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Sample records for cd95 death-inducing signaling

  1. Death Induced by CD95 or CD95 Ligand Elimination

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    Abbas Hadji

    2014-04-01

    Full Text Available CD95 (Fas/APO-1, when bound by its cognate ligand CD95L, induces cells to die by apoptosis. We now show that elimination of CD95 or CD95L results in a form of cell death that is independent of caspase-8, RIPK1/MLKL, and p53, is not inhibited by Bcl-xL expression, and preferentially affects cancer cells. All tumors that formed in mouse models of low-grade serous ovarian cancer or chemically induced liver cancer with tissue-specific deletion of CD95 still expressed CD95, suggesting that cancer cannot form in the absence of CD95. Death induced by CD95R/L elimination (DICE is characterized by an increase in cell size, production of mitochondrial ROS, and DNA damage. It resembles a necrotic form of mitotic catastrophe. No single drug was found to completely block this form of cell death, and it could also not be blocked by the knockdown of a single gene, making it a promising way to kill cancer cells.

  2. Involvement of raft aggregates enriched in Fas/CD95 death-inducing signaling complex in the antileukemic action of edelfosine in Jurkat cells.

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    Gajate, Consuelo; Gonzalez-Camacho, Fernando; Mollinedo, Faustino

    2009-01-01

    Recent evidence suggests that co-clustering of Fas/CD95 death receptor and lipid rafts plays a major role in death receptor-mediated apoptosis. By a combination of genetic, biochemical, and ultrastructural approaches, we provide here compelling evidence for the involvement of lipid raft aggregates containing recruited Fas/CD95 death receptor, Fas-associated death domain-containing protein (FADD), and procaspase-8 in the induction of apoptosis in human T-cell leukemia Jurkat cells by the antitumor drug edelfosine, the prototype compound of a promising family of synthetic antitumor lipids named as synthetic alkyl-lysophospholipid analogues. Co-immunoprecipitation assays revealed that edelfosine induced the generation of the so-called death-inducing signaling complex (DISC), made up of Fas/CD95, FADD, and procaspase-8, in lipid rafts. Electron microscopy analyses allowed to visualize the formation of raft clusters and their co-localization with DISC components Fas/CD95, FADD, and procaspase-8 following edelfosine treatment of Jurkat cells. Silencing of Fas/CD95 by RNA interference, transfection with a FADD dominant-negative mutant that blocks Fas/CD95 signaling, and specific inhibition of caspase-8 prevented the apoptotic response triggered by edelfosine, hence demonstrating the functional role of DISC in drug-induced apoptosis. By using radioactive labeled edelfosine and a fluorescent analogue, we found that edelfosine accumulated in lipid rafts, forming edelfosine-rich membrane raft clusters in Jurkat leukemic T-cells. Disruption of these membrane raft domains abrogated drug uptake and drug-induced DISC assembly and apoptosis. Thus, edelfosine uptake into lipid rafts was critical for the onset of both co-aggregation of DISC in membrane rafts and subsequent apoptotic cell death. This work shows the involvement of DISC clusters in lipid raft aggregates as a supramolecular and physical entity responsible for the induction of apoptosis in leukemic cells by the antitumor

  3. Impact of TNF-R1 and CD95 internalization on apoptotic and antiapoptotic signaling.

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    Schütze, Stefan; Schneider-Brachert, Wulf

    2009-01-01

    Internalization of cell surface receptors has long been regarded as a pure means to terminate signaling via receptor degradation. A growing body of information points to the fact that many internalized receptors are still in their active state and that signaling continues along the endocytic pathway. Thus endocytosis orchestrates cell signaling by coupling and integrating different cascades on the surface of endocytic vesicles to control the quality, duration, intensity, and distribution of signaling events. The death receptors tumor necrosis factor-receptor 1 (TNF-R1) and CD95 (Fas, APO-1) are known not only to signal for cell death via apoptosis but are also capable of inducing antiapoptotic signals via transcription factor NF-kappaB induction or activation of the proliferative mitogen-activated protein kinase (MAPK)/ERK (extracellular signal-regulated kinase) protein kinase cascades, resulting in cell protection and tissue regeneration. A clue to the understanding of these contradictory biological phenomena may arise from recent findings which reveal a regulatory role of receptor internalization and intracellular receptor trafficking in selectively transmitting signals, which lead either to apoptosis or to the survival of the cell. In this chapter, we discuss the dichotomy of pro- and antiapoptotic signaling of the death receptors TNF-R1 and CD95. First, we will address the role of lipid rafts and post-translational modifications of death receptors in regulating the formation of receptor complexes. Then, we will discuss the role of internalization in determining the fate of the receptors and subsequently the specificity of signaling events. We propose that fusion of internalized TNF-receptosomes with trans-Golgi vesicles should be recognized as a novel mechanism to transduce death signals along the endocytic route. Finally, the lessons learnt from the strategy of adenovirus to escape apoptosis by targeting death receptor internalization demonstrate the

  4. CD95-CD95L: can the brain learn from the immune system?

    DEFF Research Database (Denmark)

    Becher, B; Barker, P A; Owens, T

    1998-01-01

    Members of the tumor necrosis factor/nerve growth factor receptor superfamily of cell-surface molecules can play the dual role of mediating either cytotoxicity or cell survival, both in the immune system and in the nervous system. A member of this superfamily, CD95 (also known as ApoI or Fas......), was initially identified in the immune system and has been shown to mediate receptor-dependent programmed cell death and to be expressed in the nervous system. In neurodegenerative disorders, CD95-CD95 ligand expression on glial cells might precede receptor-mediated apoptosis by cells of the CNS. It is now...... being recognized that CD95 signaling by immune cells mediates effects other than apoptosis, such as cell survival and under inflammatory conditions expression of this protein promotes neural-immune interactions. Both neuroscientists and immunologists can contribute to defining the mechanisms underlying...

  5. Cytoplasmic Overexpression of CD95L in Esophageal Adenocarcinoma Cells Overcomes Resistance to CD95-Mediated Apoptosis

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    Gregory A. Watson

    2011-03-01

    Full Text Available Introduction: The CD95/CD95L pathway plays a critical role in tissue homeostasis and immune system regulation; however, the function of this pathway in malignancy remains poorly understood. We hypothesized that CD95L expression in esophageal adenocarcinoma confers advantages to the neoplasm other than immune privilege. Methods: CD95L expression was characterized in immortalized squamous esophagus (HET-1A and Barrett esophagus (BAR-T cells; adenocarcinoma cell lines FLO-1, SEG-1, and BIC-1, and MDA468 (- control; and KFL cells (+ control. Analyses included reverse transcription-polymerase chain reaction, immunoblots of whole cell and secretory vesicle lysates, FACScan analysis, laser scanning confocal microscopy of native proteins and fluorescent constructs, and assessment of apoptosis and ERK1/2 pathways. Results: Cleaved, soluble CD95L is expressed at both the RNA and protein levels in these cell lines derived from esophageal adenocarcinoma and other human tissues. CD95L was neither trafficked to the cell membrane nor secreted into the media or within vesicles, rather the protein seems to be sequestered in the cytoplasm. CD95 and CD95L colocalize by immunofluorescence, but an interaction was not proven by immunoprecipitation. Overexpression of CD95L in the adenocarcinoma cell lines induced robust apoptosis and, under conditions of pan-caspase inhibition, resulted in activation of ERK signaling. Conclusions: CD95L localization in EA cells is inconsistent with the conference of immune privilege and is more consistent with a function that promotes tumor growth through alternative CD95 signaling. Reduced cell surface expression of CD95 affects cell sensitivity to extracellular apoptotic signals more significantly than alterations in downstream modulators of apoptosis.

  6. Regulation of CD95 expression and CD95-mediated cell death by interferon-gamma in acute lymphoblastic leukemia with chromosomal translocation t(4;11).

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    Dörrie, J; Schuh, W; Keil, A; Bongards, E; Greil, J; Fey, G H; Zunino, S J

    1999-10-01

    The regulatory effects of IFNgamma on CD95 expression and CD95-mediated cell death were investigated in three high-risk pro-B acute lymphoblastic leukemia (ALL) lines that carry the chromosomal translocation t(4;11)(q21;q23). These leukemias are characteristically refractory to conventional chemotherapeutic treatments operating through the induction of apoptosis. However, the mechanisms leading to increased cell survival and resistance to cell death in these leukemias are largely unknown. Interferon-gamma (IFNgamma), a potent inhibitor of hematopoiesis, acts in part by upregulating CD95 and sensitizing cells to CD95-induced apoptosis. The t(4;11) lines SEM, RS4;11, and MV4;11 expressed low levels of CD95, but were completely resistant to CD95-mediated death. Addition of IFNgamma markedly upregulated CD95 expression in SEM (8-9-fold), RS4;11 (2-3-fold), and MV4;11 (2-3-fold) lines. However, after treatment with IFNgamma, only an 11% increase in sensitivity to CD95-mediated cell death was observed in SEM cells, whereas RS4;11 and MV4;11 cells remained resistant. Cycloheximide, but not actinomycin D or brefeldin A, increased CD95-specific cell death only in IFNgamma-treated RS4;11 cells by approximately 12%. Abundant levels of Bcl-2 and Bcl-XL, known to inhibit CD95-signaling in some cells, were present suggesting a possible role for both molecules in the resistance to CD95-mediated cell death. Resistance of the leukemic blasts to CD95-mediated cell death and the failure of IFNgamma to substantially sensitize the CD95-signaling pathway may contribute to the highly malignant phenotype of pro-B ALL with translocation t(4;11).

  7. CNS Macrophages Control Neurovascular Development via CD95L

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    Si Chen

    2017-05-01

    Full Text Available The development of neurons and vessels shares striking anatomical and molecular features, and it is presumably orchestrated by an overlapping repertoire of extracellular signals. CNS macrophages have been implicated in various developmental functions, including the morphogenesis of neurons and vessels. However, whether CNS macrophages can coordinately influence neurovascular development and the identity of the signals involved therein is unclear. Here, we demonstrate that activity of the cell surface receptor CD95 regulates neuronal and vascular morphogenesis in the post-natal brain and retina. Furthermore, we identify CNS macrophages as the main source of CD95L, and macrophage-specific deletion thereof reduces both neurovascular complexity and synaptic activity in the brain. CD95L-induced neuronal and vascular growth is mediated through src-family kinase (SFK and PI3K signaling. Together, our study highlights a coordinated neurovascular development instructed by CNS macrophage-derived CD95L, and it underlines the importance of macrophages for the establishment of the neurovascular network during CNS development.

  8. The naturally processed CD95L elicits a c-yes/calcium/PI3K-driven cell migration pathway.

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    Sébastien Tauzin

    2011-06-01

    Full Text Available Patients affected by chronic inflammatory disorders display high amounts of soluble CD95L. This homotrimeric ligand arises from the cleavage by metalloproteases of its membrane-bound counterpart, a strong apoptotic inducer. In contrast, the naturally processed CD95L is viewed as an apoptotic antagonist competing with its membrane counterpart for binding to CD95. Recent reports pinpointed that activation of CD95 may attract myeloid and tumoral cells, which display resistance to the CD95-mediated apoptotic signal. However, all these studies were performed using chimeric CD95Ls (oligomerized forms, which behave as the membrane-bound ligand and not as the naturally processed CD95L. Herein, we examine the biological effects of the metalloprotease-cleaved CD95L on CD95-sensitive activated T-lymphocytes. We demonstrate that cleaved CD95L (cl-CD95L, found increased in sera of systemic lupus erythematosus (SLE patients as compared to that of healthy individuals, promotes the formation of migrating pseudopods at the leading edge of which the death receptor CD95 is capped (confocal microscopy. Using different migration assays (wound healing/Boyden Chamber/endothelial transmigration, we uncover that cl-CD95L promotes cell migration through a c-yes/Ca²⁺/PI3K-driven signaling pathway, which relies on the formation of a CD95-containing complex designated the MISC for Motility-Inducing Signaling Complex. These findings revisit the role of the metalloprotease-cleaved CD95L and emphasize that the increase in cl-CD95L observed in patients affected by chronic inflammatory disorders may fuel the local or systemic tissue damage by promoting tissue-filtration of immune cells.

  9. Glucose Metabolism and AMPK Signaling Regulate Dopaminergic Cell Death Induced by Gene (α-Synuclein)-Environment (Paraquat) Interactions.

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    Anandhan, Annadurai; Lei, Shulei; Levytskyy, Roman; Pappa, Aglaia; Panayiotidis, Mihalis I; Cerny, Ronald L; Khalimonchuk, Oleh; Powers, Robert; Franco, Rodrigo

    2017-07-01

    While environmental exposures are not the single cause of Parkinson's disease (PD), their interaction with genetic alterations is thought to contribute to neuronal dopaminergic degeneration. However, the mechanisms involved in dopaminergic cell death induced by gene-environment interactions remain unclear. In this work, we have revealed for the first time the role of central carbon metabolism and metabolic dysfunction in dopaminergic cell death induced by the paraquat (PQ)-α-synuclein interaction. The toxicity of PQ in dopaminergic N27 cells was significantly reduced by glucose deprivation, inhibition of hexokinase with 2-deoxy-D-glucose (2-DG), or equimolar substitution of glucose with galactose, which evidenced the contribution of glucose metabolism to PQ-induced cell death. PQ also stimulated an increase in glucose uptake, and in the levels of glucose transporter type 4 (GLUT4) and Na + -glucose transporters isoform 1 (SGLT1) proteins, but only inhibition of GLUT-like transport with STF-31 or ascorbic acid reduced PQ-induced cell death. Importantly, while autophagy protein 5 (ATG5)/unc-51 like autophagy activating kinase 1 (ULK1)-dependent autophagy protected against PQ toxicity, the inhibitory effect of glucose deprivation on cell death progression was largely independent of autophagy or mammalian target of rapamycin (mTOR) signaling. PQ selectively induced metabolomic alterations and adenosine monophosphate-activated protein kinase (AMPK) activation in the midbrain and striatum of mice chronically treated with PQ. Inhibition of AMPK signaling led to metabolic dysfunction and an enhanced sensitivity of dopaminergic cells to PQ. In addition, activation of AMPK by PQ was prevented by inhibition of the inducible nitric oxide syntase (iNOS) with 1400W, but PQ had no effect on iNOS levels. Overexpression of wild type or A53T mutant α-synuclein stimulated glucose accumulation and PQ toxicity, and this toxic synergism was reduced by inhibition of glucose metabolism

  10. Inorganic mercury dissociates preassembled Fas/CD95 receptor oligomers in T lymphocytes

    International Nuclear Information System (INIS)

    Ziemba, Stamatina E.; McCabe, Michael J.; Rosenspire, Allen J.

    2005-01-01

    Genetically susceptible rodents exposed to low burdens of inorganic mercury (Hg 2+ ) develop autoimmune disease. Previous studies have shown that low, noncytotoxic levels of Hg 2+ inhibit Fas-mediated apoptosis in T cells. These results suggest that inhibition of the Fas death receptor pathway potentially contributes to autoimmune disease after Hg 2+ exposure, as a consequence of disruption of peripheral tolerance. The formation of active death inducing signaling complexes (DISC) following CD95/Fas receptor oligomerization is a primary step in the Fas-mediated apoptotic pathway. Other recent studies have shown that Hg 2+ at concentrations that inhibit apoptosis also inhibit formation of active DISC, suggesting that inhibition of DISC is the mechanism responsible for Hg 2+ -mediated inhibition of apotosis. Preassociated Fas receptors have been implicated as key elements necessary for the production of functional DISC. We present evidence in this study showing that low and nontoxic concentrations of Hg 2+ induce the dissociation of preassembled Fas receptor complexes in Jurkat T cells. Thus, this Hg 2+ -induced event should subsequently decrease the amount of preassembled Fas available for DISC formation, potentially resulting in the attenuation of Fas-mediated apoptosis in T lymphocytes

  11. Intravital imaging reveals p53-dependent cancer cell death induced by phototherapy via calcium signaling

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    Missiroli, Sonia; Poletti, Federica; Ramirez, Fabian Galindo; Morciano, Giampaolo; Morganti, Claudia; Pandolfi, Pier Paolo; Mammano, Fabio; Pinton, Paolo

    2015-01-01

    One challenge in biology is signal transduction monitoring in a physiological context. Intravital imaging techniques are revolutionizing our understanding of tumor and host cell behaviors in the tumor environment. However, these deep tissue imaging techniques have not yet been adopted to investigate the second messenger calcium (Ca2+). In the present study, we established conditions that allow the in vivo detection of Ca2+ signaling in three-dimensional tumor masses in mouse models. By combining intravital imaging and a skinfold chamber technique, we determined the ability of photodynamic cancer therapy to induce an increase in intracellular Ca2+ concentrations and, consequently, an increase in cell death in a p53-dependent pathway. PMID:25544762

  12. Docosahexaenoic acid counteracts attenuation of CD95-induced cell death by inorganic mercury

    Energy Technology Data Exchange (ETDEWEB)

    Gill, Randall [Department of Immunology and Microbiology, Wayne State University, Detroit MI (United States); Lanni, Lydia; Jen, K.-L. Catherine [Department of Nutrition and Food Science, Wayne State University, Detroit MI (United States); McCabe, Michael J. [Department of Environmental Medicine, University of Rochester, Rochester NY (United States); Rosenspire, Allen, E-mail: arosenspire@wayne.edu [Department of Immunology and Microbiology, Wayne State University, Detroit MI (United States)

    2015-01-01

    In the United States the principal environmental exposure to mercury is through dietary consumption of sea food. Although the mechanism by which low levels of mercury affect the nervous system is not well established, epidemiological studies suggest that low level exposure of pregnant women to dietary mercury can adversely impact cognitive development in their children, but that Docosahexaenoic acid (DHA), the most prominent n-polyunsaturated fatty acid (n-PUFA) present in fish may counteract negative effects of mercury on the nervous system. Aside from effects on the nervous system, epidemiological and animal studies have also suggested that low level mercury exposure may be a risk factor for autoimmune disease. However unlike the nervous system where a mechanism linking mercury to impaired cognitive development remains elusive, we have previously suggested a potential mechanism linking low level mercury exposures to immune system dysfunction and autoimmunity. In the immune system it is well established that disruption of CD95 mediated apoptosis leads to autoimmune disease. We have previously shown in vitro as well as in vivo that in lymphocytes burdened with low levels of mercury, CD95 mediated cell death is impaired. In this report we now show that DHA counteracts the negative effect of mercury on CD95 signaling in T lymphocytes. T cells which have been pre-exposed to DHA are able to cleave pro-caspase 3 and efficiently signal programmed cell death through the CD95 signaling pathway, whether or not they are burdened with low levels of mercury. Thus DHA may lower the risk of autoimmune disease after low level mercury exposures. - Highlights: • Inorganic mercury (Hg{sup 2+}) interferes with CD95 mediated cell death in Jurkat T cells • DHA restores the ability of CD95 to signal cell death in Hg{sup 2+} intoxicated T cells • The restoration of CD95 mediated cell death by DHA is correlated with increased activation of Caspase 3.

  13. Extracellular signal-regulated kinase (ERK) inhibition attenuates cigarette smoke extract (CSE) induced-death inducing signaling complex (DISC) formation in human lung fibroblasts (MRC-5) cells.

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    Park, Jeong-Woong; Yoon, Jin Young; Kim, Yu Jin; Kyung, Sun Young; Lee, Sang Pyo; Jeong, Sung Hwan; Moon, Chanil

    2010-02-01

    Cigarette smoke (CS), a major risk factor in emphysema, causes cell death by incompletely understood mechanisms. Death-inducing signaling complex (DISC) formation is an initial event in Fas-mediated apoptosis. We demonstrated cigarette smoke extract (CSE) induced DISC formation in human lung fibroblasts (MRC-5). The aim of this study was to investigate the involvement of extracellular signal-regulated kinase (ERK) MAPK activation in CSE induced DISC formation. Immunoprecipitation (IP) for Fas and Western Immunoblot (IB) analysis for caspase 8 were then performed to show DISC. Lactate dehydrogenase (LDH) release was measured using a cytotoxicity detection kit. MTT assay was used as a measure of cell viability. We demonstrated that CSE induces DISC formation in MRC-5 using IP for Fas and IB for caspase 8. ERK was expressed in MRC-5 exposed to CSE. MEK-1 inhibitor (PD98059) decreased DISC formation in MRC-5 exposed to 20% CSE at 1 hr, and cell viability, as assessed by colorimetric MTT assay, was increased in MEK-1 inhibitor treated MRC-5 cells after 24 hr CSE exposure compared to the control. Inhibiting ERK significantly decreased the caspase-3,-8 activity in MEK-1 inhibitor treated MRC-5 cells compared to the control.The DISC formation, initial event of extrinsic apoptotic pathway, is a primary component of CSE- induced death in MRC-5, and ERK activation plays an active role in the DISC formation and downstream pathway. These results suggest that modulation of ERK may have therapeutic potential in the prevention of smoke-related lung injury.

  14. Ordering of ceramide formation and caspase-9 activation in CD95L-induced Jurkat leukemia T cell apoptosis.

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    Lafont, Elodie; Dupont, Romain; Andrieu-Abadie, Nathalie; Okazaki, Toshiro; Schulze-Osthoff, Klaus; Levade, Thierry; Benoist, Hervé; Ségui, Bruno

    2012-04-01

    Ceramide, a biologically active sphingolipid in cell death signaling, accumulates upon CD95L treatment, concomitantly to apoptosis induction in Jurkat leukemia T cells. Herein, we show that ceramide did not increase in caspase-8 and -10-doubly deficient Jurkat cells in response to CD95L, indicating that apical caspases are essential for CD95L-triggered ceramide formation. Jurkat cells are typically defined as type 2 cells, which require the activation of the mitochondrial pathway for efficient apoptosis induction in response to CD95L. Caspase-9-deficient Jurkat cells significantly resisted CD95L-induced apoptosis, despite ceramide accumulation. Knock-down of sphingomyelin synthase 1, which metabolizes ceramide to sphingomyelin, enhanced (i) CD95L-triggered ceramide production, (ii) cytochrome c release from the mitochondria and (iii) caspase-9 activation. Exogenous ceramide-induced caspase-3 activation and apoptosis were impaired in caspase-9-deficient Jurkat cells. Conversely, caspase-9 re-expression in caspase-9-deficient Jurkat cells restored caspase-3 activation and apoptosis upon exogenous ceramide treatment. Collectively, our data provide genetic evidence that CD95L-triggered endogenous ceramide increase in Jurkat leukemia T cells (i) is not a mere consequence of cell death and occurs mainly in a caspase-9-independent manner, (ii) is likely involved in the pro-apoptotic mitochondrial pathway leading to caspase-9 activation. Copyright © 2012 Elsevier B.V. All rights reserved.

  15. Caspase-10 Negatively Regulates Caspase-8-Mediated Cell Death, Switching the Response to CD95L in Favor of NF-κB Activation and Cell Survival

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    Sebastian Horn

    2017-04-01

    Full Text Available Formation of the death-inducing signaling complex (DISC initiates extrinsic apoptosis. Caspase-8 and its regulator cFLIP control death signaling by binding to death-receptor-bound FADD. By elucidating the function of the caspase-8 homolog, caspase-10, we discover that caspase-10 negatively regulates caspase-8-mediated cell death. Significantly, we reveal that caspase-10 reduces DISC association and activation of caspase-8. Furthermore, we extend our co-operative/hierarchical binding model of caspase-8/cFLIP and show that caspase-10 does not compete with caspase-8 for binding to FADD. Utilizing caspase-8-knockout cells, we demonstrate that caspase-8 is required upstream of both cFLIP and caspase-10 and that DISC formation critically depends on the scaffold function of caspase-8. We establish that caspase-10 rewires DISC signaling to NF-κB activation/cell survival and demonstrate that the catalytic activity of caspase-10, and caspase-8, is redundant in gene induction. Thus, our data are consistent with a model in which both caspase-10 and cFLIP coordinately regulate CD95L-mediated signaling for death or survival.

  16. The apoptotic members CD95, BclxL, and Bcl-2 cooperate to promote cell migration by inducing Ca2+ flux from the endoplasmic reticulum to mitochondria

    OpenAIRE

    Fouqu?, A; Lepvrier, E; Debure, L; Gouriou, Y; Malleter, M; Delcroix, V; Ovize, M; Ducret, T; Li, C; Hammadi, M; Vacher, P; Legembre, P

    2016-01-01

    Metalloprotease-processed CD95L (cl-CD95L) is a soluble cytokine that implements a PI3K/Ca2+ signaling pathway in triple-negative breast cancer (TNBC) cells. Accordingly, high levels of cl-CD95L in TNBC women correlate with poor prognosis, and administration of this ligand in an orthotopic xenograft mouse model accelerates the metastatic dissemination of TNBC cells. The molecular mechanism underlying CD95-mediated cell migration remains unknown. Here, we present genetic and pharmacologic evid...

  17. Cutting edge: CD95 maintains effector T cell homeostasis in chronic immune activation

    NARCIS (Netherlands)

    Arens, Ramon; Baars, Paul A.; Jak, Margot; Tesselaar, Kiki; van der Valk, Martin; van Oers, Marinus H. J.; van Lier, René A. W.

    2005-01-01

    The elimination of activated T cells is important to maintain homeostasis and avoid immunopathology. CD95 (Fas/APO-1) has been identified as a death mediator for activated T cells in vitro but the function of CD95 in death of mature T cells in vivo is still controversial. Here we show that

  18. Immunoexpression of CD95 in chronic gastritis and gastric mucosa-associated lymphomas

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    Vassallo J.

    2004-01-01

    Full Text Available CD95 (Fas/APO-1-mediated apoptosis plays an important role in immunological regulation and is related to the pathogenesis of autoimmune diseases. Immunoexpression of CD95 has been reported to frequently occur in low grade non-Hodgkin lymphomas, especially of post-germinal center histogenesis, among which those originating in mucosa-associated lymphoid tissue (MALT lymphomas. However, there is no report comparing in situ immunoexpression of this marker in lymphomas and the hyperplastic lymphoid reaction (chronic gastritis related to Helicobacter pylori infection. The purpose of the present research was to compare the intensity of lymphoid CD95 immunoexpression in 15 cases of H. pylori-related chronic gastritis and 15 gastric MALT lymphomas. CD95 (anti-CD95 was detected by an immunoperoxidase technique in paraffin sections using the catalyzed amplification system. Graduation of reaction intensity (percentage of CD95-positive cells was semiquantitative, from 1+ to 4+. Nine cases of chronic gastritis were 4+, five 2+ and one 1+. Three lymphomas were 4+, three 3+, four 2+, four 1+, and one was negative. Although 14 of 15 lymphomas were positive for CD95, the intensity of the reaction was significantly weaker compared to that obtained with gastric tissue for patients with gastritis (P = 0.03. The difference in CD95 immunoexpression does not seem to be useful as an isolated criterion in the differential diagnosis between chronic gastritis and MALT lymphomas since there was overlapping of immunostaining patterns. However, it suggests the possibility of a pathogenetic role of this apoptosis-regulating protein in MALT lymphomas.

  19. The apoptotic members CD95, BclxL, and Bcl-2 cooperate to promote cell migration by inducing Ca2+ flux from the endoplasmic reticulum to mitochondria

    Science.gov (United States)

    Fouqué, A; Lepvrier, E; Debure, L; Gouriou, Y; Malleter, M; Delcroix, V; Ovize, M; Ducret, T; Li, C; Hammadi, M; Vacher, P; Legembre, P

    2016-01-01

    Metalloprotease-processed CD95L (cl-CD95L) is a soluble cytokine that implements a PI3K/Ca2+ signaling pathway in triple-negative breast cancer (TNBC) cells. Accordingly, high levels of cl-CD95L in TNBC women correlate with poor prognosis, and administration of this ligand in an orthotopic xenograft mouse model accelerates the metastatic dissemination of TNBC cells. The molecular mechanism underlying CD95-mediated cell migration remains unknown. Here, we present genetic and pharmacologic evidence that the anti-apoptotic molecules BclxL and Bcl-2 and the pro-apoptotic factors BAD and BID cooperate to promote migration of TNBC cells stimulated with cl-CD95L. BclxL was distributed in both endoplasmic reticulum (ER) and mitochondrion membranes. The mitochondrion-localized isoform promoted cell migration by interacting with voltage-dependent anion channel 1 to orchestrate Ca2+ transfer from the ER to mitochondria in a BH3-dependent manner. Mitochondrial Ca2+ uniporter contributed to this flux, which favored ATP production and cell migration. In conclusion, this study reveals a novel molecular mechanism controlled by BclxL to promote cancer cell migration and supports the use of BH3 mimetics as therapeutic options not only to kill tumor cells but also to prevent metastatic dissemination in TNBCs. PMID:27367565

  20. Src mediates extracellular signal-regulated kinase 1/2 activation and autophagic cell death induced by cardiac glycosides in human non-small cell lung cancer cell lines.

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    Wang, Yan; Zhan, Yuechen; Xu, Rong; Shao, Rongguang; Jiang, Jiandong; Wang, Zhen

    2015-06-01

    Aberrant Na(+) /K(+) -ATPases (NKA) expression is closely related to the incidence and development of cancer, making NKA targeted cancer therapy more intriguing. Cardiac glycosides (CGs) belong to NKA inhibitors and possess potent anti-cancer properties in many cancers. Our previous work demonstrates that CGs family member digoxin or ouabain induces autophagic cell death in human non-small cell lung cancer (NSCLC) cell lines through regulation of both mammalian target of rapamycin and extracellular signal-regulated kinase 1/2 (ERK1/2) pathway. However, what acts as an upstream regulator of ERK1/2 activation during autophagy induction remains obscure. In the present study, the role of Src in the ERK1/2 signaling pathway as well as autophagic cell death induced by either digoxin or ouabain was examined in A549 and H460 cells. Src is significantly activated simultaneously with mitogen-activated protein kinase kinase 1/2 (MEK1/2) and ERK1/2 activation upon the drug treatment. Moreover, Src inhibitor PP2 could block either drug induced MEK1/2 and ERK1/2 phosphorylation, together with autophagic phenotypes in the cells. Knockdown of Src with siRNA causes the similar effect as PP2, both of which markedly alleviate the drugs' cytotoxicity. In addition, increased levels of intracellular reactive oxygen species (ROS) are found to be involved in Src mediated autophagy. Together, this work provides evidences showing that Src mediates MEK1/2 and ERK1/2 pathway as well as ROS generation, and regulates autophagic cell death induced by the cardiac glycosides. These observations may further help understand the molecular mechanisms of autophagy induced by NKA inhibitors in NSCLC cells. © 2014 Wiley Periodicals, Inc.

  1. Significance of serum-soluble CD95 (Fas/APO-1) on prognosis in renal cell cancer patients

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    Kimura, M; Tomita, Y; Imai, T; Saito, T; Katagiri, A; Tanikawa, T; Takeda, M; Takahashi, K

    1999-01-01

    Serum-soluble CD95 (sCD95) levels for 72 renal cell cancer patients were significantly higher than those of 17 healthy donors. Twenty-one of 72 patients had elevated (defined as more than mean of healthy donors + 2 s.d.) sCD95. The disease-specific survival rate was significantly lower in the elevated sCD95 group. Serum sCD95 level was shown to be an independent prognostic factor by univariate and multivariate analysis, indicating a possible significant role in determining treatment strategie...

  2. Upregulation of Fas-Fas-L (CD95/CD95L)-mediated epithelial apoptosis--a putative role in pouchitis?

    LENUS (Irish Health Repository)

    Coffey, J C

    2012-02-03

    INTRODUCTION: Ileal pouch-anal anastomosis (IPAA) remains the gold standard for patients with refractory ulcerative colitis. Pouchitis causes considerable morbidity in 40% of patients with IPAA. This study examined the role of increased epithelial apoptosis in the etiology of pouchitis. METHODS: Following ethical approval pouch biopsies taken from patients with a history of pouchitis were compared with age-matched controls from patients who were pouchitis free. Apoptosis was detected immunohistochemically using a monoclonal antibody (M30) and terminal deoxyribonucleotidyl transferase (TDT)-mediated dUTP-digoxigenin end labeling (TUNEL). Villous atrophy was assessed histologically and correlated with levels of apoptosis. Epithelial Fas-ligand (L) was also assessed immunohistochemically. RESULTS: A significant increase in TUNEL staining was seen at the epithelial but not at the lamina propria level for known pouchitis patients versus controls (0.091 vs 0.035; P < 0.01). Similarly, epithelial M30 immunoreactivity (0.225 vs 0.082; P < 0.05) and villous atrophy (0.035 vs 0.10; P < 0.05) were significantly increased in pouches with previous pouchitis when compared with normal pouches. Upregulation of Fas-L expression was characteristic of this epithelium. Mononuclear cells were strongly positive for Fas-L. Increased epithelial levels of apoptosis correlated with increased levels of villous atrophy. CONCLUSIONS: Our data suggest a role for elevated Fas-Fas-L (CD95-CD95L)-mediated epithelial apoptosis in the etiology of pouchitis. Increased levels of villous atrophy may result from increased apoptosis and thereby predispose to infection by otherwise apathogenic organisms.

  3. Sildenafil (Viagra) sensitizes prostate cancer cells to doxorubicin-mediated apoptosis through CD95

    Science.gov (United States)

    Das, Anindita; Durrant, David; Mitchell, Clint; Dent, Paul; Batra, Surinder K.; Kukreja, Rakesh C.

    2016-01-01

    We previously reported that Sildenafil enhances apoptosis and antitumor efficacy of doxorubicin (DOX) while attenuating its cardiotoxic effect in prostate cancer. In the present study, we investigated the mechanism by which sildenafil sensitizes DOX in killing of prostate cancer (PCa) cells, DU145. The death receptor Fas (APO-1 or CD95) induces apoptosis in many carcinoma cells, which is negatively regulated by anti-apoptotic molecules such as FLIP (Fas-associated death domain (FADD) interleukin-1-converting enzyme (FLICE)-like inhibitory protein). Co-treatment of PCa cells with sildenafil and DOX for 48 hours showed reduced expression of both long and short forms of FLIP (FLIP-L and -S) as compared to individual drug treatment. Over-expression of FLIP-s with an adenoviral vector attentuated the enhanced cell-killing effect of DOX and sildenafil. Colony formation assays also confirmed that FLIP-S over-expression inhibited the DOX and sildenafil-induced synergistic killing effect as compared to the cells infected with an empty vector. Moreover, siRNA knock-down of CD95 abolished the effect of sildenafil in enhancing DOX lethality in cells, but had no effect on cell killing after treatment with a single agent. Sildenafil co-treatment with DOX inhibited DOX-induced NF-κB activity by reducing phosphorylation of IκB and nuclear translocation of the p65 subunit, in addition to down regulation of FAP-1 (Fas associated phosphatase-1, a known inhibitor of CD95-mediated apoptosis) expression. This data provides evidence that the CD95 is a key regulator of sildenafil and DOX mediated enhanced cell death in prostate cancer. PMID:26716643

  4. Differential activation of CD95-mediated apoptosis related proteins in proximal and distal tubules during rat renal development.

    Science.gov (United States)

    Song, Xiao-Feng; Tian, He; Zhang, Zhen-Xing

    2016-10-01

    The CD95-mediated apoptotic pathway is the best characterized of the death receptor-mediated apoptotic pathways. The present study characterized localization and expression of proteins involved in CD95-mediated apoptosis during rat renal development. Kidneys were obtained from embryonic (E) 18 and 20-day-old fetuses and postnatal (P) 1-, 3-, 5-, 7-, 14-, and 21-day-old pups. Immunohistochemical characterization revealed that CD95, FasL and cleaved caspase-3 were strongly expressed in proximal tubules and weakly expressed in distal tubules, but that expression of caspase-8 in distal tubules was stronger than that in proximal tubules. Results from terminal deoxynucleotidyl transferase dUTP nick end labeling assays showed that levels of apoptosis in proximal tubules slowly increased after E18, while those of distal tubules slowly decreased after P5. Western blotting demonstrated that expression of CD95, FasL and FADD was very weak during embryonic development, but rapidly increased at P14. Expression of cleaved caspase-3 was maintained at high levels after P1, while caspase-8 expression gradually reached a peak at P7. Results from this study reveal that the CD95-mediated apoptotic pathway is a key driver of apoptosis in proximal tubules during late postnatal kidney development in rats and suggest that apoptosis in distal tubules is mediated by a different apoptotic pathway. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Expression of Fas (CD95/APO-1) ligand by human breast cancers: significance for tumor immune privilege.

