of costimulatory molecules and Toll-like receptors (TLRs was analyzed by flow cytometry. Quantitation of intracellular levels of myeloid differentiation factor 88 (MyD88, nuclear factor kappa beta (NF-κB p50/p65, and Caspase-1 was evaluated by Western immunoblotting analysis while NF-κB p65 nuclear translocation was assessed by confocal microscopy. The results showed DC stimulation with rPmp18.1 provoked the secretion of proinflammatory cytokines and upregulated expression of TLRs and co-stimulatory molecules associated with DC maturation. These responses were significantly (p ≤ 0.001 enhanced by VCG but not CpG or FL. In addition, rPmp18.1 activated the expression of MyD88, NF-κB p50, and Caspase-1 as well as the nuclear expression of NF-κB p65 in treated DCs. Furthermore, targeting TLR4, MyD88, NF-κB p50, and Caspase-1 mRNA in BMDCs with siRNA significantly reduced their expression levels, resulting in decreased IL-1

  9. Equine grass sickness in Scotland: a case-control study of signalment- and meteorology-related risk factors.

    Science.gov (United States)

    Wylie, C E; Shaw, D J; Fordyce, F M; Lilly, A; McGorum, B C

    2014-01-01

    Equine grass sickness (EGS) remains a frequently fatal disease of equids in Britain. Since previous investigations of signalment- and meteorology-related risk factors for EGS have yielded some conflicting data, further investigation is warranted. To identify signalment- and meteorology-related risk factors for EGS in Scotland. Retrospective time-matched case-control study. This study was undertaken using data for 455 EGS cases and 910 time-matched controls that were referred to the Royal (Dick) School of Veterinary Studies, and average UK Meteorological Office weather station meteorological values from the month of admission of the animal, from the 3, 6 and 12 months prior to admission, and for the entire 1990-2006 period. Signalment-related risk factors associated with an increased risk of EGS were native Scottish pure breeds compared with crossbreeds (odds ratio [OR] = 3.56, 95% confidence interval [CI] 2.43-5.43) and animals living on premises located further north within the study region (OR = 1.08, 95% CI 1.06-1.10). There was a decreased risk of EGS in animals aged 11-20 years compared with animals 2-10 years (OR = 0.32, 95% CI 0.22-0.45), non-native Scottish pure breeds compared with crossbreeds (OR = 0.71, 95% CI 0.54-0.94), and stallions compared with mares (OR = 0.43, 95% CI 0.22-0.86). Meteorology-related risk factors associated with an increased risk of EGS were (if Ordnance Survey northing is excluded) more sun hours (OR>1.43) and more frost days (OR>1.13), while there was a decreased risk of EGS with higher average maximum temperature (ORmeteorological risk factors may assist studies on the aetiology of EGS. © 2013 EVJ Ltd.

  10. Signals, processes, and systems an interactive multimedia introduction to signal processing

    CERN Document Server

    Karrenberg, Ulrich

    2013-01-01

    This is a very new concept for learning Signal Processing, not only from the physically-based scientific fundamentals, but also from the didactic perspective, based on modern results of brain research. The textbook together with the DVD form a learning system that provides investigative studies and enables the reader to interactively visualize even complex processes. The unique didactic concept is built on visualizing signals and processes on the one hand, and on graphical programming of signal processing systems on the other. The concept has been designed especially for microelectronics, computer technology and communication. The book allows to develop, modify, and optimize useful applications using DasyLab - a professional and globally supported software for metrology and control engineering. With the 3rd edition, the software is also suitable for 64 bit systems running on Windows 7. Real signals can be acquired, processed and played on the sound card of your computer. The book provides more than 200 pre-pr...

  11. A generation proposal of management signals from the distribution technical service quality control; Una propuesta de generacion de senales de gestion a partir del control de calidad del servicio tecnico de distribucion

    Energy Technology Data Exchange (ETDEWEB)

    Vidal, Pedro [Energia San Juan S.A. (Argentina). E-mail: pfpvidal@hotmail.com; Andreoni, Alberto M. [ASINELSA S.A., San Juan (Argentina). E-mail: info@asinelsa.com.ar

    1998-07-01

    A set of management signals are presented which help to make the best decision of Operation and Maintenance actions (O and M) and/or investments within the period of technical service quality control so that, at the end of it, the total cost, included compensations to customers related to energy received with bad quality technical service, can be minimized. First, the normative in force is put forward for the measurement and quality control of the technical service according to the Concession Agreement of the distribution service of electric system of San Juan Province - Argentina managed by Energia San Juan S.A. and later, a calculation methodology for some of the signals used during the management period are introduced. These signals are the result of the analysis of interruptions and relations between indicators of the same utility resulting from the first three management periods of the electric distribution system of the province. (author)

  12. Signals and systems laboratory with Matlab

    CERN Document Server

    Palamides, Alex

    2010-01-01

    Introduction to MATLAB®Working EnvironmentGetting StartedMemory ManagementVectorsMatricesPlotting with MATLABComplex NumbersM-FilesInput-Output CommandsFile ManagementLogical-Relational OperatorsControl FlowSymbolic VariablesPolynomials(Pseudo)Random NumbersSignalsCategorization by the Variable TypeBasic Continuous-Time SignalsDiscrete-Time SignalsProperties of SignalsTransformations of the Time Variable for Continuous-Time SignalsTransformations of the Time Variable for Discrete-Time SignalsSystemsSystems ClassificationProperties of SystemsTime Domain System AnalysisImpulse ResponseContinuous Time Convolution Convolution PropertiesInterconnections of SystemsStabilityDiscrete-Time ConvolutionSystems Described by Difference EquationsFiltersStability Criterion for Discrete-Time SystemsSystems Described by Differential EquationsStep Response of a SystemFourier SeriesOrthogonality of Complex Exponential SignalsComplex Exponential Fourier SeriesTrigonometric Fourier SeriesFourier Series in the Cosine with Phase F...

  13. Cross-talk in abscisic acid signaling

    Science.gov (United States)

    Fedoroff, Nina V.

    2002-01-01

    "Cross-talk" in hormone signaling reflects an organism's ability to integrate different inputs and respond appropriately, a crucial function at the heart of signaling network operation. Abscisic acid (ABA) is a plant hormone involved in bud and seed dormancy, growth regulation, leaf senescence and abscission, stomatal opening, and a variety of plant stress responses. This review summarizes what is known about ABA signaling in the control of stomatal opening and seed dormancy and provides an overview of emerging knowledge about connections between ABA, ethylene, sugar, and auxin synthesis and signaling.

  14. Functional morphology of the bovid astragalus in relation to habitat: controlling phylogenetic signal in ecomorphology.

    Science.gov (United States)

    Barr, W Andrew

    2014-11-01

    Bovid astragali are one of the most commonly preserved bones in the fossil record. Accordingly, astragali are an important target for studies seeking to predict the habitat preferences of fossil bovids based on bony anatomy. However, previous work has not tested functional hypotheses linking astragalar morphology with habitat while controlling for body size and phylogenetic signal. This article presents a functional framework relating the morphology of the bovid astragalus to habitat-specific locomotor ecology and tests four hypotheses emanating from this framework. Highly cursorial bovids living in structurally open habitats are hypothesized to differ from their less cursorial closed-habitat dwelling relatives in having (1) relatively short astragali to maintain rotational speed throughout the camming motion of the rotating astragalus, (2) a greater range of angular excursion at the hock, (3) relatively larger joint surface areas, and (4) a more pronounced "spline-and-groove" morphology promoting lateral joint stability. A diverse sample of 181 astragali from 50 extant species was scanned using a Next Engine laser scanner. Species were assigned to one of four habitat categories based on the published ecological literature. A series of 11 linear measurements and three joint surface areas were measured on each astragalus. A geometric mean body size proxy was used to size-correct the measurement data. Phylogenetic generalized least squares (PGLS) was used to test for differences between habitat categories while controlling for body size differences and phylogenetic signal. Statistically significant PGLS results support Hypotheses 1 and 2 (which are not mutually exclusive) as well as Hypothesis 3. No support was found for Hypothesis 4. These findings confirm that the morphology of the bovid astragalus is related to habitat-specific locomotor ecology, and that this relationship is statistically significant after controlling for body size and phylogeny. Thus, this study

  15. Serotonin Signaling in Schistosoma mansoni: A Serotonin–Activated G Protein-Coupled Receptor Controls Parasite Movement

    Science.gov (United States)

    Rashid, Mohammed; Ribeiro, Paula

    2014-01-01

    Serotonin is an important neuroactive substance in all the parasitic helminths. In Schistosoma mansoni, serotonin is strongly myoexcitatory; it potentiates contraction of the body wall muscles and stimulates motor activity. This is considered to be a critical mechanism of motor control in the parasite, but the mode of action of serotonin is poorly understood. Here we provide the first molecular evidence of a functional serotonin receptor (Sm5HTR) in S. mansoni. The schistosome receptor belongs to the G protein-coupled receptor (GPCR) superfamily and is distantly related to serotonergic type 7 (5HT7) receptors from other species. Functional expression studies in transfected HEK 293 cells showed that Sm5HTR is a specific serotonin receptor and it signals through an increase in intracellular cAMP, consistent with a 5HT7 signaling mechanism. Immunolocalization studies with a specific anti-Sm5HTR antibody revealed that the receptor is abundantly distributed in the worm's nervous system, including the cerebral ganglia and main nerve cords of the central nervous system and the peripheral innervation of the body wall muscles and tegument. RNA interference (RNAi) was performed both in schistosomulae and adult worms to test whether the receptor is required for parasite motility. The RNAi-suppressed adults and larvae were markedly hypoactive compared to the corresponding controls and they were also resistant to exogenous serotonin treatment. These results show that Sm5HTR is at least one of the receptors responsible for the motor effects of serotonin in S. mansoni. The fact that Sm5HTR is expressed in nerve tissue further suggests that serotonin stimulates movement via this receptor by modulating neuronal output to the musculature. Together, the evidence identifies Sm5HTR as an important neuronal protein and a key component of the motor control apparatus in S. mansoni. PMID:24453972

  16. Histone deacetylases control neurogenesis in embryonic brain by inhibition of BMP2/4 signaling.

    Directory of Open Access Journals (Sweden)

    Maya Shakèd

    Full Text Available BACKGROUND: Histone-modifying enzymes are essential for a wide variety of cellular processes dependent upon changes in gene expression. Histone deacetylases (HDACs lead to the compaction of chromatin and subsequent silencing of gene transcription, and they have recently been implicated in a diversity of functions and dysfunctions in the postnatal and adult brain including ocular dominance plasticity, memory consolidation, drug addiction, and depression. Here we investigate the role of HDACs in the generation of neurons and astrocytes in the embryonic brain. PRINCIPAL FINDINGS: As a variety of HDACs are expressed in differentiating neural progenitor cells, we have taken a pharmacological approach to inhibit multiple family members. Inhibition of class I and II HDACs in developing mouse embryos with trichostatin A resulted in a dramatic reduction in neurogenesis in the ganglionic eminences and a modest increase in neurogenesis in the cortex. An identical effect was observed upon pharmacological inhibition of HDACs in in vitro-differentiating neural precursors derived from the same brain regions. A reduction in neurogenesis in ganglionic eminence-derived neural precursors was accompanied by an increase in the production of immature astrocytes. We show that HDACs control neurogenesis by inhibition of the bone morphogenetic protein BMP2/4 signaling pathway in radial glial cells. HDACs function at the transcriptional level by inhibiting and promoting, respectively, the expression of Bmp2 and Smad7, an intracellular inhibitor of BMP signaling. Inhibition of the BMP2/4 signaling pathway restored normal levels of neurogenesis and astrogliogenesis to both ganglionic eminence- and cortex-derived cultures in which HDACs were inhibited. CONCLUSIONS: Our results demonstrate a transcriptionally-based regulation of BMP2/4 signaling by HDACs both in vivo and in vitro that is critical for neurogenesis in the ganglionic eminences and that modulates cortical