    LENUS (Irish Health Repository)

    O'Connell, J

    2012-02-03

    Breast cancers have been shown to elicit tumor-specific immune responses. As in other types of cancer, the antitumor immune response fails to contain breast tumor growth, and a reduction in both the quantity and cytotoxic effectiveness of tumor-infiltrating lymphocytes (TILs) is associated with a poorer prognosis. Fas ligand (FasL) induces apoptotic death of activated lymphocytes that express its cell surface receptor, FasR (CD95\\/APO-1). FasL-mediated apoptosis of activated lymphocytes contributes to normal immune downregulation through its roles in tolerance acquisition, immune response termination, and maintenance of immune privilege in the eye, testis, and fetus. In this report, we demonstrate that breast carcinomas express FasL. Using in situ hybridization and immunohistochemistry, we show that breast tumors constitutively express FasL at both the mRNA and protein levels, respectively. FasL expression is prevalent in breast cancer: 100% of breast tumors (17 of 17) were found to express FasL, and expression occurred over more than 50% of the tumor area in all cases. By immunohistochemistry, FasR was found to be coexpressed with FasL throughout large areas of all the breast tumors. This suggests that the tumor cells had acquired intracellular defects in FasL-mediated apoptotic signaling. FasL and FasR expression were independent of tumor type or infiltrative capacity. FasL expressed by tumor cells has previously been shown to kill Fas-sensitive lymphoid cells in vitro and has been associated with apoptosis of TILs in vivo. We conclude that mammary carcinomas express FasL in vivo as a potential inhibitor of the antitumor immune response.

  6. Pathogen-induced proapoptotic phenotype and high CD95 (Fas expression accompany a suboptimal CD8+ T-cell response: reversal by adenoviral vaccine.

    Directory of Open Access Journals (Sweden)

    José Ronnie Vasconcelos

    Full Text Available MHC class Ia-restricted CD8(+ T cells are important mediators of the adaptive immune response against infections caused by intracellular microorganisms. Whereas antigen-specific effector CD8(+ T cells can clear infection caused by intracellular pathogens, in some circumstances, the immune response is suboptimal and the microorganisms survive, causing host death or chronic infection. Here, we explored the cellular and molecular mechanisms that could explain why CD8(+ T cell-mediated immunity during infection with the human protozoan parasite Trypanosoma cruzi is not optimal. For that purpose, we compared the CD8(+ T-cell mediated immune responses in mice infected with T. cruzi or vaccinated with a recombinant adenovirus expressing an immunodominant parasite antigen. Several functional and phenotypic characteristics of specific CD8(+ T cells overlapped. Among few exceptions was an accelerated expansion of the immune response in adenoviral vaccinated mice when compared to infected ones. Also, there was an upregulated expression of the apoptotic-signaling receptor CD95 on the surface of specific T cells from infected mice, which was not observed in the case of adenoviral-vaccinated mice. Most importantly, adenoviral vaccine provided at the time of infection significantly reduced the upregulation of CD95 expression and the proapoptotic phenotype of pathogen-specific CD8(+ cells expanded during infection. In parallel, infected adenovirus-vaccinated mice had a stronger CD8 T-cell mediated immune response and survived an otherwise lethal infection. We concluded that a suboptimal CD8(+ T-cell response is associated with an upregulation of CD95 expression and a proapoptotic phenotype. Both can be blocked by adenoviral vaccination.

  7. Neutrophil-dependent tumor rejection and priming of tumoricidal CD8+ T cell response induced by dendritic cells overexpressing CD95L.

    Science.gov (United States)

    Buonocore, Sofia; Haddou, Najate Ouled; Moore, Fabrice; Florquin, Sandrine; Paulart, Frédéric; Heirman, Carlo; Thielemans, Kris; Goldman, Michel; Flamand, Véronique

    2008-09-01

    Overexpression of CD95 (Fas/Apo-1) ligand (CD95L) has been shown to induce T cell tolerance but also, neutrophilic inflammation and rejection of allogeneic tissue. We explored the capacity of dendritic cells (DCs) genetically engineered to overexpress CD95L to induce an antitumor response. We first found that DCs overexpressing CD95L, in addition to MHC class I-restricted OVA peptides (CD95L-OVA-DCs), induced increased antigen-specific CD8(+) T cell responses as compared with DCs overexpressing OVA peptides alone. The enhanced T cell responses were associated with improved regression of a tumor expressing OVA, allowing survival of all animals. When DCs overexpressing CD95L (CD95L-DCs) were injected with the tumor expressing OVA, in vivo tumor proliferation was strikingly inhibited. A strong cellular apoptosis and a massive neutrophilic infiltrate developed in this setting. Neutrophil depletion prevented tumor regression as well as enhanced IFN-gamma production induced by CD95L-OVA-DCs. Furthermore, the CD8(+) T cell response induced by the coadministration of tumor cells and CD95L-DCs led to rejection of a tumor implanted at a distance from the DC injection site. In summary, DCs expressing CD95L promote tumor rejection involving neutrophil-mediated innate immunity and CD8(+) T cell-dependent adaptative immune responses.

  8. The Fas/CD95 receptor regulates the death of autoreactive B cells and the selection of antigen-specific B cells

    Directory of Open Access Journals (Sweden)

    Anne-Odile eHUEBER

    2012-07-01

    Full Text Available Cell death receptors have crucial roles in the regulation of immune responses. Here we review recent in vivo data confirming that the Fas death receptor (TNFSR6 on B cells is important for the regulation of autoimmunity since the impairment of only Fas function on B cells results in uncontrolled autoantibody production and autoimmunity. Fas plays a role in the elimination of the non-specific and auto-reactive B cells in germinal center, while during the selection of antigen specific B cells different escape signals ensure the resistance to Fas-mediated apoptosis. Antigen specific survival such as BCR or MHCII signal or coreceptors (CD19 cooperating with BCR inhibits the formation of death inducing signaling complex. Antigen-specific survival can be reinforced by antigen-independent signals of IL4 or CD40 overproducing the anti-apoptotic members of the Bcl-2 family proteins.

  9. In vivo UVB irradiation induces clustering of Fas (CD95) on human epidermal cells

    DEFF Research Database (Denmark)

    Bang, Bo; Gniadecki, Robert; Larsen, Jørgen K

    2003-01-01

    of soluble FasL in suction blister fluid from UVB-irradiated skin did not differ from those in unirradiated skin (n=5). Confocal laser scanning microscopy showed a rapid clustering of Fas within 30 min after irradiation. A simultaneous clustering of the adapter signalling protein FADD suggested that Fas...... clustering has a functional significance. Our results ar in accordance with previous findings from in vitro studies, and suggest that Fas is activated in vivo in human epidermis after UVB exposure....

  10. Loss of drug-induced activation of the CD95 apoptotic pathway in a cisplatin-resistant testicular germ cell tumor cell line

    NARCIS (Netherlands)

    Spierings, DCJ; de Vries, EGE; Vellenga, E; de Jong, S

    Testicular germ cell tumors (TGCTs) are unusually sensitive to cisplatin. In the present study the role of the CD95 death pathway in cisplatin sensitivity of TGCT cells was studied in Tera and its in vitro acquired cisplatin-resistant subclone Tera-CP. Cisplatin induced an increase in CD95 membrane

  11. Apoptosis induction in Jurkat cells and sCD95 levels in women's sera are related with the risk of developing cervical cancer

    Directory of Open Access Journals (Sweden)

    Bravo-Cuellar Alejandro

    2008-04-01

    Full Text Available Abstract Background Currently, there is clear evidence that apoptosis plays an important role in the development and progression of tumors. One of the best characterized apoptosis triggering systems is the CD95/Fas/APO-1 pathway; previous reports have demonstrated high levels of soluble CD95 (sCD95 in serum of patients with some types of cancer. Cervical cancer is the second most common cancer among women worldwide. As a first step in an attempt to design a minimally invasive test to predict the risk of developing cervical cancer in patients with precancerous lesions, we used a simple assay based on the capacity of human serum to induce apoptosis in Jurkat cells. We evaluated the relationship between sCD95 levels and the ability to induce apoptosis in Jurkat cells in cervical cancer patients and controls. Methods Jurkat cells were exposed to serum from 63 women (20 healthy volunteers, 21 with cervical intraepithelial neoplasia grade I [CIN 1] and 22 with cervical-uterine carcinoma. The apoptotic rate was measured by flow cytometry using Annexin-V-Fluos and Propidium Iodide as markers. Serum levels of sCD95 and soluble CD95 ligand (sCD95L were measured by ELISA kits. Results We found that serum from almost all healthy women induced apoptosis in Jurkat cells, while only fifty percent of the sera from women with CIN 1 induced cell death in Jurkat cells. Interestingly, only one serum sample from a patient with cervical-uterine cancer was able to induce apoptosis, the rest of the sera protected Jurkat cells from this killing. We were able to demonstrate that elimination of Jurkat cells was mediated by the CD95/Fas/Apo-1 apoptotic pathway. Furthermore, the serum levels of sCD95 measured by ELISA were significantly higher in women with cervical cancer. Conclusion Our results demonstrate that there is a strong correlation between low levels of sCD95 in serum of normal women and higher apoptosis induction in Jurkat cells. We suggest that an analysis of

  12. Apoptosis induction in Jurkat cells and sCD95 levels in women's sera are related with the risk of developing cervical cancer

    International Nuclear Information System (INIS)

    Aguilar-Lemarroy, Adriana; Jave-Suarez, Luis F; Romero-Ramos, Jose E; Olimon-Andalon, Vicente; Hernandez-Flores, Georgina; Lerma-Diaz, Jose M; Ortiz-Lazareno, Pablo C; Morgan-Villela, Gilberto; Toro-Arreola, Susana del; Bravo-Cuellar, Alejandro

    2008-01-01

    Currently, there is clear evidence that apoptosis plays an important role in the development and progression of tumors. One of the best characterized apoptosis triggering systems is the CD95/Fas/APO-1 pathway; previous reports have demonstrated high levels of soluble CD95 (sCD95) in serum of patients with some types of cancer. Cervical cancer is the second most common cancer among women worldwide. As a first step in an attempt to design a minimally invasive test to predict the risk of developing cervical cancer in patients with precancerous lesions, we used a simple assay based on the capacity of human serum to induce apoptosis in Jurkat cells. We evaluated the relationship between sCD95 levels and the ability to induce apoptosis in Jurkat cells in cervical cancer patients and controls. Jurkat cells were exposed to serum from 63 women (20 healthy volunteers, 21 with cervical intraepithelial neoplasia grade I [CIN 1] and 22 with cervical-uterine carcinoma). The apoptotic rate was measured by flow cytometry using Annexin-V-Fluos and Propidium Iodide as markers. Serum levels of sCD95 and soluble CD95 ligand (sCD95L) were measured by ELISA kits. We found that serum from almost all healthy women induced apoptosis in Jurkat cells, while only fifty percent of the sera from women with CIN 1 induced cell death in Jurkat cells. Interestingly, only one serum sample from a patient with cervical-uterine cancer was able to induce apoptosis, the rest of the sera protected Jurkat cells from this killing. We were able to demonstrate that elimination of Jurkat cells was mediated by the CD95/Fas/Apo-1 apoptotic pathway. Furthermore, the serum levels of sCD95 measured by ELISA were significantly higher in women with cervical cancer. Our results demonstrate that there is a strong correlation between low levels of sCD95 in serum of normal women and higher apoptosis induction in Jurkat cells. We suggest that an analysis of the apoptotic rate induced by serum in Jurkat cells and the

  13. Asymmetric dimethylarginine attenuates serum starvation-induced apoptosis via suppression of the Fas (APO-1/CD95)/JNK (SAPK) pathway

    Science.gov (United States)

    Li, H; Zhou, Y; Zhao, A; Qiu, Y; Xie, G; Jiang, Q; Zheng, X; Zhong, W; Sun, X; Zhou, Z; Jia, W

    2013-01-01

    Asymmetric dimethylarginine (ADMA) is synthesized by protein arginine methyltransferases during methylation of protein arginine residues and released into blood upon proteolysis. Higher concentrations of ADMA in blood have been observed in patients with metabolic diseases and certain cancers. However, the role of ADMA in colon cancer has not been well investigated. ADMA serum levels in human patients diagnosed with colon cancer were found to be higher than those present in healthy subjects. ADMA treatment of LoVo cells, a human colon adenocarcinoma cell line, attenuated serum starvation-induced apoptosis and suppressed the activation of the Fas (APO-1/CD95)/JNK (SAPK) (c-Jun N terminal protein kinase/stress-activated protein kinase)pathway. ADMA also suppressed the activation of JNK triggered by death receptor ligand anti-Fas mAb and exogenous C2-ceramide. Moreover, we demonstrated that ADMA pretreatment protected LoVo cells from doxorubicin hydrochloride-induced cell death and activation of the Fas/JNK pathway. In summary, our results suggest that the elevated ADMA in colon cancer patients may contribute to the blocking of apoptosis of cancer cells in response to stress and chemotherapy. PMID:24091673

  14. Ex vivo malignant glioma cells are sensitive to Fas (CD95/APO-1) ligand-mediated apoptosis.

    Science.gov (United States)

    Frei, K; Ambar, B; Adachi, N; Yonekawa, Y; Fontana, A

    1998-07-01

    Fas (also known as CD95/APO-1) is a cell surface receptor and member of the tumor necrosis factor receptor superfamily which mediates apoptosis in sensitive cells upon oligomerization by specific antibodies or by its ligand (FasL). Recently, human glioma cell lines were found to be susceptible to Fas-mediated apoptosis triggered by alpha-Fas antibodies. However, whether the Fas system can also be targeted in ex vivo high grade gliomas is at present unknown. In the present investigation, alpha-Fas antibodies and FasL were tested in short-term monolayer cultures or in colony forming assays established from freshly resected tumors of patients with anaplastic astrocytomas (WHO grade III) and glioblastoma multiforme (WHO grade IV). Anti-Fas antibodies induced only moderate apoptosis in four of the 19 tested glioma cell cultures. This contrasts FasL which induced apoptosis in all of the 19 tumor cell cultures analyzed. Mean cytotoxicity of glioma cell cultures treated for 48 h with alpha-Fas antibodies or FasL was 9.6% and 44.3%, respectively. Irrespective of whether alpha-Fas antibodies or FasL were used, pretreatment with recombinant hu (rhu) IFN-gamma and rhuTNF-alpha for 48 h did not sensitize glioma cells to Fas-mediated cytotoxicity. The long-term effect by FasL on tumor colony formation was more striking. FasL treatment resulted in more than 90% inhibition of clonal tumor cell growth of all the eight high grade gliomas analyzed. These results suggest that Fas targeting by FasL but not by alpha-Fas antibodies may provide a promising approach for locoregional glioma treatment.

  15. Safety and efficacy of the CD95-ligand inhibitor asunercept in transfusion-dependent patients with low and intermediate risk MDS.

    Science.gov (United States)

    Boch, Tobias; Luft, Thomas; Metzgeroth, Georgia; Mossner, Maximilian; Jann, Johann-Christoph; Nowak, Daniel; Meir, Franziska La; Schumann, Christiane; Klemmer, Jennifer; Brendel, Susanne; Fricke, Harald; Kunz, Claudia; Weiß, Christel; Hofmann, Wolf-Karsten; Nolte, Florian

    2018-05-01

    In low risk MDS, increased apoptosis of erythroid progenitors mediated via CD95 (Fas) activation has been described to result in peripheral cytopenia. Blockade of the CD95 system can improve erythropoiesis in MDS. Asunercept (APG101) is a fusion protein consisting of the extracellular domain of human CD95 and the Fc domain of human IgG1 blocking the interaction between CD95 and its ligand. Here we report on results from a phase I study in 20 transfusion-dependent low and intermediate risk MDS patients treated with intravenous asunercept (EudraCT 2012-003027-37). Primary objectives were safety and tolerability as well as pharmacodynamic effects. Secondary objectives were hematologic improvement, incidence and time to leukemic progression as well as overall survival. Frequency and severity of adverse events were in range of what could be expected in a patient cohort comprising of elderly MDS patients. Two patients experienced a serious adverse event with a suspected relationship to asunercept. The incidence of disease progression was low. In the 20 patients a decrease of the transfusion need from a mean of 10,8 (±5,1) pRBCs during the 12 weeks treatment phase to a mean of 10,0 (±4,2) pRBCs at the end of the study was observed. In conclusion, asunercept was well tolerated and showed efficacy in transfusion-dependent low and intermediate risk MDS patients. Further clinical investigation is warranted, particularly in combination with erythropoiesis stimulating agents (ESAs). Copyright © 2018. Published by Elsevier Ltd.

  16. Prognostic impact of FAS/CD95/APO-1 in urothelial cancers: decreased expression of Fas is associated with disease progression

    OpenAIRE

    Yamana, K; Bilim, V; Hara, N; Kasahara, T; Itoi, T; Maruyama, R; Nishiyama, T; Takahashi, K; Tomita, Y

    2005-01-01

    The death receptor Fas (Apo1/CD95) and Fas ligand (FasL) system is recognised as a major pathway for the induction of apoptosis in vivo, and antiapoptosis via its blockade plays a critical role in carcinogenesis and progression in several malignancies. However, the function of Fas?FasL system in urothelial cancer (UC) has not been elucidated. We therefore investigated the expression of Fas, FasL and Decoy receptor 3 for FasL (DcR3) in UC specimens and cell lines, and examined the cytotoxic ef...

  17. Melatonin Modulates Neuronal Cell Death Induced by Endoplasmic Reticulum Stress under Insulin Resistance Condition.

    Science.gov (United States)

    Song, Juhyun; Kim, Oh Yoen

    2017-06-10

    Insulin resistance (IR) is an important stress factor in the central nervous system, thereby aggravating neuropathogenesis and triggering cognitive decline. Melatonin, which is an antioxidant phytochemical and synthesized by the pineal gland, has multiple functions in cellular responses such as apoptosis and survival against stress. This study investigated whether melatonin modulates the signaling of neuronal cell death induced by endoplasmic reticulum (ER) stress under IR condition using SH-SY5Y neuroblastoma cells. Apoptosis cell death signaling markers (cleaved Poly [ADP-ribose] polymerase 1 (PARP), p53, and Bax) and ER stress markers (phosphorylated eIF2α (p-eIF2α), ATF4, CHOP, p-IRE1 , and spliced XBP1 (sXBP1)) were measured using reverse transcription-PCR, quantitative PCR, and western blottings. Immunofluorescence staining was also performed for p-ASK1 and p-IRE1 . The mRNA or protein expressions of cell death signaling markers and ER stress markers were increased under IR condition, but significantly attenuated by melatonin treatment. Insulin-induced activation of ASK1 ( p-ASK1 ) was also dose dependently attenuated by melatonin treatment. The regulatory effect of melatonin on neuronal cells under IR condition was associated with ASK1 signaling. In conclusion, the result suggested that melatonin may alleviate ER stress under IR condition, thereby regulating neuronal cell death signaling.

  18. Melatonin Modulates Neuronal Cell Death Induced by Endoplasmic Reticulum Stress under Insulin Resistance Condition

    Directory of Open Access Journals (Sweden)

    Juhyun Song

    2017-06-01

    Full Text Available Insulin resistance (IR is an important stress factor in the central nervous system, thereby aggravating neuropathogenesis and triggering cognitive decline. Melatonin, which is an antioxidant phytochemical and synthesized by the pineal gland, has multiple functions in cellular responses such as apoptosis and survival against stress. This study investigated whether melatonin modulates the signaling of neuronal cell death induced by endoplasmic reticulum (ER stress under IR condition using SH-SY5Y neuroblastoma cells. Apoptosis cell death signaling markers (cleaved Poly [ADP-ribose] polymerase 1 (PARP, p53, and Bax and ER stress markers (phosphorylated eIF2α (p-eIF2α, ATF4, CHOP, p-IRE1, and spliced XBP1 (sXBP1 were measured using reverse transcription-PCR, quantitative PCR, and western blottings. Immunofluorescence staining was also performed for p-ASK1 and p-IRE1. The mRNA or protein expressions of cell death signaling markers and ER stress markers were increased under IR condition, but significantly attenuated by melatonin treatment. Insulin-induced activation of ASK1 (p-ASK1 was also dose dependently attenuated by melatonin treatment. The regulatory effect of melatonin on neuronal cells under IR condition was associated with ASK1 signaling. In conclusion, the result suggested that melatonin may alleviate ER stress under IR condition, thereby regulating neuronal cell death signaling.

  19. Transfer of Fas (CD95 protein from the cell surface to the surface of polystyrene beads coated with anti-Fas antibody clone CH-11

    Directory of Open Access Journals (Sweden)

    H. Sawai

    2010-02-01

    Full Text Available Mouse monoclonal anti-Fas (CD95 antibody clone CH-11 has been widely used in research on apoptosis. CH-11 has the ability to bind to Fas protein on cell surface and induce apoptosis. Here, we used polystyrene beads coated with CH-11 to investigate the role of lipid rafts in Fas-mediated apoptosis in SKW6.4 cells. Unexpectedly, by treatment of the cells with CH-11-coated beads Fas protein was detached from cell surface and transferred to the surface of CH-11-coated beads. Western blot analysis showed that Fas protein containing both extracellular and intracellular domains was attached to the beads. Fas protein was not transferred from the cells to the surface of the beads coated with other anti-Fas antibodies or Fas ligand. Similar phenomenon was observed in Jurkat T cells. Furthermore, CH-11-induced apoptosis was suppressed by pretreatment with CH-11-coated beads in Jurkat cells. These results suggest that CH-11 might possess distinct properties on Fas protein compared with other anti-Fas antibodies or Fas ligand, and also suggest that caution should be needed to use polystyrene beads coated with antibodies such as CH-11.

  20. Tetrapeptide DEVD-aldehyde or YVAD-chloromethylketone inhibits Fas/Apo-1(CD95)-mediated apoptosis in renal-cell-cancer cells.

    Science.gov (United States)

    Tomita, Y; Kawasaki, T; Bilim, V; Takeda, M; Takahashi, K

    1996-09-27

    The apoptotic machinery has been intensively investigated, and interleukin-1-beta-converting enzyme (ICE) and its homologs directly mediate apoptosis by means of their unique protease activity. Fas/Apo1 (CD95), a member of the TNF-receptor family, mediates apoptosis by binding to its ligand, which is mainly expressed on lymphocytes. Here, we investigated the expression and function of both molecules in renal-cell cancer (RCC). The expression of Fas was examined in 6 RCC cell lines by immunoblotting and all of them expressed Fas. ICE and CPP32/YAMA were also identified among the cell lines. We earlier examined ACHN cells expressing low levels of BCL-2, as well as KRC/Y cells with high levels of BCL-2. Here, we found that the anti-Fas monoclonal antibody, CH-11, induced apoptosis in a dose-dependent fashion more remarkably in ACHN cells. Pre-incubation with the tetrapeptide YVAD-chloromethyl-ketone or DEVD-aldehyde inhibited Fas-mediated apoptosis. These findings suggest that, in RCC, apoptosis is induced by lymphocytes bearing Fas-L, and that it is achieved through the proteolytic action of CPP32/YAMA and/or ICE, or another member of the ICE/ced-3 protease family.

  1. Prognostic impact of FAS/CD95/APO-1 in urothelial cancers: decreased expression of Fas is associated with disease progression

    Science.gov (United States)

    Yamana, K; Bilim, V; Hara, N; Kasahara, T; Itoi, T; Maruyama, R; Nishiyama, T; Takahashi, K; Tomita, Y

    2005-01-01

    The death receptor Fas (Apo1/CD95) and Fas ligand (FasL) system is recognised as a major pathway for the induction of apoptosis in vivo, and antiapoptosis via its blockade plays a critical role in carcinogenesis and progression in several malignancies. However, the function of Fas–FasL system in urothelial cancer (UC) has not been elucidated. We therefore investigated the expression of Fas, FasL and Decoy receptor 3 for FasL (DcR3) in UC specimens and cell lines, and examined the cytotoxic effect of an anti-Fas-activating monoclonal antibody (mAb) in vitro. Immunohistochemical examinations of Fas-related molecules were performed on 123 UC and 30 normal urothelium surgical specimens. Normal urothelium showed Fas staining in the cell membrane and cytoplasm. In UC, less frequent Fas expression was significantly associated with a higher pathological grade (P<0.0001), a more advanced stage (P=0.023) and poorer prognosis (P=0.010). Fas and the absence thereof were suggested to be crucial factors with which to select patients requiring more aggressive treatment. Moreover, low-dose anti-Fas-activating mAb sensitised resistant cells to adriamycin, and this synergistic effect could be applied in the development of new treatment strategy for UC patients with multidrug-resistant tumours. PMID:16091761

  2. Levetiracetam differentially alters CD95 expression of neuronal cells and the mitochondrial membrane potential of immune and neuronal cells in vitro

    Directory of Open Access Journals (Sweden)

    Susannah K Rogers

    2014-02-01

    Full Text Available Epilepsy is a neurological seizure disorder that affects over 100 million people worldwide. Levetiracetam, either alone, as monotherapy, or as adjunctive treatment, is widely used to control certain types of seizures. Despite its increasing popularity as a relatively safe and effective anti-convulsive treatment option, its mechanism(s of action are poorly understood. Studies have suggested neuronal, glial, and immune mechanisms of action. Understanding the precise mechanisms of action of Levetiracetam would be extremely beneficial in helping to understand the processes involved in seizure generation and epilepsy. Moreover, a full understanding of these mechanisms would help to create more efficacious treatments while minimizing side effects. The current study examined the effects of Levetiracetam on the mitochondrial membrane potential of neuronal and non-neuronal cells, in vitro, in order to determine if Levetiracetam influences metabolic processes in these cell types. In addition, this study sought to address possible immune-mediated mechanisms by determining if Levetiracetam alters the expression of immune receptor-ligand pairs. The results show that Levetiracetam induces expression of CD95 and CD178 on NGF-treated C17.2 neuronal cells. The results also show that Levetiracetam increases mitochondrial membrane potential on C17.2 neuronal cells in the presence of nerve growth factor. In contrast, Levetiracetam decreases the mitochondrial membrane potential of splenocytes and this effect was dependent on intact invariant chain, thus implicating immune cell interactions. These results suggest that both neuronal and non-neuronal anti-epileptic activities of Levetiracetam involve control over energy metabolism, more specifically, mΔΨ. Future studies are needed to further investigate this potential mechanism of action.

  3. CD95 (Fas) ligand expression of Epstein-Barr virus (EBV)-infected lymphocytes: a possible mechanism of immune evasion in chronic active EBV infection.

    Science.gov (United States)

    Ohshima, K; Suzumiya, J; Sugihara, M; Nagafuchi, S; Ohga, S; Kikuchi, M

    1999-01-01

    The Epstein-Barr virus (EBV) induces infectious mononucleosis (IM) and can be associated with chronic active EBV infection (CAEBV). Cytotoxic T lymphocytes (CTL) play an important role in excluding EBV-infected cells. Two cytotoxic mechanisms of CTL have been demonstrated: one perforin/granzyme-based and the other Fas (CD95)/Fas ligand (FasL)-based. To clarify these two pathways in CAEBV, we analyzed six patients with CAEBV and four patients with IM using immunohistochemical staining of the lymph nodes. In both CAEBV and IM, CD8+ T-cells increased in number, but CD56+ natural killer cells were rare. In four of six cases with CAEBV, approximately half the lymphocytes were positive for T cell-restricted intracellular antigens (TIA-1), which were recognized by the cytolytic granules of CTL. In IM, the number of TIA-1 positive cells was smaller than that in CAEBV. Fas-positive lymphocytes were frequently encountered in both CAEBV and IM. However, FasL-positive lymphocytes increased in three of six patients with CAEBV, but not in patients with IM. Except for one case with CAEBV, the number of perforin- and/or granzyme-positive cells was small in number in both CAEBV and IM cases. In double-staining FasL and EBV in situ hybridization, FasL-positive EBV-infected lymphocytes were detected in CAEBV but not in IM. In CAEBV, the Fas/FasL pathway and not perforin pathways appears to play an important role in the pathogenesis. The data suggest that EBV-infected lymphocytes may evade immune attack through the expression of FasL.

  4. IκBα mediates prostate cancer cell death induced by combinatorial targeting of the androgen receptor

    International Nuclear Information System (INIS)

    Carter, Sarah Louise; Centenera, Margaret Mary; Tilley, Wayne Desmond; Selth, Luke Ashton; Butler, Lisa Maree

    2016-01-01

    Combining different clinical agents to target multiple pathways in prostate cancer cells, including androgen receptor (AR) signaling, is potentially an effective strategy to improve outcomes for men with metastatic disease. We have previously demonstrated that sub-effective concentrations of an AR antagonist, bicalutamide, and the histone deacetylase inhibitor, vorinostat, act synergistically when combined to cause death of AR-dependent prostate cancer cells. In this study, expression profiling of human prostate cancer cells treated with bicalutamide or vorinostat, alone or in combination, was employed to determine the molecular mechanisms underlying this synergistic action. Cell viability assays and quantitative real time PCR were used to validate identified candidate genes. A substantial proportion of the genes modulated by the combination of bicalutamide and vorinostat were androgen regulated. Independent pathway analysis identified further pathways and genes, most notably NFKBIA (encoding IκBα, an inhibitor of NF-κB and p53 signaling), as targets of this combinatorial treatment. Depletion of IκBα by siRNA knockdown enhanced apoptosis of prostate cancer cells, while ectopic overexpression of IκBα markedly suppressed cell death induced by the combination of bicalutamide and vorinostat. These findings implicate IκBα as a key mediator of the apoptotic action of this combinatorial AR targeting strategy and a promising new therapeutic target for prostate cancer. The online version of this article (doi:10.1186/s12885-016-2188-2) contains supplementary material, which is available to authorized users

  5. Nanosecond pulsed electric fields modulate the expression of Fas/CD95 death receptor pathway regulators in U937 and Jurkat Cells.

    Science.gov (United States)

    Estlack, Larry E; Roth, Caleb C; Thompson, Gary L; Lambert, William A; Ibey, Bennett L

    2014-12-01

    In this publication, we demonstrate that exposure of Jurkat and U937 cells to nanosecond pulsed electrical fields (nsPEF) can modulate the extrinsic-mediated apoptotic pathway via the Fas/CD95 death receptor. An inherent difference in survival between these two cell lines in response to 10 ns exposures has been previously reported (Jurkat being more sensitive to nsPEF than U937), but the reason for this sensitivity difference remains unknown. We found that exposure of each cell line to 100, 10 ns pulses at 50 kV/cm caused a marked increase in expression of cFLIP (extrinsic apoptosis inhibitor) in U937 and FasL (extrinsic apoptosis activator) in Jurkat, respectively. Measurement of basal expression levels revealed an inherent difference between U937 cells, having a higher expression of cFLIP, and Jurkat cells, having a higher expression of FasL. From these data, we hypothesize that the sensitivity difference between the cells to nsPEF exposure may be directly related to expression of extrinsic apoptotic regulators. To validate this hypothesis, we used siRNA to knockdown cFLAR (coding for cFLIP protein) expression in U937, and FasL expression in Jurkat and challenged them to 100, 10 ns pulses at 150 kV/cm, a typical lethal dose. We observed that U937 survival was reduced nearly 60% in the knockdown population while Jurkat survival improved ~40%. These findings support the hypothesis that cell survival following 10 ns pulse exposures depends on extrinsic apoptotic regulators. Interestingly, pretreatment of U937 with a 100-pulse, 50 kV/cm exposure (to amplify cFLAR expression) significantly reduced the lethality of a 150 kV/cm, 100-pulse exposure applied 24 h later. From these data, we conclude that the observed survival differences between cells, exposed to 10 ns pulsed electric fields, is due to inherent cell biochemistry rather than the biophysics of the exposure itself. Understanding cell sensitivity to nsPEF may provide researchers/clinicians with a predicable way

  6. Clinical meanings of changes of blood expression of CD95 antigen (Fas), Bcl-2 and transforming growth factor-α (TGF-α) in patients with chronic renal failure on hemodialysis

    International Nuclear Information System (INIS)

    Yang Daoli; Luo Nanping; Sun Xiaoming

    2005-01-01

    Objective: To study the changes of expression of blood CD95 antigen (Fas), and anti-apoptosis factor (Bcl-2) and TGF-α after hemodialysis in patients with chronic renal failure. Methods: The percentage of CD95 and Bcl-2 positive cells in peripheral blood monocytes were examined with flow cytometry and serum TGF-α contents were measured with RIA in 40 patients with chronic renal failure both before and after hemodialysis as well as in 25 other patients with chronic renal failure but not on dialysis and 30 controls. Results: Expressions of CD95 were significantly higher and expressions of Bcl-2, TGF-α were significantly lower in all the patients with chronic renal failure than those in the controls (P 0.05). Conclusion: The up-regulation of CD95 expression and increase of serum TGF-α contents after hemodialysis might contribute to induction of apoptosis of mesangial cells, which would be beneficial to the patient. (authors)

  7. Turkish propolis supresses MCF-7 cell death induced by homocysteine.

    Science.gov (United States)

    Tartik, Musa; Darendelioglu, Ekrem; Aykutoglu, Gurkan; Baydas, Giyasettin

    2016-08-01

    Elevated plasma homocysteine (Hcy) level is a most important risk factor for various vascular diseases including coronary, cerebral and peripheral arterial and venous thrombosis. Propolis is produced by honeybee from various oils, pollens and wax materials. Therefore, it has various biological properties including antioxidant, antitumor and antimicrobial activities. This study investigated the effects of propolis and Hcy on apoptosis in cancer cells. According to our findings, Hcy induced apoptosis in human breast adenocarcinoma (MCF-7) cells by regulating numerous genes and proteins involved in the apoptotic signal transduction pathway. In contrast, treatment with propolis inhibited caspase- 3 and -9 induced by Hcy in MCF-7 cells. It can be concluded that Hcy may augment the activity of anticancer agents that induce excessive reactive oxygen species (ROS) generation and apoptosis in their target cells. In contrast to the previous studies herein we found that propolis in low doses protected cancer cells inhibiting cellular apoptosis mediated by intracellular ROS-dependent mitochondrial pathway. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  8. Interleukin-3 prevents neuronal death induced by amyloid peptide

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    Otth Carola

    2007-10-01

    Full Text Available Abstract Background Interleukin-3 (IL-3 is an important glycoprotein involved in regulating biological responses such as cell proliferation, survival and differentiation. Its effects are mediated via interaction with cell surface receptors. Several studies have demonstrated the expression of IL-3 in neurons and astrocytes of the hippocampus and cortices in normal mouse brain, suggesting a physiological role of IL-3 in the central nervous system. Although there is evidence indicating that IL-3 is expressed in some neuronal populations, its physiological role in these cells is poorly known. Results In this study, we demonstrated the expression of IL-3 receptor in cortical neurons, and analyzed its influence on amyloid β (Aβ-treated cells. In these cells, IL-3 can activate at least three classical signalling pathways, Jak/STAT, Ras/MAP kinase and the PI 3-kinase. Viability assays indicated that IL-3 might play a neuroprotective role in cells treated with Aβ fibrils. It is of interest to note that our results suggest that cell survival induced by IL-3 required PI 3-kinase and Jak/STAT pathway activation, but not MAP kinase. In addition, IL-3 induced an increase of the anti-apoptotic protein Bcl-2. Conclusion Altogether these data strongly suggest that IL-3 neuroprotects neuronal cells against neurodegenerative agents like Aβ.

  9. Characterization of a novel epigenetic effect of ionizing radiation: the death-inducing effect

    Science.gov (United States)

    Nagar, Shruti; Smith, Leslie E.; Morgan, William F.

    2003-01-01

    The detrimental effects associated with exposure to ionizing radiation have long been thought to result from the direct targeting of the nucleus leading to DNA damage; however, the emergence of concepts such as radiation-induced genomic instability and bystander effects have challenged this dogma. After cellular exposure to ionizing radiation, we have isolated a number of clones of Chinese hamster-human hybrid GM10115 cells that demonstrate genomic instability as measured by chromosomal destabilization. These clones show dynamic and persistent generation of chromosomal rearrangements multiple generations after the original insult. We hypothesize that these unstable clones maintain this delayed instability phenotype by secreting factors into the culture medium. To test this hypothesis we transferred filtered medium from unstable cells to unirradiated GM10115 cells. No GM10115 cells were able to survive this medium. This phenomenon by which GM10115 cells die when cultured in medium from chromosomally unstable GM10115 clones is the death-inducing effect. Medium transfer experiments indicate that a factor or factors is/are secreted by unstable cells within 8 h of growth in fresh medium and result in cell killing within 24 h. These factors are stable at ambient temperature but do not survive heating or freezing, and are biologically active when diluted with fresh medium. We present the initial description and characterization of the death-inducing effect. This novel epigenetic effect of radiation has implications for radiation risk assessment and for health risks associated with radiation exposure.

  10. The anti-cell death FNK protein protects cells from death induced by freezing and thawing

    International Nuclear Information System (INIS)

    Sudo, Kentaro; Asoh, Sadamitsu; Ohsawa, Ikuroh; Ozaki, Daiya; Yamagata, Kumi; Ito, Hiromoto; Ohta, Shigeo

    2005-01-01

    The FNK protein, constructed from anti-apoptotic Bcl-x L with enhanced activity, was fused with the protein transduction domain (PTD) of the HIV/Tat protein to mediate the delivery of FNK into cells. The fusion protein PTD-FNK was introduced into chondrocytes in isolated articular cartilage-bone sections, cultured neurons, and isolated bone marrow mononuclear cells to evaluate its ability to prevent cell death induced by freezing and thawing. PTD-FNK protected the cells from freeze-thaw damage in a concentration-dependent manner. Addition of PTD-FNK with conventional cryoprotectants (dimethyl sulfoxide and hydroxyethyl starch) increased surviving cell numbers around 2-fold compared with controls treated only with the cryoprotectants. Notably, PTD-FNK allowed CD34 + cells among bone marrow mononuclear cells to survive more efficiently (12-fold more than the control cells) from two successive freeze-thaw cycles. Thus, PTD-FNK prevented cell death induced by freezing and thawing, suggesting that it provides for the successful cryopreservation of biological materials

  11. Prototypical antipsychotic drugs protect hippocampal neuronal cultures against cell death induced by growth medium deprivation

    Directory of Open Access Journals (Sweden)

    Williams Sylvain

    2006-03-01

    Full Text Available Abstract Background Several clinical studies suggested that antipsychotic-based medications could ameliorate cognitive functions impaired in certain schizophrenic patients. Accordingly, we investigated the effects of various dopaminergic receptor antagonists – including atypical antipsychotics that are prescribed for the treatment of schizophrenia – in a model of toxicity using cultured hippocampal neurons, the hippocampus being a region of particular relevance to cognition. Results Hippocampal cell death induced by deprivation of growth medium constituents was strongly blocked by drugs including antipsychotics (10-10-10-6 M that display nM affinities for D2 and/or D4 receptors (clozapine, haloperidol, (±-sulpiride, domperidone, clozapine, risperidone, chlorpromazine, (+-butaclamol and L-741,742. These effects were shared by some caspases inhibitors and were not accompanied by inhibition of reactive oxygen species. In contrast, (--raclopride and remoxipride, two drugs that preferentially bind D2 over D4 receptors were ineffective, as well as the selective D3 receptor antagonist U 99194. Interestingly, (--raclopride (10-6 M was able to block the neuroprotective effect of the atypical antipsychotic clozapine (10-6 M. Conclusion Taken together, these data suggest that D2-like receptors, particularly the D4 subtype, mediate the neuroprotective effects of antipsychotic drugs possibly through a ROS-independent, caspase-dependent mechanism.

  12. Mechanisms of cell death induced by infusion sets leachables in in vitro experimental settings.

    Science.gov (United States)

    Kozlovskaya, Luba; Stepensky, David

    2015-01-30

    Leachable materials that are released from infusion sets during their use can induce local and systemic toxic effects. We studied the mechanisms and kinetics of cell death induced by infusion sets leachates in vitro using L-929 and bEnd. 3 cells. Changes in cell morphology and metabolic activity were determined using light microscopy and the MTT test, respectively. Detailed analysis of the mechanisms of cell death was performed using membrane integrity and caspases 3 and 7 activity tests, annexin V-FITC/7-AAD analysis by FACS, and DAPI nuclear staining followed by confocal microscopy. Infusion sets released toxic leachables and induced toxic effects. Latex flashball was the most toxic part of the studied infusion sets, and it potently induced cell oncosis via increased permeability of the cell membrane. Latex-induced decrease in cells metabolic activity and cell death were not accompanied by activation of caspases 3 and 7, changes in nuclear morphology, or substantial annexin V-FITC cell staining. Leachables from the tube part of the infusion sets were less toxic, and induced some biochemical changes without altering the cells morphology. Further studies are needed to reveal the in vivo toxicity of infusion sets and its correlation with the results of in vitro toxicity studies. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Induction of morphological changes in death-induced cancer cells monitored by holographic microscopy.

    Science.gov (United States)

    El-Schich, Zahra; Mölder, Anna; Tassidis, Helena; Härkönen, Pirkko; Falck Miniotis, Maria; Gjörloff Wingren, Anette

    2015-03-01

    We are using the label-free technique of holographic microscopy to analyze cellular parameters including cell number, confluence, cellular volume and area directly in the cell culture environment. We show that death-induced cells can be distinguished from untreated counterparts by the use of holographic microscopy, and we demonstrate its capability for cell death assessment. Morphological analysis of two representative cell lines (L929 and DU145) was performed in the culture flasks without any prior cell detachment. The two cell lines were treated with the anti-tumour agent etoposide for 1-3days. Measurements by holographic microscopy showed significant differences in average cell number, confluence, volume and area when comparing etoposide-treated with untreated cells. The cell volume of the treated cell lines was initially increased at early time-points. By time, cells decreased in volume, especially when treated with high doses of etoposide. In conclusion, we have shown that holographic microscopy allows label-free and completely non-invasive morphological measurements of cell growth, viability and death. Future applications could include real-time monitoring of these holographic microscopy parameters in cells in response to clinically relevant compounds. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Amelioration of neurodegenerative diseases by cell death-induced cytoplasmic delivery of humanin.

    Science.gov (United States)

    Park, Tae-Yoon; Kim, Seung-Hyung; Shin, Yoon-Chul; Lee, Nae-Hyun; Lee, Rae-Kyung Christina; Shim, Jae-Hyuck; Glimcher, Laurie H; Mook-Jung, Inhee; Cheong, Eunji; Kim, Won-Ki; Honda, Fumiko; Morio, Tomohiro; Lim, Jong-Soon; Lee, Sang-Kyou

    2013-03-28

    Inhibition of the early intracellular event that triggers neurodegenerative cascades and reversal of neuronal cell death are essential for effective treatment of Alzheimer's disease (AD). In this study, a novel therapeutic for AD, a transducible humanin with an extended caspase-3 cleavage sequence (tHN-C3), was developed and showed multiple mechanisms of therapeutic action. These included targeted delivery of anti-apoptotic protein humanin through the blood-brain barrier (BBB) to neuronal cells, specific inhibition of caspase-3 activation to inhibit the early triggering of AD progression, and delivery of humanin into the cytoplasm of neuronal cells undergoing apoptosis where it exerts its anti-apoptotic functions effectively. The tHN-C3 prevented neuronal cell death induced by H2O2, or soluble Aβ42, via Bax binding. In animal models of AD induced by amyloid beta, in Tg2576 mice, and in the rat middle cerebral artery occlusion model of stroke, tHN-C3 effectively prevented neuronal cell death, inflammatory cell infiltration into the brain, and improved cognitive memory. The therapeutic effectiveness of tHN-C3 was comparable to that of Aricept, a clinically approved drug for AD treatment. Therefore, tHN-C3 may be a new remedy with multiple therapeutic functions targeting the early and late stages of neurodegeneration in AD and other brain injuries. Copyright © 2013 Elsevier B.V. All rights reserved.

  15. Brain death induces renal expression of heme oxygenase-1 and heat shock protein 70

    Directory of Open Access Journals (Sweden)

    van Dullemen Leon FA

    2013-01-01

    Full Text Available Abstract Background Kidneys derived from brain dead donors have lower graft survival and higher graft-function loss compared to their living donor counterpart. Heat Shock Proteins (HSP are a large family of stress proteins involved in maintaining cell homeostasis. We studied the role of stress-inducible genes Heme Oxygenase-1 (HO-1, HSP27, HSP40, and HSP70 in the kidney following a 4 hour period of brain death. Methods Brain death was induced in rats (n=6 by inflating a balloon catheter in the epidural space. Kidneys were analysed for HSPs using RT-PCR, Western blotting, and immunohistochemistry. Results RT-PCR data showed a significant increase in gene expression for HO-1 and HSP70 in kidneys of brain dead rats. Western blotting revealed a massive increase in HO-1 protein in brain dead rat kidneys. Immunohistochemistry confirmed these findings, showing extensive HO-1 protein expression in the renal cortical tubules of brain dead rats. HSP70 protein was predominantly increased in renal distal tubules of brain dead rats treated for hypotension. Conclusion Renal stress caused by brain death induces expression of the cytoprotective genes HO-1 and HSP70, but not of HSP27 and HSP40. The upregulation of these cytoprotective genes indicate that renal damage occurs during brain death, and could be part of a protective or recuperative mechanism induced by brain death-associated stress.

  16. Type of cell death induced by seven metals in cultured mouse osteoblastic cells.

    Science.gov (United States)

    Contreras, René García; Vilchis, José Rogelio Scougall; Sakagami, Hiroshi; Nakamura, Yuko; Nakamura, Yukio; Hibino, Yasushi; Nakajima, Hiroshi; Shimada, Jun

    2010-01-01

    The use of dental metal alloys in the daily clinic makes it necessary to evaluate the cytotoxicity of eluted metal components against oral cells. However, the cytotoxic mechanism and the type of cell death induced by dental metals in osteoblasts have not been well characterized. This study investigated the cytotoxicity of seven metals against the mouse osteoblastic cell line MC3T3-E1. alpha-MEM was used as a culture medium, since this medium provided much superior proliferation of MC3T3-E1 cells over DMEM. Ag (NH(3))(2)F was the most cytotoxic, followed by CuCl>CuCl(2) >CoCl(2), NiCl(2)>FeCl(3) and FeCl(2) (least toxic). None of the metals showed any apparent growth stimulating effect (so-called 'hormesis') at lower concentrations. A time course study demonstrated that two hours of contact between oral cells and Ag (NH(3))(2)F, CuCl, CoCl(2) or NiCl(2) induced irreversible cell death. Contact with these metals induced a smear pattern of DNA fragmentation without activation of caspase-3. Preincubation of MC3T3-E1 cells with either a caspase inhibitor (Z-VAD-FMK) or autophagy inhibitors (3-methyladenine, bafilomycin) failed to rescue them from metal cytotoxicity. These data suggest the induction of necrotic cell death rather than apoptosis and autophagy by metals in this osteoblastic cell line.

  17. Bimodal cell death induced by high radiation doses in the radioresistant sf9 insect cell line

    International Nuclear Information System (INIS)

    Chandna, S.

    2003-01-01

    Full text: This study was conducted to investigate the mode(s) of cell death induced by high radiation doses in the highly radioresistant Sf9 insect ovarian cell line. Methods: Cells were exposed to γ-radiation doses 200Gy and 500Gy, harvested at various time intervals (6h-72h) following irradiation, and subjected to cell morphology assay, DNA agarose gel electrophoresis, single cell gel electrophoresis (SCGE; comet assay) and Annexin-V labeling for the detection of membrane phosphatidylserine externalization. Cell morphology was assessed in cells entrapped and fixed in agarose gel directly from the cell suspension, thus preventing the possible loss of fragments/ apoptotic bodies. Surviving fraction of Sf9 cells was 0.01 at 200Gy and 98%) undergoing extensive DNA fragmentation at 500Gy, whereas the frequency of cells with DNA fragmentation was considerably less (∼12%) at 200Gy. Conclusions: While the mode of cell death at 200Gy seems to be different from typical apoptosis, a dose of 500Gy induced bimodal cell death, with typical apoptotic as well as the atypical cell death observed at 200Gy

  18. Protective effect of aqueous extract from Spirulina platensis against cell death induced by free radicals

    Directory of Open Access Journals (Sweden)

    Radhakrishnan Ammu

    2010-09-01

    Full Text Available Abstract Background Spirulina is a commercial alga well known to contain various antioxidants, especially phycocyanin. Apart from being sold as a nutraceutical, Spirulina is incorporated as a functional ingredient in food products and beverages. Most of the previous reports on antioxidant activity of Spirulina were based on chemical rather than cell-based assays. The primary objective of this study was to assess the antioxidant activity of aqueous extract from Spirulina based on its protective effect against cell death induced by free radicals. Methods The antioxidant activity of the cold water extract from food-grade Spirulina platensis was assessed using both chemical and cell-based assays. In the cell-based assay, mouse fibroblast cells (3T3 cells were incubated for 1 h in medium containing aqueous extract of Spirulina or vitamin C (positive control at 25, 125 and 250 μg/mL before the addition of 50 μM 1,1-diphenyl-2-picrylhydrazyl (DPPH or 3-ethylbenzothiazoline-6-sulfonic acid (ABTS. The cells were incubated for another 24 h before being assessed for cell death due to apoptosis using the Cell Death Detection ELISA Kit. Spectrophotometric assays based on DPPH and ABTS were also used to assess the antioxidant activity of the extract compared to vitamin C and vitamin E (positive controls. Results Spirulina extract did not cause cytotoxic effect on 3T3 cells within the range of concentrations tested (0 - 250 μg/mL. The extract reduced significantly (p Conclusions The results showed that aqueous extract of Spirulina has a protective effect against apoptotic cell death due to free radicals. The potential application of incorporating Spirulina into food products and beverages to enhance their antioxidant capacity is worth exploring.

  19. Caspase-2 mediated apoptotic and necrotic murine macrophage cell death induced by rough Brucella abortus.

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    Fang Chen

    Full Text Available Brucella species are Gram-negative, facultative intracellular bacteria that cause zoonotic brucellosis. Survival and replication inside macrophages is critical for establishment of chronic Brucella infection. Virulent smooth B. abortus strain 2308 inhibits programmed macrophage cell death and replicates inside macrophages. Cattle B. abortus vaccine strain RB51 is an attenuated rough, lipopolysaccharide O antigen-deficient mutant derived from smooth strain 2308. B. abortus rough mutant RA1 contains a single wboA gene mutation in strain 2308. Our studies demonstrated that live RB51 and RA1, but not strain 2308 or heat-killed Brucella, induced both apoptotic and necrotic cell death in murine RAW264.7 macrophages and bone marrow derived macrophages. The same phenomenon was also observed in primary mouse peritoneal macrophages from mice immunized intraperitoneally with vaccine strain RB51 using the same dose as regularly performed in protection studies. Programmed macrophage cell death induced by RB51 and RA1 was inhibited by a caspase-2 inhibitor (Z-VDVAD-FMK. Caspase-2 enzyme activation and cleavage were observed at the early infection stage in macrophages infected with RB51 and RA1 but not strain 2308. The inhibition of macrophage cell death promoted the survival of rough Brucella cells inside macrophages. The critical role of caspase-2 in mediating rough B. abortus induced macrophage cell death was confirmed using caspase-2 specific shRNA. The mitochondrial apoptosis pathway was activated in macrophages infected with rough B. abortus as demonstrated by increase in mitochondrial membrane permeability and the release of cytochrome c to cytoplasm in macrophages infected with rough Brucella. These results demonstrate that rough B. abortus strains RB51 and RA1 induce apoptotic and necrotic murine macrophage cell death that is mediated by caspase-2. The biological relevance of Brucella O antigen and caspase-2-mediated macrophage cell death in Brucella

  20. Caspase-2 mediated apoptotic and necrotic murine macrophage cell death induced by rough Brucella abortus.

    Science.gov (United States)

    Chen, Fang; He, Yongqun

    2009-08-28

    Brucella species are Gram-negative, facultative intracellular bacteria that cause zoonotic brucellosis. Survival and replication inside macrophages is critical for establishment of chronic Brucella infection. Virulent smooth B. abortus strain 2308 inhibits programmed macrophage cell death and replicates inside macrophages. Cattle B. abortus vaccine strain RB51 is an attenuated rough, lipopolysaccharide O antigen-deficient mutant derived from smooth strain 2308. B. abortus rough mutant RA1 contains a single wboA gene mutation in strain 2308. Our studies demonstrated that live RB51 and RA1, but not strain 2308 or heat-killed Brucella, induced both apoptotic and necrotic cell death in murine RAW264.7 macrophages and bone marrow derived macrophages. The same phenomenon was also observed in primary mouse peritoneal macrophages from mice immunized intraperitoneally with vaccine strain RB51 using the same dose as regularly performed in protection studies. Programmed macrophage cell death induced by RB51 and RA1 was inhibited by a caspase-2 inhibitor (Z-VDVAD-FMK). Caspase-2 enzyme activation and cleavage were observed at the early infection stage in macrophages infected with RB51 and RA1 but not strain 2308. The inhibition of macrophage cell death promoted the survival of rough Brucella cells inside macrophages. The critical role of caspase-2 in mediating rough B. abortus induced macrophage cell death was confirmed using caspase-2 specific shRNA. The mitochondrial apoptosis pathway was activated in macrophages infected with rough B. abortus as demonstrated by increase in mitochondrial membrane permeability and the release of cytochrome c to cytoplasm in macrophages infected with rough Brucella. These results demonstrate that rough B. abortus strains RB51 and RA1 induce apoptotic and necrotic murine macrophage cell death that is mediated by caspase-2. The biological relevance of Brucella O antigen and caspase-2-mediated macrophage cell death in Brucella pathogenesis and

  1. Cell death induced by the application of alternating magnetic fields to nanoparticle-loaded dendritic cells

    Energy Technology Data Exchange (ETDEWEB)

    Marcos-Campos, I; AsIn, L; Torres, T E; Tres, A; Ibarra, M R; Goya, G F [Instituto de Nanociencia de Aragon (INA), Mariano Esquillor s/n, CP 50018, Zaragoza (Spain); Marquina, C, E-mail: goya@unizar.es [Condensed Matter Department, Sciences Faculty, University of Zaragoza, 50009 (Spain)

    2011-05-20

    In this work, the capability of primary, monocyte-derived dendritic cells (DCs) to uptake iron oxide magnetic nanoparticles (MNPs) is assessed and a strategy to induce selective cell death in these MNP-loaded DCs using external alternating magnetic fields (AMFs) is reported. No significant decrease in the cell viability of MNP-loaded DCs, compared to the control samples, was observed after five days of culture. The number of MNPs incorporated into the cytoplasm was measured by magnetometry, which confirmed that 1-5 pg of the particles were uploaded per cell. The intracellular distribution of these MNPs, assessed by transmission electron microscopy, was found to be primarily inside the endosomic structures. These cells were then subjected to an AMF for 30 min and the viability of the blank DCs (i.e. without MNPs), which were used as control samples, remained essentially unaffected. However, a remarkable decrease of viability from approximately 90% to 2-5% of DCs previously loaded with MNPs was observed after the same 30 min exposure to an AMF. The same results were obtained using MNPs having either positive (NH{sub 2}{sup +}) or negative (COOH{sup -}) surface functional groups. In spite of the massive cell death induced by application of AMF to MNP-loaded DCs, the number of incorporated magnetic particles did not raise the temperature of the cell culture. Clear morphological changes at the cell structure after magnetic field application were observed using scanning electron microscopy. Therefore, local damage produced by the MNPs could be the main mechanism for the selective cell death of MNP-loaded DCs under an AMF. Based on the ability of these cells to evade the reticuloendothelial system, these complexes combined with an AMF should be considered as a potentially powerful tool for tumour therapy.

  2. Protective effect of aqueous extract from Spirulina platensis against cell death induced by free radicals

    Science.gov (United States)

    2010-01-01

    Background Spirulina is a commercial alga well known to contain various antioxidants, especially phycocyanin. Apart from being sold as a nutraceutical, Spirulina is incorporated as a functional ingredient in food products and beverages. Most of the previous reports on antioxidant activity of Spirulina were based on chemical rather than cell-based assays. The primary objective of this study was to assess the antioxidant activity of aqueous extract from Spirulina based on its protective effect against cell death induced by free radicals. Methods The antioxidant activity of the cold water extract from food-grade Spirulina platensis was assessed using both chemical and cell-based assays. In the cell-based assay, mouse fibroblast cells (3T3) cells were incubated for 1 h in medium containing aqueous extract of Spirulina or vitamin C (positive control) at 25, 125 and 250 μg/mL before the addition of 50 μM 1,1-diphenyl-2-picrylhydrazyl (DPPH) or 3-ethylbenzothiazoline-6-sulfonic acid (ABTS). The cells were incubated for another 24 h before being assessed for cell death due to apoptosis using the Cell Death Detection ELISA Kit. Spectrophotometric assays based on DPPH and ABTS were also used to assess the antioxidant activity of the extract compared to vitamin C and vitamin E (positive controls). Results Spirulina extract did not cause cytotoxic effect on 3T3 cells within the range of concentrations tested (0 - 250 μg/mL). The extract reduced significantly (p Spirulina has a protective effect against apoptotic cell death due to free radicals. The potential application of incorporating Spirulina into food products and beverages to enhance their antioxidant capacity is worth exploring. PMID:20858231

  3. Hyaluronan Protects Bovine Articular Chondrocytes against Cell Death Induced by Bupivacaine under Supraphysiologic Temperatures

    Science.gov (United States)

    Liu, Sen; Zhang, Qing-Song; Hester, William; O’Brien, Michael J.; Savoie, Felix H.; You, Zongbing

    2013-01-01

    Background Bupivacaine and supraphysiologic temperature can independently reduce cell viability of articular chondrocytes. In combination these two deleterious factors could further impair cell viability. Hypothesis Hyaluronan may protect chondrocytes from death induced by bupivacaine at supraphysiologic temperatures. Study Design Controlled laboratory study. Methods Bovine articular chondrocytes were treated with hyaluronan at physiologic (37°C) and supraphysiologic temperatures (45°C and 50°C) for one hour, and then exposed to bupivacaine for one hour at room temperature. Cell viability was assessed at three time points: immediately after treatment, six hours later, and twenty-four hours later using flow cytometry and fluorescence microscopy. The effects of hyaluronan on the levels of sulfated glycosaminoglycan in the chondrocytes were determined using Alcian blue staining. Results (1) Bupivacaine alone did not induce noticeable chondrocyte death at 37°C; (2) bupivacaine and temperature synergistically increased chondrocyte death, that is, when the chondrocytes were conditioned to 45°C and 50°C, 0.25% and 0.5% bupivacaine increased the cell death rate by 131% to 383% in comparison to the phosphate-buffered saline control group; and, (3) addition of hyaluronan reduced chondrocyte death rates to approximately 14% and 25% at 45°C and 50°C, respectively. Hyaluronan’s protective effects were still observed at six and twenty-four hours after bupivacaine treatment at 45°C. However, at 50°C, hyaluronan delayed but did not prevent the cell death caused by bupivacaine. One-hour treatment with hyaluronan significantly increased sulfated glycosaminoglycan levels in the chondrocytes. Conclusions Bupivacaine and supraphysiologic temperature synergistically increase chondrocyte death and hyaluronan may protect articular chondrocytes from death caused by bupivacaine. Clinical Relevance This study provides a rationale to perform pre-clinical and clinical studies to

  4. Cell-Centric View of Apoptosis and Apoptotic Cell Death-Inducing Antitumoral Strategies

    Directory of Open Access Journals (Sweden)

    Maria Dolores Boyano

    2011-03-01

    Full Text Available Programmed cell death and especially apoptotic cell death, occurs under physiological conditions and is also desirable under pathological circumstances. However, the more we learn about cellular signaling cascades, the less plausible it becomes to find restricted and well-limited signaling pathways. In this context, an extensive description of pathway-connections is necessary in order to point out the main regulatory molecules as well as to select the most appropriate therapeutic targets. On the other hand, irregularities in programmed cell death pathways often lead to tumor development and cancer-related mortality is projected to continue increasing despite the effort to develop more active and selective antitumoral compounds. In fact, tumor cell plasticity represents a major challenge in chemotherapy and improvement on anticancer therapies seems to rely on appropriate drug combinations. An overview of the current status regarding apoptotic pathways as well as available chemotherapeutic compounds provides a new perspective of possible future anticancer strategies.

  5. Use of nanotechnology for improved pharmacokinetics and activity of immunogenic cell death inducers used in cancer chemotherapy.

    Science.gov (United States)

    Janicka, Martyna; Gubernator, Jerzy

    2017-09-01

    Immunogenic cell death inducers (ICD inducers) are a diverse group of therapeutic molecules capable of eliciting an adaptive immune response against the antigens present on the surface of dying cancer cells. Most of these molecules suffer from low bioavailability, high toxicity and poor pharmacokinetics which limit their application. It is believed that nanotechnology, in particular nano-sized nanocarriers, can address most of the issues that limit the use of ICD inducers. Area covered: The mechanism of action of ICD inducers and their limitations is discussed. In addition, we cover the novel possibilities arising from the use of nanotechnology to improve delivery of ICD inducers to the target tissue as well as the restrictions of modern nanotechnology. Expert opinion: At present, nanocarrier formulations suffer from low bioavailability, poor pharmacokinetics and stability issues. Nonetheless, there is a tremendous future for combinatorial immune-pharmacological treatments of human tumors based on nanocarrier delivery of ICD inducers.

  6. Microglial cell death induced by glycated bovine serum albumin: nitric oxide involvement.

    Science.gov (United States)

    Khazaei, Mohammad R; Habibi-Rezaei, Mehran; Karimzadeh, Fereshteh; Moosavi-Movahedi, Ali Akbar; Sarrafnejhad, Abdo Alfattah; Sabouni, Farzaneh; Bakhti, Mostafa

    2008-08-01

    Nonenzymatic glycation results in the formation of advanced glycation end products (AGEs) through a nonenzymatic multistep reaction of reducing sugars with proteins. AGEs have been suspected to be involved in the pathogenesis of several chronic clinical neurodegenerative complications including Alzheimer's disease, which is characterized with the activation of microglial cells in neuritic plaques. To find out the consequence of this activation on microglial cells, we treated the cultured microglial cells with different glycation levels of Bovine Serum Albumin (BSA) which were prepared in vitro. Extent of glycation of protein has been characterized during 16 weeks of incubation with glucose. Treatment of microglial cells with various levels of glycated albumin induced nitric oxide (NO) production and consequently cell death. We also tried to find out the mode of death in AGE-activated microglial cells. Altogether, our results suggest that AGE treatment causes microglia to undergo NO-mediated apoptotic and necrotic cell death in short term and long term, respectively. NO production is a consequence of iNOS expression in a JNK dependent RAGE signalling after activation of RAGE by AGE-BSA.

  7. Calcium Channel Blocker Verapamil Enhances Reticulum Stress and Death Induced by Proteasome Inhibition in Myeloma Cells

    Directory of Open Access Journals (Sweden)

    Silke Meister

    2010-07-01

    Full Text Available The proteasome inhibitor bortezomib is clinically approved for the treatment of multiple myeloma. However, long-term remissions are difficult to achieve, and myeloma cells often develop secondary resistance to proteasome inhibitors. We recently demonstrated that the extraordinary sensitivity of myeloma cells toward bortezomib is dependent on their extensive immunoglobulin synthesis, thereby triggering the terminal unfolded protein response (UPR. Here, we investigated whether verapamil, an inhibitor of the multidrug resistance (MDR gene product, can enhance the cytotoxicity of bortezomib. The combination of bortezomib and verapamil synergistically decreased the viability of myeloma cells by inducing cell death. Importantly, bortezomib-mediated activation of major UPR components was enhanced byverapamil. The combination of bortezomib and verapamil resulted in caspase activation followed by poly(ADP-ribose polymerase cleavage, whereas nuclear factor κB (NF-κB activity declined in myeloma cells. Also, we found reduced immunoglobulin G secretion along with increased amounts of ubiquitinylated proteins within insoluble fractions of myeloma cells when using the combination treatment. Verapamil markedly induced reactive oxygen species production and autophagiclike processes. Furthermore, verapamil decreased MDR1 expression. We conclude that verapamil increased the antimyeloma effect of bortezomib by enhancing ER stress signals along with NF-κB inhibition, leading to cell death. Thus, the combination of bortezomib with verapamil may improve the efficacy of proteasome inhibitory therapy.

  8. CD 95 mediated apoptosis in embryogenesis: implication in tooth development.

    Czech Academy of Sciences Publication Activity Database

    Matalová, Eva; Šetková, Jana; Blackburn, J.; Míšek, Ivan; Sharpe, P. T.

    2006-01-01

    Roč. 9, 3 (2006), s. 123-128 ISSN 1397-5927 R&D Projects: GA ČR GA304/04/0101; GA MŠk OC B23.001 Institutional research plan: CEZ:AV0Z50450515 Keywords : fas * embryonic development * odontogenesis Subject RIV: EB - Genetics ; Molecular Biology

  9. Apoptotic Cell Death Induced by Resveratrol Is Partially Mediated by the Autophagy Pathway in Human Ovarian Cancer Cells.

    Directory of Open Access Journals (Sweden)

    Fangfang Lang

    Full Text Available Resveratrol (trans-3,4,5'-trihydroxystilbene is an active compound in food, such as red grapes, peanuts, and berries. Resveratrol exhibits an anticancer effect on various human cancer cells. However, the mechanism of resveratrol-induced anti-cancer effect at the molecular level remains to be elucidated. In this study, the mechanism underlying the anti-cancer effect of resveratrol in human ovarian cancer cells (OVCAR-3 and Caov-3 was investigated using various molecular biology techniques, such as flow cytometry, western blotting, and RNA interference, with a major focus on the potential role of autophagy in resveratrol-induced apoptotic cell death. We demonstrated that resveratrol induced reactive oxygen species (ROS generation, which triggers autophagy and subsequent apoptotic cell death. Resveratrol induced ATG5 expression and promoted LC3 cleavage. The apoptotic cell death induced by resveratrol was attenuated by both pharmacological and genetic inhibition of autophagy. The autophagy inhibitor chloroquine, which functions at the late stage of autophagy, significantly reduced resveratrol-induced cell death and caspase 3 activity in human ovarian cancer cells. We also demonstrated that targeting ATG5 by siRNA also suppressed resveratrol-induced apoptotic cell death. Thus, we concluded that a common pathway between autophagy and apoptosis exists in resveratrol-induced cell death in OVCAR-3 human ovarian cancer cells.

  10. Cell death induced on cell cultures and nude mouse skin by non-thermal, nanosecond-pulsed generated plasma.

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    Arnaud Duval

    Full Text Available Non-thermal plasmas are gaseous mixtures of molecules, radicals, and excited species with a small proportion of ions and energetic electrons. Non-thermal plasmas can be generated with any high electro-magnetic field. We studied here the pathological effects, and in particular cell death, induced by nanosecond-pulsed high voltage generated plasmas homogeneously applied on cell cultures and nude mouse skin. In vitro, Jurkat cells and HMEC exhibited apoptosis and necrosis, in dose-dependent manner. In vivo, on nude mouse skin, cell death occurred for doses above 113 J/cm(2 for the epidermis, 281 J/cm(2 for the dermis, and 394 J/cm(2 for the hypodermis. Using electron microscopy, we characterized apoptosis for low doses and necrosis for high doses. We demonstrated that these effects were not related to thermal, photonic or pH variations, and were due to the production of free radicals. The ability of cold plasmas to generate apoptosis on cells in suspension and, without any sensitizer, on precise skin areas, opens new fields of application in dermatology for extracorporeal blood cell treatment and the eradication of superficial skin lesions.

  11. Lytic cell death induced by melittin bypasses pyroptosis but induces NLRP3 inflammasome activation and IL-1β release.

    Science.gov (United States)

    Martín-Sánchez, Fátima; Martínez-García, Juan José; Muñoz-García, María; Martínez-Villanueva, Miriam; Noguera-Velasco, José A; Andreu, David; Rivas, Luís; Pelegrín, Pablo

    2017-08-10

    The nucleotide-binding domain and leucine-rich repeat-containing receptor with a pyrin domain 3 (NLRP3) inflammasome is a sensor for different types of infections and alterations of homeostatic parameters, including abnormally high levels of the extracellular nucleotide ATP or crystallization of different metabolites. All NLRP3 activators trigger a similar intracellular pathway, where a decrease in intracellular K + concentration and permeabilization of plasma membrane are key steps. Cationic amphipathic antimicrobial peptides and peptide toxins permeabilize the plasma membrane. In fact, some of them have been described to activate the NLRP3 inflammasome. Among them, the bee venom antimicrobial toxin peptide melittin is known to elicit an inflammatory reaction via the NLRP3 inflammasome in response to bee venom. Our study found that melittin induces canonical NLRP3 inflammasome activation by plasma membrane permeabilization and a reduction in the intracellular K + concentration. Following melittin treatment, the apoptosis-associated speck-like protein, an adaptor protein with a caspase recruitment domain (ASC), was necessary to activate caspase-1 and induce IL-1β release. However, cell death induced by melittin prevented the formation of large ASC aggregates, amplification of caspase-1 activation, IL-18 release and execution of pyroptosis. Therefore, melittin-induced activation of the NLRP3 inflammasome results in an attenuated inflammasome response that does not result in caspase-1 dependent cell death.

  12. Evidence of programmed cell death induced by reconditioning after cold stress in cucumber fruit and possible involvement of ethylene.

    Science.gov (United States)

    Chen, Xiaohong; Nie, Peng; Deng, Hongjun; Mi, Hongbo; Hou, Xiaorong; Li, Ping; Mao, Linchun

    2014-05-01

    Cucumber fruit is susceptible to chilling injury (CI), which could be accelerated significantly with subsequent shelf-life. This type of CI culminates in deterioration of organs and eventually leads to cell death. In this study, evidence of programmed cell death (PCD), involving cell death induced by cold stress, was investigated in cucumber. Harvested cucumber (Cucumis sativus L. cv. Zhexiu-1) fruits were stored at 2 °C for 3, 6 or 9 days and subsequently transferred to 20 °C for 2 days. Significant cell death acceleration was observed upon reconditioning after 9 days' cold stress when the hallmark of PCD - DNA laddering - was clearly observed. Further evidence of nuclear DNA cleavage was confirmed by the in situ TdT-mediated dUTP nick end labeling (TUNEL) assay. Chromatin condensation and nucleus distortion were observed by nuclear staining of DPI. Ethylene burst was observed upon reconditioning after 9 days of consecutive cold stress. The features of PCD process induced by reconditioning after cold stress in cucumber fruit may be mainly attributed to ethylene burst. © 2013 Society of Chemical Industry.

  13. Trypanosoma cruzi cell death induced by the Morita-Baylis-Hillman adduct 3-Hydroxy-2-methylene-3-(4-nitrophenylpropanenitrile.