  17. Fringe Controls Naïve CD4+T Cells Differentiation through Modulating Notch Signaling in Asthmatic Rat Models

    Science.gov (United States)

    Gu, Wen; Xu, Weiguo; Ding, Tao; Guo, Xuejun

    2012-01-01

    The ability of Notch signaling to regulate T helper cell development and differentiation has been widely accepted. Fringe, O-fucose-β1,3-N-acetylglucosaminyltransferases modulate Notch receptor expression and promote the Notch signaling pathway through receptor-ligand binding. In this study, we assayed the expression levels of three Fringe homologs in naive CD4+T cells in asthmatic rats. We found that Radical Fringe (Rfng) was highly expressed, whereas both Lunatic Fringe (Lfng) and Manic Fringe (Mfng) were expressed at low levels. Down-regulation of Rfng using siRNA, and overexpression of Lfng or Mfng enhanced Th1 subset lineages and diminished Th2 subset lineages. Notch signaling was more activated in asthmatic naïve CD4+T cells than in control cells, and Lfng, but not Mfng or Rfng, partly inhibited Notch signaling in asthmatic naïve CD4+T lymphocytes. Lfng overexpression resulted in significantly decreased Th2 cytokine production in asthma, which was the same effect as the GSI (γ-secretase inhibitor) treatment alone, but had an increased effect on Th1 cytokines than GSI treatment. Collectively, these data identify the essential role of Fringe modulating naïve CD4+T cells differentiation through Notch signaling. Lfng regulated Th2 cells differentiation via a Notch-dependent manner and Th1 cells differentiation via a Notch-independent manner. Fringe could be a therapeutic strategy for the management and prevention of allergic asthma. PMID:23071776

  18. Fringe controls naïve CD4(+)T cells differentiation through modulating notch signaling in asthmatic rat models.

    Science.gov (United States)

    Gu, Wen; Xu, Weiguo; Ding, Tao; Guo, Xuejun

    2012-01-01

    The ability of Notch signaling to regulate T helper cell development and differentiation has been widely accepted. Fringe, O-fucose-β1,3-N-acetylglucosaminyltransferases modulate Notch receptor expression and promote the Notch signaling pathway through receptor-ligand binding. In this study, we assayed the expression levels of three Fringe homologs in naive CD4(+)T cells in asthmatic rats. We found that Radical Fringe (Rfng) was highly expressed, whereas both Lunatic Fringe (Lfng) and Manic Fringe (Mfng) were expressed at low levels. Down-regulation of Rfng using siRNA, and overexpression of Lfng or Mfng enhanced Th1 subset lineages and diminished Th2 subset lineages. Notch signaling was more activated in asthmatic naïve CD4(+)T cells than in control cells, and Lfng, but not Mfng or Rfng, partly inhibited Notch signaling in asthmatic naïve CD4(+)T lymphocytes. Lfng overexpression resulted in significantly decreased Th2 cytokine production in asthma, which was the same effect as the GSI (γ-secretase inhibitor) treatment alone, but had an increased effect on Th1 cytokines than GSI treatment. Collectively, these data identify the essential role of Fringe modulating naïve CD4(+)T cells differentiation through Notch signaling. Lfng regulated Th2 cells differentiation via a Notch-dependent manner and Th1 cells differentiation via a Notch-independent manner. Fringe could be a therapeutic strategy for the management and prevention of allergic asthma.

  19. Mitochondrial Energy and Redox Signaling in Plants

    Science.gov (United States)

    Schwarzländer, Markus

    2013-01-01

    Abstract Significance: For a plant to grow and develop, energy and appropriate building blocks are a fundamental requirement. Mitochondrial respiration is a vital source for both. The delicate redox processes that make up respiration are affected by the plant's changing environment. Therefore, mitochondrial regulation is critically important to maintain cellular homeostasis. This involves sensing signals from changes in mitochondrial physiology, transducing this information, and mounting tailored responses, by either adjusting mitochondrial and cellular functions directly or reprogramming gene expression. Recent Advances: Retrograde (RTG) signaling, by which mitochondrial signals control nuclear gene expression, has been a field of very active research in recent years. Nevertheless, no mitochondrial RTG-signaling pathway is yet understood in plants. This review summarizes recent advances toward elucidating redox processes and other bioenergetic factors as a part of RTG signaling of plant mitochondria. Critical Issues: Novel insights into mitochondrial physiology and redox-regulation provide a framework of upstream signaling. On the other end, downstream responses to modified mitochondrial function have become available, including transcriptomic data and mitochondrial phenotypes, revealing processes in the plant that are under mitochondrial control. Future Directions: Drawing parallels to chloroplast signaling and mitochondrial signaling in animal systems allows to bridge gaps in the current understanding and to deduce promising directions for future research. It is proposed that targeted usage of new technical approaches, such as quantitative in vivo imaging, will provide novel leverage to the dissection of plant mitochondrial signaling. Antioxid. Redox Signal. 18, 2122–2144. PMID:23234467

  20. Design of Embedded System for Multivariate Classification of Finger and Thumb Movements Using EEG Signals for Control of Upper Limb Prosthesis

    Science.gov (United States)

    Javed, Amna; Tiwana, Mohsin I.; Khan, Umar Shahbaz

    2018-01-01

    Brain Computer Interface (BCI) determines the intent of the user from a variety of electrophysiological signals. These signals, Slow Cortical Potentials, are recorded from scalp, and cortical neuronal activity is recorded by implanted electrodes. This paper is focused on design of an embedded system that is used to control the finger movements of an upper limb prosthesis using Electroencephalogram (EEG) signals. This is a follow-up of our previous research which explored the best method to classify three movements of fingers (thumb movement, index finger movement, and first movement). Two-stage logistic regression classifier exhibited the highest classification accuracy while Power Spectral Density (PSD) was used as a feature of the filtered signal. The EEG signal data set was recorded using a 14-channel electrode headset (a noninvasive BCI system) from right-handed, neurologically intact volunteers. Mu (commonly known as alpha waves) and Beta Rhythms (8–30 Hz) containing most of the movement data were retained through filtering using “Arduino Uno” microcontroller followed by 2-stage logistic regression to obtain a mean classification accuracy of 70%. PMID:29888252

  1. Design of Embedded System for Multivariate Classification of Finger and Thumb Movements Using EEG Signals for Control of Upper Limb Prosthesis

    Directory of Open Access Journals (Sweden)

    Nasir Rashid

    2018-01-01

    Full Text Available Brain Computer Interface (BCI determines the intent of the user from a variety of electrophysiological signals. These signals, Slow Cortical Potentials, are recorded from scalp, and cortical neuronal activity is recorded by implanted electrodes. This paper is focused on design of an embedded system that is used to control the finger movements of an upper limb prosthesis using Electroencephalogram (EEG signals. This is a follow-up of our previous research which explored the best method to classify three movements of fingers (thumb movement, index finger movement, and first movement. Two-stage logistic regression classifier exhibited the highest classification accuracy while Power Spectral Density (PSD was used as a feature of the filtered signal. The EEG signal data set was recorded using a 14-channel electrode headset (a noninvasive BCI system from right-handed, neurologically intact volunteers. Mu (commonly known as alpha waves and Beta Rhythms (8–30 Hz containing most of the movement data were retained through filtering using “Arduino Uno” microcontroller followed by 2-stage logistic regression to obtain a mean classification accuracy of 70%.

  2. Design of Embedded System for Multivariate Classification of Finger and Thumb Movements Using EEG Signals for Control of Upper Limb Prosthesis.

    Science.gov (United States)

    Rashid, Nasir; Iqbal, Javaid; Javed, Amna; Tiwana, Mohsin I; Khan, Umar Shahbaz

    2018-01-01

    Brain Computer Interface (BCI) determines the intent of the user from a variety of electrophysiological signals. These signals, Slow Cortical Potentials, are recorded from scalp, and cortical neuronal activity is recorded by implanted electrodes. This paper is focused on design of an embedded system that is used to control the finger movements of an upper limb prosthesis using Electroencephalogram (EEG) signals. This is a follow-up of our previous research which explored the best method to classify three movements of fingers (thumb movement, index finger movement, and first movement). Two-stage logistic regression classifier exhibited the highest classification accuracy while Power Spectral Density (PSD) was used as a feature of the filtered signal. The EEG signal data set was recorded using a 14-channel electrode headset (a noninvasive BCI system) from right-handed, neurologically intact volunteers. Mu (commonly known as alpha waves) and Beta Rhythms (8-30 Hz) containing most of the movement data were retained through filtering using "Arduino Uno" microcontroller followed by 2-stage logistic regression to obtain a mean classification accuracy of 70%.

  3. Intrarenal purinergic signaling in the control of renal tubular transport

    DEFF Research Database (Denmark)

    Prætorius, Helle; Leipziger, Jens Georg

    2010-01-01

    Renal tubular epithelial cells receive hormonal input that regulates volume and electrolyte homeostasis. In addition, numerous intrarenal, local signaling agonists have appeared on the stage of renal physiology. One such system is that of intrarenal purinergic signaling. This system involves all......-reaching advances indicate that ATP is often used as a local transmitter for classical sensory transduction. This transmission apparently also applies to sensory functions in the kidney. Locally released ATP is involved in sensing of renal tubular flow or in detecting the distal tubular load of NaCl at the macula...

  4. An interplay between 2 signaling pathways: Melatonin-cAMP and IP3–Ca2+ signaling pathways control intraerythrocytic development of the malaria parasite Plasmodium falciparum

    International Nuclear Information System (INIS)

    Furuyama, Wakako; Enomoto, Masahiro; Mossaad, Ehab; Kawai, Satoru; Mikoshiba, Katsuhiko; Kawazu, Shin-ichiro

    2014-01-01

    Highlights: • A melatonin receptor antagonist blocked Ca 2+ oscillation in P. falciparum and inhibited parasite growth. • P. falciparum development is controlled by Ca 2+ - and cAMP-signaling pathways. • The cAMP-signaling pathway at ring form and late trophozoite stages governs parasite growth of P. falciparum. - Abstract: Plasmodium falciparum spends most of its asexual life cycle within human erythrocytes, where proliferation and maturation occur. Development into the mature forms of P. falciparum causes severe symptoms due to its distinctive sequestration capability. However, the physiological roles and the molecular mechanisms of signaling pathways that govern development are poorly understood. Our previous study showed that P. falciparum exhibits stage-specific spontaneous Calcium (Ca 2+ ) oscillations in ring and early trophozoites, and the latter was essential for parasite development. In this study, we show that luzindole (LZ), a selective melatonin receptor antagonist, inhibits parasite growth. Analyses of development and morphology of LZ-treated P. falciparum revealed that LZ severely disrupted intraerythrocytic maturation, resulting in parasite death. When LZ was added at ring stage, the parasite could not undergo further development, whereas LZ added at the trophozoite stage inhibited development from early into late schizonts. Live-cell Ca 2+ imaging showed that LZ treatment completely abolished Ca 2+ oscillation in the ring forms while having little effect on early trophozoites. Further, the melatonin-induced cAMP increase observed at ring and late trophozoite stage was attenuated by LZ treatment. These suggest that a complex interplay between IP 3 –Ca 2+ and cAMP signaling pathways is involved in intraerythrocytic development of P. falciparum

  5. An intelligent vehicular traffic signal control system with state flow chart design and fpga prototyping

    International Nuclear Information System (INIS)

    Solangi, U.S.; Memon, T.D.; Noonari, A.S.; Ansari, O.A.