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    Jana M Sandes

    Full Text Available Chagas disease, caused by the protozoan Trypanosoma cruzi, remains a serious health concern due to the lack of effective vaccines or satisfactory treatment. In the search for new compounds against this neglected disease, we have previously demonstrated that the compound 3-Hydroxy-2-methylene-3-(4-nitrophenylpropanenitrile (MBHA3, derived from the Morita-Baylis-Hillman reaction, effectively caused a loss of viability in both the epimastigote and trypomastigote forms. However, the mechanisms of parasite death elicited by MBHA3 remain unknown. The aim of this study was to better understand the morphophysiological changes and the mechanism of cell death induced by MBHA3 treatment on T. cruzi. To perform this analysis, we used confocal microscopy and flow cytometry to monitor the fluorescent probes such as annexin-V/propidium iodide (AV/PI, calcein-AM/ethidium homodimer (CA/EH, acridine orange (AO and rhodamine 123 (Rho 123. Lower concentrations of MBHA3 led to alterations in the mitochondrial membrane potential and AO labeling, but did not decrease the viability of the epimastiogote forms, as determined by the CA/EH and AV/PI assays. Conversely, treatment with higher concentrations of MBHA3 led to extensive plasma membrane damage, loss of mitochondrion membrane potential, DNA fragmentation and acidification of the cytoplasm. Our findings suggest that at higher concentrations, MBHA3 induces T. cruzi epimastigote death by necrosis in a mitochondrion-dependent manner.

  14. Trypanosoma cruzi cell death induced by the Morita-Baylis-Hillman adduct 3-Hydroxy-2-methylene-3-(4-nitrophenylpropanenitrile).

    Science.gov (United States)

    Sandes, Jana M; Fontes, Adriana; Regis-da-Silva, Carlos G; de Castro, Maria C A Brelaz; Lima-Junior, Claudio G; Silva, Fábio P L; Vasconcellos, Mário L A A; Figueiredo, Regina C B Q

    2014-01-01

    Chagas disease, caused by the protozoan Trypanosoma cruzi, remains a serious health concern due to the lack of effective vaccines or satisfactory treatment. In the search for new compounds against this neglected disease, we have previously demonstrated that the compound 3-Hydroxy-2-methylene-3-(4-nitrophenylpropanenitrile) (MBHA3), derived from the Morita-Baylis-Hillman reaction, effectively caused a loss of viability in both the epimastigote and trypomastigote forms. However, the mechanisms of parasite death elicited by MBHA3 remain unknown. The aim of this study was to better understand the morphophysiological changes and the mechanism of cell death induced by MBHA3 treatment on T. cruzi. To perform this analysis, we used confocal microscopy and flow cytometry to monitor the fluorescent probes such as annexin-V/propidium iodide (AV/PI), calcein-AM/ethidium homodimer (CA/EH), acridine orange (AO) and rhodamine 123 (Rho 123). Lower concentrations of MBHA3 led to alterations in the mitochondrial membrane potential and AO labeling, but did not decrease the viability of the epimastiogote forms, as determined by the CA/EH and AV/PI assays. Conversely, treatment with higher concentrations of MBHA3 led to extensive plasma membrane damage, loss of mitochondrion membrane potential, DNA fragmentation and acidification of the cytoplasm. Our findings suggest that at higher concentrations, MBHA3 induces T. cruzi epimastigote death by necrosis in a mitochondrion-dependent manner.

  15. Vacuolar H+ -ATPase c protects glial cell death induced by sodium nitroprusside under glutathione-depleted condition.

    Science.gov (United States)

    Byun, Yu Jeong; Lee, Seong-Beom; Lee, Hwa Ok; Son, Min Jeong; Kim, Ho-Shik; Kwon, Oh-Joo; Jeong, Seong-Whan

    2011-08-01

    We examined the role of the c subunit (ATP6L) of vacuolar H(+) -ATPase and its molecular mechanisms in glial cell death induced by sodium nitroprusside (SNP). ATP6L siRNA-transfected cells treated with SNP showed a significant increase in cytotoxicity under glutathione (GSH)-depleted conditions after pretreatment with buthionine sulfoximine, but reduction of ATP6L did not affect the regulation of lysosomal pH in analyses with lysosomal pH-dependent fluorescence probes. Photodegraded SNP and ferrous sulfate induced cytotoxicity with the same pattern as that of SNP, but SNAP and potassium cyanide did not show activity. Pretreatment of the transfected cells with deferoxamine (DFO) reduced ROS production and significantly inhibited the cytotoxicity, which indicates that primarily iron rather than nitric oxide or cyanide from SNP contributes to cell death. Involvement of apoptotic processes in the cells was not shown. Pretreatment with JNK or p38 chemical inhibitor significantly inhibited the cytotoxicity, and we also confirmed that the MAPKs were activated in the cells by immunoblot analysis. Significant increase of LC3-II conversion was observed in the cells, and the conversions were inhibited by cotransfection of the MAPK siRNAs and pretreatment with DFO. Introduction of Atg5 siRNA inhibited the cytotoxicity and inhibited the activation of MAPKs and the conversion of LC3. We finally confirmed autophagic cell death and involvement of MAPKs by observation of autophagic vacuoles via electron microscopy. These data suggest that ATP6L has a protective role against SNP-induced autophagic cell death via inhibition of JNK and p38 in GSH-depleted glial cells. Copyright © 2011 Wiley-Liss, Inc.

  16. Human Peritoneal Mesothelial Cell Death Induced by High-Glucose Hypertonic Solution Involves Ca2+ and Na+ Ions and Oxidative Stress with the Participation of PKC/NOX2 and PI3K/Akt Pathways

    Directory of Open Access Journals (Sweden)

    Felipe Simon

    2017-06-01

    Full Text Available Chronic peritoneal dialysis (PD therapy is equally efficient as hemodialysis while providing greater patient comfort and mobility. Therefore, PD is the treatment of choice for several types of renal patients. During PD, a high-glucose hyperosmotic (HGH solution is administered into the peritoneal cavity to generate an osmotic gradient that promotes water and solutes transport from peritoneal blood to the dialysis solution. Unfortunately, PD has been associated with a loss of peritoneal viability and function through the generation of a severe inflammatory state that induces human peritoneal mesothelial cell (HPMC death. Despite this deleterious effect, the precise molecular mechanism of HPMC death as induced by HGH solutions is far from being understood. Therefore, the aim of this study was to explore the pathways involved in HGH solution-induced HPMC death. HGH-induced HPMC death included influxes of intracellular Ca2+ and Na+. Furthermore, HGH-induced HPMC death was inhibited by antioxidant and reducing agents. In line with this, HPMC death was induced solely by increased oxidative stress. In addition to this, the cPKC/NOX2 and PI3K/Akt intracellular signaling pathways also participated in HGH-induced HPMC death. The participation of PI3K/Akt intracellular is in agreement with previously shown in rat PMC apoptosis. These findings contribute toward fully elucidating the underlying molecular mechanism mediating peritoneal mesothelial cell death induced by high-glucose solutions during peritoneal dialysis.

  17. The pro-apoptotic protein Bmf co-operates with Bim and Puma in neuron death induced by β-amyloid or NGF deprivation.

    Science.gov (United States)

    Akhter, Rumana; Saleem, Suraiya; Saha, Akash; Biswas, Subhas Chandra

    2018-04-01

    The pro-apoptotic Bcl-2 homology 3 domain only (BH3-only) proteins are central regulators of cell death in various physiological and pathological conditions, including Alzheimer's disease (AD). Bcl-2 modifying factor (Bmf) is one such BH3-only protein that is implicated in various death paradigms such as anoikis, seizures, cancer and autoimmunity. It also co-operates with other BH3-only proteins such as Bim in various death paradigms. However, its role in neurodegeneration is under-investigated. Here, we report for the first time the essential role of Bmf and its co-operativity with direct activator BH3-only proteins Bim and Puma in neuron death induced by beta-amyloid (Aβ) toxicity or NGF deprivation. Oligomeric Aβ is main pathologic species in AD and NGF deprivation is relevant for both developmental as well as pathologic neuron death. We find that Bmf over-expression causes cell death and Bmf knockdown protects neurons against death evoked by Aβ or NGF deprivation. We also find that Bmf co-operates with other important BH3-only proteins such as Bim and Puma in neuron death induced by Aβ or NGF deprivation. Simultaneous knocking down of these molecules by their respective shRNAs provide enhanced protection against Aβ. Taken together, our results elucidate the essential role of Bmf and its co-operative effects with already known neuron death inducers, Bim and Puma, in neuron death evoked by Aβ treatment or NGF deprivation. Copyright © 2018 Elsevier Inc. All rights reserved.

  18. Jasmonates are induced by the PAMP flg22 but not the cell death-inducing elicitor Harpin in Vitis rupestris.

    Science.gov (United States)

    Chang, Xiaoli; Seo, Mitsunori; Takebayashi, Yumiko; Kamiya, Yuji; Riemann, Michael; Nick, Peter

    2017-01-01

    Plants employ two layers of defence that differ with respect to cell death: pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI) and effector-triggered immunity (ETI). In our previous work, we have comparatively mapped the molecular events in a cell system derived from the wild American grape Vitis rupestris, where cell death-independent defence can be triggered by PAMP flg22, whereas the elicitor Harpin activates a cell death-related ETI-like response. Both defence responses overlapped with respect to early events, such as calcium influx, apoplastic alkalinisation, oxidative burst, mitogen-activated protein kinase (MAPK) signalling, activation of defence-related genes and accumulation of phytoalexins. However, timing and amplitude of early signals differed. In the current study, we address the role of jasmonates (JAs) as key signalling compounds in hypersensitive cell death. We find, in V. rupestris, that jasmonic acid and its bioactive conjugate jasmonoyl-isoleucine (JA-Ile) rapidly accumulate in response to flg22 but not in response to Harpin. However, Harpin can induce programmed cell death, whereas exogenous methyl jasmonate (MeJA) fails to do so, although both signals induce a similar response of defence genes. Also in a second cell line from V. vinifera cv. 'Pinot Noir', where Harpin cannot activate cell death and where flg22 fails to induce JA and JA-Ile, defence genes are activated in a similar manner. These findings indicate that the signal pathway culminating in cell death must act independently from the events culminating in the accumulation of toxic stilbenes.

  19. Role of SIRT1-mediated mitochondrial and Akt pathways in glioblastoma cell death induced by Cotinus coggygria flavonoid nanoliposomes

    Directory of Open Access Journals (Sweden)

    Wang G

    2015-08-01

    phosphorylated p53. Together, these results indicated SIRT1/p53-mediated cell death was induced by CCF-NLs, but not by extracellular signal-regulated kinase, in DBTRG-05MG cells. Overall, this study suggested caspase-dependent activation of both the intrinsic and extrinsic signaling pathways, probably through blockade of the SIRT1/p53-mediated mitochondrial and Akt pathways to exert the proapoptotic effect of CCF-NLs in DBTRG-05MG GBM cells. Keywords: Cotinus coggygria flavonoid nanoliposomes, cell death, SIRT1, mitochondrial, PI3K/Akt pathway

  20. Nuclear calcium controls the apoptotic-like cell death induced by d-erythro-sphinganine in tobacco cells.

    Science.gov (United States)

    Lachaud, Christophe; Da Silva, Daniel; Cotelle, Valérie; Thuleau, Patrice; Xiong, Tou Cheu; Jauneau, Alain; Brière, Christian; Graziana, Annick; Bellec, Yannick; Faure, Jean-Denis; Ranjeva, Raoul; Mazars, Christian

    2010-01-01

    Studies performed in animals have highlighted the major role of sphingolipids in regulating the balance between cell proliferation and cell death. Sphingolipids have also been shown to induce cell death in plants via calcium-based signalling pathways but the contribution of free cytosolic and/or nuclear calcium in the overall process has never been evaluated. Here, we show that increase in tobacco BY-2 cells of the endogenous content of Long Chain Bases (LCBs) caused by external application of d-erythro-sphinganine (DHS) is followed by immediate dose-dependent elevations of cellular free calcium concentration within the first minute in the cytosol and 10min later in the nucleus. Cells challenged with DHS enter a death process through apoptotic-like mechanisms. Lanthanum chloride, a general blocker of calcium entry, suppresses the cellular calcium variations and the PCD induced by DHS. Interestingly, dl-2-amino-5-phosphopentanoic acid (AP5) and [(+)-dizocilpine] (MK801), two inhibitors of animal and plant ionotropic glutamate receptors, suppress DHS-induced cell death symptoms by selectively inhibiting the variations of nuclear calcium concentration. The selective action of these compounds demonstrates the crucial role of nuclear calcium signature in controlling DHS-induced cell death in tobacco cells. 2009 Elsevier Ltd. All rights reserved.

  1. Divergent effects of resveratrol, a polyphenolic phytostilbene, on free radical levels and type of cell death induced by the histone deacetylase inhibitors butyrate and trichostatin A.

    Science.gov (United States)

    Galfi, Peter; Jakus, Judit; Molnar, Tamas; Neogrady, Susan; Csordas, Adam

    2005-02-01

    We investigated the effects of the polyphenolic phytostilbene resveratrol on the steady-state free radical (FR) concentration and mode of cell death induced by the histone deacetylase inhibitors butyrate and trichostatin A. (i) There was no correlation between cell death induction by butyrate or trichostatin A (TSA) and FR levels. (ii) Treatment with resveratrol or N-acetyl-l-cystein (NAC) of cells, in which the FR concentration was high, resulted in an almost complete reduction of FR levels. (iii) When, however, the cellular FR concentration was marginal, resveratrol caused a minor, and NAC a marked increase of FRs as well as of the extent of cell death. Thus, resveratrol and NAC acted as antioxidants only when the cellular FR levels were high, and acted as pro-oxidants when facing a low FR concentration. (iv) Since resveratrol and the antioxidant NAC exhibited analogous effects, it is concluded that the observed actions of resveratrol are due to polyphenolic redox reactions and not related to the stilbene moiety of the molecule. (v) The results indicate that the redox status of a given cell type plays an important role in determining whether resveratrol and other antioxidants promote cell death or protect cells from it.

  2. A novel neuron-enriched protein SDIM1 is down regulated in Alzheimer's brains and attenuates cell death induced by DNAJB4 over-expression in neuro-progenitor cells

    Directory of Open Access Journals (Sweden)

    Lei Joy X

    2011-01-01

    Full Text Available Abstract Background Molecular changes in multiple biological processes contribute to the development of chronic neurodegeneration such as late onset Alzheimer's disease (LOAD. To discover how these changes are reflected at the level of gene expression, we used a subtractive transcription-based amplification of mRNA procedure to identify novel genes that have altered expression levels in the brains of Alzheimer's disease (AD patients. Among the genes altered in expression level in AD brains was a transcript encoding a novel protein, SDIM1, that contains 146 amino acids, including a typical signal peptide and two transmembrane domains. Here we examined its biochemical properties and putative roles in neuroprotection/neurodegeneration. Results QRT-PCR analysis of additional AD and control post-mortem human brains showed that the SDIM1 transcript was indeed significantly down regulated in all AD brains. SDIM1 is more abundant in NT2 neurons than astrocytes and present throughout the cytoplasm and neural processes, but not in the nuclei. In NT2 neurons, it is highly responsive to stress conditions mimicking insults that may cause neurodegeneration in AD brains. For example, SDIM1 was significantly down regulated 2 h after oxygen-glucose deprivation (OGD, though had recovered 16 h later, and also appeared significantly up regulated compared to untreated NT2 neurons. Overexpression of SDIM1 in neuro-progenitor cells improved cells' ability to survive after injurious insults and its downregulation accelerated cell death induced by OGD. Yeast two-hybrid screening and co-immunoprecipitation approaches revealed, both in vitro and in vivo, an interaction between SDIM1 and DNAJB4, a heat shock protein hsp40 homolog, recently known as an enhancer of apoptosis that also interacts with the mu opioid receptor in human brain. Overexpression of DNAJB4 alone significantly reduced cell viability and SDIM1 co-overexpression was capable of attenuating the cell death

  3. Ascorbic acid has superior ex vivo antiproliferative, cell death-inducing and immunomodulatory effects over IFN-α in HTLV-1-associated myelopathy.

    Directory of Open Access Journals (Sweden)

    Britta Moens

    Full Text Available BACKGROUND: Clear therapeutic guidelines for HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP are missing due to the lack of randomized double-blind controlled clinical trials. Moderate yet similar clinical benefit has been demonstrated for IFN-α and high-dose ascorbic acid (AA monotherapy in a large open clinical trial. However, there is a lack of in vivo and in vitro studies exploring and comparing the effects of high-dose AA and IFN-α treatment in the context of HAM/TSP. Therefore, we performed the first comparative analysis of the ex vivo and in vitro molecular and cellular mechanisms of action of IFN-α and high-dose AA in HAM/TSP. PRINCIPAL FINDINGS: Through thymidine incorporation and quantification of Th1/Th2/Th17 cytokines, we demonstrate that high-dose AA displays differential and superior antiproliferative and immunomodulatory effects over IFN-α in HAM/TSP PBMCs ex vivo. In addition, high-dose AA, but not IFN-α, induced cell death in both HAM/TSP PBMCs and HTLV-1-infected T-cell lines MT-2 and MT-4. Microarray data combined with pathway analysis of MT-2 cells revealed AA-induced regulation of genes associated with cell death, including miR-155. Since miR-155 has recently been demonstrated to up-regulate IFN-γ, this microRNA might represent a novel therapeutic target in HAM/TSP, as recently demonstrated in multiple sclerosis, another neuroinflammatory disease. On the other hand, IFN-α selectively up-regulated antiviral and immune-related genes. CONCLUSIONS: In comparison to IFN-α, high-dose AA treatment has superior ex vivo and in vitro cell death-inducing, antiproliferative and immunomodulatory anti-HTLV-1 effects. Differential pathway activation by both drugs opens up avenues for targeted treatment in specific patient subsets.

  4. Overexpression of alpha-synuclein at non-toxic levels increases dopaminergic cell death induced by copper exposure via modulation of protein degradation pathways.

    Science.gov (United States)

    Anandhan, Annadurai; Rodriguez-Rocha, Humberto; Bohovych, Iryna; Griggs, Amy M; Zavala-Flores, Laura; Reyes-Reyes, Elsa M; Seravalli, Javier; Stanciu, Lia A; Lee, Jaekwon; Rochet, Jean-Christophe; Khalimonchuk, Oleh; Franco, Rodrigo

    2015-09-01

    Gene multiplications or point mutations in alpha (α)-synuclein are associated with familial and sporadic Parkinson's disease (PD). An increase in copper (Cu) levels has been reported in the cerebrospinal fluid and blood of PD patients, while occupational exposure to Cu has been suggested to augment the risk to develop PD. We aimed to elucidate the mechanisms by which α-synuclein and Cu regulate dopaminergic cell death. Short-term overexpression of wild type (WT) or mutant A53T α-synuclein had no toxic effect in human dopaminergic cells and primary midbrain cultures, but it exerted a synergistic effect on Cu-induced cell death. Cell death induced by Cu was potentiated by overexpression of the Cu transporter protein 1 (Ctr1) and depletion of intracellular glutathione (GSH) indicating that the toxic effects of Cu are linked to alterations in its intracellular homeostasis. Using the redox sensor roGFP, we demonstrated that Cu-induced oxidative stress was primarily localized in the cytosol and not in the mitochondria. However, α-synuclein overexpression had no effect on Cu-induced oxidative stress. WT or A53T α-synuclein overexpression exacerbated Cu toxicity in dopaminergic and yeast cells in the absence of α-synuclein aggregation. Cu increased autophagic flux and protein ubiquitination. Impairment of autophagy by overexpression of a dominant negative Atg5 form or inhibition of the ubiquitin/proteasome system (UPS) with MG132 enhanced Cu-induced cell death. However, only inhibition of the UPS stimulated the synergistic toxic effects of Cu and α-synuclein overexpression. Our results demonstrate that α-synuclein stimulates Cu toxicity in dopaminergic cells independent from its aggregation via modulation of protein degradation pathways. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. In vivo UVB irradiation induces clustering of Fas (CD95) on human epidermal cells

    DEFF Research Database (Denmark)

    Bang, Bo; Gniadecki, Robert; Larsen, Jørgen K

    2003-01-01

    In vitro studies with human cell lines have demonstrated that the death receptor Fas plays a role in ultraviolet (UV)-induced apoptosis. The purpose of the present study was to investigate the relation between Fas expression and apoptosis as well as clustering of Fas in human epidermis after...... clustering has a functional significance. Our results ar in accordance with previous findings from in vitro studies, and suggest that Fas is activated in vivo in human epidermis after UVB exposure....

  6. Fas antigen (CD95) expression and apoptosis in hepatocytes of patients with chronic viral hepatitis.

    Science.gov (United States)

    Kiyici, Murat; Gurel, Selim; Budak, Ferah; Dolar, Enver; Gulten, Macit; Nak, Selim Giray; Memik, Faruk

    2003-10-01

    Apoptosis may be defined as programmed cell death. It is involved in the normal development and homeostasis of tissues in multicellular organisms. An increased or decreased rate of apoptosis may lead to a range of diseases. Fas antigen is a cell-surface receptor that induces apoptotic pathways when treated with Fas ligand or anti-Fas antibody. There is increasing evidence that apoptosis plays an important role in the immunopathogenesis of chronic viral hepatitis, in which the Fas antigen-Fas ligand pathway is particularly involved. Fas antigen expression and apoptosis (apoptotic index) were assayed using flow cytometry in the hepatocytes of 27 patients with chronic viral hepatitis. Histopathological activity, scored by Knodell's histological activity index, other histopathological parameters, serum transaminase values and patient age were then compared with apoptotic index and Fas antigen expression. Apoptosis and Fas antigen expression in hepatocytes were correlated closely with histological activity (grade) of chronic viral hepatitis, but there were no correlations with histological stage, patient age or serum transaminase levels. Apoptosis and its triggering molecule, Fas antigen, induce mechanisms that appear to be associated with the pathogenesis of chronic viral hepatitis.

  7. CHIP, a carboxy terminus HSP-70 interacting protein, prevents cell death induced by endoplasmic reticulum stress in the central nervous system

    Directory of Open Access Journals (Sweden)

    Felipe eCabral Miranda

    2015-01-01

    Full Text Available Endoplasmic reticulum (ER stress and protein misfolding are associated with various neurodegenerative diseases. ER stress activates Unfolded Protein Response (UPR, an adaptative response. However, severe ER stress can induce cell death. Here we show that the E3 ubiquitin ligase and co-chaperone Carboxyl Terminus HSP70/90 Interacting Protein (CHIP prevents neuron death in the hippocampus induced by severe ER stress. Organotypic hippocampal slice cultures (OHSCs were exposed to Tunicamycin, a pharmacological ER stress inducer, to trigger cell death. Overexpression of CHIP was achieved with a recombinant adeno-associated viral vector (rAAV and significantly diminished ER stress-induced cell death, as shown by analysis of propidium iodide (PI uptake, condensed chromatin, TUNEL and cleaved caspase 3 in the CA1 region of OHSCs. In addition, overexpression of CHIP prevented upregulation of both CHOP and p53 both pro-apoptotic pathways induced by ER stress. We also detected an attenuation of eIF2a phosphorylation promoted by ER stress. However, CHIP did not prevent upregulation of BiP/GRP78 induced by UPR. These data indicate that overexpression of CHIP attenuates ER-stress death response while maintain ER stress adaptative response in the central nervous system. These results indicate a neuroprotective role for CHIP upon UPR signalling. CHIP emerge as a candidate for clinical intervention in neurodegenerative diseases associated with ER stress.

  8. Role of oxidative stress, mitochondrial membrane potential, and calcium homeostasis in human lymphocyte death induced by nickel carbonate hydroxide in vitro

    Energy Technology Data Exchange (ETDEWEB)

    M' Bemba-Meka, Prosper [Faculty of Medicine, Universite de Montreal, QC (Canada); University of Louisville, Department of Pharmacology and Toxicology, Center for Genetics and Molecular Medicine, Louisville, KY (United States); Lemieux, Nicole [Universite de Montreal, Department of Pathology and Cellular Biology, Main Station, P.O. Box 6128, Montreal, QC (Canada); Chakrabarti, Saroj K. [Faculty of Medicine, Universite de Montreal, QC (Canada)

    2006-07-15

    When isolated human lymphocytes were treated in vitro with various concentrations of soluble form of nickel carbonate hydroxide (NiCH) (0-1 mM), at 37 C for 4 h, both concentration- and time-dependent effects of NiCH on lymphocyte death were observed. Increased generation of hydrogen peroxide (H{sub 2}O{sub 2}), superoxide anion (O{sub 2} {sup -}), depletion of both no protein (NP-) and protein (P-) sulfhydryl (SH) contents and lipid peroxidation (LPO) were induced by NiCH. Pretreatment of lymphocytes with either catalase (H{sub 2}O{sub 2} scavenger), or deferoxamine (DFO) (iron chelator), or excess glutathione (GSH) (an antioxidant) not only significantly reduced the NiCH-induced generation of H{sub 2}O{sub 2} and LPO, but also increased the NP-SH and P-SH contents initially reduced by NiCH. NiCH-induced generation of excess O{sub 2} {sup -} but not excess LPO was significantly reduced by pretreatment with superoxide dismutase (SOD). NiCH-induced lymphocyte death was significantly prevented by pre-treatment with either catalase, or dimethylthiourea/mannitol (hydroxyl radical scavengers), or DFO, or excess GSH/N-acetylcysteine. NiCH-induced lymphocyte death was also significantly prevented by pretreatment with excess SOD. Thus, various types of oxidative stresses play an important role in NiCH-induced lymphocyte death. Cotreatment with cyclosporin A, a specific inhibitor of alteration in mitochondrial membrane potential ({delta}{psi}{sub m}), not only inhibited NiCH-induced alteration in {delta}{psi}{sub m}, but also significantly prevented Ni-compound-induced lymphocyte death. Furthermore, NiCH-induced destabilization of cellular calcium homeostasis. As such, NiCH-induced lymphocyte death was significantly prevented by modulating intracellular calcium fluxes such as Ca{sup 2+} channel blockers and intracellular Ca{sup 2+} antagonist. Thus, the mechanism of NiCH (soluble form)-induced activation of lymphocyte death signalling pathways involves not only the excess

  9. Retrograde signaling

    DEFF Research Database (Denmark)

    Kleine, Tatjana; Leister, Dario Michael

    2016-01-01

    The term retrograde signaling refers to the fact that chloroplasts and mitochondria utilize specific signaling molecules to convey information on their developmental and physiological states to the nucleus and modulate the expression of nuclear genes accordingly. Signals emanating from plastids...... of retrograde signaling has since been extended and revised. Elements of several 'operational' signaling circuits have come to light, including metabolites, signaling cascades in the cytosol and transcription factors. Here, we review recent advances in the identification and characterization of retrograde...

  10. Analysis of cell death inducing compounds

    DEFF Research Database (Denmark)

    Spicker, Jeppe; Pedersen, Henrik Toft; Nielsen, Henrik Bjørn

    2007-01-01

    Biomarkers for early detection of toxicity hold the promise of improving the failure rates in drug development. In the present study, gene expression levels were measured using full-genome RAE230 version 2 Affymetrix GeneChips on rat liver tissue 48 h after administration of six different compounds......), ornithine aminotransferase (OAT) and Cytochrome P450, subfamily IIC (mephenytoin 4-hydroxylase) (Cyp2C29). RT-PCR for these three genes was performed and four additional compounds were included for validation. The quantitative RT-PCR analysis confirmed the findings based on the microarray data and using...... the three genes a classification rate of 55 of 57 samples was achieved for the classification of not toxic versus toxic. The single most promising biomarker (OAT) alone resulted in a surprisingly 100% correctly classified samples. OAT has not previously been linked to toxicity and cell death...

  11. How Kidney Cell Death Induces Renal Necroinflammation.

    Science.gov (United States)

    Mulay, Shrikant R; Kumar, Santhosh V; Lech, Maciej; Desai, Jyaysi; Anders, Hans-Joachim

    2016-05-01

    The nephrons of the kidney are independent functional units harboring cells of a low turnover during homeostasis. As such, physiological renal cell death is a rather rare event and dead cells are flushed away rapidly with the urinary flow. Renal cell necrosis occurs in acute kidney injuries such as thrombotic microangiopathies, necrotizing glomerulonephritis, or tubular necrosis. All of these are associated with intense intrarenal inflammation, which contributes to further renal cell loss, an autoamplifying process referred to as necroinflammation. But how does renal cell necrosis trigger inflammation? Here, we discuss the role of danger-associated molecular patterns (DAMPs), mitochondrial (mito)-DAMPs, and alarmins, as well as their respective pattern recognition receptors. The capacity of DAMPs and alarmins to trigger cytokine and chemokine release initiates the recruitment of leukocytes into the kidney that further amplify necroinflammation. Infiltrating neutrophils often undergo neutrophil extracellular trap formation associated with neutrophil death or necroptosis, which implies a release of histones, which act not only as DAMPs but also elicit direct cytotoxic effects on renal cells, namely endothelial cells. Proinflammatory macrophages and eventually cytotoxic T cells further drive kidney cell death and inflammation. Dissecting the molecular mechanisms of necroinflammation may help to identify the best therapeutic targets to limit nephron loss in kidney injury. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Involvement of extrinsic and intrinsic apoptotic pathways together with endoplasmic reticulum stress in cell death induced by naphthylchalcones in a leukemic cell line: advantages of multi-target action.

    Science.gov (United States)

    Winter, Evelyn; Chiaradia, Louise Domeneghini; Silva, Adny Henrique; Nunes, Ricardo José; Yunes, Rosendo Augusto; Creczynski-Pasa, Tânia Beatriz

    2014-08-01

    Chalcones, naturally occurring open-chain flavonoids abundant in plants, have demonstrated anticancer activity in multiple tumor cells. In a previous work, the potential anticancer activity of three naphthylchalcones named R7, R13 and R15 was shown. In this study, the mechanism of actions of these chalcones was originally shown. The chalcones presented concentration and time-dependent cytotoxicity. To determine the type of cell death induced by chalcones, we assessed a series of assays including measurements of the caspase-8, -9 and -12 activities, expression of important apoptosis-related genes and proteins, changes in the cell calcium concentration and cytochrome c release. The activities of caspase-8, -9 and -12 increased after the treatment of L1210 cells with the three compounds. Chalcones R7 and R13 induced an increase of pro-apoptotic proteins Bax, Bid and Bak (only chalcone R13), as well as a decrease in anti-apoptotic Bcl-2 expression. These chalcones also induced an increase in Fas and a decrease in p21 and p53 expression. Chalcone R15 seems to act by a different mechanism to promote cell death, as it did not change the mitochondrion-related proteins, nor did it induce the cytochrome c release. All compounds induced an increase in cell calcium concentration and an increase in CHOP expression, which together with an increase in caspase-12 activity, suggest that chalcones could induce an endoplasmic reticulum (ER) stress. Taken together, these results suggest that chalcones induce apoptosis by different pathways, being an interesting strategy to suggest for cancer therapy. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. 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

  14. Receptor-mediated endocytosis is not required for tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis.

    Science.gov (United States)

    Kohlhaas, Susan L; Craxton, Andrew; Sun, Xiao-Ming; Pinkoski, Michael J; Cohen, Gerald M

    2007-04-27

    Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is selectively toxic to tumor compared with normal cells. Other members of the TNF family of death ligands (TNF, CD95L) engage their respective receptors (TNF-R1 and CD95), resulting in internalization of receptor and ligand and recruitment of adaptor proteins to the caspase activation platform known as the death-inducing signaling complex (DISC). Recently, TNF-R1 and CD95 have been shown to induce apoptosis with an absolute requirement for internalization of their corresponding receptors in the formation of a DISC. We show that TRAIL and its receptors are rapidly endocytosed in a time- and concentration-dependent manner. Blockade of receptor internalization with hyperosmotic sucrose did not inhibit TRAIL-induced apoptosis but, rather, amplified the apoptotic signaling of TRAIL. Plate-bound and soluble TRAIL induced similar levels of apoptosis. Together these results suggest that neither ligand nor receptor internalization is required for TRAIL-induced apoptosis. Internalization of TRAIL is mediated primarily by clathrin-dependent endocytosis and also by clathrin-independent pathways. Inhibition of clathrin-dependent internalization by overexpression of dominant negative forms of dynamin or AP180 did not inhibit TRAIL-induced apoptosis. Consistent with the finding that neither internalization of TRAIL nor its receptors is required for transmission of its apoptotic signal, recruitment of FADD (Fas-associated death domain) and procaspase-8 to form the TRAIL-associated DISC occurred at 4 degrees C, independent of endocytosis. Our findings demonstrate that TRAIL and TRAIL receptor 1/2, unlike TNF-TNF-R1 or CD95L-CD95, do not require internalization for formation of the DISC, activation of caspase-8, or transmission of an apoptotic signal in BJAB type I cells.

  15. Phosphoinositide signaling.

    Science.gov (United States)

    Boss, Wendy F; Im, Yang Ju

    2012-01-01

    "All things flow and change…even in the stillest matter there is unseen flux and movement." Attributed to Heraclitus (530-470 BC), from The Story of Philosophy by Will Durant. Heraclitus, a Greek philosopher, was thinking on a much larger scale than molecular signaling; however, his visionary comments are an important reminder for those studying signaling today. Even in unstimulated cells, signaling pathways are in constant metabolic flux and provide basal signals that travel throughout the organism. In addition, negatively charged phospholipids, such as the polyphosphorylated inositol phospholipids, provide a circuit board of on/off switches for attracting or repelling proteins that define the membranes of the cell. This template of charged phospholipids is sensitive to discrete changes and metabolic fluxes-e.g., in pH and cations-which contribute to the oscillating signals in the cell. The inherent complexities of a constantly fluctuating system make understanding how plants integrate and process signals challenging. In this review we discuss one aspect of lipid signaling: the inositol family of negatively charged phospholipids and their functions as molecular sensors and regulators of metabolic flux in plants.

  16. Dissection of pathways leading to antigen receptor-induced and Fas/CD95-induced apoptosis in human B cells

    NARCIS (Netherlands)

    Lens, S. M.; den Drijver, B. F.; Pötgens, A. J.; Tesselaar, K.; van Oers, M. H.; van Lier, R. A.

    1998-01-01

    To dissect intracellular pathways involved in B cell Ag receptor (BCR)-mediated and Fas-induced human B cell death, we isolated clones of the Burkitt lymphoma cell line Ramos with different apoptosis sensitivities. Selection for sensitivity to Fas-induced apoptosis also selected for clones with

  17. Changing of expression level of fas-antigen (CD95), cytokines synthesis and production after irradiation in low doses

    International Nuclear Information System (INIS)

    Kalinina, N.M.; Solntceva, O.S.; Bytchkova, N.V.; Nikiforov, A.M.

    1997-01-01

    It is known that bone marrow progenitor (CD34+), tymocytes and peripheral blood lymphocytes (PBL) are most radiosensitive than other cell types. Even low doses of radiation induce apoptosis. The investigators suggest that it is possible relationship between synthesis and production of cytokines and apoptotic process. With the purpose to determine correlation between expression of Fas-antigen and synthesis of cytokines after low doses irradiation the experiments by irradiation PBL of healthy persons in vitro were held. Cells were X-irradiated by 12,5, 25 and 50 cGy. In consequence of the experiments increasing of Fas-antigen was revealed. This increasing correlated with changing in synthesis and production of cytokines. Also the Chernobyl's accident liquidators (CAL) were investigated. After comparison data in the group CAL (I) with data in the control group (II) increasing of Fas-antigen expression was revealed. Also in I group was discovered increasing of the cell number sinthesied interleukine-4 (IL-4) and interleukine-6 (IL-6). Interleukine-lβ (IL-1 β) producing pell were decreased. These changes have been correlated with degree of immunodeficiency at CAL. These data allow to consider the apoptosis as cell mechanism included in pathogenesis of diseases, which can be showed later long time after irradiation. (author)

  18. Asymmetric dimethylarginine attenuates serum starvation-induced apoptosis via suppression of the Fas (APO-1/CD95)/JNK (SAPK) pathway

    OpenAIRE

    Li, H; Zhou, Y; Zhao, A; Qiu, Y; Xie, G; Jiang, Q; Zheng, X; Zhong, W; Sun, X; Zhou, Z; Jia, W

    2013-01-01

    Asymmetric dimethylarginine (ADMA) is synthesized by protein arginine methyltransferases during methylation of protein arginine residues and released into blood upon proteolysis. Higher concentrations of ADMA in blood have been observed in patients with metabolic diseases and certain cancers. However, the role of ADMA in colon cancer has not been well investigated. ADMA serum levels in human patients diagnosed with colon cancer were found to be higher than those present in healthy subjects. A...