    2017-01-01

    The problem of vehicular traffic congestion is a persistent constraint in the socio-economic development of Pakistan. This paper presents design and implementation of an intelligent traffic controller based on FPGA (Field Programmable Gate Array) to provide an efficient traffic management by optimizing functioning of traffic lights which will result in minimizing traffic congestion at intersections. The existent Traffic Signal system in Pakistan is fixed-time based and offers only Open Loop method for Traffic Control. The Intelligent Traffic Controller presented here uses feedback sensors to read the Traffic density present at a four way intersection to provide an efficient alternative for better supervisory Control of Traffic flow. The traffic density based control logic has been developed in a State Flow Chart for improved visualization of State Machine based operation, and implemented as a Subsystem in Simulink and transferred into VHDL (Hardware Description Language) code using HDL Coder for reducing development time and time to market, which are essential to capitalize Embedded Systems Market. The VHDL code is synthesized with Altera QUARTUS, simulated timing waveform is obtained to verify correctness of the algorithm for different Traffic Scenarios. For implementation purpose estimations were obtained for Cyclone-III and Stratix-III. (author)

  6. An Intelligent Vehicular Traffic Signal Control System with State Flow Chart Design and FPGA Prototyping

    Directory of Open Access Journals (Sweden)

    UMAIR SAEEDSOLANGI

    2017-04-01

    Full Text Available The problem of vehicular traffic congestion is a persistent constraint in the socio-economic development of Pakistan. This paper presents design and implementation of an intelligent traffic controller based on FPGA (Field Programmable Gate Array to provide an efficient traffic management by optimizing functioning of traffic lights which will result in minimizing traffic congestion at intersections. The existent Traffic Signal system in Pakistan is fixed-time based and offers only Open Loop method for Traffic Control. The Intelligent Traffic Controller presented here uses feedback sensors to read the Traffic density present at a four way intersection to provide an efficient alternative for better supervisory Control of Traffic flow. The traffic density based control logic has been developed in a State Flow Chart for improved visualization of State Machine based operation, and implemented as a Subsystem in Simulink and transferred into VHDL (Hardware Description Language code using HDL Coder for reducing development time and time to market, which are essential to capitalize Embedded Systems Market. The VHDL code is synthesized with Altera QUARTUS, simulated timing waveform is obtained to verify correctness of the algorithm for different Traffic Scenarios. For implementation purpose estimations were obtained for Cyclone-III and Stratix-III.

  7. Stop feeling: inhibition of emotional interference following stop-signal trials.

    Science.gov (United States)

    Kalanthroff, Eyal; Cohen, Noga; Henik, Avishai

    2013-01-01

    Although a great deal of literature has been dedicated to the mutual links between emotion and the selective attention component of executive control, there is very little data regarding the links between emotion and the inhibitory component of executive control. In the current study we employed an emotional stop-signal task in order to examine whether emotion modulates and is modulated by inhibitory control. Results replicated previous findings showing reduced inhibitory control [longer stop-signal reaction time (SSRT)] following negative, compared to neutral pictures. Most importantly, results show decreased emotional interference following stop-signal trials. These results show that the inhibitory control component of executive control can serve to decrease emotional effects. We suggest that inhibitory control and emotion have a two-way connection in which emotion disrupts inhibitory control and activation of inhibitory control disrupts emotion.

  8. Stop feeling: Inhibition of emotional interference following stop-signal trials

    Directory of Open Access Journals (Sweden)

    Eyal eKalanthroff

    2013-03-01

    Full Text Available Although a great deal of literature has been dedicated to the mutual links between emotion and the selective attention component of executive control, there is very little data regarding the links between emotion and the inhibitory component of executive control. In the current study we employed an emotional stop-signal task in order to examine whether emotion modulates and is modulated by inhibitory control. Results replicated previous findings showing reduced inhibitory control (longer stop-signal reaction time following negative, compared to neutral pictures. Most importantly, results show decreased emotional interference following stop-signal trials. These results show that the inhibitory control component of executive control can serve to decrease emotional effects. We suggest that inhibitory control and emotion have a two-way connection in which emotion disrupts inhibitory control and activation of inhibitory control disrupts emotion.

  9. Canonical Wnt signaling in diabetic retinopathy.

    Science.gov (United States)

    Chen, Qian; Ma, Jian-Xing

    2017-10-01

    Diabetic retinopathy (DR) is a common eye complication of diabetes, and the pathogenic mechanism of DR is still under investigation. The canonical Wnt signaling pathway is an evolutionarily conserved pathway that plays fundamental roles in embryogenesis and adult tissue homeostasis. Wnt signaling regulates expression of multiple genes that control retinal development and eye organogenesis, and dysregulated Wnt signaling plays pathophysiological roles in many ocular diseases, including DR. This review highlights recent progress in studies of Wnt signaling in DR. We discuss Wnt signaling regulation in the retina and dysregulation of Wnt signaling associated with ocular diseases with an emphasis on DR. We also discuss the therapeutic potential of modulating Wnt signaling in DR. Continued studies in this field will advance our current understanding on DR and contribute to the development of new treatments. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Tailless and Atrophin control Drosophila aggression by regulating neuropeptide signalling in the pars intercerebralis

    Science.gov (United States)

    Davis, Shaun M.; Thomas, Amanda L.; Nomie, Krystle J.; Huang, Longwen; Dierick, Herman A.

    2014-02-01

    Aggressive behaviour is widespread throughout the animal kingdom. However, its mechanisms are poorly understood, and the degree of molecular conservation between distantly related species is unknown. Here we show that knockdown of tailless (tll) increases aggression in Drosophila, similar to the effect of its mouse orthologue Nr2e1. Tll localizes to the adult pars intercerebralis (PI), which shows similarity to the mammalian hypothalamus. Knockdown of tll in the PI is sufficient to increase aggression and is rescued by co-expressing human NR2E1. Knockdown of Atrophin, a Tll co-repressor, also increases aggression, and both proteins physically interact in the PI. tll knockdown-induced aggression is fully suppressed by blocking neuropeptide processing or release from the PI. In addition, genetically activating PI neurons increases aggression, mimicking the aggression-inducing effect of hypothalamic stimulation. Together, our results suggest that a transcriptional control module regulates neuropeptide signalling from the neurosecretory cells of the brain to control aggressive behaviour.

  11. SCF(KMD) controls cytokinin signaling by regulating the degradation of type-B response regulators.

    Science.gov (United States)

    Kim, Hyo Jung; Chiang, Yi-Hsuan; Kieber, Joseph J; Schaller, G Eric

    2013-06-11

    Cytokinins are plant hormones that play critical roles in growth and development. In Arabidopsis, the transcriptional response to cytokinin is regulated by action of type-B Arabidopsis response regulators (ARRs). Although central elements in the cytokinin signal transduction pathway have been identified, mechanisms controlling output remain to be elucidated. Here we demonstrate that a family of F-box proteins, called the kiss me deadly (KMD) family, targets type-B ARR proteins for degradation. KMD proteins form an S-phase kinase-associated PROTEIN1 (SKP1)/Cullin/F-box protein (SCF) E3 ubiquitin ligase complex and directly interact with type-B ARR proteins. Loss-of-function KMD mutants stabilize type-B ARRs and exhibit an enhanced cytokinin response. In contrast, plants with elevated KMD expression destabilize type-B ARR proteins leading to cytokinin insensitivity. Our results support a model in which an SCF(KMD) complex negatively regulates cytokinin responses by controlling levels of a key family of transcription factors.

  12. Msx homeobox genes critically regulate embryo implantation by controlling paracrine signaling between uterine stroma and epithelium.

    Directory of Open Access Journals (Sweden)

    Shanmugasundaram Nallasamy

    Full Text Available The mammalian Msx homeobox genes, Msx1 and Msx2, encode transcription factors that control organogenesis and tissue interactions during embryonic development. We observed overlapping expression of these factors in uterine epithelial and stromal compartments of pregnant mice prior to embryo implantation. Conditional ablation of both Msx1 and Msx2 in the uterus resulted in female infertility due to a failure in implantation. In these mutant mice (Msx1/2(d/d, the uterine epithelium exhibited persistent proliferative activity and failed to attach to the embryos. Gene expression profiling of uterine epithelium and stroma of Msx1/2(d/d mice revealed an elevated expression of several members of the Wnt gene family in the preimplantation uterus. Increased canonical Wnt signaling in the stromal cells activated β-catenin, stimulating the production of a subset of fibroblast growth factors (FGFs in these cells. The secreted FGFs acted in a paracrine manner via the FGF receptors in the epithelium to promote epithelial proliferation, thereby preventing differentiation of this tissue and creating a non-receptive uterus refractory to implantation. Collectively, these findings delineate a unique signaling network, involving Msx1/2, Wnts, and FGFs, which operate in the uterus at the time of implantation to control the mesenchymal-epithelial dialogue critical for successful establishment of pregnancy.

  13. Epithelial control of gut-associated lymphoid tissue formation through p38α-dependent restraint of NF-κB signaling

    Science.gov (United States)

    Caballero-Franco, Celia; Guma, Monica; Choo, Min-Kyung; Sano, Yasuyo; Enzler, Thomas; Karin, Michael; Mizoguchi, Atsushi; Park, Jin Mo

    2015-01-01

    The protein kinase p38α mediates cellular responses to environmental and endogenous cues that direct tissue homeostasis and immune responses. Studies of mice lacking p38α in several different cell types have demonstrated that p38α signaling is essential to maintaining the proliferation-differentiation balance in developing and steady-state tissues. The mechanisms underlying these roles involve cell-autonomous control of signaling and gene expression by p38α. Here we show that p38α regulates gut-associated lymphoid tissue (GALT) formation in a non-cell-autonomous manner. From an investigation of mice with intestinal epithelial cell-specific deletion of the p38α gene, we find that p38α serves to limit NF-κB signaling and thereby attenuate GALT-promoting chemokine expression in the intestinal epithelium. Loss of this regulation results in GALT hyperplasia and, in some animals, mucosa-associated B cell lymphoma. These anomalies occur independently of luminal microbial stimuli and are likely driven by direct epithelial-lymphoid interactions. Our study illustrates a novel p38α-dependent mechanism preventing excessive generation of epithelial-derived signals that drive lymphoid tissue overgrowth and malignancy. PMID:26792803

  14. Hcm1 integrates signals from Cdk1 and calcineurin to control cell proliferation.

    Science.gov (United States)

    Arsenault, Heather E; Roy, Jagoree; Mapa, Claudine E; Cyert, Martha S; Benanti, Jennifer A

    2015-10-15

    Cyclin-dependent kinase (Cdk1) orchestrates progression through the cell cycle by coordinating the activities of cell-cycle regulators. Although phosphatases that oppose Cdk1 are likely to be necessary to establish dynamic phosphorylation, specific phosphatases that target most Cdk1 substrates have not been identified. In budding yeast, the transcription factor Hcm1 activates expression of genes that regulate chromosome segregation and is critical for maintaining genome stability. Previously we found that Hcm1 activity and degradation are stimulated by Cdk1 phosphorylation of distinct clusters of sites. Here we show that, upon exposure to environmental stress, the phosphatase calcineurin inhibits Hcm1 by specifically removing activating phosphorylations and that this regulation is important for cells to delay proliferation when they encounter stress. Our work identifies a mechanism by which proliferative signals from Cdk1 are removed in response to stress and suggests that Hcm1 functions as a rheostat that integrates stimulatory and inhibitory signals to control cell proliferation. © 2015 Arsenault, Roy, et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  15. Field-programmable gate array based controller for multi spot light-addressable potentiometric sensors with integrated signal correction mode

    Energy Technology Data Exchange (ETDEWEB)

    Werner, Carl Frederik; Schusser, Sebastian; Spelthahn, Heiko [Aachen University of Applied Sciences, Juelich Campus, Institute of Nano- and Biotechnologies, Heinrich-Mussmann-Strasse 1, 52428 Juelich (Germany); Institute of Bio- and Nanosystems (IBN-2), Research Centre Juelich GmbH, 52425 Juelich (Germany); Wagner, Torsten; Yoshinobu, Tatsuo [Tohoku University, Department of Electronic Engineering, 6-6-05 Aramaki Aza Aoba, Aoba-ku, Sendai, Miyagi 980-8579 (Japan); Schoening, Michael J., E-mail: schoening@fh-aachen.de [Aachen University of Applied Sciences, Juelich Campus, Institute of Nano- and Biotechnologies, Heinrich-Mussmann-Strasse 1, 52428 Juelich (Germany); Institute of Bio- and Nanosystems (IBN-2), Research Centre Juelich GmbH, 52425 Juelich (Germany)

    2011-11-01

    Highlights: > Flexible up-scalable design of a light-addressable potentiometric sensor set-up. > Utilisation of a field-programmable gate array to address LAPS measurement spots. > Measurements in amplitude-mode and phase-mode for different pH solutions. > Amplitude, phase and frequency behaviour of LAPS for single and multiple light stimulus. > Signal calibration method by brightness control to compensated systematic errors. - Abstract: A light-addressable potentiometric sensor (LAPS) can measure the concentration of one or several analytes at the sensor surface simultaneously in a spatially resolved manner. A modulated light pointer stimulates the semiconductor structure at the area of interest and a responding photocurrent can be read out. By simultaneous stimulation of several areas with light pointers of different modulation frequencies, the read out can be performed at the same time. With the new proposed controller electronic based on a field-programmable gate array (FPGA), it is possible to control the modulation frequencies, phase shifts, and light brightness of multiple light pointers independently and simultaneously. Thus, it is possible to investigate the frequency response of the sensor, and to examine the analyte concentration by the determination of the surface potential with the help of current/voltage curves and phase/voltage curves. Additionally, the ability to individually change the light intensities of each light pointer is used to perform signal correction.