  19. Synaptic activity and nuclear calcium signaling protect hippocampal neurons from death signal-associated nuclear translocation of FoxO3a induced by extrasynaptic N-methyl-D-aspartate receptors.

    Science.gov (United States)

    Dick, Oliver; Bading, Hilmar

    2010-06-18

    Synaptic activity and the generation of nuclear calcium signals promote neuronal survival through a transcription-dependent process that is not fully understood. Here we show that one mechanism of activity-induced acquired neuroprotection involves the Forkhead transcription factor, FoxO3a, which is known to induce genomic death responses upon translocation from the cytosol to the nucleus. Depletion of endogenous FoxO3a using RNA interference renders hippocampal neurons more resistant to excitotoxic cell death. Using a FoxO3a-green fluorescent protein (GFP) fusion protein to monitor in real time the localization of FoxO3a in hippocampal neurons, we found that several cell death inducing stimuli, including the stimulation of extrasynaptic N-methyl-D-aspartate receptors, growth factor withdrawal, and oxygen-glucose deprivation, caused a swift translocation of FoxO3a-GFP from the cytosol to the cell nucleus. This translocation was inhibited in hippocampal neurons that had undergone prolonged periods of synaptic activity before exposure to cell death-inducing conditions. The activity-dependent protection from death signal-induced FoxO3a-GFP nuclear translocation required synaptic N-methyl-D-aspartate receptor activation and was dependent on nuclear calcium signaling and calcium/calmodulin-dependent protein kinase IV. The modulation of nucleo-cytoplasmic shuttling of FoxO3a may represent one mechanism through which nuclear calcium-induced genomic responses affect cell death processes.

  20. Synaptic Activity and Nuclear Calcium Signaling Protect Hippocampal Neurons from Death Signal-associated Nuclear Translocation of FoxO3a Induced by Extrasynaptic N-Methyl-d-aspartate Receptors*

    Science.gov (United States)

    Dick, Oliver; Bading, Hilmar

    2010-01-01

    Synaptic activity and the generation of nuclear calcium signals promote neuronal survival through a transcription-dependent process that is not fully understood. Here we show that one mechanism of activity-induced acquired neuroprotection involves the Forkhead transcription factor, FoxO3a, which is known to induce genomic death responses upon translocation from the cytosol to the nucleus. Depletion of endogenous FoxO3a using RNA interference renders hippocampal neurons more resistant to excitotoxic cell death. Using a FoxO3a-green fluorescent protein (GFP) fusion protein to monitor in real time the localization of FoxO3a in hippocampal neurons, we found that several cell death inducing stimuli, including the stimulation of extrasynaptic N-methyl-d-aspartate receptors, growth factor withdrawal, and oxygen-glucose deprivation, caused a swift translocation of FoxO3a-GFP from the cytosol to the cell nucleus. This translocation was inhibited in hippocampal neurons that had undergone prolonged periods of synaptic activity before exposure to cell death-inducing conditions. The activity-dependent protection from death signal-induced FoxO3a-GFP nuclear translocation required synaptic N-methyl-d-aspartate receptor activation and was dependent on nuclear calcium signaling and calcium/calmodulin-dependent protein kinase IV. The modulation of nucleo-cytoplasmic shuttling of FoxO3a may represent one mechanism through which nuclear calcium-induced genomic responses affect cell death processes. PMID:20404335

  1. Signal Processing

    International Nuclear Information System (INIS)

    Anon.

    1992-01-01

    Signal processing techniques, extensively used nowadays to maximize the performance of audio and video equipment, have been a key part in the design of hardware and software for high energy physics detectors since pioneering applications in the UA1 experiment at CERN in 1979

  2. Involvement of NtERF3 in the cell death signalling pathway mediated by SIPK/WIPK and WRKY1 in tobacco plants.

    Science.gov (United States)

    Ogata, T; Okada, H; Kawaide, H; Takahashi, H; Seo, S; Mitsuhara, I; Matsushita, Y

    2015-09-01

    We previously reported that one of the ethylene response factors (ERFs), NtERF3, and other members of the subgroup VIII-a ERFs of the AP2/ERF family exhibit cell death-inducing ability in tobacco leaves. In this study, we focused on the involvement of NtERF3 in a cell death signalling pathway in tobacco plants, particularly downstream of NtSIPK/NtWIPK and NtWRKY1, which are mitogen-activated protein kinases and a phosphorylation substrate of NtSIPK, respectively. An ERF-associated amphiphilic repression (EAR) motif-deficient NtERF3b mutant (NtERF3bΔEAR) that lacked cell death-inducing ability suppressed the induction of cell death caused by NtERF3a. The transient co-expression of NtERF3bΔEAR suppressed the hypersensitive reaction (HR)-like cell death induced by NtSIPK and NtWRKY1. The induction of cell death by NtSIPK and NtWRKY1 was also inhibited in transgenic plants expressing NtERF3bΔEAR. Analysis of gene expression, ethylene production and cell death symptoms in salicylic acid-deficient tobacco plants suggested the existence of some feedback regulation in the HR cell death signalling pathway mediated by SIPK/WIPK and WRKY1. Overall, these results suggest that NtERF3 functions downstream of NtSIPK/NtWIPK and NtWRKY1 in a cell death signalling pathway, with some feedback regulation. © 2015 German Botanical Society and The Royal Botanical Society of the Netherlands.

  3. Prosocial Signalling

    DEFF Research Database (Denmark)

    Kahsay, Goytom Abraha

    signalling can cause reverse price reactions resembling the crowding-out of pre-existing motives for prosocial behavior seen in situations of volunteering and charitable giving. Using a unique combination of questionnaire and purchase panel data, it presents evidence of such reputation-driven reverse price...... reactions in the Danish market for organic milk. The second paper proposes a self-image model to account consumers’ behaviour under PWYW. It finds that when a good’s fixed price is lower than an exogenously given threshold fair value, PWYW can lead to a lower utility, which may lead to lower purchase rate...

  4. Induction of DISE in ovarian cancer cells in vivo

    OpenAIRE

    Murmann, Andrea E.; McMahon, Kaylin M.; Haluck-Kangas, Ashley; Ravindran, Nandini; Patel, Monal; Law, Calvin Y.; Brockway, Sonia; Wei, Jian-Jun; Thaxton, C. Shad; Peter, Marcus E.

    2017-01-01

    The death receptor CD95/Fas can be activated by immune cells to kill cancer cells. shRNAs and siRNAs derived from CD95 or CD95 ligand (CD95L) are highly toxic to most cancer cells. We recently found that these sh/siRNAs kill cancer cells in the absence of the target by targeting the 3’UTRs of critical survival genes through canonical RNAi. We have named this unique form of off-target effect DISE (for death induced by survival gene elimination). DISE preferentially kills transformed cells and ...

  5. Lipid raft-mediated Akt signaling as a therapeutic target in mantle cell lymphoma

    International Nuclear Information System (INIS)

    Reis-Sobreiro, M; Roué, G; Moros, A; Gajate, C; Iglesia-Vicente, J de la; Colomer, D; Mollinedo, F

    2013-01-01

    Recent evidence shows that lipid raft membrane domains modulate both cell survival and death. Here, we have found that the phosphatidylinositol-3-kinase (PI3K)/Akt signaling pathway is present in the lipid rafts of mantle cell lymphoma (MCL) cells, and this location seems to be critical for full activation and MCL cell survival. The antitumor lipids (ATLs) edelfosine and perifosine target rafts, and we found that ATLs exerted in vitro and in vivo antitumor activity against MCL cells by displacing Akt as well as key regulatory kinases p-PDK1 (phosphatidylinositol-dependent protein kinase 1), PI3K and mTOR (mammalian TOR) from lipid rafts. This raft reorganization led to Akt dephosphorylation, while proapoptotic Fas/CD95 death receptor was recruited into rafts. Raft integrity was critical for Ser473 Akt phosphorylation. ATL-induced apoptosis appeared to correlate with the basal Akt phosphorylation status in MCL cell lines and primary cultures, and could be potentiated by the PI3K inhibitor wortmannin, or inhibited by the Akt activator pervanadate. Classical Akt inhibitors induced apoptosis in MCL cells. Microenvironmental stimuli, such as CD40 ligation or stromal cell contact, did not prevent ATL-induced apoptosis in MCL cell lines and patient-derived cells. These results highlight the role of raft-mediated PI3K/Akt signaling in MCL cell survival and chemotherapy, thus becoming a new target for MCL treatment

  6. Basic digital signal processing

    CERN Document Server

    Lockhart, Gordon B

    1985-01-01

    Basic Digital Signal Processing describes the principles of digital signal processing and experiments with BASIC programs involving the fast Fourier theorem (FFT). The book reviews the fundamentals of the BASIC program, continuous and discrete time signals including analog signals, Fourier analysis, discrete Fourier transform, signal energy, power. The text also explains digital signal processing involving digital filters, linear time-variant systems, discrete time unit impulse, discrete-time convolution, and the alternative structure for second order infinite impulse response (IIR) sections.

  7. Signal Processing and Restoration

    NARCIS (Netherlands)

    Biemond, J.; Slump, C.H.; Lagendijk, R.L.; Tolhuizen, L.M.G.M.; de With, P.H.N.

    2004-01-01

    Digital Signal Processing (DSP) concerns the theoretical and practical aspects of representing information-bearing signals in digital form and the use of processors or special purpose hardware to extract that information or to transform the signals in useful ways. Areas where digital signal

  8. Retroactive signaling in short signaling pathways.

    Directory of Open Access Journals (Sweden)

    Jacques-Alexandre Sepulchre

    Full Text Available In biochemical signaling pathways without explicit feedback connections, the core signal transduction is usually described as a one-way communication, going from upstream to downstream in a feedforward chain or network of covalent modification cycles. In this paper we explore the possibility of a new type of signaling called retroactive signaling, offered by the recently demonstrated property of retroactivity in signaling cascades. The possibility of retroactive signaling is analysed in the simplest case of the stationary states of a bicyclic cascade of signaling cycles. In this case, we work out the conditions for which variables of the upstream cycle are affected by a change of the total amount of protein in the downstream cycle, or by a variation of the phosphatase deactivating the same protein. Particularly, we predict the characteristic ranges of the downstream protein, or of the downstream phosphatase, for which a retroactive effect can be observed on the upstream cycle variables. Next, we extend the possibility of retroactive signaling in short but nonlinear signaling pathways involving a few covalent modification cycles.

  9. Signal verification can promote reliable signalling.

    Science.gov (United States)

    Broom, Mark; Ruxton, Graeme D; Schaefer, H Martin

    2013-11-22

    The central question in communication theory is whether communication is reliable, and if so, which mechanisms select for reliability. The primary approach in the past has been to attribute reliability to strategic costs associated with signalling as predicted by the handicap principle. Yet, reliability can arise through other mechanisms, such as signal verification; but the theoretical understanding of such mechanisms has received relatively little attention. Here, we model whether verification can lead to reliability in repeated interactions that typically characterize mutualisms. Specifically, we model whether fruit consumers that discriminate among poor- and good-quality fruits within a population can select for reliable fruit signals. In our model, plants either signal or they do not; costs associated with signalling are fixed and independent of plant quality. We find parameter combinations where discriminating fruit consumers can select for signal reliability by abandoning unprofitable plants more quickly. This self-serving behaviour imposes costs upon plants as a by-product, rendering it unprofitable for unrewarding plants to signal. Thus, strategic costs to signalling are not a prerequisite for reliable communication. We expect verification to more generally explain signal reliability in repeated consumer-resource interactions that typify mutualisms but also in antagonistic interactions such as mimicry and aposematism.

  10. Protection of Momordica charantia polysaccharide against intracerebral hemorrhage-induced brain injury through JNK3 signaling pathway.

    Science.gov (United States)

    Duan, Zhen-Zhen; Zhou, Xiao-Ling; Li, Yi-Hang; Zhang, Feng; Li, Feng-Ying; Su-Hua, Qi

    2015-01-01

    It has been well documented that Momordica charantia polysaccharide (MCP) has multiple biological effects such as immune enhancement, anti-oxidation and anti-cancer. However, the potential protective effects of MCP on stroke damage and its relative mechanisms remain unclear. Our present study demonstrated that MCP could scavenge reactive oxygen species (ROS) in intra-cerebral hemorrhage damage, significantly attenuating the neuronal death induced by thrombin in primary hippocampal neurons. Furthermore, we found that MCP prevented the activation of the c-Jun N-terminal protein kinase (JNK3), c-Jun and caspase-3, which was caused by the intra-cerebral hemorrhage injury. Taken together, our study demonstrated that MCP had a neuroprotective effect in response to intra-cerebral hemorrhage and its mechanisms involved the inhibition of JNK3 signaling pathway.

  11. Targeted cancer cell death induced by biofunctionalized magnetic nanowires

    KAUST Repository

    Contreras, Maria F.

    2014-02-01

    Magnetic micro and nanomaterials are increasingly interesting for biomedical applications since they possess many advantageous properties: they can become biocompatible, they can be functionalized to target specific cells and they can be remotely manipulated by magnetic fields. The goal of this study is to use antibody-functionalized nickel nanowires (Ab-NWs) as an alternative method in cancer therapy overcoming the limitations of current treatments that lack specificity and are highly cytotoxic. Ab-NWs have been incubated with cancer cells and a 12% drop on cell viability was observed for a treatment of only 10 minutes and an alternating magnetic field of low intensity and low frequency. It is believed that the Ab-NWs vibrate transmitting a mechanical force to the targeted cells inducing cell death. © 2014 IEEE.

  12. Cell death induced by gamma irradiation of developing skeletal muscle

    International Nuclear Information System (INIS)

    Olive, M.; Blanco, R.; Rivera, R.; Cinos, C.; Ferrer, I.

    1995-01-01

    Newborn Sprague-Dawley rats were exposed to a single dose of 2 Gy gamma rays and killed from 6 h to 5 d later. Increased numbers of dying cells, characterised by their extreme chromatin condensation and often nuclear fragmentation were seen in skeletal muscle 6 h after irradiation. Dying cells decreased to nearly normal values 48 h later. In situ labelling of nuclear DNA fragmentation identified individual cells bearing fragmented DNA. The effects of gamma rays were suppressed following cycloheximide i.p. at a dose of 1 μg/g body weight given at the time of irradiation. Taken together, the present morphological and pharmacological results suggest that gamma ray induced cell death in skeletal muscle is apoptotic, and that the process is associated with protein synthesis. Finally, proliferating cell nuclear antigen-immunoreactive cells, which were abundant in control rats, decreased in number 48 h after irradiation. However, a marked increase significantly above normal age values was observed at the 5th day, thus suggesting that regeneration occurs following irradiation-induced cell death in developing muscle. (author)

  13. TRAIL receptor-selective mutants signal to apoptosis via TRAIL-R1 in primary lymphoid malignancies.

    Science.gov (United States)

    MacFarlane, Marion; Kohlhaas, Susan L; Sutcliffe, Michael J; Dyer, Martin J S; Cohen, Gerald M

    2005-12-15

    Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its agonistic antibodies, which are currently in early clinical trials for treating various malignancies, induce apoptosis through triggering of either TRAIL-R1 or TRAIL-R2. Based on studies using agonistic monoclonal antibodies, we recently proposed that primary chronic lymphocytic leukemic cells seem to signal apoptosis primarily through TRAIL-R1. We have now synthesized mutant forms of TRAIL specific for TRAIL-R1 or TRAIL-R2. The selectivity of these mutants to induce apoptosis in cell lines is due to selective binding to their cognate receptors resulting in apoptosis via formation of a death-inducing signaling complex. Using these mutants, we now unequivocally show that primary cells from patients with chronic lymphocytic leukemia and mantle cell lymphoma signal to apoptosis almost exclusively through TRAIL-R1. Thus, no significant therapeutic benefit can be anticipated from treating such patients with agents currently in clinical trials that signal predominantly through TRAIL-R2, such as HGS-ETR2 or Apo2L/TRAIL. Our study highlights the necessity to determine whether primary cells from a particular tumor signal via TRAIL-R1 or TRAIL-R2. Such information will provide a rational approach to optimize TRAIL therapy.

  14. An Evolution-Guided Analysis Reveals a Multi-Signaling Regulation of Fas by Tyrosine Phosphorylation and its Implication in Human Cancers

    Science.gov (United States)

    Chakrabandhu, Krittalak; Huault, Sébastien; Durivault, Jérôme; Lang, Kévin; Ta Ngoc, Ly; Bole, Angelique; Doma, Eszter; Dérijard, Benoit; Gérard, Jean-Pierre; Pierres, Michel; Hueber, Anne-Odile

    2016-01-01

    Demonstrations of both pro-apoptotic and pro-survival abilities of Fas (TNFRSF6/CD95/APO-1) have led to a shift from the exclusive “Fas apoptosis” to “Fas multisignals” paradigm and the acceptance that Fas-related therapies face a major challenge, as it remains unclear what determines the mode of Fas signaling. Through protein evolution analysis, which reveals unconventional substitutions of Fas tyrosine during divergent evolution, evolution-guided tyrosine-phosphorylated Fas proxy, and site-specific phosphorylation detection, we show that the Fas signaling outcome is determined by the tyrosine phosphorylation status of its death domain. The phosphorylation dominantly turns off the Fas-mediated apoptotic signal, while turning on the pro-survival signal. We show that while phosphorylations at Y232 and Y291 share some common functions, their contributions to Fas signaling differ at several levels. The findings that Fas tyrosine phosphorylation is regulated by Src family kinases (SFKs) and the phosphatase SHP-1 and that Y291 phosphorylation primes clathrin-dependent Fas endocytosis, which contributes to Fas pro-survival signaling, reveals for the first time the mechanistic link between SFK/SHP-1-dependent Fas tyrosine phosphorylation, internalization route, and signaling choice. We also demonstrate that levels of phosphorylated Y232 and Y291 differ among human cancer types and differentially respond to anticancer therapy, suggesting context-dependent involvement of Fas phosphorylation in cancer. This report provides a new insight into the control of TNF receptor multisignaling by receptor phosphorylation and its implication in cancer biology, which brings us a step closer to overcoming the challenge in handling Fas signaling in treatments of cancer as well as other pathologies such as autoimmune and degenerative diseases. PMID:26942442

  15. Loss of T-cadherin (CDH-13) regulates AKT signaling and desensitizes cells to apoptosis in melanoma.

    Science.gov (United States)

    Bosserhoff, Anja K; Ellmann, Lisa; Quast, Annika S; Eberle, Juergen; Boyle, Glen M; Kuphal, Silke

    2014-08-01

    An understanding of signaling pathways is a basic requirement for the treatment of melanoma. Currently, kinases are at the center of melanoma therapies. According to our research, additional alternative molecules are equally important for development of melanoma. In this regard, cancer progression is, among other factors, driven by an altered adhesion via cadherins. For instance, the de-regulated expression of the adhesion molecule T-cadherin is found in various cancer types, including melanoma, and influences migration and invasion. T-cadherin is thought to affect cellular function largely through its signaling and not its adhesion properties because the molecule is anchored into the cell membrane by a glycosylphosphatidylinositol (GPI) moiety. However, detailed knowledge about the consequences of the loss of T-cadherin in melanoma is currently lacking. For this reason, we were interested in assessing which signaling pathways are initiated by T-cadherin. The tumor growth of subcutaneously injected T-cadherin-positive melanoma cells was diminished compared with T-cadherin-negative cells in nude mice. The difference in tumor volume was not due to decreased proliferation but rather due to increased apoptosis. After the expression of T-cadherin was induced, we detected V-AKT murine thymoma viral oncogene homolog (AKT) and FoxO3a hypophosphorylation accompanied by the downregulation of the antiapoptotic molecules BCL-2, BCL-x and Clusterin. Furthermore, we detected a diminished transcriptional activity of CREB and AP-1. We demonstrated that T-cadherin functions as a pro-apoptotic tumor suppressor that antagonizes AKT/CREB/AP-1/FoxO3a signaling, whereas NFκB, TCF/LEF and mTOR are not part of the T-cadherin signaling pathway. Notably, we found that the restoration of T-cadherin in melanoma cells causes sensitization to apoptosis induced by CD95/Fas antibody CH-11. © 2013 Wiley Periodicals, Inc.

  16. 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

  17. Traffic signal timing manual

    Science.gov (United States)

    2008-06-01

    This report serves as a comprehensive guide to traffic signal timing and documents the tasks completed in association with its development. The focus of this document is on traffic signal control principles, practices, and procedures. It describes th...

  18. 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.

  19. Biomedical signal processing

    CERN Document Server

    Akay, Metin

    1994-01-01

    Sophisticated techniques for signal processing are now available to the biomedical specialist! Written in an easy-to-read, straightforward style, Biomedical Signal Processing presents techniques to eliminate background noise, enhance signal detection, and analyze computer data, making results easy to comprehend and apply. In addition to examining techniques for electrical signal analysis, filtering, and transforms, the author supplies an extensive appendix with several computer programs that demonstrate techniques presented in the text.

  20. Optimal Signal Quality Index for Photoplethysmogram Signals

    Directory of Open Access Journals (Sweden)

    Mohamed Elgendi

    2016-09-01

    Full Text Available A photoplethysmogram (PPG is a noninvasive circulatory signal related to the pulsatile volume of blood in tissue and is typically collected by pulse oximeters. PPG signals collected via mobile devices are prone to artifacts that negatively impact measurement accuracy, which can lead to a significant number of misleading diagnoses. Given the rapidly increased use of mobile devices to collect PPG signals, developing an optimal signal quality index (SQI is essential to classify the signal quality from these devices. Eight SQIs were developed and tested based on: perfusion, kurtosis, skewness, relative power, non-stationarity, zero crossing, entropy, and the matching of systolic wave detectors. Two independent annotators annotated all PPG data (106 recordings, 60 s each and a third expert conducted the adjudication of differences. The independent annotators labeled each PPG signal with one of the following labels: excellent, acceptable or unfit for diagnosis. All indices were compared using Mahalanobis distance, linear discriminant analysis, quadratic discriminant analysis, and support vector machine with leave-one-out cross-validation. The skewness index outperformed the other seven indices in differentiating between excellent PPG and acceptable, acceptable combined with unfit, and unfit recordings, with overall F 1 scores of 86.0%, 87.2%, and 79.1%, respectively.

  1. Optimal Signal Quality Index for Photoplethysmogram Signals.

    Science.gov (United States)

    Elgendi, Mohamed

    2016-09-22

    A photoplethysmogram (PPG) is a noninvasive circulatory signal related to the pulsatile volume of blood in tissue and is typically collected by pulse oximeters. PPG signals collected via mobile devices are prone to artifacts that negatively impact measurement accuracy, which can lead to a significant number of misleading diagnoses. Given the rapidly increased use of mobile devices to collect PPG signals, developing an optimal signal quality index (SQI) is essential to classify the signal quality from these devices. Eight SQIs were developed and tested based on: perfusion, kurtosis, skewness, relative power, non-stationarity, zero crossing, entropy, and the matching of systolic wave detectors. Two independent annotators annotated all PPG data (106 recordings, 60 s each) and a third expert conducted the adjudication of differences. The independent annotators labeled each PPG signal with one of the following labels: excellent, acceptable or unfit for diagnosis. All indices were compared using Mahalanobis distance, linear discriminant analysis, quadratic discriminant analysis, and support vector machine with leave-one-out cross-validation. The skewness index outperformed the other seven indices in differentiating between excellent PPG and acceptable, acceptable combined with unfit, and unfit recordings, with overall F 1 scores of 86.0%, 87.2%, and 79.1%, respectively.

  2. Role of Caspases and CD95/Fas in the Apoptotic Effects of a Nucleotide Analog PMEG in CCRF-CEM Cells

    Czech Academy of Sciences Publication Activity Database

    Mertlíková-Kaiserová, Helena; Votruba, Ivan; Matoušová, Marika; Holý, Antonín; Hájek, Miroslav

    2010-01-01

    Roč. 30, č. 7 (2010), s. 2791-2798 ISSN 0250-7005 R&D Projects: GA MŠk 1M0508 Institutional research plan: CEZ:AV0Z40550506 Keywords : acyclic nucleoside phosphonate * programmed cell death * CCRF-CEM cells * cell cycle Subject RIV: CC - Organic Chemistry Impact factor: 1.656, year: 2010

  3. Yondelis® (ET-743, Trabectedin) sensitizes cancer cell lines to CD95-mediated cell death: new molecular insight into the mechanism of action.

    Science.gov (United States)

    Martínez-Serra, Jordi; Maffiotte, Elena; Martín, Javier; Bex, Teresa; Navarro-Palou, María; Ros, Teresa; Plazas, Joana M; Vögler, Oliver; Gutiérrez, Antonio; Amat, Juan Carlos; Ramos, Rafael; Saus, Carlos; Ginés, Jordi; Alemany, Regina; Diaz, Matias; Besalduch, Joan

    2011-05-11

    Trabectedin, a naturally occurring substance isolated from the Caribbean marine invertebrate Ecteinascidia turbinata, is the active compound of the antitumor drug Yondelis®. The mechanism of action of Trabectedin has been attributed to interactions with the minor groove of the DNA double helix, thereby affecting transcription of different genes involved in DNA repair and thus facilitating lethal DNA strand breaks. Nevertheless, the existence of other clinically important molecular mechanisms has not yet been fully explored. In this paper we demonstrate how Yondelis®, apart from activating the caspase-8-dependent cascade of apoptosis, sensitizes cancer cells to Fas-mediated cell death at achievable concentrations similar to those found in the plasma of patients. In addition we show that the facilitated apoptosis activated through the Fas death receptor, is associated with a significant increase of membrane Fas/FasL, as well as the modulation of accessory proteins regulating this route, such as FLIP (L) or Akt. Thus, our results propose that the sensitization of the death receptor pathway is an essential mechanism amplifying the cytotoxic properties of Yondelis® that could explain the hepatotoxicity observed in patients treated with this drug. Finally, we also show how the use of dexamethasone as a prophylactic agent that protects against hepatotoxicity induced by Yondelis® may also inhibit some of the cytotoxic properties described in this work. The study of this important mechanism of action should set up the basis for reassessing clinical therapy with Yondelis® in order to improve antitumor treatment outcome. Copyright © 2011 Elsevier B.V. All rights reserved.

  4. Evasion of Cytotoxic T Lymphocyte (CTL) Responses by Nef-dependent Induction of Fas Ligand (CD95L) Expression on Simian Immunodeficiency Virus?infected Cells

    OpenAIRE

    Xu, Xiao-Ning; Screaton, Gavin R.; Gotch, Frances M.; Dong, Tao; Tan, Rusung; Almond, Neil; Walker, Barry; Stebbings, Richard; Kent, Karen; Nagata, Shigekazu; Stott, Jim E.; McMichael, Andrew J.

    1997-01-01

    Inoculation of macaques with live attenuated SIV strains has been shown to protect against subsequent challenge with wild-type SIV. The protective mechanism(s) remain obscure. To study the effect in more detail, we have investigated the role of virus-specific CTL responses in macaques infected with an attenuated SIV strain (pC8), which has a four?amino acid deletion in the nef gene, as compared with the wild-type SIVmac32H clone (pJ5). Cynomolgus macaques infected with pC8 were protected agai...

  5. Evasion of cytotoxic T lymphocyte (CTL) responses by nef-dependent induction of Fas ligand (CD95L) expression on simian immunodeficiency virus-infected cells.

    Science.gov (United States)

    Xu, X N; Screaton, G R; Gotch, F M; Dong, T; Tan, R; Almond, N; Walker, B; Stebbings, R; Kent, K; Nagata, S; Stott, J E; McMichael, A J

    1997-07-07

    Inoculation of macaques with live attenuated SIV strains has been shown to protect against subsequent challenge with wild-type SIV. The protective mechanism(s) remain obscure. To study the effect in more detail, we have investigated the role of virus-specific CTL responses in macaques infected with an attenuated SIV strain (pC8), which has a four-amino acid deletion in the nef gene, as compared with the wild-type SIVmac32H clone (pJ5). Cynomolgus macaques infected with pC8 were protected against subsequent challenge with pJ5 and did not develop any AIDS-like symptoms in the 12 months after infection. The pC8-induced protection was associated with high levels of virus-specific CTL responses to a variety of viral antigens. In contrast, pJ5-infected macaques had little, if any, detectable CTL response to the viral proteins after three months. The latter group of macaques also showed increased Fas expression and apoptotic cell death in both the CD4(+) and CD8(+) populations. In vitro, pJ5 but not pC8 leads to an increase in FasL expression on infected cells. Thus the expression of FasL may protect infected cells from CTL attack, killing viral-specific CTLs in the process, and providing a route for escaping the immune response, leading to the increased pathogenicity of pJ5. pC8, on the other hand does not induce FasL expression, allowing the development of a protective CTL response. Furthermore, interruption of the Fas-FasL interaction allows the regeneration of viral-specific CTL responses in pJ5-infected animals. This observation suggests an additional therapeutic approach to the treatment of AIDS.

  6. The Signal Distribution System

    CERN Document Server

    Belohrad, D; CERN. Geneva. AB Department

    2005-01-01

    For the purpose of LHC signal observation and high frequency signal distribution, the Signal Distribution System (SDS) was built. The SDS can contain up to 5 switching elements, where each element allows the user to switch between one of the maximum 8 bi-directional signals. The coaxial relays are used to switch the signals. Depending of the coaxial relay type used, the transfer bandwidth can go up to 18GHz. The SDS is controllable via TCP/IP, parallel port, or locally by rotary switch.

  7. Acoustic Signals and Systems

    DEFF Research Database (Denmark)

    2008-01-01

    The Handbook of Signal Processing in Acoustics will compile the techniques and applications of signal processing as they are used in the many varied areas of Acoustics. The Handbook will emphasize the interdisciplinary nature of signal processing in acoustics. Each Section of the Handbook...... will present topics on signal processing which are important in a specific area of acoustics. These will be of interest to specialists in these areas because they will be presented from their technical perspective, rather than a generic engineering approach to signal processing. Non-specialists, or specialists...

  8. Method of signal analysis

    International Nuclear Information System (INIS)

    Berthomier, Charles

    1975-01-01

    A method capable of handling the amplitude and the frequency time laws of a certain kind of geophysical signals is described here. This method is based upon the analytical signal idea of Gabor and Ville, which is constructed either in the time domain by adding an imaginary part to the real signal (in-quadrature signal), or in the frequency domain by suppressing negative frequency components. The instantaneous frequency of the initial signal is then defined as the time derivative of the phase of the analytical signal, and his amplitude, or envelope, as the modulus of this complex signal. The method is applied to three types of magnetospheric signals: chorus, whistlers and pearls. The results obtained by analog and numerical calculations are compared to results obtained by classical systems using filters, i.e. based upon a different definition of the concept of frequency. The precision with which the frequency-time laws are determined leads then to the examination of the principle of the method and to a definition of instantaneous power density spectrum attached to the signal, and to the first consequences of this definition. In this way, a two-dimensional representation of the signal is introduced which is less deformed by the analysis system properties than the usual representation, and which moreover has the advantage of being obtainable practically in real time [fr

  9. 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

  10. 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

  11. Digital signal processing

    CERN Document Server

    O'Shea, Peter; Hussain, Zahir M

    2011-01-01

    In three parts, this book contributes to the advancement of engineering education and that serves as a general reference on digital signal processing. Part I presents the basics of analog and digital signals and systems in the time and frequency domain. It covers the core topics: convolution, transforms, filters, and random signal analysis. It also treats important applications including signal detection in noise, radar range estimation for airborne targets, binary communication systems, channel estimation, banking and financial applications, and audio effects production. Part II considers sel

  12. Geolocation of RF signals

    CERN Document Server

    Progri, Ilir

    2011-01-01

    ""Geolocation of RF Signals - Principles and Simulations"" offers an overview of the best practices and innovative techniques in the art and science of geolocation over the last twenty years. It covers all research and development aspects including theoretical analysis, RF signals, geolocation techniques, key block diagrams, and practical principle simulation examples in the frequency band from 100 MHz to 18 GHz or even 60 GHz. Starting with RF signals, the book progressively examines various signal bands - such as VLF, LF, MF, HF, VHF, UHF, L, S, C, X, Ku, and, K and the corresponding geoloca

  13. Many checkpoints on the road to cell death: regulation of Fas-FasL interactions and Fas signaling in peripheral immune responses

    Science.gov (United States)

    Ramaswamy, Madhu; Cleland, Sophia Y.; Cruz, Anthony C.; Siegel, Richard M.

    2009-01-01

    Interactions between the TNF-family receptor Fas (CD95) and Fas Ligand (FasL, CD178) can efficiently induce apoptosis and are critical for maintenance of immunological self-tolerance. FasL is kept under strict control by transcriptional and post-translational regulation. Surface FasL can be cleaved by metalloproteases, resulting in shed extracellular domains, and FasL can also traffic to secretory lysosomes. Each form of FasL has distinct biological functions. Fas is more ubiquitously expressed, but its apoptosis-inducing function is regulated by a number of mechanisms including submembrane localization, efficiency of receptor signaling complex assembly and activation, and bcl-2 family members in some circumstances. When apoptosis is not induced, Fas-FasL interactions can also trigger a number of activating and pro-inflammatory signals. Harnessing the apoptosis-inducing potential of Fas for therapy for cancer and autoimmune disease has been actively pursued, and despite a number of unexpected side-effects that result from manipulating Fas-FasL interactions, this remains a worthy goal. PMID:19132321

  14. Signaling in symbiosis

    NARCIS (Netherlands)

    Limpens, E.H.M.; Bisseling, T.

    2003-01-01

    In recent years, the major focus in nodulation research has been on the genetic dissection of Nod-factor signaling. Components of this pathway appear to be shared with signaling processes that are induced during the formation of mycorrhiza. With the cloning of orthologs of the NIN and DMI2 genes

  15. SignalR blueprints

    CERN Document Server

    Ingebrigtsen, Einar

    2015-01-01

    This book is designed for software developers, primarily those with knowledge of C#, .NET, and JavaScript. Good knowledge and understanding of SignalR is assumed to allow efficient programming of core elements and applications in SignalR.

  16. Digital Signal Processors

    Indian Academy of Sciences (India)

    A computer controlling the motion of a satellite should acquire signals from the satellite while it is in motion, compute corrections (if required) to the trajectory and send control signals back within a specified time for effective control. Delays may be fatal to ..... emulators and system evaluation tools have facilitated concurrent.

  17. Ubiquitination in apoptosis signaling

    NARCIS (Netherlands)

    van de Kooij, L.W.

    2014-01-01

    The work described in this thesis focuses on ubiquitination and protein degradation, with an emphasis on how these processes regulate apoptosis signaling. More specifically, our aims were: 1. To increase the understanding of ubiquitin-mediated regulation of apoptosis signaling. 2. To identify the E3

  18. Second-hand signals

    DEFF Research Database (Denmark)

    Bergenholtz, Carsten

    2014-01-01

    used by various agents in their search for and assessment of products and firms. I conclude by arguing how this second‐hand nature of signals goes beyond a simple dyadic focus on senders and receivers of signals, and thus elucidates the more complex interrelations of the various types of agents...

  19. Quantum cloning without signaling

    OpenAIRE

    Gisin, Nicolas

    1998-01-01

    Perfect Quantum Cloning Machines (QCM) would allow to use quantum nonlocality for arbitrary fast signaling. However perfect QCM cannot exist. We derive a bound on the fidelity of QCM compatible with the no-signaling constraint. This bound equals the fidelity of the Bu\\v{z}ek-Hillery QCM.