  16. A Hybrid Fuzzy Genetic Algorithm for an Adaptive Traffic Signal System

    Directory of Open Access Journals (Sweden)

    S. M. Odeh

    2015-01-01

    Full Text Available This paper presents a hybrid algorithm that combines Fuzzy Logic Controller (FLC and Genetic Algorithms (GAs and its application on a traffic signal system. FLCs have been widely used in many applications in diverse areas, such as control system, pattern recognition, signal processing, and forecasting. They are, essentially, rule-based systems, in which the definition of these rules and fuzzy membership functions is generally based on verbally formulated rules that overlap through the parameter space. They have a great influence over the performance of the system. On the other hand, the Genetic Algorithm is a metaheuristic that provides a robust search in complex spaces. In this work, it has been used to adapt the decision rules of FLCs that define an intelligent traffic signal system, obtaining a higher performance than a classical FLC-based control. The simulation results yielded by the hybrid algorithm show an improvement of up to 34% in the performance with respect to a standard traffic signal controller, Conventional Traffic Signal Controller (CTC, and up to 31% in the comparison with a traditional logic controller, FLC.

  17. Signal Transduction Pathways that Regulate CAB Gene Expression

    Energy Technology Data Exchange (ETDEWEB)

    Chory, Joanne

    2004-12-31

    The process of chloroplast differentiation, involves the coordinate regulation of many nuclear and chloroplast genes. The cues for the initiation of this developmental program are both extrinsic (e.g., light) and intrinsic (cell-type and plastid signals). During this project period, we utilized a molecular genetic approach to select for Arabidopsis mutants that did not respond properly to environmental light conditions, as well as mutants that were unable to perceive plastid damage. These latter mutants, called gun mutants, define two retrograde signaling pathways that regulate nuclear gene expression in response to chloroplasts. A major finding was to identify a signal from chloroplasts that regulates nuclear gene transcription. This signal is the build-up of Mg-Protoporphyrin IX, a key intermediate of the chlorophyll biosynthetic pathway. The signaling pathways downstream of this signal are currently being studied. Completion of this project has provided an increased understanding of the input signals and retrograde signaling pathways that control nuclear gene expression in response to the functional state of chloroplasts. These studies should ultimately influence our abilities to manipulate plant growth and development, and will aid in the understanding of the developmental control of photosynthesis.

  18. Signal Transduction Pathways that Regulate CAB Gene Expression

    Energy Technology Data Exchange (ETDEWEB)

    Chory, Joanne

    2006-01-16

    The process of chloroplast differentiation, involves the coordinate regulation of many nuclear and chloroplast genes. The cues for the initiation of this developmental program are both extrinsic (e.g., light) and intrinsic (cell-type and plastid signals). During this project period, we utilized a molecular genetic approach to select for Arabidopsis mutants that did not respond properly to environmental light conditions, as well as mutants that were unable to perceive plastid damage. These latter mutants, called gun mutants, define two retrograde signaling pathways that regulate nuclear gene expression in response to chloroplasts. A major finding was to identify a signal from chloroplasts that regulates nuclear gene transcription. This signal is the build-up of Mg-Protoporphyrin IX, a key intermediate of the chlorophyll biosynthetic pathway. The signaling pathways downstream of this signal are currently being studied. Completion of this project has provided an increased understanding of the input signals and retrograde signaling pathways that control nuclear gene expression in response to the functional state of chloroplasts. These studies should ultimately influence our abilities to manipulate plant growth and development, and will aid in the understanding of the developmental control of photosynthesis.

  19. Primary Cilia, Signaling Networks and Cell Migration

    DEFF Research Database (Denmark)

    Veland, Iben Rønn

    Primary cilia are microtubule-based, sensory organelles that emerge from the centrosomal mother centriole to project from the surface of most quiescent cells in the human body. Ciliary entry is a tightly controlled process, involving diffusion barriers and gating complexes that maintain a unique...... this controls directional cell migration as a physiological response. The ciliary pocket is a membrane invagination with elevated activity of clathrin-dependent endocytosis (CDE). In paper I, we show that the primary cilium regulates TGF-β signaling and the ciliary pocket is a compartment for CDE...... on formation of the primary cilium and CDE at the pocket region. The ciliary protein Inversin functions as a molecular switch between canonical and non-canonical Wnt signaling. In paper II, we show that Inversin and the primary cilium control Wnt signaling and are required for polarization and cell migration...

  20. Maternal xNorrin, a canonical Wnt signaling agonist and TGF-β antagonist, controls early neuroectoderm specification in Xenopus.

    Directory of Open Access Journals (Sweden)

    Suhong Xu

    Full Text Available Dorsal-ventral specification in the amphibian embryo is controlled by β-catenin, whose activation in all dorsal cells is dependent on maternal Wnt11. However, it remains unknown whether other maternally secreted factors contribute to β-catenin activation in the dorsal ectoderm. Here, we show that maternal Xenopus Norrin (xNorrin promotes anterior neural tissue formation in ventralized embryos. Conversely, when xNorrin function is inhibited, early canonical Wnt signaling in the dorsal ectoderm and the early expression of the zygotic neural inducers Chordin, Noggin, and Xnr3 are severely suppressed, causing the loss of anterior structures. In addition, xNorrin potently inhibits BMP- and Nodal/Activin-related functions through direct binding to the ligands. Moreover, a subset of Norrin mutants identified in humans with Norrie disease retain Wnt activation but show defective inhibition of Nodal/Activin-related signaling in mesoderm induction, suggesting that this disinhibition causes Norrie disease. Thus, xNorrin is an unusual molecule that acts on two major signaling pathways, Wnt and TGF-β, in opposite ways and is essential for early neuroectoderm specification.

  1. NKCC1 controls GABAergic signaling and neuroblast migration in the postnatal forebrain

    Directory of Open Access Journals (Sweden)

    Murray Kerren

    2011-02-01

    Full Text Available Abstract From an early postnatal period and throughout life there is a continuous production of olfactory bulb (OB interneurons originating from neuronal precursors in the subventricular zone. To reach the OB circuits, immature neuroblasts migrate along the rostral migratory stream (RMS. In the present study, we employed cultured postnatal mouse forebrain slices and used lentiviral vectors to label neuronal precursors with GFP and to manipulate the expression levels of the Na-K-2Cl cotransporter NKCC1. We investigated the role of this Cl- transporter in different stages of postnatal neurogenesis, including neuroblast migration and integration in the OB networks once they have reached the granule cell layer (GCL. We report that NKCC1 activity is necessary for maintaining normal migratory speed. Both pharmacological and genetic manipulations revealed that NKCC1 maintains high [Cl-]i and regulates the resting membrane potential of migratory neuroblasts whilst its functional expression is strongly reduced at the time cells reach the GCL. As in other developing systems, NKCC1 shapes GABAA-dependent signaling in the RMS neuroblasts. Also, we show that NKCC1 controls the migration of neuroblasts in the RMS. The present study indeed indicates that the latter effect results from a novel action of NKCC1 on the resting membrane potential, which is independent of GABAA-dependent signaling. All in all, our findings show that early stages of the postnatal recruitment of OB interneurons rely on precise, orchestrated mechanisms that depend on multiple actions of NKCC1.

  2. Spatiotemporal Control of GPR37 Signaling and Its Behavioral Effects by Optogenetics

    Directory of Open Access Journals (Sweden)

    Wu Zheng

    2018-03-01

    Full Text Available Despite the progress in deorphanization of G Protein-Coupled Receptors (GPCRs, ≈100 GPCRs are still classified as orphan receptors without identified endogenous ligands and with unknown physiological functions. The lack of endogenous ligands triggering GPCR signaling has hampered the study of orphan GPCR functions. Using GPR37 as an example, we provide here the first demonstration of the channelrhodopsin 2 (ChR2-GPCR approach to bypass the endogenous ligand and selectively activate the orphan GPCR signal by optogenetics. Inspired by the opto-XR approach, we designed the ChR2-GPR37 chimera, in which the corresponding parts of GPR37 replaced the intracellular portions of ChR2. We showed that optogenetic activation of ChR2/opto-GPR37 elicited specific GPR37 signaling, as evidenced by reduced cAMP level, enhanced ERK phosphorylation and increased motor activity, confirming the specificity of opto-GPR37 signaling. Besides, optogenetic activation of opto-GPR37 uncovered novel aspects of GPR37 signaling (such as IP-3 signaling and anxiety-related behavior. Optogenetic activation of opto-GPR37 permits the causal analysis of GPR37 activity in the defined cells and behavioral responses of freely moving animals. Importantly, given the evolutionarily conserved seven-helix transmembrane structures of ChR2 and orphan GPCRs, we propose that opto-GPR37 approach can be readily applied to other orphan GPCRs for their deorphanization in freely moving animals.

  3. Nuclear pulse signal processing techniques based on blind deconvolution method

    International Nuclear Information System (INIS)

    Hong Pengfei; Yang Lei; Qi Zhong; Meng Xiangting; Fu Yanyan; Li Dongcang

    2012-01-01

    This article presents a method of measurement and analysis of nuclear pulse signal, the FPGA to control high-speed ADC measurement of nuclear radiation signals and control the high-speed transmission status of the USB to make it work on the Slave FIFO mode, using the LabVIEW online data processing and display, using the blind deconvolution method to remove the accumulation of signal acquisition, and to restore the nuclear pulse signal with a transmission speed, real-time measurements show that the advantages. (authors)

  4. Plasma position control device

    International Nuclear Information System (INIS)

    Takase, Haruhiko.

    1987-01-01

    Purpose: To conduct position control stably to various plasmas and reduce the burden on the control coil power source. Constitution: Among the proportional, integration and differentiation controls, a proportional-differentiation control section and an integration control section are connected in parallel. Then, a signal switching circuit is disposed to the control signal input section for the proportional-differentiation control section such that either a present position of plasmas or deviation between the present plasma position and an aimed value can be selected as a control signal depending on the control procedures or the state of the plasmas. For instance, if a rapid response is required for the control, the deviation between the present plasma position and the aimed value is selected as the input signal to conduct proportional, integration and differentiation controls. While on the other hand, if it is intended to reduce the burden on the control coil power source, it is adapted such that the control signal inputted to the proportional-differentiation control section itself can select the present plasma position. (Yoshihara, H.)

  5. Control rod drives

    International Nuclear Information System (INIS)

    Asano, Hiromitsu.