  20. Signal sampling circuit

    NARCIS (Netherlands)

    Louwsma, S.M.; Vertregt, Maarten

    2011-01-01

    A sampling circuit for sampling a signal is disclosed. The sampling circuit comprises a plurality of sampling channels adapted to sample the signal in time-multiplexed fashion, each sampling channel comprising a respective track-and-hold circuit connected to a respective analogue to digital

  1. Signal sampling circuit

    NARCIS (Netherlands)

    Louwsma, S.M.; Vertregt, Maarten

    2010-01-01

    A sampling circuit for sampling a signal is disclosed. The sampling circuit comprises a plurality of sampling channels adapted to sample the signal in time-multiplexed fashion, each sampling channel comprising a respective track-and-hold circuit connected to a respective analogue to digital

  2. Optimal fault signal estimation

    NARCIS (Netherlands)

    Stoorvogel, Antonie Arij; Niemann, H.H.; Saberi, A.; Sannuti, P.

    2002-01-01

    We consider here both fault identification and fault signal estimation. Regarding fault identification, we seek either exact or almost fault identification. On the other hand, regarding fault signal estimation, we seek either $H_2$ optimal, $H_2$ suboptimal or Hinfinity suboptimal estimation. By

  3. Neutron signal transfer analysis

    CERN Document Server

    Pleinert, H; Lehmann, E

    1999-01-01

    A new method called neutron signal transfer analysis has been developed for quantitative determination of hydrogenous distributions from neutron radiographic measurements. The technique is based on a model which describes the detector signal obtained in the measurement as a result of the action of three different mechanisms expressed by signal transfer functions. The explicit forms of the signal transfer functions are determined by Monte Carlo computer simulations and contain only the distribution as a variable. Therefore an unknown distribution can be determined from the detector signal by recursive iteration. This technique provides a simple and efficient tool for analysis of this type while also taking into account complex effects due to the energy dependency of neutron interaction and single and multiple scattering. Therefore this method provides an efficient tool for precise quantitative analysis using neutron radiography, as for example quantitative determination of moisture distributions in porous buil...

  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. Adaptive signal processor

    Energy Technology Data Exchange (ETDEWEB)

    Walz, H.V.

    1980-07-01

    An experimental, general purpose adaptive signal processor system has been developed, utilizing a quantized (clipped) version of the Widrow-Hoff least-mean-square adaptive algorithm developed by Moschner. The system accommodates 64 adaptive weight channels with 8-bit resolution for each weight. Internal weight update arithmetic is performed with 16-bit resolution, and the system error signal is measured with 12-bit resolution. An adapt cycle of adjusting all 64 weight channels is accomplished in 8 ..mu..sec. Hardware of the signal processor utilizes primarily Schottky-TTL type integrated circuits. A prototype system with 24 weight channels has been constructed and tested. This report presents details of the system design and describes basic experiments performed with the prototype signal processor. Finally some system configurations and applications for this adaptive signal processor are discussed.

  6. Adaptive signal processor

    International Nuclear Information System (INIS)

    Walz, H.V.

    1980-07-01

    An experimental, general purpose adaptive signal processor system has been developed, utilizing a quantized (clipped) version of the Widrow-Hoff least-mean-square adaptive algorithm developed by Moschner. The system accommodates 64 adaptive weight channels with 8-bit resolution for each weight. Internal weight update arithmetic is performed with 16-bit resolution, and the system error signal is measured with 12-bit resolution. An adapt cycle of adjusting all 64 weight channels is accomplished in 8 μsec. Hardware of the signal processor utilizes primarily Schottky-TTL type integrated circuits. A prototype system with 24 weight channels has been constructed and tested. This report presents details of the system design and describes basic experiments performed with the prototype signal processor. Finally some system configurations and applications for this adaptive signal processor are discussed

  7. Orexin/Hypocretin Signaling.

    Science.gov (United States)

    Kukkonen, Jyrki P

    Orexin/hypocretin peptide (orexin-A and orexin-B) signaling is believed to take place via the two G-protein-coupled receptors (GPCRs), named OX 1 and OX 2 orexin receptors, as described in the previous chapters. Signaling of orexin peptides has been investigated in diverse endogenously orexin receptor-expressing cells - mainly neurons but also other types of cells - and in recombinant cells expressing the receptors in a heterologous manner. Findings in the different systems are partially convergent but also indicate cellular background-specific signaling. The general picture suggests an inherently high degree of diversity in orexin receptor signaling.In the current chapter, I present orexin signaling on the cellular and molecular levels. Discussion of the connection to (potential) physiological orexin responses is only brief since these are in focus of other chapters in this book. The same goes for the post-synaptic signaling mechanisms, which are dealt with in Burdakov: Postsynaptic actions of orexin. The current chapter is organized according to the tissue type, starting from the central nervous system. Finally, receptor signaling pathways are discussed across tissues, cell types, and even species.

  8. Signal flow analysis

    CERN Document Server

    Abrahams, J R; Hiller, N

    1965-01-01

    Signal Flow Analysis provides information pertinent to the fundamental aspects of signal flow analysis. This book discusses the basic theory of signal flow graphs and shows their relation to the usual algebraic equations.Organized into seven chapters, this book begins with an overview of properties of a flow graph. This text then demonstrates how flow graphs can be applied to a wide range of electrical circuits that do not involve amplification. Other chapters deal with the parameters as well as circuit applications of transistors. This book discusses as well the variety of circuits using ther

  9. Brefeldin A-Inhibited Guanine Nucleotide-Exchange Factor 1 (BIG1 Governs the Recruitment of Tumor Necrosis Factor Receptor-Associated Factor 2 (TRAF2 to Tumor Necrosis Factor Receptor 1 (TNFR1 Signaling Complexes

    Directory of Open Access Journals (Sweden)

    Takuya Noguchi

    2016-11-01

    Full Text Available Tumor necrosis factor receptor-associated factor 2 (TRAF2 is a critical mediator of tumor necrosis factor-α (TNF-α signaling. However, the regulatory mechanisms of TRAF2 are not fully understood. Here we show evidence that TRAF2 requires brefeldin A-inhibited guanine nucleotide-exchange factor 1 (BIG1 to be recruited into TNF receptor 1 (TNFR1 signaling complexes. In BIG1 knockdown cells, TNF-α-induced c-Jun N-terminal kinase (JNK activation was attenuated and the sensitivity to TNF-α-induced apoptosis was increased. Since these trends correlated well with those of TRAF2 deficient cells as previously demonstrated, we tested whether BIG1 functions as an upstream regulator of TRAF2 in TNFR1 signaling. As expected, we found that knockdown of BIG1 suppressed TNF-α-dependent ubiquitination of TRAF2 that is required for JNK activation, and impaired the recruitment of TRAF2 to the TNFR1 signaling complex (complex I. Moreover, we found that the recruitment of TRAF2 to the death-inducing signaling complex termed complex II was also impaired in BIG1 knockdown cells. These results suggest that BIG1 is a key component of the machinery that drives TRAF2 to the signaling complexes formed after TNFR1 activation. Thus, our data demonstrate a novel and unexpected function of BIG1 that regulates TNFR1 signaling by targeting TRAF2.

  10. Purinergic signalling and diabetes

    DEFF Research Database (Denmark)

    Burnstock, Geoffrey; Novak, Ivana

    2013-01-01

    The pancreas is an organ with a central role in nutrient breakdown, nutrient sensing and release of hormones regulating whole body nutrient homeostasis. In diabetes mellitus, the balance is broken-cells can be starving in the midst of plenty. There are indications that the incidence of diabetes...... molecules in purinergic signalling cascades. This signalling takes place at the level of the pancreas, where the close apposition of various cells-endocrine, exocrine, stromal and immune cells-contributes to the integrated function. Following an introduction to diabetes, the pancreas and purinergic...... signalling, we will focus on the role of purinergic signalling and its changes associated with diabetes in the pancreas and selected tissues/organ systems affected by hyperglycaemia and other stress molecules of diabetes. Since this is the first review of this kind, a comprehensive historical angle is taken...

  11. Topological signal processing

    CERN Document Server

    Robinson, Michael

    2014-01-01

    Signal processing is the discipline of extracting information from collections of measurements. To be effective, the measurements must be organized and then filtered, detected, or transformed to expose the desired information.  Distortions caused by uncertainty, noise, and clutter degrade the performance of practical signal processing systems. In aggressively uncertain situations, the full truth about an underlying signal cannot be known.  This book develops the theory and practice of signal processing systems for these situations that extract useful, qualitative information using the mathematics of topology -- the study of spaces under continuous transformations.  Since the collection of continuous transformations is large and varied, tools which are topologically-motivated are automatically insensitive to substantial distortion. The target audience comprises practitioners as well as researchers, but the book may also be beneficial for graduate students.

  12. Transmembrane Signalling: Membrane messengers

    Science.gov (United States)

    Cockroft, Scott L.

    2017-05-01

    Life has evolved elaborate means of communicating essential chemical information across cell membranes. Inspired by biology, two new artificial mechanisms have now been developed that use synthetic messenger molecules to relay chemical signals into or across lipid membranes.

  13. 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....

  14. Acoustic MIMO signal processing

    CERN Document Server

    Huang, Yiteng; Chen, Jingdong

    2006-01-01

    A timely and important book addressing a variety of acoustic signal processing problems under multiple-input multiple-output (MIMO) scenarios. It uniquely investigates these problems within a unified framework offering a novel and penetrating analysis.

  15. Signals and systems

    CERN Document Server

    Rao, K Deergha

    2018-01-01

    This textbook covers the fundamental theories of signals and systems analysis, while incorporating recent developments from integrated circuits technology into its examples. Starting with basic definitions in signal theory, the text explains the properties of continuous-time and discrete-time systems and their representation by differential equations and state space. From those tools, explanations for the processes of Fourier analysis, the Laplace transform, and the z-Transform provide new ways of experimenting with different kinds of time systems. The text also covers the separate classes of analog filters and their uses in signal processing applications. Intended for undergraduate electrical engineering students, chapter sections include exercise for review and practice for the systems concepts of each chapter. Along with exercises, the text includes MATLAB-based examples to allow readers to experiment with signals and systems code on their own. An online repository of the MATLAB code from this textbook can...

  16. Signal Station Inspection Reports

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Handwritten reports resulting from detailed inspections of US Army Signal Service Stations, 1871-1889. Features reported included instrument exposure and condition,...

  17. Foundations of signal processing

    CERN Document Server

    Vetterli, Martin; Goyal, Vivek K

    2014-01-01

    This comprehensive and engaging textbook introduces the basic principles and techniques of signal processing, from the fundamental ideas of signals and systems theory to real-world applications. Students are introduced to the powerful foundations of modern signal processing, including the basic geometry of Hilbert space, the mathematics of Fourier transforms, and essentials of sampling, interpolation, approximation and compression. The authors discuss real-world issues and hurdles to using these tools, and ways of adapting them to overcome problems of finiteness and localisation, the limitations of uncertainty and computational costs. Standard engineering notation is used throughout, making mathematical examples easy for students to follow, understand and apply. It includes over 150 homework problems and over 180 worked examples, specifically designed to test and expand students' understanding of the fundamentals of signal processing, and is accompanied by extensive online materials designed to aid learning, ...

  18. Traffic Signal Cycle Lengths

    Data.gov (United States)

    Town of Chapel Hill, North Carolina — Traffic signal location list for the town of Chapel Hill. This data set includes light cycle information as well as as intersection information.The Town of Chapel...

  19. 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.

  20. Digital Signal Processing applied to Physical Signals

    CERN Document Server

    Alberto, Diego; Musa, L

    2011-01-01

    It is well known that many of the scientific and technological discoveries of the XXI century will depend on the capability of processing and understanding a huge quantity of data. With the advent of the digital era, a fully digital and automated treatment can be designed and performed. From data mining to data compression, from signal elaboration to noise reduction, a processing is essential to manage and enhance features of interest after every data acquisition (DAQ) session. In the near future, science will go towards interdisciplinary research. In this work there will be given an example of the application of signal processing to different fields of Physics from nuclear particle detectors to biomedical examinations. In Chapter 1 a brief description of the collaborations that allowed this thesis is given, together with a list of the publications co-produced by the author in these three years. The most important notations, definitions and acronyms used in the work are also provided. In Chapter 2, the last r...

  1. Endogenous Nod-factor-like signal molecules promote early somatic embryo development in Norway spruce.

    Science.gov (United States)

    Dyachok, Julia V; Wiweger, Malgorzata; Kenne, Lennart; von Arnold, Sara

    2002-02-01

    Embryogenic cultures of Norway spruce (Picea abies) are composed of pro-embryogenic masses (PEMs) and somatic embryos of various developmental stages. Auxin is important for PEM formation and proliferation. In this report we show that depletion of auxin blocks PEM development and causes large-scale cell death. Extracts of the media conditioned by embryogenic cultures stimulate development of PEM aggregates in auxin-deficient cultures. Partial characterization of the conditioning factor shows that it is a lipophilic, low-molecular-weight molecule, which is sensitive to chitinase and contains GlcNAc residues. On the basis of this information, we propose that the factor is a lipophilic chitin oligosaccharide (LCO). The amount of LCO correlates to the developmental stages of PEMs and embryos, with the highest level in the media conditioned by developmentally blocked cultures. LCO is not present in nonembryogenic cultures. Cell death, induced by withdrawal of auxin, is suppressed by extra supply of endogenous LCO or Nod factor from Rhizobium sp. NGR234. The effect can be mimicked by a chitotetraose or chitinase from Streptomyces griseus. Taken together, our data suggest that endogenous LCO acts as a signal molecule stimulating PEM and early embryo development in Norway spruce.

  2. Cellular signalling properties in microcircuits

    DEFF Research Database (Denmark)

    Toledo-Rodriguez, Maria; El Manira, Abdeljabbar; Wallén, Peter

    2005-01-01

    Molecules and cells are the signalling elements in microcircuits. Recent studies have uncovered bewildering diversity in postsynaptic signalling properties in all areas of the vertebrate nervous system. Major effort is now being invested in establishing the specialized signalling properties...

  3. BDNF Reduces Toxic Extrasynaptic NMDA Receptor Signaling via Synaptic NMDA Receptors and Nuclear-Calcium-Induced Transcription of inhba/Activin A

    Directory of Open Access Journals (Sweden)

    David Lau

    2015-08-01

    Full Text Available The health of neurons is critically dependent on the relative signaling intensities of survival-promoting synaptic and death-inducing extrasynaptic NMDA receptors. Here, we show that BDNF is a regulator of this balance and promotes neuroprotection by reducing toxic NMDA receptor signaling. BDNF acts by initiating synaptic NMDA-receptor/nuclear-calcium-driven adaptogenomics, leading to increased expression of inhibin β-A (inhba. Inhibin β-A (its homodimer is known as activin A in turn reduces neurotoxic extrasynaptic NMDA-receptor-mediated calcium influx, thereby shielding neurons against mitochondrial dysfunction, a major cause of excitotoxicity. Thus, BDNF induces acquired neuroprotection by enhancing synaptic activity and lowering extrasynaptic NMDA receptor death signaling through a nuclear calcium-inhibin β-A pathway. This process, which confers protection against ischemic brain damage in a mouse stroke model, may be compromised in Huntington’s disease, Alzheimer’s disease, or aging-related neurodegenerative conditions that are associated with reduced BDNF levels and/or enhanced extrasynaptic NMDA receptor signaling.

  4. VLSI signal processing technology

    CERN Document Server

    Swartzlander, Earl

    1994-01-01

    This book is the first in a set of forthcoming books focussed on state-of-the-art development in the VLSI Signal Processing area. It is a response to the tremendous research activities taking place in that field. These activities have been driven by two factors: the dramatic increase in demand for high speed signal processing, especially in consumer elec­ tronics, and the evolving microelectronic technologies. The available technology has always been one of the main factors in determining al­ gorithms, architectures, and design strategies to be followed. With every new technology, signal processing systems go through many changes in concepts, design methods, and implementation. The goal of this book is to introduce the reader to the main features of VLSI Signal Processing and the ongoing developments in this area. The focus of this book is on: • Current developments in Digital Signal Processing (DSP) pro­ cessors and architectures - several examples and case studies of existing DSP chips are discussed in...

  5. Honest signalling with costly gambles.

    Science.gov (United States)

    Meacham, Frazer; Perlmutter, Aaron; Bergstrom, Carl T

    2013-10-06

    Costly signalling theory is commonly invoked as an explanation for how honest communication can be stable when interests conflict. However, the signal costs predicted by costly signalling models often turn out to be unrealistically high. These models generally assume that signal cost is determinate. Here, we consider the case where signal cost is instead stochastic. We examine both discrete and continuous signalling games and show that, under reasonable assumptions, stochasticity in signal costs can decrease the average cost at equilibrium for all individuals. This effect of stochasticity for decreasing signal costs is a fundamental mechanism that probably acts in a wide variety of circumstances.

  6. Quantum signaling game

    International Nuclear Information System (INIS)

    Frackiewicz, Piotr

    2014-01-01

    We present a quantum approach to a signaling game; a special kind of extensive game of incomplete information. Our model is based on quantum schemes for games in strategic form where players perform unitary operators on their own qubits of some fixed initial state and the payoff function is given by a measurement on the resulting final state. We show that the quantum game induced by our scheme coincides with a signaling game as a special case and outputs nonclassical results in general. As an example, we consider a quantum extension of the signaling game in which the chance move is a three-parameter unitary operator whereas the players' actions are equivalent to classical ones. In this case, we study the game in terms of Nash equilibria and refine the pure Nash equilibria adapting to the quantum game the notion of a weak perfect Bayesian equilibrium. (paper)

  7. Signal integrity characterization techniques

    CERN Document Server

    Bogatin, Eric

    2009-01-01

    "Signal Integrity Characterization Techniques" addresses the gap between traditional digital and microwave curricula all while focusing on a practical and intuitive understanding of signal integrity effects within the data transmission channel. High-speed interconnects such as connectors, PCBs, cables, IC packages, and backplanes are critical elements of differential channels that must be designed using today's most powerful analysis and characterization tools.Both measurements and simulation must be done on the device under test, and both activities must yield data that correlates with each other. Most of this book focuses on real-world applications of signal integrity measurements - from backplane for design challenges to error correction techniques to jitter measurement technologies. The authors' approach wisely addresses some of these new high-speed technologies, and it also provides valuable insight into its future direction and will teach the reader valuable lessons on the industry.

  8. PKD signaling and pancreatitis

    Science.gov (United States)

    Yuan, Jingzhen; Pandol, Stephen J.

    2016-01-01

    Background Acute pancreatitis is a serious medical disorder with no current therapies directed to the molecular pathogenesis of the disorder. Inflammation, inappropriate intracellular activation of digestive enzymes, and parenchymal acinar cell death by necrosis are the critical pathophysiologic processes of acute pancreatitis. Thus, it is necessary to elucidate the key molecular signals that mediate these pathobiologic processes and develop new therapeutic strategies to attenuate the appropriate signaling pathways in order to improve outcomes for this disease. A novel serine/threonine protein kinase D (PKD) family has emerged as key participants in signal transduction, and this family is increasingly being implicated in the regulation of multiple cellular functions and diseases. Methods This review summarizes recent findings of our group and others regarding the signaling pathway and the biological roles of the PKD family in pancreatic acinar cells. In particular, we highlight our studies of the functions of PKD in several key pathobiologic processes associated with acute pancreatitis in experimental models. Results Our findings reveal that PKD signaling is required for NF-κB activation/inflammation, intracellular zymogen activation, and acinar cell necrosis in rodent experimental pancreatitis. Novel small-molecule PKD inhibitors attenuate the severity of pancreatitis in both in vitro and in vivo experimental models. Further, this review emphasizes our latest advances in the therapeutic application of PKD inhibitors to experimental pancreatitis after the initiation of pancreatitis. Conclusions These novel findings suggest that PKD signaling is a necessary modulator in key initiating pathobiologic processes of pancreatitis, and that it constitutes a novel therapeutic target for treatments of this disorder. PMID:26879861

  9. CD99 triggering induces methuosis of Ewing sarcoma cells through IGF-1R/RAS/Rac1 signaling.

    Science.gov (United States)

    Manara, Maria Cristina; Terracciano, Mario; Mancarella, Caterina; Sciandra, Marika; Guerzoni, Clara; Pasello, Michela; Grilli, Andrea; Zini, Nicoletta; Picci, Piero; Colombo, Mario P; Morrione, Andrea; Scotlandi, Katia

    2016-11-29

    CD99 is a cell surface molecule that has emerged as a novel target for Ewing sarcoma (EWS), an aggressive pediatric bone cancer. This report provides the first evidence of methuosis in EWS, a non-apoptotic form of cell death induced by an antibody directed against the CD99 molecule. Upon mAb triggering, CD99 induces an IGF-1R/RAS/Rac1 complex, which is internalized into RAB5-positive endocytic vacuoles. This complex is then dissociated, with the IGF-1R recycling to the cell membrane while CD99 and RAS/Rac1 are sorted into immature LAMP-1-positive vacuoles, whose excessive accumulation provokes methuosis. This process, which is not detected in CD99-expressing normal mesenchymal cells, is inhibited by disruption of the IGF-1R signaling, whereas enhanced by IGF-1 stimulation. Induction of IGF-1R/RAS/Rac1 was also observed in the EWS xenografts that respond to anti-CD99 mAb, further supporting the role of the IGF/RAS/Rac1 axis in the hyperstimulation of macropinocytosis and selective death of EWS cells. Thus, we describe a vulnerability of EWS cells, including those resistant to standard chemotherapy, to a treatment with anti-CD99 mAb, which requires IGF-1R/RAS signaling but bypasses the need for their direct targeting. Overall, we propose CD99 targeting as new opportunity to treat EWS patients resistant to canonical apoptosis-inducing agents.

  10. Electronic signal conditioning

    CERN Document Server

    NEWBY, BRUCE

    1994-01-01

    At technician level, brief references to signal conditioning crop up in a fragmented way in various textbooks, but there has been no single textbook, until now!More advanced texts do exist but they are more mathematical and presuppose a higher level of understanding of electronics and statistics. Electronic Signal Conditioning is designed for HNC/D students and City & Guilds Electronics Servicing 2240 Parts 2 & 3. It will also be useful for BTEC National, Advanced GNVQ, A-level electronics and introductory courses at degree level.

  11. Purinergic Signalling: Therapeutic Developments

    OpenAIRE

    Burnstock, Geoffrey

    2017-01-01

    Purinergic signalling, i.e., the role of nucleotides as extracellular signalling molecules, was proposed in 1972. However, this concept was not well accepted until the early 1990’s when receptor subtypes for purines and pyrimidines were cloned and characterised, which includes four subtypes of the P1 (adenosine) receptor, seven subtypes of P2X ion channel receptors and 8 subtypes of the P2Y G protein-coupled receptor. Early studies were largely concerned with the physiology, pharmacology and ...

  12. Genomic signal processing

    CERN Document Server

    Shmulevich, Ilya

    2007-01-01

    Genomic signal processing (GSP) can be defined as the analysis, processing, and use of genomic signals to gain biological knowledge, and the translation of that knowledge into systems-based applications that can be used to diagnose and treat genetic diseases. Situated at the crossroads of engineering, biology, mathematics, statistics, and computer science, GSP requires the development of both nonlinear dynamical models that adequately represent genomic regulation, and diagnostic and therapeutic tools based on these models. This book facilitates these developments by providing rigorous mathema

  13. TOR signalling in plants.

    Science.gov (United States)

    Rexin, Daniel; Meyer, Christian; Robaglia, Christophe; Veit, Bruce

    2015-08-15

    Although the eukaryotic TOR (target of rapamycin) kinase signalling pathway has emerged as a key player for integrating nutrient-, energy- and stress-related cues with growth and metabolic outputs, relatively little is known of how this ancient regulatory mechanism has been adapted in higher plants. Drawing comparisons with the substantial knowledge base around TOR kinase signalling in fungal and animal systems, functional aspects of this pathway in plants are reviewed. Both conserved and divergent elements are discussed in relation to unique aspects associated with an autotrophic mode of nutrition and adaptive strategies for multicellular development exhibited by plants. © 2015 Authors; published by Portland Press Limited.

  14. Signaling and Accounting Information

    OpenAIRE

    Stewart C. Myers

    1989-01-01

    This paper develops a signaling model in which accounting information improves real investment decisions. Pure cash flow reporting is shown to lead to underinvestment when managers have superior information but are acting in shareholders' interests. Accounting by prespecified, "objective" rules alleviates the underinvestment problem.

  15. Analog signal isolation techniques

    Energy Technology Data Exchange (ETDEWEB)

    Beadle, E.R.

    1992-12-31

    This paper discusses several techniques for isolating analog signals in an accelerator environment. The techniques presented here encompass isolation amplifiers, voltage-to-frequency converters (VIFCs), transformers, optocouplers, discrete fiber optics, and commercial fiber optic links. Included within the presentation of each method are the design issues that must be considered when selecting the isolation method for a specific application.

  16. Analog signal isolation techniques

    Energy Technology Data Exchange (ETDEWEB)

    Beadle, E.R.

    1992-01-01

    This paper discusses several techniques for isolating analog signals in an accelerator environment. The techniques presented here encompass isolation amplifiers, voltage-to-frequency converters (VIFCs), transformers, optocouplers, discrete fiber optics, and commercial fiber optic links. Included within the presentation of each method are the design issues that must be considered when selecting the isolation method for a specific application.

  17. Calcium signaling in neurodegeneration

    Directory of Open Access Journals (Sweden)

    Dreses-Werringloer Ute

    2009-05-01

    Full Text Available Abstract Calcium is a key signaling ion involved in many different intracellular and extracellular processes ranging from synaptic activity to cell-cell communication and adhesion. The exact definition at the molecular level of the versatility of this ion has made overwhelming progress in the past several years and has been extensively reviewed. In the brain, calcium is fundamental in the control of synaptic activity and memory formation, a process that leads to the activation of specific calcium-dependent signal transduction pathways and implicates key protein effectors, such as CaMKs, MAPK/ERKs, and CREB. Properly controlled homeostasis of calcium signaling not only supports normal brain physiology but also maintains neuronal integrity and long-term cell survival. Emerging knowledge indicates that calcium homeostasis is not only critical for cell physiology and health, but also, when deregulated, can lead to neurodegeneration via complex and diverse mechanisms involved in selective neuronal impairments and death. The identification of several modulators of calcium homeostasis, such as presenilins and CALHM1, as potential factors involved in the pathogenesis of Alzheimer's disease, provides strong support for a role of calcium in neurodegeneration. These observations represent an important step towards understanding the molecular mechanisms of calcium signaling disturbances observed in different brain diseases such as Alzheimer's, Parkinson's, and Huntington's diseases.

  18. Quantum cloning and signaling

    International Nuclear Information System (INIS)

    Simon, C.; Weihs, G.; Zeilinger, A.

    1999-01-01

    We discuss the close connections between cloning of quantum states and superluminal signaling. We present an optimal universal cloning machine based on stimulated emission recently proposed by the authors. As an instructive example, we show how a scheme for superluminal communication based on this cloning machine fails. (Authors)

  19. Intersection auxiliary signal system

    Science.gov (United States)

    Zhang, Jian

    1995-12-01

    Many intersection accidents are related to drivers' inappropriate responses to an amber signal light, due to their misjudgment on the traffic situation and/or their aggressive behavior. To reduce intersection accidents of this nature, this paper proposes the Intersection Auxiliary Signal System (IAS). IAS can be installed at selected intersections, where information regarding signal phasing, intersection geometry and speed limit is transmitted from an ultrasonic/infra-red transmitter. An on-vehicle device receivers and processes the information, the provides the driver with explicit suggestions on the correct action to take (continue to pass or decelerate to stop), or warnings against on-going incorrect actions. IAS is expected to be more effective in suburban intersections, which are usually characterized by greater dimension, longer amber phases, and higher vehicle speeds. Both the intersection transmitters and the on-vehicle processors are expected to have simple structures and low costs. Simulation results show that IAS has a significant effect on reducing red signal violation, especially when there is no significant dilemma zones.

  20. Signalling control strength.

    Science.gov (United States)

    Westerhoff, Hans V

    2008-06-07

    Metabolic control analysis (MCA) has become what it is, largely because the special organization of living cells led to rather specific questions. These questions focused on the role of enzymes, genes, and, in subsequent generalizations, on well-defined process activities. With an emphasis on the work by Heinrich and co-workers, the theory behind MCA is summarized in a way that leads naturally to its extensions to hierarchical systems, such as gene expression and signal transduction, and to control beyond the steady state. The analysis of the control properties of signal transduction cascades is reviewed with an emphasis on the relative importance of the protein kinases and the protein phosphatases. The two types of enzyme are both important for the amplitude of signal transduction, whereas phosphatases may be more important for the later phases of signal transduction and for its duration. Novel MCA of concentrations and fluxes that vary with time is explicated. It is concluded that the clarity and operationality of concepts such as control strength (now control coefficient) plus the clear theoretical frameworks provided by Heinrich and colleagues, should enable us greatly to reduce the Babylonian confusion that could otherwise occur in the data deluges of Systems Biology.

  1. Multimodal signalling in estrildid finches

    DEFF Research Database (Denmark)

    Gomes, A. C. R.; Funghi, C.; Soma, M.

    2017-01-01

    Sexual traits (e.g. visual ornaments, acoustic signals, courtship behaviour) are often displayed together as multimodal signals. Some hypotheses predict joint evolution of different sexual signals (e.g. to increase the efficiency of communication) or that different signals trade off with each oth...

  2. Sinusoidal Representation of Acoustic Signals

    Science.gov (United States)

    Honda, Masaaki

    Sinusoidal representation of acoustic signals has been an important tool in speech and music processing like signal analysis, synthesis and time scale or pitch modifications. It can be applicable to arbitrary signals, which is an important advantage over other signal representations like physical modeling of acoustic signals. In sinusoidal representation, acoustic signals are composed as sums of sinusoid (sine wave) with different amplitudes, frequencies and phases, which is based on the timedependent short-time Fourier transform (STFT). This article describes the principles of acoustic signal analysis/synthesis based on a sinusoid representation with focus on sine waves with rapidly varying frequency.

  3. The newest digital signal processing

    International Nuclear Information System (INIS)

    Lee, Chae Uk

    2002-08-01

    This book deal with the newest digital signal processing, which contains introduction on conception of digital signal processing, constitution and purpose, signal and system such as signal, continuos signal, discrete signal and discrete system, I/O expression on impress response, convolution, mutual connection of system and frequency character,z transform of definition, range, application of z transform and relationship with laplace transform, Discrete fourier, Fast fourier transform on IDFT algorithm and FFT application, foundation of digital filter of notion, expression, types, frequency characteristic of digital filter and design order of filter, Design order of filter, Design of FIR digital filter, Design of IIR digital filter, Adaptive signal processing, Audio signal processing, video signal processing and application of digital signal processing.

  4. Variable reflectivity signal mirrors and signal response measurements

    International Nuclear Information System (INIS)

    Vine, Glenn de; Shaddock, Daniel A; McClelland, David E

    2002-01-01

    Future gravitational wave detectors will include some form of signal mirror in order to alter the signal response of the device. We introduce interferometer configurations which utilize a variable reflectivity signal mirror allowing a tunable peak frequency and variable signal bandwidth. A detector configured with a Fabry-Perot cavity as the signal mirror is compared theoretically with one using a Michelson interferometer for a signal mirror. A system for the measurement of the interferometer signal responses is introduced. This technique is applied to a power-recycled Michelson interferometer with resonant sideband extraction. We present broadband measurements of the benchtop prototype's signal response for a range of signal cavity detunings. This technique is also applicable to most other gravitational wave detector configurations

  5. Variable reflectivity signal mirrors and signal response measurements

    CERN Document Server

    Vine, G D; McClelland, D E

    2002-01-01

    Future gravitational wave detectors will include some form of signal mirror in order to alter the signal response of the device. We introduce interferometer configurations which utilize a variable reflectivity signal mirror allowing a tunable peak frequency and variable signal bandwidth. A detector configured with a Fabry-Perot cavity as the signal mirror is compared theoretically with one using a Michelson interferometer for a signal mirror. A system for the measurement of the interferometer signal responses is introduced. This technique is applied to a power-recycled Michelson interferometer with resonant sideband extraction. We present broadband measurements of the benchtop prototype's signal response for a range of signal cavity detunings. This technique is also applicable to most other gravitational wave detector configurations.

  6. ASM-3 acid sphingomyelinase functions as a positive regulator of the DAF-2/AGE-1 signaling pathway and serves as a novel anti-aging target.

    Directory of Open Access Journals (Sweden)

    Yongsoon Kim

    Full Text Available In C. elegans, the highly conserved DAF-2/insulin/insulin-like growth factor 1 receptor signaling (IIS pathway regulates longevity, metabolism, reproduction and development. In mammals, acid sphingomyelinase (ASM is an enzyme that hydrolyzes sphingomyelin to produce ceramide. ASM has been implicated in CD95 death receptor signaling under certain stress conditions. However, the involvement of ASM in growth factor receptor signaling under physiological conditions is not known. Here, we report that in vivo ASM functions as a positive regulator of the DAF-2/IIS pathway in C. elegans. We have shown that inactivation of asm-3 extends animal lifespan and promotes dauer arrest, an alternative developmental process. A significant cooperative effect on lifespan is observed between asm-3 deficiency and loss-of-function alleles of the age-1/PI 3-kinase, with the asm-3; age-1 double mutant animals having a mean lifespan 259% greater than that of the wild-type animals. The lifespan extension phenotypes caused by the loss of asm-3 are dependent on the functions of daf-16/FOXO and daf-18/PTEN. We have demonstrated that inactivation of asm-3 causes nuclear translocation of DAF-16::GFP protein, up-regulates endogenous DAF-16 protein levels and activates the downstream targeting genes of DAF-16. Together, our findings reveal a novel role of asm-3 in regulation of lifespan and diapause by modulating IIS pathway. Importantly, we have found that two drugs known to inhibit mammalian ASM activities, desipramine and clomipramine, markedly extend the lifespan of wild-type animals, in a manner similar to that achieved by genetic inactivation of the asm genes. Our studies illustrate a novel strategy of anti-aging by targeting ASM, which may potentially be extended to mammals.

  7. ASM-3 Acid Sphingomyelinase Functions as a Positive Regulator of the DAF-2/AGE-1 Signaling Pathway and Serves as a Novel Anti-Aging Target

    Science.gov (United States)

    Kim, Yongsoon; Sun, Hong

    2012-01-01

    In C. elegans, the highly conserved DAF-2/insulin/insulin-like growth factor 1 receptor signaling (IIS) pathway regulates longevity, metabolism, reproduction and development. In mammals, acid sphingomyelinase (ASM) is an enzyme that hydrolyzes sphingomyelin to produce ceramide. ASM has been implicated in CD95 death receptor signaling under certain stress conditions. However, the involvement of ASM in growth factor receptor signaling under physiological conditions is not known. Here, we report that in vivo ASM functions as a positive regulator of the DAF-2/IIS pathway in C. elegans. We have shown that inactivation of asm-3 extends animal lifespan and promotes dauer arrest, an alternative developmental process. A significant cooperative effect on lifespan is observed between asm-3 deficiency and loss-of-function alleles of the age-1/PI 3-kinase, with the asm-3; age-1 double mutant animals having a mean lifespan 259% greater than that of the wild-type animals. The lifespan extension phenotypes caused by the loss of asm-3 are dependent on the functions of daf-16/FOXO and daf-18/PTEN. We have demonstrated that inactivation of asm-3 causes nuclear translocation of DAF-16::GFP protein, up-regulates endogenous DAF-16 protein levels and activates the downstream targeting genes of DAF-16. Together, our findings reveal a novel role of asm-3 in regulation of lifespan and diapause by modulating IIS pathway. Importantly, we have found that two drugs known to inhibit mammalian ASM activities, desipramine and clomipramine, markedly extend the lifespan of wild-type animals, in a manner similar to that achieved by genetic inactivation of the asm genes. Our studies illustrate a novel strategy of anti-aging by targeting ASM, which may potentially be extended to mammals. PMID:23049887

  8. ASM-3 acid sphingomyelinase functions as a positive regulator of the DAF-2/AGE-1 signaling pathway and serves as a novel anti-aging target.