    1979-01-01

    Purpose: To drive control rods at an optimum safety speed corresponding to the reactor core output. Constitution: The reactor power is detected by a neutron detector and the output signal is applied to a process computer. The process computer issues a signal representing the reactor core output, which is converted through a function generator into a signal representing the safety speed of control rods. The converted signal is further supplied to a V/F converter and converted into a pulse signal. The pulse signal is inputted to a step motor driving circuit, which actuates a step motor to operate the control rods always at a safety speed corresponding to the reactor core power. (Furukawa, Y.)

  6. Converging Light, Energy and Hormonal Signaling Control Meristem Activity, Leaf Initiation, and Growth1[CC-BY

    Science.gov (United States)

    Mohammed, Binish; Bilooei, Sara Farahi; Grove, Elliot; Railo, Saana; Palme, Klaus

    2018-01-01

    The development of leaf primordia is subject to light control of meristematic activity. Light regulates the expression of thousands of genes with roles in cell proliferation, organ development, and differentiation of photosynthetic cells. Previous work has highlighted roles for hormone homeostasis and the energy-dependent Target of Rapamycin (TOR) kinase in meristematic activity, yet a picture of how these two regulatory mechanisms depend on light perception and interact with each other has yet to emerge. Their relevance beyond leaf initiation also is unclear. Here, we report the discovery that the dark-arrested meristematic region of Arabidopsis (Arabidopsis thaliana) experiences a local energy deprivation state and confirm previous findings that the PIN1 auxin transporter is diffusely localized in the dark. Light triggers a rapid removal of the starvation state and the establishment of PIN1 polar membrane localization consistent with auxin export, both preceding the induction of cell cycle- and cytoplasmic growth-associated genes. We demonstrate that shoot meristematic activity can occur in the dark through the manipulation of auxin and cytokinin activity as well as through the activation of energy signaling, both targets of photomorphogenesis action, but the organ developmental outcomes differ: while TOR-dependent energy signals alone stimulate cell proliferation, the development of a normal leaf lamina requires photomorphogenesis-like hormonal responses. We further show that energy signaling adjusts the extent of cell cycle activity and growth of young leaves non-cellautonomously to available photosynthates and leads to organs constituted of a greater number of cells developing under higher irradiance. This makes energy signaling perhaps the most important biomass growth determinant under natural, unstressed conditions. PMID:29284741

  7. Neural networks in signal processing

    International Nuclear Information System (INIS)

    Govil, R.

    2000-01-01

    Nuclear Engineering has matured during the last decade. In research and design, control, supervision, maintenance and production, mathematical models and theories are used extensively. In all such applications signal processing is embedded in the process. Artificial Neural Networks (ANN), because of their nonlinear, adaptive nature are well suited to such applications where the classical assumptions of linearity and second order Gaussian noise statistics cannot be made. ANN's can be treated as nonparametric techniques, which can model an underlying process from example data. They can also adopt their model parameters to statistical change with time. Algorithms in the framework of Neural Networks in Signal processing have found new applications potentials in the field of Nuclear Engineering. This paper reviews the fundamentals of Neural Networks in signal processing and their applications in tasks such as recognition/identification and control. The topics covered include dynamic modeling, model based ANN's, statistical learning, eigen structure based processing and generalization structures. (orig.)

  8. The Rac1 hypervariable region in targeting and signaling

    Science.gov (United States)

    Lam, B. Daniel; Hordijk, Peter L.

    2013-01-01

    Cellular signaling by small GTPases is critically dependent on proper spatio-temporal orchestration of activation and output. In addition to their core G (guanine nucleotide binding)-domain, small GTPases comprise a hypervariable region (HVR) and a lipid anchor that are generally accepted to control subcellullar localization. The HVR encodes in many small GTPases a polybasic region (PBR) that permits charge-mediated association to the inner leaflet of the plasma membrane or to intracellular organelles. Over the past 15–20 years, evidence has accumulated for specific protein–protein interactions, mediated by the HVR, that control both targeting and signaling specificity of small GTPases. Using the RhoGTPase Rac1 as a paradigm we here review a series of protein partners that require the Rac1 HVR for association and that control various aspects of localized Rac1 signaling. Some of these proteins represent Rac1 activators, whereas others mediate Rac1 inactivation and degradation and yet others potentiate Rac1 downstream signaling. Finally, evidence is discussed which shows that the HVR of Rac1 also contributes to effector interactions, co-operating with the N-terminal effector domain. The complexity of localized Rac1 signaling, reviewed here, is most likely exemplary for many other small GTPases as well, representing a challenge to identify and define similar mechanisms controlling the specific signaling induced by small GTPases. PMID:23354415

  9. INVARIAN AUTOMATIC CONTROL SYSTEM, USING THE INTERMEDIATE-FREQUENCY SIGNALS OF HEAT POWER PARAMETERS

    Directory of Open Access Journals (Sweden)

    G. T. Kulakov

    2015-01-01

    Full Text Available The usage of digital micro-processing automatic means allow to use design methods (technique of automatic control systems  more wider, and also to apply optimal ways of control, for example, it is possible to combine the Method of structural-parameter optimization and invariance theory. This method allow to increase essential system speed in processing of task jump and to reduce operation time of outside external disturbance up to two  values of regulated influence, and the usage of invariance principle is based on an additional measuring of the most dangerous perturbation influence and in connection with it the improvement of regulation quality is achieved.In this article the principle of invariance is applied in order to improve greatly external disturbance attack by consumption of over-heated steam. Compensation of disturbance influence on regulated value is achieving by introduction of additional signal on input of correction regulator from output of compensation device, measuring the external disturbance by consumption of over-heated steam.Modeling results of transient processes of cascade system of automatic control (CSAC, on the base of which were realized the unity of these methods, demonstrated the fact that, in processing of external disturbance by consumption of steam, the reduction of maximal dynamic regulation error is six times and cutting of regulation time by 30 % in comparison with CSAC without compensation device of external disturbance. And that is why it leads to the further reduction of maximal dynamic regulation error in processing of external disturbance by consumption of steam, and this allows to improve the quality of control.

  10. Conversion of control systems, protection and engineering safeguard system signals of Almaraz NPP model from RELAP5 into TRAC-M

    International Nuclear Information System (INIS)

    Mulas, J.; Queral, C.; Collazo, I.; Concejal, A.; Burbano, N.; Lopez Lechas, A.; Tarrega, I.

    2002-01-01

    In the scope of a joint project between the Spanish Regulatory Commission (CSN) and the electric energy industry of Spain (UNESA) about the USNRC state-of-art thermal hydraulic code, TRAC-M, there is a task relating to the translation of the Spanish NPP models from other TH codes to the new one. As a part of this project, our team is working on the translation of Almaraz NPP model from RELAP5/MOD3.2 to TRAC-M. One of the goals of the project is to analyze the conversion of control blocks, signal variables and trips in order to correct modelling all instrumentation and control systems, and also protection and engineering safeguard system-signals of the NPP. At present, several portions of the input deck have been converted to TRAC-M, and the output data have also been compared with RELAP5 data. This paper describes the problems found in the conversion and the solutions achieved.(author)

  11. The role of GαO-mediated signaling in the rostral ventrolateral medulla oblongata in cardiovascular reflexes and control of cardiac ventricular excitability.

    Science.gov (United States)

    Ang, Richard; Abramowitz, Joel; Birnbaumer, Lutz; Gourine, Alexander V; Tinker, Andrew

    2016-08-01

    The heart is controlled by the sympathetic and parasympathetic limbs of the autonomic nervous system with inhibitory signaling mechanisms recruited in both limbs. The aim of this study was to determine the role of inhibitory heterotrimeric G proteins in the central nervous mechanisms underlying autonomic control of the heart and its potential role in arrhythmogenesis. Mice with conditional deletion of the inhibitory heterotrimeric G protein GαO in the presympathetic area of the rostral ventral lateral medulla (RVLM) were generated to determine the role of GαO-mediated signalling in autonomic control and electrophysiological properties of the heart. GαO deletion within the RVLM was not associated with changes in heart rate (HR) or the arterial blood pressure at rest (home cage, normal behavior). However, exposure to stressful conditions (novel environment, hypoxia, or hypercapnia) in these mice was associated with abnormal HR responses and an increased baroreflex gain when assessed under urethane anesthesia. This was associated with shortening of the ventricular effective refractory period. This phenotype was reversed by systemic beta-adrenoceptor blockade, suggesting that GαO depletion in the RVLM increases central sympathetic drive. The data obtained support the hypothesis that GαO-mediated signaling within the presympathetic circuits of the RVLM contributes to the autonomic control of the heart. GαO deficiency in the RVLM has a significant impact on cardiovascular responses to stress, cardiovascular reflexes and electrical properties of the heart. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  12. Adaptive Neuro-Fuzzy Inference System for Classification of Background EEG Signals from ESES Patients and Controls

    Directory of Open Access Journals (Sweden)

    Zhixian Yang

    2014-01-01

    Full Text Available Background electroencephalography (EEG, recorded with scalp electrodes, in children with electrical status epilepticus during slow-wave sleep (ESES syndrome and control subjects has been analyzed. We considered 10 ESES patients, all right-handed and aged 3–9 years. The 10 control individuals had the same characteristics of the ESES ones but presented a normal EEG. Recordings were undertaken in the awake and relaxed states with their eyes open. The complexity of background EEG was evaluated using the permutation entropy (PE and sample entropy (SampEn in combination with the ANOVA test. It can be seen that the entropy measures of EEG are significantly different between the ESES patients and normal control subjects. Then, a classification framework based on entropy measures and adaptive neuro-fuzzy inference system (ANFIS classifier is proposed to distinguish ESES and normal EEG signals. The results are promising and a classification accuracy of about 89% is achieved.

  13. An anthropomorphic transhumeral prosthesis socket developed based on an oscillometric pump and controlled by force-sensitive resistor pressure signals.

    Science.gov (United States)

    Razak, N A Abd; Gholizadeh, H; Hasnan, N; Osman, N A Abu; Fadzil, S S Mohd; Hashim, N A

    2017-02-01

    While considering the importance of the interface between amputees and prosthesis sockets, we study an anthropomorphic prosthesis socket whose size can be dynamically changed according to the requirements of the residual limb. First, we introduce the structure and function of the anthropomorphic prosthesis socket. Second, we study the dynamic model of the prosthesis system and analyze the dynamic characteristics of the prosthesis socket system, the inputs of an oscillometric pump, and the control mechanism of force-sensitive resistor (FSR) pressure signals. Experiments on 10 healthy subjects using the designed system yield an average detection result between 102 and 112 kPa for the FSR pressure sensor and 39 and 41 kPa for the oscillometric pump. Results show the function of the FSR pressure signal in maintaining the contact pressure between the sockets and the residual limb. The potential development of an auto-adjusted socket that uses an oscillometric pump system will provide prosthetic sockets with controllable contact pressure at the residual limb. Moreover, this development is an attractive research area for researchers involved in rehabilitation engineering, prosthetics, and orthotics.

  14. Peroxiredoxin-controlled G-CSF signalling at the endoplasmic reticulum-early endosome interface

    NARCIS (Netherlands)

    K.K. Palande (Karishma); O. Roovers (Onno); J. Gits (Judith); C. Verwijmeren (Carola); Y. Iuchi (Yoshihito); J. Fujii (Junichi); B. Neel; R. Karisch (Robert); J. Tavernier; I.P. Touw (Ivo)

    2011-01-01

    textabstractReactive oxygen species (ROS) regulate growth factor receptor signalling at least in part by inhibiting oxidation-sensitive phosphatases. An emerging concept is that ROS act locally to affect signal transduction in different subcellular compartments and that ROS levels are regulated by

  15. 1.8 Å structure of murine GITR ligand dimer expressed in Drosophila melanogaster S2 cells

    International Nuclear Information System (INIS)

    Chattopadhyay, Kausik; Ramagopal, Udupi A.; Nathenson, Stanley G.; Almo, Steven C.

    2009-01-01

    1.8 Å X-ray crystal structure of mouse GITRL expressed in D. melanogaster S2 cells shows an identical ‘strand-exchanged’ dimeric assembly similar to that observed previously for the E. coli-expressed protein. Glucocorticoid-induced TNF receptor ligand (GITRL), a prominent member of the TNF superfamily, activates its receptor on both effector and regulatory T cells to generate critical costimulatory signals that have been implicated in a wide range of T-cell immune functions. The crystal structures of murine and human orthologs of GITRL recombinantly expressed in Escherichia coli have previously been determined. In contrast to all classical TNF structures, including the human GITRL structure, murine GITRL demonstrated a unique ‘strand-exchanged’ dimeric organization. Such a novel assembly behavior indicated a dramatic impact on receptor activation as well as on the signaling mechanism associated with the murine GITRL costimulatory system. In this present work, the 1.8 Å resolution crystal structure of murine GITRL expressed in Drosophila melanogaster S2 cells is reported. The eukaryotic protein-expression system allows transport of the recombinant protein into the extracellular culture medium, thus maximizing the possibility of obtaining correctly folded material devoid of any folding/assembly artifacts that are often suspected with E. coli-expressed proteins. The S2 cell-expressed murine GITRL adopts an identical ‘strand-exchanged’ dimeric structure to that observed for the E. coli-expressed protein, thus conclusively demonstrating the novel quaternary structure assembly behavior of murine GITRL

  16. 1.8 Å structure of murine GITR ligand dimer expressed in Drosophila melanogaster S2 cells

    Energy Technology Data Exchange (ETDEWEB)

    Chattopadhyay, Kausik [Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461 (United States); Ramagopal, Udupi A. [Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461 (United States); Nathenson, Stanley G., E-mail: nathenso@aecom.yu.edu [Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461 (United States); Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York 10461 (United States); Almo, Steven C., E-mail: nathenso@aecom.yu.edu [Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461 (United States); Department of Physiology and Biophysics, Albert Einstein College of Medicine, Bronx, New York 10461 (United States); Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461 (United States)

    2009-05-01

    1.8 Å X-ray crystal structure of mouse GITRL expressed in D. melanogaster S2 cells shows an identical ‘strand-exchanged’ dimeric assembly similar to that observed previously for the E. coli-expressed protein. Glucocorticoid-induced TNF receptor ligand (GITRL), a prominent member of the TNF superfamily, activates its receptor on both effector and regulatory T cells to generate critical costimulatory signals that have been implicated in a wide range of T-cell immune functions. The crystal structures of murine and human orthologs of GITRL recombinantly expressed in Escherichia coli have previously been determined. In contrast to all classical TNF structures, including the human GITRL structure, murine GITRL demonstrated a unique ‘strand-exchanged’ dimeric organization. Such a novel assembly behavior indicated a dramatic impact on receptor activation as well as on the signaling mechanism associated with the murine GITRL costimulatory system. In this present work, the 1.8 Å resolution crystal structure of murine GITRL expressed in Drosophila melanogaster S2 cells is reported. The eukaryotic protein-expression system allows transport of the recombinant protein into the extracellular culture medium, thus maximizing the possibility of obtaining correctly folded material devoid of any folding/assembly artifacts that are often suspected with E. coli-expressed proteins. The S2 cell-expressed murine GITRL adopts an identical ‘strand-exchanged’ dimeric structure to that observed for the E. coli-expressed protein, thus conclusively demonstrating the novel quaternary structure assembly behavior of murine GITRL.

  17. Environmental control of plant nuclear gene expression by chloroplast redox signals

    Directory of Open Access Journals (Sweden)

    Jeannette ePfalz

    2012-11-01

    Full Text Available Plant photosynthesis takes place in specialised cell organelles, the chloroplasts, which perform all essential steps of this process. The proteins involved in photosynthesis are encoded by genes located on the plastid and nuclear genomes. Proper function and regulation of light harvesting and energy fixation thus requires a tight coordination of the gene expression machineries in the two genetic compartments. This is achieved by a bi-directional exchange of information between nucleus and plastids. Signals emerging from plastids report the functional and developmental state of the organelle to the nucleus and initiate distinct nuclear gene expression profiles, which trigger responses that support or improve plastid functions. Recent research indicated that this signalling is absolutely essential for plant growth and development. Reduction/oxidation (redox signals from photosynthesis are key players in this information network since they do report functional disturbances in photosynthesis, the primary energy source of plants. Such disturbances are caused by environmental fluctuations for instance in illumination, temperature or water availability. These environmental changes affect the linear electron flow of photosynthesis and result in changes of the redox state of the components involved (e.g. the plastoquinone pool or coupled to it (e.g. the thioredoxin pool. Thus, the changes in redox state directly reflect the environmental impact and serve as immediate plastidial signals to the nucleus. The triggered responses range from counterbalancing reactions within the physiological range up to severe stress responses including cell death. This review focuses on physiological redox signals from photosynthetic electron transport, their relation to the environment, potential transduction pathways to the nucleus and their impact on nuclear gene expression.

  18. Reactor power control device

    International Nuclear Information System (INIS)

    Kobayashi, Akira.

    1980-01-01

    Purpose: To prevent misoperation in a control system for the adjustment of core coolant flow rate, and the increase in the neutron flux density caused from the misoperation in BWR type reactors. Constitution: In a reactor power control system adapted to control the reactor power by the adjustment of core flow rate, average neutron flux signals of a reactor core, entire core flow rate signals and operation state signals for coolant recycling system are inputted to a microcomputer. The outputs from the computer are sent to a recycling MG set speed controller to control the reactor core flow rate. The computer calculates the change ratio with time in the average neutron flux signals, correlation between the average neutron flux signals and the entire core flow rate signals, change ratio with time in the operation state signals for the coolant recycling system and the like and judges the abnormality in the coolant recycling system based on the calculated results. (Ikeda, J.)

  19. Wnt Signaling in Kidney Development and Disease.

    Science.gov (United States)

    Wang, Yongping; Zhou, Chengji J; Liu, Youhua

    2018-01-01

    Wnt signal cascade is an evolutionarily conserved, developmental pathway that regulates embryogenesis, injury repair, and pathogenesis of human diseases. It is well established that Wnt ligands transmit their signal via canonical, β-catenin-dependent and noncanonical, β-catenin-independent mechanisms. Mounting evidence has revealed that Wnt signaling plays a key role in controlling early nephrogenesis and is implicated in the development of various kidney disorders. Dysregulations of Wnt expression cause a variety of developmental abnormalities and human diseases, such as congenital anomalies of the kidney and urinary tract, cystic kidney, and renal carcinoma. Multiple Wnt ligands, their receptors, and transcriptional targets are upregulated during nephron formation, which is crucial for mediating the reciprocal interaction between primordial tissues of ureteric bud and metanephric mesenchyme. Renal cysts are also associated with disrupted Wnt signaling. In addition, Wnt components are important players in renal tumorigenesis. Activation of Wnt/β-catenin is instrumental for tubular repair and regeneration after acute kidney injury. However, sustained activation of this signal cascade is linked to chronic kidney diseases and renal fibrosis in patients and experimental animal models. Mechanistically, Wnt signaling controls a diverse array of biologic processes, such as cell cycle progression, cell polarity and migration, cilia biology, and activation of renin-angiotensin system. In this chapter, we have reviewed recent findings that implicate Wnt signaling in kidney development and diseases. Targeting this signaling may hold promise for future treatment of kidney disorders in patients. Copyright © 2018 Elsevier Inc. All rights reserved.

  20. Altered mitochondrial quality control signaling in muscle of old gastric cancer patients with cachexia.

    Science.gov (United States)

    Marzetti, Emanuele; Lorenzi, Maria; Landi, Francesco; Picca, Anna; Rosa, Fausto; Tanganelli, Fabiana; Galli, Marco; Doglietto, Giovanni Battista; Pacelli, Fabio; Cesari, Matteo; Bernabei, Roberto; Calvani, Riccardo; Bossola, Maurizio

    2017-01-01

    Mitochondrial dysfunction is involved in the loss of muscle featuring both aging and cancer cachexia (CC). Whether mitochondrial quality control (MQC) is altered in skeletal myocytes of old patients with CC is unclear. The present investigation therefore sought to preliminarily characterize MQC pathways in muscle of old gastric cancer patients with cachexia. The study followed a case-control cross-sectional design. Intraoperative biopsies of the rectus abdominis muscle were obtained from 18 patients with gastric adenocarcinoma (nine with CC and nine non-cachectic) and nine controls, and assayed for the expression of a set of MQC mediators. The mitofusin 2 expression was reduced in cancer patients compared with controls, independent of CC. Fission protein 1 was instead up-regulated in CC patients relative to the other groups. The mitophagy regulators PTEN-induced putative kinase 1 and Parkin were both down-regulated in cancer patients compared with controls. The ratio between the protein content of the lipidated and non-lipidated forms of microtubule-associated protein 1 light chain 3B was lower in CC patients relative to controls and non-cachectic cancer patients. Finally, the expression of autophagy-associated protein 7, lysosome-associated membrane protein 2, peroxisome proliferator-activated receptor-γ coactivator-1α, and mitochondrial transcription factor A was unvarying among groups. Collectively, our findings indicate that, in old patients with gastric cancer, cachexia is associated with derangements of the muscular MQC axis at several checkpoints: mitochondrial dynamics, mitochondrial tagging for disposal, and mitophagy signaling. Further investigations are needed to corroborate these preliminary findings and determine whether MQC pathways may become target for future interventions. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. 300 Area signal cable study

    International Nuclear Information System (INIS)

    Whattam, J.W.

    1994-01-01

    This report was prepared to discuss the alternatives available for removing the 300 Area overhead signal cable system. This system, installed in 1969, has been used for various monitoring and communication signaling needs throughout the 300 Area. Over the years this cabling system has deteriorated, has been continually reconfigured, and has been poorly documented to the point of nonreliability. The first step was to look at the systems utilizing the overhead signal cable that are still required for operation. Of the ten systems that once operated via the signal cable, only five are still required; the civil defense evacuation alarms, the public address (PA) system, the criticality alarms, the Pacific Northwest Laboratory Facilities Management Control System (FMCS), and the 384 annunciator panel. Of these five, the criticality alarms and the FMCS have been dealt with under other proposals. Therefore, this study focused on the alternatives available for the remaining three systems (evacuation alarms, PA system, and 384 panel) plus the accountability aid phones. Once the systems to be discussed were determined, then three alternatives for providing the signaling pathway were examined for each system: (1) re-wire using underground communication ducts, (2) use the Integrated Voice/Data Telecommunications System (IVDTS) already installed and operated by US West, and (3) use radio control. Each alternative was developed with an estimated cost, advantages, and disadvantages. Finally, a recommendation was provided for the best alternative for each system

  2. Epithelial Control of Gut-Associated Lymphoid Tissue Formation through p38α-Dependent Restraint of NF-κB Signaling.

    Science.gov (United States)

    Caballero-Franco, Celia; Guma, Monica; Choo, Min-Kyung; Sano, Yasuyo; Enzler, Thomas; Karin, Michael; Mizoguchi, Atsushi; Park, Jin Mo

    2016-03-01

    The protein kinase p38α mediates cellular responses to environmental and endogenous cues that direct tissue homeostasis and immune responses. Studies of mice lacking p38α in several different cell types have demonstrated that p38α signaling is essential to maintaining the proliferation-differentiation balance in developing and steady-state tissues. The mechanisms underlying these roles involve cell-autonomous control of signaling and gene expression by p38α. In this study, we show that p38α regulates gut-associated lymphoid tissue (GALT) formation in a noncell-autonomous manner. From an investigation of mice with intestinal epithelial cell-specific deletion of the p38α gene, we find that p38α serves to limit NF-κB signaling and thereby attenuate GALT-promoting chemokine expression in the intestinal epithelium. Loss of this regulation results in GALT hyperplasia and, in some animals, mucosa-associated B cell lymphoma. These anomalies occur independently of luminal microbial stimuli and are most likely driven by direct epithelial-lymphoid interactions. Our study illustrates a novel p38α-dependent mechanism preventing excessive generation of epithelial-derived signals that drive lymphoid tissue overgrowth and malignancy. Copyright © 2016 by The American Association of Immunologists, Inc.