    Science.gov (United States)

    Kim, Yongsoon; Sun, Hong

    2012-01-01

    In C. elegans, the highly conserved DAF-2/insulin/insulin-like growth factor 1 receptor signaling (IIS) pathway regulates longevity, metabolism, reproduction and development. In mammals, acid sphingomyelinase (ASM) is an enzyme that hydrolyzes sphingomyelin to produce ceramide. ASM has been implicated in CD95 death receptor signaling under certain stress conditions. However, the involvement of ASM in growth factor receptor signaling under physiological conditions is not known. Here, we report that in vivo ASM functions as a positive regulator of the DAF-2/IIS pathway in C. elegans. We have shown that inactivation of asm-3 extends animal lifespan and promotes dauer arrest, an alternative developmental process. A significant cooperative effect on lifespan is observed between asm-3 deficiency and loss-of-function alleles of the age-1/PI 3-kinase, with the asm-3; age-1 double mutant animals having a mean lifespan 259% greater than that of the wild-type animals. The lifespan extension phenotypes caused by the loss of asm-3 are dependent on the functions of daf-16/FOXO and daf-18/PTEN. We have demonstrated that inactivation of asm-3 causes nuclear translocation of DAF-16::GFP protein, up-regulates endogenous DAF-16 protein levels and activates the downstream targeting genes of DAF-16. Together, our findings reveal a novel role of asm-3 in regulation of lifespan and diapause by modulating IIS pathway. Importantly, we have found that two drugs known to inhibit mammalian ASM activities, desipramine and clomipramine, markedly extend the lifespan of wild-type animals, in a manner similar to that achieved by genetic inactivation of the asm genes. Our studies illustrate a novel strategy of anti-aging by targeting ASM, which may potentially be extended to mammals.

  9. Biomedical signal analysis

    CERN Document Server

    Rangayyan, Rangaraj M

    2015-01-01

    The book will help assist a reader in the development of techniques for analysis of biomedical signals and computer aided diagnoses with a pedagogical examination of basic and advanced topics accompanied by over 350 figures and illustrations. Wide range of filtering techniques presented to address various applications. 800 mathematical expressions and equations. Practical questions, problems and laboratory exercises. Includes fractals and chaos theory with biomedical applications.

  10. Plant peptide hormone signalling.

    Science.gov (United States)

    Motomitsu, Ayane; Sawa, Shinichiro; Ishida, Takashi

    2015-01-01

    The ligand-receptor-based cell-to-cell communication system is one of the most important molecular bases for the establishment of complex multicellular organisms. Plants have evolved highly complex intercellular communication systems. Historical studies have identified several molecules, designated phytohormones, that function in these processes. Recent advances in molecular biological analyses have identified phytohormone receptors and signalling mediators, and have led to the discovery of numerous peptide-based signalling molecules. Subsequent analyses have revealed the involvement in and contribution of these peptides to multiple aspects of the plant life cycle, including development and environmental responses, similar to the functions of canonical phytohormones. On the basis of this knowledge, the view that these peptide hormones are pivotal regulators in plants is becoming increasingly accepted. Peptide hormones are transcribed from the genome and translated into peptides. However, these peptides generally undergo further post-translational modifications to enable them to exert their function. Peptide hormones are expressed in and secreted from specific cells or tissues. Apoplastic peptides are perceived by specialized receptors that are located at the surface of target cells. Peptide hormone-receptor complexes activate intracellular signalling through downstream molecules, including kinases and transcription factors, which then trigger cellular events. In this chapter we provide a comprehensive summary of the biological functions of peptide hormones, focusing on how they mature and the ways in which they modulate plant functions. © 2015 Authors; published by Portland Press Limited.

  11. Plasmalogens rescue neuronal cell death through an activation of AKT and ERK survival signaling.

    Directory of Open Access Journals (Sweden)

    Md Shamim Hossain

    Full Text Available Neuronal cells are susceptible to many stresses, which will cause the apoptosis and neurodegenerative diseases. The precise molecular mechanism behind the neuronal protection against these apoptotic stimuli is necessary for drug discovery. In the present study, we have found that plasmalogens (Pls, which are glycerophospholipids containing vinyl ether linkage at sn-1 position, can protect the neuronal cell death upon serum deprivation. Interestingly, caspse-9, but not caspase-8 and caspase-12, was cleaved upon the serum starvation in Neuro-2A cells. Pls treatments effectively reduced the activation of caspase-9. Furthermore, cellular signaling experiments showed that Pls enhanced phosphorylation of the phosphoinositide 3-kinase (PI3K-dependent serine/threonine-specific protein kinase AKT and extracellular-signal-regulated kinases ERK1/2. PI3K/AKT inhibitor LY294002 and MAPK/ERK kinase (MEK inhibitor U0126 treatments study clearly indicated that Pls-mediated cell survival was dependent on the activation of these kinases. In addition, Pls also inhibited primary mouse hippocampal neuronal cell death induced by nutrient deprivation, which was associated with the inhibition of caspase-9 and caspase-3 cleavages. It was reported that Pls content decreased in the brain of the Alzheimer's patients, which indicated that the reduction of Pls content could endanger neurons. The present findings, taken together, suggest that Pls have an anti-apoptotic action in the brain. Further studies on precise mechanisms of Pls-mediated protection against cell death may lead us to establish a novel therapeutic approach to cure neurodegenerative disorders.

  12. Biomedical signal and image processing

    CERN Document Server

    Najarian, Kayvan

    2012-01-01

    INTRODUCTION TO DIGITAL SIGNAL AND IMAGE PROCESSINGSignals and Biomedical Signal ProcessingIntroduction and OverviewWhat is a ""Signal""?Analog, Discrete, and Digital SignalsProcessing and Transformation of SignalsSignal Processing for Feature ExtractionSome Characteristics of Digital ImagesSummaryProblemsFourier TransformIntroduction and OverviewOne-Dimensional Continuous Fourier TransformSampling and NYQUIST RateOne-Dimensional Discrete Fourier TransformTwo-Dimensional Discrete Fourier TransformFilter DesignSummaryProblemsImage Filtering, Enhancement, and RestorationIntroduction and Overview

  13. Purinergic Signalling: Therapeutic Developments.

    Science.gov (United States)

    Burnstock, Geoffrey

    2017-01-01

    Purinergic signalling, i.e., the role of nucleotides as extracellular signalling molecules, was proposed in 1972. However, this concept was not well accepted until the early 1990's when receptor subtypes for purines and pyrimidines were cloned and characterised, which includes four subtypes of the P1 (adenosine) receptor, seven subtypes of P2X ion channel receptors and 8 subtypes of the P2Y G protein-coupled receptor. Early studies were largely concerned with the physiology, pharmacology and biochemistry of purinergic signalling. More recently, the focus has been on the pathophysiology and therapeutic potential. There was early recognition of the use of P1 receptor agonists for the treatment of supraventricular tachycardia and A 2A receptor antagonists are promising for the treatment of Parkinson's disease. Clopidogrel, a P2Y 12 antagonist, is widely used for the treatment of thrombosis and stroke, blocking P2Y 12 receptor-mediated platelet aggregation. Diquafosol, a long acting P2Y 2 receptor agonist, is being used for the treatment of dry eye. P2X3 receptor antagonists have been developed that are orally bioavailable and stable in vivo and are currently in clinical trials for the treatment of chronic cough, bladder incontinence, visceral pain and hypertension. Antagonists to P2X7 receptors are being investigated for the treatment of inflammatory disorders, including neurodegenerative diseases. Other investigations are in progress for the use of purinergic agents for the treatment of osteoporosis, myocardial infarction, irritable bowel syndrome, epilepsy, atherosclerosis, depression, autism, diabetes, and cancer.

  14. Purinergic Signalling: Therapeutic Developments

    Directory of Open Access Journals (Sweden)

    Geoffrey Burnstock

    2017-09-01

    Full Text Available Purinergic signalling, i.e., the role of nucleotides as extracellular signalling molecules, was proposed in 1972. However, this concept was not well accepted until the early 1990’s when receptor subtypes for purines and pyrimidines were cloned and characterised, which includes four subtypes of the P1 (adenosine receptor, seven subtypes of P2X ion channel receptors and 8 subtypes of the P2Y G protein-coupled receptor. Early studies were largely concerned with the physiology, pharmacology and biochemistry of purinergic signalling. More recently, the focus has been on the pathophysiology and therapeutic potential. There was early recognition of the use of P1 receptor agonists for the treatment of supraventricular tachycardia and A2A receptor antagonists are promising for the treatment of Parkinson’s disease. Clopidogrel, a P2Y12 antagonist, is widely used for the treatment of thrombosis and stroke, blocking P2Y12 receptor-mediated platelet aggregation. Diquafosol, a long acting P2Y2 receptor agonist, is being used for the treatment of dry eye. P2X3 receptor antagonists have been developed that are orally bioavailable and stable in vivo and are currently in clinical trials for the treatment of chronic cough, bladder incontinence, visceral pain and hypertension. Antagonists to P2X7 receptors are being investigated for the treatment of inflammatory disorders, including neurodegenerative diseases. Other investigations are in progress for the use of purinergic agents for the treatment of osteoporosis, myocardial infarction, irritable bowel syndrome, epilepsy, atherosclerosis, depression, autism, diabetes, and cancer.

  15. Generation of earthquake signals

    International Nuclear Information System (INIS)

    Kjell, G.

    1994-01-01

    Seismic verification can be performed either as a full scale test on a shaker table or as numerical calculations. In both cases it is necessary to have an earthquake acceleration time history. This report describes generation of such time histories by filtering white noise. Analogue and digital filtering methods are compared. Different methods of predicting the response spectrum of a white noise signal filtered by a band-pass filter are discussed. Prediction of both the average response level and the statistical variation around this level are considered. Examples with both the IEEE 301 standard response spectrum and a ground spectrum suggested for Swedish nuclear power stations are included in the report

  16. Signal Processing for Communications

    CERN Document Server

    Prandoni, Paolo

    2008-01-01

    Taking a novel, less classical approach to the subject, the authors have written this book with the conviction that signal processing should be fun. Their treatment is less focused on the mathematics and more on the conceptual aspects, allowing students to think about the subject at a higher conceptual level, thus building the foundations for more advanced topics and helping students solve real-world problems. The last chapter pulls together the individual topics into an in-depth look at the development of an end-to-end communication system. Richly illustrated with examples and exercises in ea

  17. Phonocardiography Signal Processing

    CERN Document Server

    Abbas, Abbas K

    2009-01-01

    The auscultation method is an important diagnostic indicator for hemodynamic anomalies. Heart sound classification and analysis play an important role in the auscultative diagnosis. The term phonocardiography refers to the tracing technique of heart sounds and the recording of cardiac acoustics vibration by means of a microphone-transducer. Therefore, understanding the nature and source of this signal is important to give us a tendency for developing a competent tool for further analysis and processing, in order to enhance and optimize cardiac clinical diagnostic approach. This book gives the

  18. Transmembrane Signaling Proteoglycans

    DEFF Research Database (Denmark)

    Couchman, John R

    2010-01-01

    and their glycosaminoglycan chains is matched by diverse functions. However, all assume roles as coreceptors, often working alongside high-affinity growth factor receptors or adhesion receptors such as integrins. Other common themes are an ability to signal through their cytoplasmic domains, often to the actin cytoskeleton......, and linkage to PDZ protein networks. Many transmembrane proteoglycans associate on the cell surface with metzincin proteases and can be shed by them. Work with model systems in vivo and in vitro reveal roles in growth, adhesion, migration, and metabolism. Furthermore, a wide range of phenotypes for the core...

  19. Multiscale Signal Analysis and Modeling

    CERN Document Server

    Zayed, Ahmed

    2013-01-01

    Multiscale Signal Analysis and Modeling presents recent advances in multiscale analysis and modeling using wavelets and other systems. This book also presents applications in digital signal processing using sampling theory and techniques from various function spaces, filter design, feature extraction and classification, signal and image representation/transmission, coding, nonparametric statistical signal processing, and statistical learning theory. This book also: Discusses recently developed signal modeling techniques, such as the multiscale method for complex time series modeling, multiscale positive density estimations, Bayesian Shrinkage Strategies, and algorithms for data adaptive statistics Introduces new sampling algorithms for multidimensional signal processing Provides comprehensive coverage of wavelets with presentations on waveform design and modeling, wavelet analysis of ECG signals and wavelet filters Reviews features extraction and classification algorithms for multiscale signal and image proce...

  20. Hedgehog: an unusual signal transducer

    NARCIS (Netherlands)

    Bijlsma, Maarten F.; Spek, C. Arnold; Peppelenbosch, Maikel P.

    2004-01-01

    Hedgehog proteins are of pivotal importance for development and maintenance of tissue patterns in adult organisms. Despite the role of Hedgehogs in differentiation and tumorigenesis, signal transduction of Hedgehog remains a relatively uncharted area of signalling biochemistry. For proper Hedgehog

  1. Biological signals classification and analysis

    CERN Document Server

    Kiasaleh, Kamran

    2015-01-01

    This authored monograph presents key aspects of signal processing analysis in the biomedical arena. Unlike wireless communication systems, biological entities produce signals with underlying nonlinear, chaotic nature that elude classification using the standard signal processing techniques, which have been developed over the past several decades for dealing primarily with standard communication systems. This book separates what is random from that which appears to be random, and yet is truly deterministic with random appearance. At its core, this work gives the reader a perspective on biomedical signals and the means to classify and process such signals. In particular, a review of random processes along with means to assess the behavior of random signals is also provided. The book also includes a general discussion of biological signals in order to demonstrate the inefficacy of the well-known techniques to correctly extract meaningful information from such signals. Finally, a thorough discussion of recently ...

  2. Two-dimensional signal analysis

    CERN Document Server

    Garello, René

    2010-01-01

    This title sets out to show that 2-D signal analysis has its own role to play alongside signal processing and image processing.Concentrating its coverage on those 2-D signals coming from physical sensors (such as radars and sonars), the discussion explores a 2-D spectral approach but develops the modeling of 2-D signals and proposes several data-oriented analysis techniques for dealing with them. Coverage is also given to potential future developments in this area.

  3. Astrocytes in endocannabinoid signalling.

    Science.gov (United States)

    Navarrete, Marta; Díez, Adolfo; Araque, Alfonso

    2014-10-19

    Astrocytes are emerging as integral functional components of synapses, responding to synaptically released neurotransmitters and regulating synaptic transmission and plasticity. Thus, they functionally interact with neurons establishing tripartite synapses: a functional concept that refers to the existence of communication between astrocytes and neurons and its crucial role in synaptic function. Here, we discuss recent evidence showing that astrocytes are involved in the endocannabinoid (ECB) system, responding to exogenous cannabinoids as well as ECBs through activation of type 1 cannabinoid receptors, which increase intracellular calcium and stimulate the release of glutamate that modulates synaptic transmission and plasticity. We also discuss the consequences of ECB signalling in tripartite synapses on the astrocyte-mediated regulation of synaptic function, which reveal novel properties of synaptic regulation by ECBs, such as the spatially controlled dual effect on synaptic strength and the lateral potentiation of synaptic efficacy. Finally, we discuss the potential implications of ECB signalling for astrocytes in brain pathology and animal behaviour. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

  4. Critical nodes in signalling pathways

    DEFF Research Database (Denmark)

    Taniguchi, Cullen M; Emanuelli, Brice; Kahn, C Ronald

    2006-01-01

    Physiologically important cell-signalling networks are complex, and contain several points of regulation, signal divergence and crosstalk with other signalling cascades. Here, we use the concept of 'critical nodes' to define the important junctions in these pathways and illustrate their unique role...

  5. Detection of signals in noise

    CERN Document Server

    Whalen, Anthony D; Declaris, Nicholas

    1971-01-01

    Detection of Signals in Noise serves as an introduction to the principles and applications of the statistical theory of signal detection. The book discusses probability and random processes; narrowband signals, their complex representation, and their properties described with the aid of the Hilbert transform; and Gaussian-derived processes. The text also describes the application of hypothesis testing for the detection of signals and the fundamentals required for statistical detection of signals in noise. Problem exercises, references, and a supplementary bibliography are included after each c

  6. Signals and systems for dummies

    CERN Document Server

    Wickert, Mark

    2013-01-01

    Getting mixed signals in your signals and systems course? The concepts covered in a typical signals and systems course are often considered by engineering students to be some of the most difficult to master. Thankfully, Signals & Systems For Dummies is your intuitive guide to this tricky course, walking you step-by-step through some of the more complex theories and mathematical formulas in a way that is easy to understand. From Laplace Transforms to Fourier Analyses, Signals & Systems For Dummies explains in plain English the difficult concepts that can trip you up

  7. LPA1 Mediates Antidepressant-Induced ERK1/2 Signaling and Protection from Oxidative Stress in Glial Cells.

    Science.gov (United States)

    Olianas, Maria C; Dedoni, Simona; Onali, Pierluigi

    2016-11-01

    Antidepressants have been shown to affect glial cell functions and intracellular signaling through mechanisms that are still not completely understood. In the present study, we provide evidence that in glial cells the lysophosphatidic acid (LPA) receptor LPA 1 mediates antidepressant-induced growth factor receptor transactivation, ERK1/2 signaling, and protection from oxidative stress. Thus, in C6 glioma cells and rat cortical astrocytes, ERK1/2 activation induced by either amitriptyline or mianserin was antagonized by Ki16425 and VPC 12249 (S), which block LPA 1 and LPA 3 receptors, and by AM966, which selectively blocks LPA 1 Cell depletion of LPA 1 with siRNA treatment markedly reduced antidepressant- and LPA-induced ERK1/2 phosphorylation. LPA 1 blockade prevented antidepressant-induced phosphorylation of the transcription factors CREB and Elk-1. Antidepressants and LPA signaling to ERK1/2 was abrogated by cell treatment with pertussis toxin and by the inhibition of fibroblast growth factor (FGF) receptor (FGF-R) and platelet-derived growth factor receptor (PDGF-R) tyrosine kinases. Both Ki16425 and AM966 suppressed antidepressant-induced phosphorylation of FGF-R. Moreover, blockade of LPA 1 or inhibition of FGF-R and PDGF-R activities prevented antidepressant-stimulated Akt and GSK-3β phosphorylations. Mianserin protected C6 glioma cells and astrocytes from apoptotic cell death induced by H 2 O 2 , as indicated by increased cell viability, decreased expression of cleaved caspase 3, reduced cleavage of poly-ADP ribose polymerase and inhibition of DNA fragmentation. The protective effects of mianserin were antagonized by AM966. These data indicate that LPA 1 constitutes a novel molecular target of the regulatory actions of tricyclic and tetracyclic antidepressants in glial cells. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

  8. Machine intelligence and signal processing

    CERN Document Server

    Vatsa, Mayank; Majumdar, Angshul; Kumar, Ajay

    2016-01-01

    This book comprises chapters on key problems in machine learning and signal processing arenas. The contents of the book are a result of a 2014 Workshop on Machine Intelligence and Signal Processing held at the Indraprastha Institute of Information Technology. Traditionally, signal processing and machine learning were considered to be separate areas of research. However in recent times the two communities are getting closer. In a very abstract fashion, signal processing is the study of operator design. The contributions of signal processing had been to device operators for restoration, compression, etc. Applied Mathematicians were more interested in operator analysis. Nowadays signal processing research is gravitating towards operator learning – instead of designing operators based on heuristics (for example wavelets), the trend is to learn these operators (for example dictionary learning). And thus, the gap between signal processing and machine learning is fast converging. The 2014 Workshop on Machine Intel...

  9. [Progress on Hedgehog signaling transduction].

    Science.gov (United States)

    Tang, Ying; Cheng, Steven

    2014-08-25

    Hedgehog (Hh) signaling pathway plays an important role during embryonic development and pattern formation. Disruption of Hh pathway results in various developmental disorders and increasing cancer incidence. Here we provide a comprehensive review of the pathway members, focusing on how mammalian Hh regulates the Gli family of transcription factors through its downstream members, the so-called "canonical signaling pathway". Hh signaling pathway is highly conserved among species, and primary cilia plays an important role as a "signaling center" during vertebrate signal transduction. Further, in the past few years, numerous studies have shown that Hh signal can also be transduced through Gli-independent ways collectively referred to as "non-canonical signaling pathways", which can be subdivided into two modules: (i) those not requiring Smo and (ii) those downstream of Smo that do not require Gli transcription factors. Thus, we review the rapid progress on canonical and non-canonical Hh pathways.

  10. Measuring signal generators theory & design

    CERN Document Server

    Rybin, Yuriy K

    2014-01-01

    The book brings together the following issues: Theory of deterministic, random and discrete signals reproducible in oscillatory systems of generators; Generation of periodic signals with a specified spectrum, harmonic distortion factor and random signals with specified probability density function and spectral density; Synthesis of oscillatory system structures; Analysis of oscillatory systems with non-linear elements and oscillation amplitude stabilization systems; It considers the conditions and criteria of steady-state modes in signal generators on active four-pole elements with unidirectional and bidirectional transmission of signals and on two-pole elements; analogues of Barkhausen criteria; Optimization of oscillatory system structures by harmonic distortion level, minimization of a frequency error and set-up time of the steady state mode; Theory of construction of random signal generators; Construction of discrete and digital signal generators; Practical design of main units of generators; Practical bl...

  11. [Signal Processing Suite Design

    Science.gov (United States)

    Sahr, John D.; Mir, Hasan; Morabito, Andrew; Grossman, Matthew

    2003-01-01

    Our role in this project was to participate in the design of the signal processing suite to analyze plasma density measurements on board a small constellation (3 or 4) satellites in Low Earth Orbit. As we are new to space craft experiments, one of the challenges was to simply gain understanding of the quantity of data which would flow from the satellites, and possibly to interact with the design teams in generating optimal sampling patterns. For example, as the fleet of satellites were intended to fly through the same volume of space (displaced slightly in time and space), the bulk plasma structure should be common among the spacecraft. Therefore, an optimal, limited bandwidth data downlink would take advantage of this commonality. Also, motivated by techniques in ionospheric radar, we hoped to investigate the possibility of employing aperiodic sampling in order to gain access to a wider spatial spectrum without suffering aliasing in k-space.

  12. Wavelet analysis for nonstationary signals

    International Nuclear Information System (INIS)

    Penha, Rosani Maria Libardi da

    1999-01-01

    Mechanical vibration signals play an important role in anomalies identification resulting of equipment malfunctioning. Traditionally, Fourier spectral analysis is used where the signals are assumed to be stationary. However, occasional transient impulses and start-up process are examples of nonstationary signals that can be found in mechanical vibrations. These signals can provide important information about the equipment condition, as early fault detection. The Fourier analysis can not adequately be applied to nonstationary signals because the results provide data about the frequency composition averaged over the duration of the signal. In this work, two methods for nonstationary signal analysis are used: Short Time Fourier Transform (STFT) and wavelet transform. The STFT is a method of adapting Fourier spectral analysis for nonstationary application to time-frequency domain. To have a unique resolution throughout the entire time-frequency domain is its main limitation. The wavelet transform is a new analysis technique suitable to nonstationary signals, which handles the STFT drawbacks, providing multi-resolution frequency analysis and time localization in a unique time-scale graphic. The multiple frequency resolutions are obtained by scaling (dilatation/compression) the wavelet function. A comparison of the conventional Fourier transform, STFT and wavelet transform is made applying these techniques to: simulated signals, arrangement rotor rig vibration signal and rotate machine vibration signal Hanning window was used to STFT analysis. Daubechies and harmonic wavelets were used to continuos, discrete and multi-resolution wavelet analysis. The results show the Fourier analysis was not able to detect changes in the signal frequencies or discontinuities. The STFT analysis detected the changes in the signal frequencies, but with time-frequency resolution problems. The wavelet continuos and discrete transform demonstrated to be a high efficient tool to detect

  13. Singapore grouper iridovirus, a large DNA virus, induces nonapoptotic cell death by a cell type dependent fashion and evokes ERK signaling.

    Science.gov (United States)

    Huang, Xiaohong; Huang, Youhua; Ouyang, Zhengliang; Xu, Lixiao; Yan, Yang; Cui, Huachun; Han, Xin; Qin, Qiwei

    2011-08-01

    Virus induced cell death, including apoptosis and nonapoptotic cell death, plays a critical role in the pathogenesis of viral diseases. Singapore grouper iridovirus (SGIV), a novel iridovirus of genus Ranavirus, causes high mortality and heavy economic losses in grouper aquaculture. Here, using fluorescence microscopy, electron microscopy and biochemical assays, we found that SGIV infection in host (grouper spleen, EAGS) cells evoked nonapoptotic programmed cell death (PCD), characterized by appearance of cytoplasmic vacuoles and distended endoplasmic reticulum, in the absence of DNA fragmentation, apoptotic bodies and caspase activation. In contrast, SGIV induced typical apoptosis in non-host (fathead minnow, FHM) cells, as evidenced by caspase activation and DNA fragmentation, suggesting that SGIV infection induced nonapoptotic cell death by a cell type dependent fashion. Furthermore, viral replication was essential for SGIV induced nonapoptotic cell death, but not for apoptosis. Notably, the disruption of mitochondrial transmembrane potential (ΔΨm) and externalization of phosphatidylserine (PS) were not detected in EAGS cells but in FHM cells after SGIV infection. Moreover, the extracellular signal-regulated kinase (ERK) signaling was involved in SGIV infection induced nonapoptotic cell death and viral replication. This is a first demonstration of ERK-mediated nonapoptotic cell death induced by a DNA virus. These findings contribute to understanding the mechanisms of iridovirus pathogenesis.

  14. Steganography in arrhythmic electrocardiogram signal.

    Science.gov (United States)

    Edward Jero, S; Ramu, Palaniappan; Ramakrishnan, S

    2015-08-01

    Security and privacy of patient data is a vital requirement during exchange/storage of medical information over communication network. Steganography method hides patient data into a cover signal to prevent unauthenticated accesses during data transfer. This study evaluates the performance of ECG steganography to ensure secured transmission of patient data where an abnormal ECG signal is used as cover signal. The novelty of this work is to hide patient data into two dimensional matrix of an abnormal ECG signal using Discrete Wavelet Transform and Singular Value Decomposition based steganography method. A 2D ECG is constructed according to Tompkins QRS detection algorithm. The missed R peaks are computed using RR interval during 2D conversion. The abnormal ECG signals are obtained from the MIT-BIH arrhythmia database. Metrics such as Peak Signal to Noise Ratio, Percentage Residual Difference, Kullback-Leibler distance and Bit Error Rate are used to evaluate the performance of the proposed approach.

  15. Unmixing binocular signals

    Directory of Open Access Journals (Sweden)

    Sidney R Lehky

    2011-08-01

    Full Text Available Incompatible images presented to the two eyes lead to perceptual oscillations in which one image at a time is visible. Early models portrayed this binocular rivalry as involving reciprocal inhibition between monocular representations of images, occurring at an early visual stage prior to binocular mixing. However, psychophysical experiments found conditions where rivalry could also occur at a higher, more abstract level of representation. In those cases, the rivalry was between image representations dissociated from eye-of-origin information, rather than between monocular representations from the two eyes. Moreover, neurophysiological recordings found the strongest rivalry correlate in inferotemporal cortex, a high-level, predominantly binocular visual area involved in object recognition, rather than early visual structures. An unresolved issue is how can the separate identities of the two images be maintained after binocular mixing in order for rivalry to be possible at higher levels? Here we demonstrate that after the two images are mixed, they can be unmixed at any subsequent stage using a physiologically plausible nonlinear signal-processing algorithm, non-negative matrix factorization, previously proposed for parsing object parts during object recognition. The possibility that unmixed left and right images can be regenerated at late stages within the visual system provides a mechanism for creating various binocular representations and interactions de novo in different cortical areas for different purposes, rather than inheriting then from early areas. This is a clear example how nonlinear algorithms can lead to highly non-intuitive behavior in neural information processing.

  16. Digitally programmable signal generator

    International Nuclear Information System (INIS)

    Priatko, G.J.; Kaskey, J.A.

    1988-01-01

    A digitally programmable signal generator (DPSG) includes a first memory from which data is written into a second memory formed of n banks. Each bank includes four memories and a multiplexer, the banks being read once during each time frame, the read-out bits being multiplexed and fed out serially in synchronism with a plurality of clock pulses occuring during a time frame. The resulting serial bit streams may be fed in parallel to a digital-to-analog converter. The DPSG can be used in applications such as Atomic Vapor Laser Isotope Separation (AVLIS) to create an optimal match between the process laser's spectral profile and that of the vaporized material, optical telecommunications, non-optical telecommunication in the microwave and radio spectrum, radar, electronic countermeasures, high speed computer interconnects, local area networks, high definition video transport and the multiplexing of large quantities of slow digital memory into high speed data streams. This invention extends the operation of DPSGs into the GHz range. (author)

  17. Volcanic signals in oceans

    KAUST Repository

    Stenchikov, Georgiy L.

    2009-08-22

    Sulfate aerosols resulting from strong volcanic explosions last for 2–3 years in the lower stratosphere. Therefore it was traditionally believed that volcanic impacts produce mainly short-term, transient climate perturbations. However, the ocean integrates volcanic radiative cooling and responds over a wide range of time scales. The associated processes, especially ocean heat uptake, play a key role in ongoing climate change. However, they are not well constrained by observations, and attempts to simulate them in current climate models used for climate predictions yield a range of uncertainty. Volcanic impacts on the ocean provide an independent means of assessing these processes. This study focuses on quantification of the seasonal to multidecadal time scale response of the ocean to explosive volcanism. It employs the coupled climate model CM2.1, developed recently at the National Oceanic and Atmospheric Administration\\'s Geophysical Fluid Dynamics Laboratory, to simulate the response to the 1991 Pinatubo and the 1815 Tambora eruptions, which were the largest in the 20th and 19th centuries, respectively. The simulated climate perturbations compare well with available observations for the Pinatubo period. The stronger Tambora forcing produces responses with higher signal-to-noise ratio. Volcanic cooling tends to strengthen the Atlantic meridional overturning circulation. Sea ice extent appears to be sensitive to volcanic forcing, especially during the warm season. Because of the extremely long relaxation time of ocean subsurface temperature and sea level, the perturbations caused by the Tambora eruption could have lasted well into the 20th century.

  18. Fundamentals of statistical signal processing

    CERN Document Server

    Kay, Steven M

    1993-01-01

    A unified presentation of parameter estimation for those involved in the design and implementation of statistical signal processing algorithms. Covers important approaches to obtaining an optimal estimator and analyzing its performance; and includes numerous examples as well as applications to real- world problems. MARKETS: For practicing engineers and scientists who design and analyze signal processing systems, i.e., to extract information from noisy signals — radar engineer, sonar engineer, geophysicist, oceanographer, biomedical engineer, communications engineer, economist, statistician, physicist, etc.

  19. Queen signaling in social wasps

    DEFF Research Database (Denmark)

    van Zweden, Jelle Stijn; Bonckaert, Wim; Wenseleers, Tom

    2014-01-01

    , thereby arguing against fast evolution of signals as a result of a queen-worker arms race ensuing from queen control. Lastly, levels of worker reproduction in these species correspond well with their average colony kin structures, as predicted by the queen signaling hypothesis but not the queen control...... hypothesis. Altogether, this correlative yet comprehensive analysis provides compelling evidence that honest signaling explains levels of reproductive division of labor in social wasps....

  20. Semi-classical signal analysis

    KAUST Repository

    Laleg-Kirati, Taous-Meriem

    2012-09-30

    This study introduces a new signal analysis method, based on a semi-classical approach. The main idea in this method is to interpret a pulse-shaped signal as a potential of a Schrödinger operator and then to use the discrete spectrum of this operator for the analysis of the signal. We present some numerical examples and the first results obtained with this method on the analysis of arterial blood pressure waveforms. © 2012 Springer-Verlag London Limited.

  1. Signal generation in gas detectors

    International Nuclear Information System (INIS)

    Stillman, A.

    1993-01-01

    This tutorial describes the generation of electrical signals in gas detectors. Ionization of the gas by the passage of charged particles generates these signals. Starting with the Bethe-Bloch equation, the treatment is a general introduction to the production of ion-pairs in gas devices. I continue with the characterization of the ionization as an electrical signal, and calculate the signal current in a simple example. Another example demonstrates the effect of space charge on the design of a detector. The AGS Booster ionization profile monitor is a model for this calculation

  2. Signal generation in gas detectors

    Energy Technology Data Exchange (ETDEWEB)

    Stillman, A.

    1993-11-01

    This tutorial describes the generation of electrical signals in gas detectors. Ionization of the gas by the passage of charged particles generates these signals. Starting with the Bethe-Bloch equation, the treatment is a general introduction to the production of ion-pairs in gas devices. I continue with the characterization of the ionization as an electrical signal, and calculate the signal current in a simple example. Another example demonstrates the effect of space charge on the design of a detector. The AGS Booster ionization profile monitor is a model for this calculation.

  3. Virtual Vertical Aircraft Signal Training

    National Research Council Canada - National Science Library

    Norling, William

    1998-01-01

    .... Advances in virtual environments may provide a cost effective solution to the current live helicopter operations method of training, provided technical issues associated with hand and wand signal...

  4. Signal anomaly detection and characterization

    International Nuclear Information System (INIS)

    Morgenstern, V.M.; Upadhyaya, B.R.; Gloeckler, O.

    1988-08-01

    As part of a comprehensive signal validation system, we have developed a signal anomaly detector, without specifically establishing the cause of the anomaly. A signal recorded from process instrumentation is said to have an anomaly, if during steady-state operation, the deviation in the level of the signal, its root-mean-square (RMS) value, or its statistical distribution changes by a preset value. This deviation could be an unacceptable increase or a decrease in the quantity being monitored. An anomaly in a signal may be characterized by wideband or single-frequency noise, bias error, pulse-type error, nonsymmetric behavior, or a change in the signal bandwidth. Various signatures can be easily computed from data samples and compared against specified threshold values. We want to point out that in real processes, pulses can appear with different time widths, and at different rates of change of the signal. Thus, in characterizing an anomaly as a pulse-type, the fastest pulse width is constrained by the signal sampling interval. For example, if a signal is sampled at 100 Hz, we will not be able to detect pulses occurring at kHz rates. Discussion with utility and Combustion Engineering personnel indicated that it is not practical to detect pulses having a narrow time width. 9 refs., 11 figs., 8 tabs

  5. Pragmatic circuits signals and filters

    CERN Document Server

    Eccles, William

    2006-01-01

    Pragmatic Circuits: Signals and Filters is built around the processing of signals. Topics include spectra, a short introduction to the Fourier series, design of filters, and the properties of the Fourier transform. The focus is on signals rather than power. But the treatment is still pragmatic. For example, the author accepts the work of Butterworth and uses his results to design filters in a fairly methodical fashion. This third of three volumes finishes with a look at spectra by showing how to get a spectrum even if a signal is not periodic. The Fourier transform provides a way of dealing wi

  6. Smoke Signal or Smoke Screen?

    DEFF Research Database (Denmark)

    Vergne, Jean-Philippe; Wernicke, Georg; Brenner, Steffen

    This paper explains the amount of disapproval faced by firms that overpay their CEO by integrating signaling and categorization theories. We argue that, in contexts characterized by intense scrutiny, ambivalent signals sent by firms suspend categorization by stakeholders, leading to further disap...

  7. Signals in Communication Engineering History

    Science.gov (United States)

    Consonni, Denise; Silva, Magno T. M.

    2010-01-01

    This paper is a study of various electric signals, which have been employed throughout the history of communication engineering in its two main landmarks: the telegraph and the telephone. The signals are presented in their time and frequency domain representations. The historical order has been followed in the presentation: wired systems, spark…

  8. Cellular semiotics and signal transduction

    DEFF Research Database (Denmark)

    Bruni, Luis Emilio

    2007-01-01

    (s)" in signal transduction; i.e.: how specificity is determined, how ubiquitous signals or messengers convey specific information, how undesired cross-talk is avoided, how redundancy integrates the system. This chapter proposes a basic conceptual toolbox for interpreting empirical data that deals...