  3. EEG Controlled Wheelchair

    Directory of Open Access Journals (Sweden)

    Swee Sim Kok

    2016-01-01

    Full Text Available This paper describes the development of a brainwave controlled wheelchair. The main objective of this project is to construct a wheelchair which can be directly controlled by the brain without requires any physical feedback as controlling input from the user. The method employed in this project is the Brain-computer Interface (BCI, which enables direct communication between the brain and the electrical wheelchair. The best method for recording the brain’s activity is electroencephalogram (EEG. EEG signal is also known as brainwaves signal. The device that used for capturing the EEG signal is the Emotiv EPOC headset. This headset is able to transmit the EEG signal wirelessly via Bluetooth to the PC (personal computer. By using the PC software, the EEG signals are processed and converted into mental command. According to the mental command (e.g. forward, left... obtained, the output electrical signal is sent out to the electrical wheelchair to perform the desired movement. Thus, in this project, a computer software is developed for translating the EEG signal into mental commands and transmitting out the controlling signal wirelessly to the electrical wheelchair.

  4. Biomechanics and energetics of walking in powered ankle exoskeletons using myoelectric control versus mechanically intrinsic control.

    Science.gov (United States)

    Koller, Jeffrey R; Remy, C David; Ferris, Daniel P

    2018-05-25

    Controllers for assistive robotic devices can be divided into two main categories: controllers using neural signals and controllers using mechanically intrinsic signals. Both approaches are prevalent in research devices, but a direct comparison between the two could provide insight into their relative advantages and disadvantages. We studied subjects walking with robotic ankle exoskeletons using two different control modes: dynamic gain proportional myoelectric control based on soleus muscle activity (neural signal), and timing-based mechanically intrinsic control based on gait events (mechanically intrinsic signal). We hypothesized that subjects would have different measures of metabolic work rate between the two controllers as we predicted subjects would use each controller in a unique manner due to one being dependent on muscle recruitment and the other not. The two controllers had the same average actuation signal as we used the control signals from walking with the myoelectric controller to shape the mechanically intrinsic control signal. The difference being the myoelectric controller allowed step-to-step variation in the actuation signals controlled by the user's soleus muscle recruitment while the timing-based controller had the same actuation signal with each step regardless of muscle recruitment. We observed no statistically significant difference in metabolic work rate between the two controllers. Subjects walked with 11% less soleus activity during mid and late stance and significantly less peak soleus recruitment when using the timing-based controller than when using the myoelectric controller. While walking with the myoelectric controller, subjects walked with significantly higher average positive and negative total ankle power compared to walking with the timing-based controller. We interpret the reduced ankle power and muscle activity with the timing-based controller relative to the myoelectric controller to result from greater slacking effects

  5. MOSFET analog memory circuit achieves long duration signal storage

    Science.gov (United States)

    1966-01-01

    Memory circuit maintains the signal voltage at the output of an analog signal amplifier when the input signal is interrupted or removed. The circuit uses MOSFET /Metal Oxide Semiconductor Field Effect Transistor/ devices as voltage-controlled switches, triggered by an external voltage-sensing device.

  6. Emergency automatic signalling system using time scheduling

    Science.gov (United States)

    Rayavel, P.; Surenderanath, S.; Rathnavel, P.; Prakash, G.

    2018-04-01

    It is difficult to handle traffic congestion and maintain roads during traffic mainly in India. As the people migrate from rural to urban and sub-urban areas, it becomes still more critical. Presently Roadways is a standout amongst the most vital transportation. At the point when a car crash happens, crisis vehicles, for example, ambulances and fire trucks must rush to the mischance scene. There emerges a situation where a portion of the crisis vehicles may cause another car crash. Therefore it becomes still more difficult for emergency vehicle to reach the destination within a predicted time. To avoid that kind of problem we have come out with an effective idea which can reduce the potential in the traffic system. The traffic system is been modified using a wireless technology and high speed micro controller to provide smooth and clear flow of traffic for ambulance to reach the destination on time. This is achieved by using RFID Tag at the ambulance and RFID Reader at the traffic system i.e., traffic signal. This mainly deals with identifying the emergency vehicle and providing a green signal to traffic signal at time of traffic jam. — By assigning priorities to various traffic movements, we can control the traffic jam. In some moments like ambulance emergency, high delegates arrive people facing lot of trouble. To overcome this problem in this paper we propose a time priority based traffic system achieved by using RFID transmitter at the emergency vehicle and RFID receiver at the traffic system i.e., traffic signal. The signal from the emergency vehicle is sent to traffic system which after detecting it sends it to microcontroller which controls the traffic signal. If any emergency vehicle is detected the system goes to emergency system mode where signal switch to green and if it is not detected normal system mode.

  7. Modularized TGFbeta-Smad Signaling Pathway

    Science.gov (United States)

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

    2011-01-01

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

  8. Sirtuin signaling controls mitochondrial function in glycogen storage disease type Ia.

    Science.gov (United States)

    Cho, Jun-Ho; Kim, Goo-Young; Mansfield, Brian C; Chou, Janice Y

    2018-05-08

    Glycogen storage disease type Ia (GSD-Ia) deficient in glucose-6-phosphatase-α (G6Pase-α) is a metabolic disorder characterized by impaired glucose homeostasis and a long-term complication of hepatocellular adenoma/carcinoma (HCA/HCC). Mitochondrial dysfunction has been implicated in GSD-Ia but the underlying mechanism and its contribution to HCA/HCC development remain unclear. We have shown that hepatic G6Pase-α deficiency leads to downregulation of sirtuin 1 (SIRT1) signaling that underlies defective hepatic autophagy in GSD-Ia. SIRT1 is a NAD + -dependent deacetylase that can deacetylate and activate peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α), a master regulator of mitochondrial integrity, biogenesis, and function. We hypothesized that downregulation of hepatic SIRT1 signaling in G6Pase-α-deficient livers impairs PGC-1α activity, leading to mitochondrial dysfunction. Here we show that the G6Pase-α-deficient livers display defective PGC-1α signaling, reduced numbers of functional mitochondria, and impaired oxidative phosphorylation. Overexpression of hepatic SIRT1 restores PGC-1α activity, normalizes the expression of electron transport chain components, and increases mitochondrial complex IV activity. We have previously shown that restoration of hepatic G6Pase-α expression normalized SIRT1 signaling. We now show that restoration of hepatic G6Pase-α expression also restores PGC-1α activity and mitochondrial function. Finally, we show that HCA/HCC lesions found in G6Pase-α-deficient livers contain marked mitochondrial and oxidative DNA damage. Taken together, our study shows that downregulation of hepatic SIRT1/PGC-1α signaling underlies mitochondrial dysfunction and that oxidative DNA damage incurred by damaged mitochondria may contribute to HCA/HCC development in GSD-Ia.

  9. Fuzzy logic control and optimization system

    Science.gov (United States)

    Lou, Xinsheng [West Hartford, CT

    2012-04-17

    A control system (300) for optimizing a power plant includes a chemical loop having an input for receiving an input signal (369) and an output for outputting an output signal (367), and a hierarchical fuzzy control system (400) operably connected to the chemical loop. The hierarchical fuzzy control system (400) includes a plurality of fuzzy controllers (330). The hierarchical fuzzy control system (400) receives the output signal (367), optimizes the input signal (369) based on the received output signal (367), and outputs an optimized input signal (369) to the input of the chemical loop to control a process of the chemical loop in an optimized manner.

  10. Evolutionary Interactions Between Visual and Chemical Signals: Chemosignals Compensate for the Loss of a Visual Signal in Male Sceloporus Lizards.

    Science.gov (United States)

    Pruett, Jake A; Zúñiga-Vega, J Jaime; Campos, Stephanie M; Soini, Helena A; Novotny, Milos V; Vital-García, Cuauhcihuatl; Martins, Emília P; Hews, Diana K

    2016-11-01

    Animals rely on multimodal signals to obtain information from conspecifics through alternative sensory systems, and the evolutionary loss of a signal in one modality may lead to compensation through increased use of signals in an alternative modality. We investigated associations between chemical signaling and evolutionary loss of abdominal color patches in males of four species (two plain-bellied and two colorful-bellied) of Sceloporus lizards. We conducted field trials to compare behavioral responses of male lizards to swabs with femoral gland (FG) secretions from conspecific males and control swabs (clean paper). We also analyzed the volatile organic compound (VOC) composition of male FG secretions by stir bar extraction and gas chromatography-mass spectrometry (GC-MS) to test the hypothesis that loss of the visual signal is associated with elaboration of the chemical signal. Males of plain-bellied, but not colorful-bellied species exhibited different rates of visual displays when exposed to swabs of conspecific FG secretions relative to control swabs. The VOC composition of male Sceloporus FG secretions was similar across all four species, and no clear association between relative abundances of VOCs and evolutionary loss of abdominal color patches was observed. The emerging pattern is that behavioral responses to conspecific chemical signals are species- and context-specific in male Sceloporus, and compensatory changes in receivers, but not signalers may be involved in mediating increased responsiveness to chemical signals in males of plain-bellied species.

  11. Blockade of CD26-mediated T cell costimulation with soluble caveolin-1-Ig fusion protein induces anergy in CD4{sup +}T cells

    Energy Technology Data Exchange (ETDEWEB)

    Ohnuma, Kei [Department of Rheumatology and Allergy, Research Hospital, The Institute of Medical Science, The University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo 108-8639 (Japan); Division of Clinical Immunology, The Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo 108-8639 (Japan); Uchiyama, Masahiko [Department of Rheumatology and Allergy, Research Hospital, The Institute of Medical Science, The University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo 108-8639 (Japan); Department of Computational Intelligence and System Science, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama, Kanagawa 226-8503 (Japan); Hatano, Ryo; Takasawa, Wataru; Endo, Yuko [Department of Rheumatology and Allergy, Research Hospital, The Institute of Medical Science, The University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo 108-8639 (Japan); Dang, Nam H. [Department of Hematologic Malignancies, Nevada Cancer Institute, Las Vegas, NV 89135 (United States); Morimoto, Chikao, E-mail: morimoto@ims.u-tokyo.ac.jp [Department of Rheumatology and Allergy, Research Hospital, The Institute of Medical Science, The University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo 108-8639 (Japan); Division of Clinical Immunology, The Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo 108-8639 (Japan)

    2009-08-21

    CD26 binds to caveolin-1 in antigen-presenting cells (APC), and that ligation of CD26 by caveolin-1 induces T cell proliferation in a TCR/CD3-dependent manner. We report herein the effects of CD26-caveolin-1 costimulatory blockade by fusion protein caveolin-1-Ig (Cav-Ig). Soluble Cav-Ig inhibits T cell proliferation and cytokine production in response to recall antigen, or allogeneic APC. Our data hence suggest that blocking of CD26-associated signaling by soluble Cav-Ig may be an effective approach as immunosuppressive therapy.

  12. Role of CD28 co-stimulation in generation and maintenance of virus-specific T cells

    DEFF Research Database (Denmark)

    Christensen, Jeanette Erbo; Christensen, Jan P; Kristensen, Nanna N

    2002-01-01

    Efficient induction of T cell responses is normally assumed to require both TCR-mediated signaling and engagement of co-stimulatory molecules, in particular CD28. However, the importance of CD28 co-stimulation in induction and maintenance of antiviral T cell responses is not clearly established....... For this reason antiviral CD4(+) and CD8(+) T cell responses in CD28-deficient mice were studied using two different viruses [vesicular stomatitis virus and lymphocytic choriomeningitis virus (LCMV)]. Intracellular cytokine staining and/or MHC-peptide tetramers were used to enumerate antigen-specific T cells...

  13. Quantification of analytes affected by relevant interfering signals under quality controlled conditions

    International Nuclear Information System (INIS)

    Bettencourt da Silva, Ricardo J.N.; Santos, Julia R.; Camoes, M. Filomena G.F.C.

    2006-01-01

    The analysis of organic contaminants or residues in biological samples is frequently affected by the presence of compounds producing interfering instrumental signals. This feature is responsible for the higher complexity and cost of these analyses and/or by a significant reduction of the number of studied analytes in a multi-analyte method. This work presents a methodology to estimate the impact of the interfering compounds on the quality of the analysis of complex samples, based on separative instrumental methods of analysis, aiming at supporting the inclusion of analytes affected by interfering compounds in the list of compounds analysed in the studied samples. The proposed methodology involves the study of the magnitude of the signal produced by the interfering compounds in the analysed matrix, and is applicable to analytical systems affected by interfering compounds with varying concentration in the studied matrix. The proposed methodology is based on the comparison of the signals from a representative number of examples of the studied matrix, in order to estimate the impact of the presence of such compounds on the measurement quality. The treatment of the chromatographic signals necessary to collect these data can be easily performed considering algorithms of subtraction of chromatographic signals available in most of the analytical instrumentation software. The subtraction of the interfering compounds signal from the sample signal allows the compensation of the interfering effect irrespective of the relative magnitude of the interfering and analyte signals, supporting the applicability of the same model of the method performance for a broader concentration range. The quantification of the measurement uncertainty was performed using the differential approach, which allows the estimation of the contribution of the presence of the interfering compounds to the quality of the measurement. The proposed methodology was successfully applied to the analysis of

  14. Control rod drives

    International Nuclear Information System (INIS)

    Hayakawa, Hiroyasu; Kawamura, Atsuo.

    1979-01-01

    Purpose: To reduce pellet-clad mechanical interactions, as well as improve the fuel safety. Constitution: In the rod drive of a bwr type reactor, an electric motor operated upon intermittent input such as of pulse signals is connected to a control rod. A resolver for converting the rotational angle of the motor to electric signals is connected to the rotational shaft of the motor and the phase difference between the output signal from the resolver and a reference signal is adapted to detect by a comparator. Based on the detection result, the controller is actuated to control a motor for control rod drive so that fine control for the movement of the control rod is made possible. This can reduce the moving distance of the control rod, decrease the thermal stress applied to the control rod and decrease the pellet clad mechanical interaction failures due to thermal expansion between the cladding tube and the pellets caused by abrupt changes in the generated power. (Furukawa, Y.)

  15. Impact of Vehicular Countdown Signals on Driving Psychologies and Behaviors: Taking China as an Example

    Directory of Open Access Journals (Sweden)

    Fuquan Pan

    2017-01-01

    Full Text Available Countdown signal control is a relatively new control mode that can inform a driver in advance about the remaining time to pass through intersections or the time needed to wait for other drivers and pedestrians. At present, few countries apply vehicular countdown signals. However, in China, some cities have applied vehicular countdown signals for years, though it is unclear how and how much such signals influence driving psychologies and behaviors compared with non-countdown signal controls. The present work aims to clarify the impact of vehicular countdown signals on driving psychologies and behaviors on the cognitive level. A questionnaire survey with 32 questions about driving psychologies and behaviors was designed, and an online survey was conducted. A total of 1051 valid questionnaires were received. The survey data were analyzed, and the main results indicate that most of the surveyed drivers prefer countdown signal controls and think that such controls can improve not only traffic safety but also traffic operational efficiency. The surveyed drivers also think that countdown signal controls have an impact on driving psychologies and behaviors and the survey results have demonstrated that the driving behaviors of female drivers surveyed are not conservative under the clear conditions of green countdown signal control. Further studies and methods concerning the effects of countdown signals on driving psychologies and behaviors are discussed.

  16. OX62+OX6+OX35+ rat dendritic cells are unable to prime CD4+ T cells for an effective immune response following acute burn injury.

    Science.gov (United States)

    Fazal, Nadeem

    2013-01-01

    Co-stimulatory molecules expressed on Dendritic Cells (DCs) function to coordinate an efficient immune response by T cells in the peripheral lymph nodes. We hypothesized that CD4+ T cell-mediated immune suppression following burn injury may be related to dysfunctional DCs residing in gut associated lymphoid tissues (GALT), such as Mesenteric Lymph Nodes (MLN). Therefore, we studied co-stimulatory molecules expressed on burn rat MLN DCs as an index of functional DCs that would mount an effective normal CD4+ T cell immune response. In a rat model of 30% Total Body Surface Area (TBSA) scald burn, OX62+OX6+OX35+ DCs and CD4+ T cells were isolated from MLN of day 3 post-burn and sham control rats. DCs were tested for their expression of co-stimulatory molecules, and prime CD4+ T cell (DC:CD4+T cell co-culture assays) to determine an effector immune response such as CD4+ T cell proliferation. The surface receptor expressions of MLN DCs co-stimulatory molecules, i.e., MHC-II, CD40, CD80 (B7-1), and CD86 (B7-2) were determined by Flow cytometry (quantitatively) and confocal microscopy (qualitatively). Tritiated thymidine and CFDA-SE determined CD4+ T cell proliferation following co-incubation with DCs. Cytokine milieu of MLN (IL-12 and IL-10) was assessed by mRNA determination by RT-PCR. The results showed down-regulated expressions of co-stimulatory markers (CD80, CD86, CD40 and MHC-II) of MLN DCs obtained from burn-injured rats, as well as lack of ability of these burn-induced DCs to stimulate CD4+ T cell proliferation in co-culture assays, as compared to the sham rats. Moreover, anti-CD40 stimulation of affected burn MLN DCs did not reverse this alteration. Furthermore, a marked up-regulation of mRNA IL-10 and down-regulation of mRNA IL-12 in burn MLN as compared to sham animals was also observed. To surmise, the data indicated that dysfunctional OX62+OX6+OX35+ rat MLN DCs may contribute to CD4+ T-cell-mediated immune suppression observed following acute burn injury.

  17. OX62+OX6+OX35+ rat dendritic cells are unable to prime CD4+ T cells for an effective immune response following acute burn injury☆

    Science.gov (United States)

    Fazal, Nadeem

    2013-01-01

    Co-stimulatory molecules expressed on Dendritic Cells (DCs) function to coordinate an efficient immune response by T cells in the peripheral lymph nodes. We hypothesized that CD4+ T cell-mediated immune suppression following burn injury may be related to dysfunctional DCs residing in gut associated lymphoid tissues (GALT), such as Mesenteric Lymph Nodes (MLN). Therefore, we studied co-stimulatory molecules expressed on burn rat MLN DCs as an index of functional DCs that would mount an effective normal CD4+ T cell immune response. In a rat model of 30% Total Body Surface Area (TBSA) scald burn, OX62+OX6+OX35+ DCs and CD4+ T cells were isolated from MLN of day 3 post-burn and sham control rats. DCs were tested for their expression of co-stimulatory molecules, and prime CD4+ T cell (DC:CD4+T cell co-culture assays) to determine an effector immune response such as CD4+ T cell proliferation. The surface receptor expressions of MLN DCs co-stimulatory molecules, i.e., MHC-II, CD40, CD80 (B7-1), and CD86 (B7-2) were determined by Flow cytometry (quantitatively) and confocal microscopy (qualitatively). Tritiated thymidine and CFDA-SE determined CD4+ T cell proliferation following co-incubation with DCs. Cytokine milieu of MLN (IL-12 and IL-10) was assessed by mRNA determination by RT-PCR. The results showed down-regulated expressions of co-stimulatory markers (CD80, CD86, CD40 and MHC-II) of MLN DCs obtained from burn-injured rats, as well as lack of ability of these burn-induced DCs to stimulate CD4+ T cell proliferation in co-culture assays, as compared to the sham rats. Moreover, anti-CD40 stimulation of affected burn MLN DCs did not reverse this alteration. Furthermore, a marked up-regulation of mRNA IL-10 and down-regulation of mRNA IL-12 in burn MLN as compared to sham animals was also observed. To surmise, the data indicated that dysfunctional OX62+OX6+OX35+ rat MLN DCs may contribute to CD4+ T-cell-mediated immune suppression observed following acute burn injury

  18. Development of a signal-extraction scheme for resonant sideband extraction

    International Nuclear Information System (INIS)

    Kokeyama, K; Kawazoe, F; Sugamoto, A; Somiya, K; Sato, S; Kawamura, S

    2008-01-01

    As a future plan, an advanced gravitational-wave detector will employ an optical configuration of resonant sideband extraction (RSE), achieved with an additional mirror at the signal-detection port of the power-recycled Fabry-Perot Michelson interferometer. To control the complex coupled cavity system, one of the most important design issues is how to extract the longitudinal control signals of the cavities. We have developed a new signal-extraction scheme which provides an appropriate sensing matrix. The new method uses two sets of sidebands: one of the sideband components satisfies the critical coupling condition for the RSE interferometer and reaches the signal-extraction port, and the other sideband is completely reflected by the Michelson interferometer. They provide a diagonalized sensing matrix and enable the RSE control to be robust

  19. Regulator of G-protein signaling - 5 (RGS5 is a novel repressor of hedgehog signaling.

    Directory of Open Access Journals (Sweden)

    William M Mahoney

    Full Text Available Hedgehog (Hh signaling plays fundamental roles in morphogenesis, tissue repair, and human disease. Initiation of Hh signaling is controlled by the interaction of two multipass membrane proteins, patched (Ptc and smoothened (Smo. Recent studies identify Smo as a G-protein coupled receptor (GPCR-like protein that signals through large G-protein complexes which contain the Gαi subunit. We hypothesize Regulator of G-Protein Signaling (RGS proteins, and specifically RGS5, are endogenous repressors of Hh signaling via their ability to act as GTPase activating proteins (GAPs for GTP-bound Gαi, downstream of Smo. In support of this hypothesis, we demonstrate that RGS5 over-expression inhibits sonic hedgehog (Shh-mediated signaling and osteogenesis in C3H10T1/2 cells. Conversely, signaling is potentiated by siRNA-mediated knock-down of RGS5 expression, but not RGS4 expression. Furthermore, using immuohistochemical analysis and co-immunoprecipitation (Co-IP, we demonstrate that RGS5 is present with Smo in primary cilia. This organelle is required for canonical Hh signaling in mammalian cells, and RGS5 is found in a physical complex with Smo in these cells. We therefore conclude that RGS5 is an endogenous regulator of Hh-mediated signaling and that RGS proteins are potential targets for novel therapeutics in Hh-mediated diseases.

  20. Interacting signal pathways control defense gene expression in Arabidopsis in response to cell wall-degrading enzymes from Erwinia carotovora.

    Science.gov (United States)

    Norman-Setterblad, C; Vidal, S; Palva, E T

    2000-04-01

    We have characterized the role of salicylic acid (SA)-independent defense signaling in Arabidopsis thaliana in response to the plant pathogen Erwinia carotovora subsp. carotovora. Use of pathway-specific target genes as well as signal mutants allowed us to elucidate the role and interactions of ethylene, jasmonic acid (JA), and SA signal pathways in this response. Gene expression studies suggest a central role for both ethylene and JA pathways in the regulation of defense gene expression triggered by the pathogen or by plant cell wall-degrading enzymes (CF) secreted by the pathogen. Our results suggest that ethylene and JA act in concert in this regulation. In addition, CF triggers another, strictly JA-mediated response inhibited by ethylene and SA. SA does not appear to have a major role in activating defense gene expression in response to CF. However, SA may have a dual role in controlling CF-induced gene expression, by enhancing the expression of genes synergistically induced by ethylene and JA and repressing genes induced by JA alone.