  9. Hippo signalling directs intestinal fate

    DEFF Research Database (Denmark)

    le Bouteiller, Marie Catherine M; Jensen, Kim Bak

    2015-01-01

    Hippo signalling has been associated with many important tissue functions including the regulation of organ size. In the intestinal epithelium differing functions have been proposed for the effectors of Hippo signalling, YAP and TAZ1. These are now shown to have a dual role in the intestinal epit...

  10. 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.

  11. Signaling a Change of Heart

    DEFF Research Database (Denmark)

    Schumacher, Gijs

    2011-01-01

    introduced welfare state retrenchment measures. Social Democrats can win votes and join coalitions by shifting rightwards. In contrast, they can pursue policy objectives by shifting leftwards. To communicate these shifts, in other words, ‘changes of heart’, parties send signals to voters and other parties...... after having signalled ‘a change of heart’....

  12. Intracellular signal modulation by nanomaterials.

    Science.gov (United States)

    Hussain, Salik; Garantziotis, Stavros; Rodrigues-Lima, Fernando; Dupret, Jean-Marie; Baeza-Squiban, Armelle; Boland, Sonja

    2014-01-01

    A thorough understanding of the interactions of nanomaterials with biological systems and the resulting activation of signal transduction pathways is essential for the development of safe and consumer friendly nanotechnology. Here we present an overview of signaling pathways induced by nanomaterial exposures and describe the possible correlation of their physicochemical characteristics with biological outcomes. In addition to the hierarchical oxidative stress model and a review of the intrinsic and cell-mediated mechanisms of reactive oxygen species (ROS) generating capacities of nanomaterials, we also discuss other oxidative stress dependent and independent cellular signaling pathways. Induction of the inflammasome, calcium signaling, and endoplasmic reticulum stress are reviewed. Furthermore, the uptake mechanisms can be of crucial importance for the cytotoxicity of nanomaterials and membrane-dependent signaling pathways have also been shown to be responsible for cellular effects of nanomaterials. Epigenetic regulation by nanomaterials, effects of nanoparticle-protein interactions on cell signaling pathways, and the induction of various cell death modalities by nanomaterials are described. We describe the common trigger mechanisms shared by various nanomaterials to induce cell death pathways and describe the interplay of different modalities in orchestrating the final outcome after nanomaterial exposures. A better understanding of signal modulations induced by nanomaterials is not only essential for the synthesis and design of safer nanomaterials but will also help to discover potential nanomedical applications of these materials. Several biomedical applications based on the different signaling pathways induced by nanomaterials are already proposed and will certainly gain a great deal of attraction in the near future.

  13. A Serpentine Way to Signaling

    Indian Academy of Sciences (India)

    IAS Admin

    tude inside the cells, leading to activation of effectors molecules. Effectors are protein molecules that bind to DNA and cause. Figure 1. Simplified diagram of a signal transduction cas- cade. A signal transduction cascade represents the route of transfer of information from outside to inside the cell. There are many molecules.

  14. Signal processing for radiation detectors

    CERN Document Server

    Nakhostin, Mohammad

    2018-01-01

    This book provides a clear understanding of the principles of signal processing of radiation detectors. It puts great emphasis on the characteristics of pulses from various types of detectors and offers a full overview on the basic concepts required to understand detector signal processing systems and pulse processing techniques. Signal Processing for Radiation Detectors covers all of the important aspects of signal processing, including energy spectroscopy, timing measurements, position-sensing, pulse-shape discrimination, and radiation intensity measurement. The book encompasses a wide range of applications so that readers from different disciplines can benefit from all of the information. In addition, this resource: * Describes both analog and digital techniques of signal processing * Presents a complete compilation of digital pulse processing algorithms * Extrapolates content from more than 700 references covering classic papers as well as those of today * Demonstrates concepts with more than 340 origin...

  15. Signal focusing through active transport

    Science.gov (United States)

    Godec, Aljaž; Metzler, Ralf

    2015-07-01

    The accuracy of molecular signaling in biological cells and novel diagnostic devices is ultimately limited by the counting noise floor imposed by the thermal diffusion. Motivated by the fact that messenger RNA and vesicle-engulfed signaling molecules transiently bind to molecular motors and are actively transported in biological cells, we show here that the random active delivery of signaling particles to within a typical diffusion distance to the receptor generically reduces the correlation time of the counting noise. Considering a variety of signaling particle sizes from mRNA to vesicles and cell sizes from prokaryotic to eukaryotic cells, we show that the conditions for active focusing—faster and more precise signaling—are indeed compatible with observations in living cells. Our results improve the understanding of molecular cellular signaling and novel diagnostic devices.

  16. Endocannabinoid signaling and synaptic function

    Science.gov (United States)

    Castillo, Pablo E.; Younts, Thomas J.; Chávez, Andrés E.; Hashimotodani, Yuki

    2012-01-01

    Endocannabinoids are key modulators of synaptic function. By activating cannabinoid receptors expressed in the central nervous system, these lipid messengers can regulate several neural functions and behaviors. As experimental tools advance, the repertoire of known endocannabinoid-mediated effects at the synapse, and their underlying mechanism, continues to expand. Retrograde signaling is the principal mode by which endocannabinoids mediate short- and long-term forms of plasticity at both excitatory and inhibitory synapses. However, growing evidence suggests that endocannabinoids can also signal in a non-retrograde manner. In addition to mediating synaptic plasticity, the endocannabinoid system is itself subject to plastic changes. Multiple points of interaction with other neuromodulatory and signaling systems have now been identified. Synaptic endocannabinoid signaling is thus mechanistically more complex and diverse than originally thought. In this review, we focus on new advances in endocannabinoid signaling and highlight their role as potent regulators of synaptic function in the mammalian brain. PMID:23040807

  17. Piezoelectric extraction of ECG signal

    Science.gov (United States)

    Ahmad, Mahmoud Al

    2016-11-01

    The monitoring and early detection of abnormalities or variations in the cardiac cycle functionality are very critical practices and have significant impact on the prevention of heart diseases and their associated complications. Currently, in the field of biomedical engineering, there is a growing need for devices capable of measuring and monitoring a wide range of cardiac cycle parameters continuously, effectively and on a real-time basis using easily accessible and reusable probes. In this paper, the revolutionary generation and extraction of the corresponding ECG signal using a piezoelectric transducer as alternative for the ECG will be discussed. The piezoelectric transducer pick up the vibrations from the heart beats and convert them into electrical output signals. To this end, piezoelectric and signal processing techniques were employed to extract the ECG corresponding signal from the piezoelectric output voltage signal. The measured electrode based and the extracted piezoelectric based ECG traces are well corroborated. Their peaks amplitudes and locations are well aligned with each other.

  18. Aberrant Signaling Pathways in Glioma

    International Nuclear Information System (INIS)

    Nakada, Mitsutoshi; Kita, Daisuke; Watanabe, Takuya; Hayashi, Yutaka; Teng, Lei; Pyko, Ilya V.; Hamada, Jun-Ichiro

    2011-01-01

    Glioblastoma multiforme (GBM), a WHO grade IV malignant glioma, is the most common and lethal primary brain tumor in adults; few treatments are available. Median survival rates range from 12–15 months. The biological characteristics of this tumor are exemplified by prominent proliferation, active invasiveness, and rich angiogenesis. This is mainly due to highly deregulated signaling pathways in the tumor. Studies of these signaling pathways have greatly increased our understanding of the biology and clinical behavior of GBM. An integrated view of signal transduction will provide a more useful approach in designing novel therapies for this devastating disease. In this review, we summarize the current understanding of GBM signaling pathways with a focus on potential molecular targets for anti-signaling molecular therapies

  19. MHC signaling during social communication

    Science.gov (United States)

    Ruff, James S.; Nelson, Adam C.; Kubinak, Jason L.; Potts, Wayne K.

    2016-01-01

    The major histocompatibility complex (MHC) has been known to play a critical role in immune recognition since the 1950s. It was a surprise, then, in the 1970s when the first report appeared indicating MHC might also function in social signaling and in mate choice. Since this seminal discovery, MHC signaling has been found throughout vertebrates and its known functions have expanded beyond mate choice to include a suite of behaviors from kin-biased cooperation, parent-progeny recognition to pregnancy block. The widespread occurrence of MHC in social signaling has revealed conserved behavioral-genetic mechanisms that span vertebrates and includes humans. The identity of the signal’s chemical constituents and the receptors responsible for the perception of the signal have remained elusive, but recent advances have enabled the identification of the key components of the behavioral circuit. In this chapter we organize recent findings from the literature and discuss them in relation to four non-mutually exclusive models wherein MHC functions as a signal of (i) individuality, (ii) relatedness, (iii) genetic compatibility and (iv) quality. We also synthesize current mechanistic studies, showing how knowledge about the molecular basis of MHC signaling can lead to elegant and informative experimental manipulations. Finally, we discuss current evidence relating to the primordial functions of the MHC, including the possibility that its role in social signaling may be ancestral to its central role in adaptive immunity. PMID:22399386

  20. Quorum Quenching Revisited—From Signal Decays to Signalling Confusion

    Directory of Open Access Journals (Sweden)

    Kok-Gan Chan

    2012-04-01

    Full Text Available In a polymicrobial community, while some bacteria are communicating with neighboring cells (quorum sensing, others are interrupting the communication (quorum quenching, thus creating a constant arms race between intercellular communication. In the past decade, numerous quorum quenching enzymes have been found and initially thought to inactivate the signalling molecules. Though this is widely accepted, the actual roles of these quorum quenching enzymes are now being uncovered. Recent evidence extends the role of quorum quenching to detoxification or metabolism of signalling molecules as food and energy source; this includes “signalling confusion”, a term coined in this paper to refer to the phenomenon of non-destructive modification of signalling molecules. While quorum quenching has been explored as a novel anti-infective therapy targeting, quorum sensing evidence begins to show the development of resistance against quorum quenching.

  1. Baird's beaked whale echolocation signals.

    Science.gov (United States)

    Baumann-Pickering, Simone; Yack, Tina M; Barlow, Jay; Wiggins, Sean M; Hildebrand, John A

    2013-06-01

    Echolocation signals from Baird's beaked whales were recorded during visual and acoustic shipboard surveys of cetaceans in the California Current ecosystem and with autonomous, long-term recorders in the Southern California Bight. The preliminary measurement of the visually validated Baird's beaked whale echolocation signals from towed array data were used as a basis for identifying Baird's signals in the autonomous recorder data. Two distinct signal types were found, one being a beaked whale-like frequency modulated (FM) pulse, the other being a dolphin-like broadband click. The median FM inter-pulse interval was 230 ms. Both signal types showed a consistent multi-peak structure in their spectra with peaks at ~9, 16, 25, and 40 kHz. Depending on signal type, as well as recording aspect and distance to the hydrophone, these peaks varied in relative amplitude. The description of Baird's echolocation signals will allow for studies of their distribution and abundance using towed array data without associated visual sightings and from autonomous seafloor hydrophones.

  2. Signal transduction by growth factor receptors: signaling in an instant

    DEFF Research Database (Denmark)

    Dengjel, Joern; Akimov, Vyacheslav; Blagoev, Blagoy

    2007-01-01

    -out by mass spectrometry-based proteomics has allowed exciting views on the very early events in signal transduction. Activation profiles of regulated phosphorylation sites on epidermal growth factor receptor and downstream signal transducers showed different kinetics within the first ten seconds......Phosphorylation-based signaling events happening within the first minute of receptor stimulation have so far only been analyzed by classical cell biological approaches like live-cell microscopy. The development of a quench flow system with a time resolution of one second coupled to a read...... of stimulation. This new technique opens the perspectives for accurate analysis of rapid cellular processes and will help to establish models describing signal initiation at the plasma membrane....

  3. Microsystem for signal processing applications

    Science.gov (United States)

    Frankenstein, B.; Froehlich, K.-J.; Hentschel, D.; Reppe, G.

    2005-05-01

    Acoustic monitoring of technological processes requires methods that eliminate noise as much as possible. Sensor-near signal evaluation can contribute substantially. Frequently, a further necessity exists to integrate the measuring technique in the monitored structure. The solution described contains components for analog preprocessing of acoustic signals, their digitization, algorithms for data reduction, and digital communication. The core component is a digital signal processor (DSP). Digital signal processors perform the algorithms necessary for filtering, down sampling, FFT computation and correlation of spectral components particularly effective. A compact, sensor-near signal processing structure was realized. It meets the Match-X standard, which as specified by the German Association for Mechanical and Plant Engineering (VDMA) for development of micro-technical modules, which can be combined to applicaiton specific systems. The solution is based on AL2O3 ceramic components including different signal processing modules as ADC, as well as memory and power supply. An arbitrary waveform generator has been developed and combined with a power amplifier for piezoelectric transducers in a special module. A further module interfaces to these transducers. It contains a multi-channel preamplifier, some high-pass filters for analog signal processing and an ADC-driver. A Bluetooth communication chip for wireless data transmission and a DiscOnChip module are under construction. As a first application, the combustion behavior of safety-relevant contacts is monitored. A special waveform up to 5MHz is produced and sent to the monitored object. The resulting signal form is evaluated with special algorithms, which extract significant parameters of the signal, and transmitted via CAN-bus.

  4. Advanced optical signal processing of broadband parallel data signals

    DEFF Research Database (Denmark)

    Oxenløwe, Leif Katsuo; Hu, Hao; Kjøller, Niels-Kristian

    2016-01-01

    Optical signal processing may aid in reducing the number of active components in communication systems with many parallel channels, by e.g. using telescopic time lens arrangements to perform format conversion and allow for WDM regeneration.......Optical signal processing may aid in reducing the number of active components in communication systems with many parallel channels, by e.g. using telescopic time lens arrangements to perform format conversion and allow for WDM regeneration....

  5. Fast digitizing and digital signal processing of detector signals

    International Nuclear Information System (INIS)

    Hannaske, Roland

    2008-01-01

    A fast-digitizer data acquisition system recently installed at the neutron time-of-flight experiment nELBE, which is located at the superconducting electron accelerator ELBE of Forschungszentrum Dresden-Rossendorf, is tested with two different detector types. Preamplifier signals from a high-purity germanium detector are digitized, stored and finally processed. For a precise determination of the energy of the detected radiation, the moving-window deconvolution algorithm is used to compensate the ballistic deficit and different shaping algorithms are applied. The energy resolution is determined in an experiment with γ-rays from a 22 Na source and is compared to the energy resolution achieved with analogously processed signals. On the other hand, signals from the photomultipliers of barium fluoride and plastic scintillation detectors are digitized. These signals have risetimes of a few nanoseconds only. The moment of interaction of the radiation with the detector is determined by methods of digital signal processing. Therefore, different timing algorithms are implemented and tested with data from an experiment at nELBE. The time resolutions achieved with these algorithms are compared to each other as well as to reference values coming from analog signal processing. In addition to these experiments, some properties of the digitizing hardware are measured and a program for the analysis of stored, digitized data is developed. The analysis of the signals shows that the energy resolution achieved with the 10-bit digitizer system used here is not competitive to a 14-bit peak-sensing ADC, although the ballistic deficit can be fully corrected. However, digital methods give better result in sub-ns timing than analog signal processing. (orig.)

  6. ESR signals of irradiated insects

    International Nuclear Information System (INIS)

    Ukai, Mitsuko; Kameya, Hiromi; Imamura, Taro; Miyanoshita, Akihiro; Todoriki, Setsuko; Shimoyama, Yuhei

    2009-01-01

    Analysis of irradiated insects using Electron Spin Resonance (ESR) spectroscopy was reported. The insects were maize weevil, red flour beetle, Indian meal moth and cigarette beetle that are hazardous to crops. The ESR spectra were consisted of a singlet at g=2 and a sextet centered at the similar g-value. The singlet signal is due to an organic free radical. The sextet signal is attributable to the hyperfine interactions from Mn 2+ ions. Upon irradiation, new signals were not detected. The relaxation times, T 1 and T 2 , showed no variations before and after irradiation. (author)

  7. Ultrasound imaging using coded signals

    DEFF Research Database (Denmark)

    Misaridis, Athanasios

    coded excitation can be used for increasing the frame rate. The work includes both simulated results using Field II, and experimental results based on measurements on phantoms as well as clinical images. Initially a mathematical foundation of signal modulation is given. Pulse compression based...... is described. Application of coded excitation in array imaging is evaluated through simulations in Field II. The low degree of the orthogonality among coded signals for ultrasound systems is first discussed, and the effect of mismatched filtering in the cross-correlation properties of the signals is evaluated...... emissions. Finally, a novel coding technique which uses pulse train excitation is presented....

  8. Statistical theory of signal detection

    CERN Document Server

    Helstrom, Carl Wilhelm; Costrell, L; Kandiah, K

    1968-01-01

    Statistical Theory of Signal Detection, Second Edition provides an elementary introduction to the theory of statistical testing of hypotheses that is related to the detection of signals in radar and communications technology. This book presents a comprehensive survey of digital communication systems. Organized into 11 chapters, this edition begins with an overview of the theory of signal detection and the typical detection problem. This text then examines the goals of the detection system, which are defined through an analogy with the testing of statistical hypotheses. Other chapters consider

  9. Subjective Evaluation of Audiovisual Signals

    Directory of Open Access Journals (Sweden)

    F. Fikejz

    2010-01-01

    Full Text Available This paper deals with subjective evaluation of audiovisual signals, with emphasis on the interaction between acoustic and visual quality. The subjective test is realized by a simple rating method. The audiovisual signal used in this test is a combination of images compressed by JPEG compression codec and sound samples compressed by MPEG-1 Layer III. Images and sounds have various contents. It simulates a real situation when the subject listens to compressed music and watches compressed pictures without the access to original, i.e. uncompressed signals.

  10. EUROmediCAT signal detection

    DEFF Research Database (Denmark)

    Given, Joanne E; Loane, Maria; Luteijn, Johannes Michiel

    2016-01-01

    AIMS: To evaluate congenital anomaly (CA)-medication exposure associations produced by the new EUROmediCAT signal detection system and determine which require further investigation. METHODS: Data from 15 EUROCAT registries (1995-2011) with medication exposures at the chemical substance (5th level...... persisted after data validation, a literature review was conducted for prior evidence of human teratogenicity. RESULTS: Thirteen out of 27 CA-medication exposure signals, based on 389 exposed cases, passed data validation. There was some prior evidence in the literature to support six signals (gastroschisis...

  11. On Generalized Fractional Differentiator Signals

    Directory of Open Access Journals (Sweden)

    Hamid A. Jalab

    2013-01-01

    Full Text Available By employing the generalized fractional differential operator, we introduce a system of fractional order derivative for a uniformly sampled polynomial signal. The calculation of the bring in signal depends on the additive combination of the weighted bring-in of N cascaded digital differentiators. The weights are imposed in a closed formula containing the Stirling numbers of the first kind. The approach taken in this work is to consider that signal function in terms of Newton series. The convergence of the system to a fractional time differentiator is discussed.

  12. Terminality implies non-signalling

    Directory of Open Access Journals (Sweden)

    Bob Coecke

    2014-12-01

    Full Text Available A 'process theory' is any theory of systems and processes which admits sequential and parallel composition. `Terminality' unifies normalisation of pure states, trace-preservation of CP-maps, and adding up to identity of positive operators in quantum theory, and generalises this to arbitrary process theories. We show that terminality and non-signalling coincide in any process theory, provided one makes causal structure explicit. In fact, making causal structure explicit is necessary to even make sense of non-signalling in process theories. We conclude that because of its much simpler mathematical form, terminality should be taken to be a more fundamental notion than non-signalling.

  13. Subcellular Organization of GPCR Signaling.

    Science.gov (United States)

    Eichel, Kelsie; von Zastrow, Mark

    2018-02-01

    G protein-coupled receptors (GPCRs) comprise a large and diverse class of signal-transducing receptors that undergo dynamic and isoform-specific membrane trafficking. GPCRs thus have an inherent potential to initiate or regulate signaling reactions from multiple membrane locations. This review discusses emerging insights into the subcellular organization of GPCR function in mammalian cells, focusing on signaling transduced by heterotrimeric G proteins and β-arrestins. We summarize recent evidence indicating that GPCR-mediated activation of G proteins occurs not only from the plasma membrane (PM) but also from endosomes and Golgi membranes and that β-arrestin-dependent signaling can be transduced from the PM by β-arrestin trafficking to clathrin-coated pits (CCPs) after dissociation from a ligand-activated GPCR. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Automobile Crash Sensor Signal Processor

    Science.gov (United States)

    1973-11-01

    The crash sensor signal processor described interfaces between an automobile-installed doppler radar and an air bag activating solenoid or equivalent electromechanical device. The processor utilizes both digital and analog techniques to produce an ou...

  15. Endothelial signaling in leukocyte transmigration

    NARCIS (Netherlands)

    Hordijk, Peter

    2003-01-01

    Leukocyte transendothelial migration is a multistep process coordinated by chemokine receptors, integrins and cell adhesion molecules. The interaction between leukocytes and endothelial cells is accompanied by bidirectional signaling in both cell types, which is initiated following formation of

  16. Invariants of DNA genomic signals

    Science.gov (United States)

    Cristea, Paul Dan A.

    2005-02-01

    For large scale analysis purposes, the conversion of genomic sequences into digital signals opens the possibility to use powerful signal processing methods for handling genomic information. The study of complex genomic signals reveals large scale features, maintained over the scale of whole chromosomes, that would be difficult to find by using only the symbolic representation. Based on genomic signal methods and on statistical techniques, the paper defines parameters of DNA sequences which are invariant to transformations induced by SNPs, splicing or crossover. Re-orienting concatenated coding regions in the same direction, regularities shared by the genomic material in all exons are revealed, pointing towards the hypothesis of a regular ancestral structure from which the current chromosome structures have evolved. This property is not found in non-nuclear genomic material, e.g., plasmids.

  17. Dopamine signaling: target in glioblastoma

    Czech Academy of Sciences Publication Activity Database

    Bartek, Jiří; Hodný, Zdeněk

    2014-01-01

    Roč. 5, č. 5 (2014), 1116-1117 ISSN 1949-2553 Institutional support: RVO:68378050 Keywords : Dopamine signaling * glioblastoma * MAPK Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 6.359, year: 2014

  18. Digital storage of repeated signals

    International Nuclear Information System (INIS)

    Prozorov, S.P.

    1984-01-01

    An independent digital storage system designed for repeated signal discrimination from background noises is described. The signal averaging is performed off-line in the real time mode by means of multiple selection of the investigated signal and integration in each point. Digital values are added in a simple summator and the result is recorded the storage device with the volume of 1024X20 bit from where it can be output on an oscillograph, a plotter or transmitted to a compUter for subsequent processing. The described storage is reliable and simple device on one base of which the systems for the nuclear magnetic resonapce signal acquisition in different experiments are developed

  19. Signal transforms in dynamic measurements

    CERN Document Server

    Layer, Edward

    2015-01-01

    This book is devoted to the analysis of measurement signals which requires specific mathematical operations like Convolution, Deconvolution, Laplace, Fourier, Hilbert, Wavelet or Z transform which are all presented in the present book. The different problems refer to the modulation of signals, filtration of disturbance as well as to the orthogonal signals and their use in digital form for the measurement of current, voltage, power and frequency are also widely discussed. All the topics covered in this book are presented in detail and illustrated by means of examples in MathCad and LabVIEW. This book provides a useful source for researchers, scientists and engineers who in their daily work are required to deal with problems of measurement and signal processing and can also be helpful to undergraduate students of electrical engineering.    

  20. Nuclear Receptor Signaling Atlas (NURSA)

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Nuclear Receptor Signaling Atlas (NURSA) is designed to foster the development of a comprehensive understanding of the structure, function, and role in disease...

  1. 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...

  2. Cytonemes as specialized signaling filopodia

    OpenAIRE

    Kornberg, Thomas B.; Roy, Sougata

    2014-01-01

    Development creates a vast array of forms and patterns with elegant economy, using a small vocabulary of pattern-generating proteins such as BMPs, FGFs and Hh in similar ways in many different contexts. Despite much theoretical and experimental work, the signaling mechanisms that disperse these morphogen signaling proteins remain controversial. Here, we review the conceptual background and evidence that establishes a fundamental and essential role for cytonemes as specialized filopodia that t...

  3. RET Signaling in Prostate Cancer.

    Science.gov (United States)

    Ban, Kechen; Feng, Shu; Shao, Longjiang; Ittmann, Michael

    2017-08-15

    Purpose: Large diameter perineural prostate cancer is associated with poor outcomes. GDNF, with its coreceptor GFRα1, binds RET and activates downstream pro-oncogenic signaling. Because both GDNF and GFRα1 are secreted by nerves, we examined the role of RET signaling in prostate cancer. Experimental Design: Expression of RET, GDNF, and/or GFRα1 was assessed. The impact of RET signaling on proliferation, invasion and soft agar colony formation, perineural invasion, and growth in vivo was determined. Cellular signaling downstream of RET was examined by Western blotting. Results: RET is expressed in all prostate cancer cell lines. GFRα1 is only expressed in 22Rv1 cells, which is the only line that responds to exogenous GDNF. In contrast, all cell lines respond to GDNF plus GFRα1. Conditioned medium from dorsal root ganglia contains secreted GFRα1 and promotes transformation-related phenotypes, which can be blocked by anti-GFRα1 antibody. Perineural invasion in the dorsal root ganglion assay is inhibited by anti-GFRα antibody and RET knockdown. In vivo , knockdown of RET inhibits tumor growth. RET signaling activates ERK or AKT signaling depending on context, but phosphorylation of p70S6 kinase is markedly increased in all cases. Knockdown of p70S6 kinase markedly decreases RET induced transformed phenotypes. Finally, RET is expressed in 18% of adenocarcinomas and all three small-cell carcinomas examined. Conclusions: RET promotes transformation associated phenotypes, including perineural invasion in prostate cancer via activation of p70S6 kinase. GFRα1, which is secreted by nerves, is a limiting factor for RET signaling, creating a perineural niche where RET signaling can occur. Clin Cancer Res; 23(16); 4885-96. ©2017 AACR . ©2017 American Association for Cancer Research.

  4. Neurotransmitter signaling in white matter.

    Science.gov (United States)

    Butt, Arthur M; Fern, Robert F; Matute, Carlos

    2014-11-01

    White matter (WM) tracts are bundles of myelinated axons that provide for rapid communication throughout the CNS and integration in grey matter (GM). The main cells in myelinated tracts are oligodendrocytes and astrocytes, with small populations of microglia and oligodendrocyte precursor cells. The prominence of neurotransmitter signaling in WM, which largely exclude neuronal cell bodies, indicates it must have physiological functions other than neuron-to-neuron communication. A surprising aspect is the diversity of neurotransmitter signaling in WM, with evidence for glutamatergic, purinergic (ATP and adenosine), GABAergic, glycinergic, adrenergic, cholinergic, dopaminergic and serotonergic signaling, acting via a wide range of ionotropic and metabotropic receptors. Both axons and glia are potential sources of neurotransmitters and may express the respective receptors. The physiological functions of neurotransmitter signaling in WM are subject to debate, but glutamate and ATP-mediated signaling have been shown to evoke Ca(2+) signals in glia and modulate axonal conduction. Experimental findings support a model of neurotransmitters being released from axons during action potential propagation acting on glial receptors to regulate the homeostatic functions of astrocytes and myelination by oligodendrocytes. Astrocytes also release neurotransmitters, which act on axonal receptors to strengthen action potential propagation, maintaining signaling along potentially long axon tracts. The co-existence of multiple neurotransmitters in WM tracts suggests they may have diverse functions that are important for information processing. Furthermore, the neurotransmitter signaling phenomena described in WM most likely apply to myelinated axons of the cerebral cortex and GM areas, where they are doubtless important for higher cognitive function. © 2014 Wiley Periodicals, Inc.

  5. Sentiment analysis for PTSD signals

    CERN Document Server

    Kagan, Vadim; Sapounas, Demetrios

    2013-01-01

    This book describes a computational framework for real-time detection of psychological signals related to Post-Traumatic Stress Disorder (PTSD) in online text-based posts, including blogs and web forums. Further, it explores how emerging computational techniques such as sentiment mining can be used in real-time to identify posts that contain PTSD-related signals, flag those posts, and bring them to the attention of psychologists, thus providing an automated flag and referral capability.

  6. Hedgehog signalling in foregut malignancy.

    Science.gov (United States)

    Watkins, D N; Peacock, C D

    2004-09-15

    Hedgehog (Hh) signalling mediates axial patterning and stem cell fate in development. This is mediated by Sonic, Desert and Indian Hedgehogs whose morphogen gradients determine the level of signalling in recipient tissues. Aberrant, cell autonomous, ligand-dependent Hh signalling has recently been demonstrated in small cell lung cancer (SCLC), as well as in upper gastrointestinal malignancies arising from pancreas, esophagus and stomach. These tumors lack mutations in the Hh receptor PATCHED, identifying a mechanism of pathway activation distinct from Gorlin's syndrome associated neural and skin tumors. We believe that this phenomenon represents a conserved mechanism for establishing niche-independent stem cell fates in cancer which is essential for malignant transformation and metastasis. Specific inhibition of Hh signalling by the naturally occurring plant alkaloid cyclopamine provides the opportunity for pharmacologic assessment of the role of Hh signalling in these tumors. Cyclopamine inhibits growth of SCLC and a wide range of foregut derived malignancies both in vitro and in vivo. This demonstrates an ongoing requirement for Hh signalling in these highly lethal and aggressive tumors. A novel therapeutic strategy is proposed using pharmacologic targeting of Hh dependent tumors with high potency pathway antagonists.

  7. Insulin Signaling and Heart Failure

    Science.gov (United States)

    Riehle, Christian; Abel, E. Dale

    2016-01-01

    Heart failure is associated with generalized insulin resistance. Moreover, insulin resistant states such as type 2 diabetes and obesity increases the risk of heart failure even after adjusting for traditional risk factors. Insulin resistance or type 2 diabetes alters the systemic and neurohumoral milieu leading to changes in metabolism and signaling pathways in the heart that may contribute to myocardial dysfunction. In addition, changes in insulin signaling within cardiomyocytes develop in the failing heart. The changes range from activation of proximal insulin signaling pathways that may contribute to adverse left ventricular remodeling and mitochondrial dysfunction to repression of distal elements of insulin signaling pathways such as forkhead (FOXO) transcriptional signaling or glucose transport which may also impair cardiac metabolism, structure and function. This article will review the complexities of insulin signaling within the myocardium and ways in which these pathways are altered in heart failure or in conditions associated with generalized insulin resistance. The implications of these changes for therapeutic approaches to treating or preventing heart failure will be discussed. PMID:27034277

  8. Metabolites in vertebrate Hedgehog signaling.

    Science.gov (United States)

    Roberg-Larsen, Hanne; Strand, Martin Frank; Krauss, Stefan; Wilson, Steven Ray

    2014-04-11

    The Hedgehog (HH) signaling pathway is critical in embryonic development, stem cell biology, tissue homeostasis, chemoattraction and synapse formation. Irregular HH signaling is associated with a number of disease conditions including congenital disorders and cancer. In particular, deregulation of HH signaling has been linked to skin, brain, lung, colon and pancreatic cancers. Key mediators of the HH signaling pathway are the 12-pass membrane protein Patched (PTC), the 7-pass membrane protein Smoothened (SMO) and the GLI transcription factors. PTC shares homology with the RND family of small-molecule transporters and it has been proposed that it interferes with SMO through metabolites. Although a conclusive picture is lacking, substantial efforts are made to identify and understand natural metabolites/sterols, including cholesterol, vitamin D3, oxysterols and glucocorticoides, that may be affected by, or influence the HH signaling cascade at the level of PTC and SMO. In this review we will elaborate the role of metabolites in HH signaling with a focus on oxysterols, and discuss advancements in modern analytical approaches in the field. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. SignalPlant: an open signal processing software platform.

    Science.gov (United States)

    Plesinger, F; Jurco, J; Halamek, J; Jurak, P

    2016-07-01

    The growing technical standard of acquisition systems allows the acquisition of large records, often reaching gigabytes or more in size as is the case with whole-day electroencephalograph (EEG) recordings, for example. Although current 64-bit software for signal processing is able to process (e.g. filter, analyze, etc) such data, visual inspection and labeling will probably suffer from rather long latency during the rendering of large portions of recorded signals. For this reason, we have developed SignalPlant-a stand-alone application for signal inspection, labeling and processing. The main motivation was to supply investigators with a tool allowing fast and interactive work with large multichannel records produced by EEG, electrocardiograph and similar devices. The rendering latency was compared with EEGLAB and proves significantly faster when displaying an image from a large number of samples (e.g. 163-times faster for 75  ×  10(6) samples). The presented SignalPlant software is available free and does not depend on any other computation software. Furthermore, it can be extended with plugins by third parties ensuring its adaptability to future research tasks and new data formats.

  10. Lipid-Induced Signaling Causes Release of Inflammatory Extracellular Vesicles From Hepatocytes.

    Science.gov (United States)

    Hirsova, Petra; Ibrahim, Samar H; Krishnan, Anuradha; Verma, Vikas K; Bronk, Steven F; Werneburg, Nathan W; Charlton, Michael R; Shah, Vijay H; Malhi, Harmeet; Gores, Gregory J

    2016-04-01

    Hepatocyte cellular dysfunction and death induced by lipids and macrophage-associated inflammation are characteristics of nonalcoholic steatohepatitis (NASH). The fatty acid palmitate can activate death receptor 5 (DR5) on hepatocytes, leading to their death, but little is known about how this process contributes to macrophage-associated inflammation. We investigated whether lipid-induced DR5 signaling results in the release of extracellular vesicles (EVs) from hepatocytes, and whether these can induce an inflammatory macrophage phenotype. Primary mouse and human hepatocytes and Huh7 cells were incubated with palmitate, its metabolite lysophosphatidylcholine, or diluent (control). The released EV were isolated, characterized, quantified, and applied to macrophages. C57BL/6 mice were placed on chow or a diet high in fat, fructose, and cholesterol to induce NASH. Some mice also were given the ROCK1 inhibitor fasudil; 2 weeks later, serum EVs were isolated and characterized by immunoblot and nanoparticle-tracking analyses. Livers were collected and analyzed by histology, immunohistochemistry, and quantitative polymerase chain reaction. Incubation of primary hepatocytes and Huh7 cells with palmitate or lysophosphatidylcholine increased their release of EVs, compared with control cells. This release was reduced by inactivating mediators of the DR5 signaling pathway or rho-associated, coiled-coil-containing protein kinase 1 (ROCK1) inhibition. Hepatocyte-derived EVs contained tumor necrosis factor-related apoptosis-inducing ligand and induced expression of interleukin 1β and interleukin 6 messenger RNAs in mouse bone marrow-derived macrophages. Activation of macrophages required DR5 and receptor-interacting protein kinase 1. Administration of the ROCK1 inhibitor fasudil to mice with NASH reduced serum levels of EVs; this reduction was associated with decreased liver injury, inflammation, and fibrosis. Lipids, which stimulate DR5, induce release of hepatocyte EVs, which

  11. Bystander signaling via oxidative metabolism

    Directory of Open Access Journals (Sweden)

    Sawal HA

    2017-08-01

    Full Text Available Humaira Aziz Sawal,1 Kashif Asghar,2 Matthias Bureik,3 Nasir Jalal4 1Healthcare Biotechnology Department, Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad, 2Basic Sciences Research, Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan; 3Health Science Platform, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, China; 4Health Science Platform, Department of Molecular and Cellular Pharmacology, Tianjin University, Tianjin, China Abstract: The radiation-induced bystander effect (RIBE is the initiation of biological end points in cells (bystander cells that are not directly traversed by an incident-radiation track, but are in close proximity to cells that are receiving the radiation. RIBE has been indicted of causing DNA damage via oxidative stress, besides causing direct damage, inducing tumorigenesis, producing micronuclei, and causing apoptosis. RIBE is regulated by signaling proteins that are either endogenous or secreted by cells as a means of communication between cells, and can activate intracellular or intercellular oxidative metabolism that can further trigger signaling pathways of inflammation. Bystander signals can pass through gap junctions in attached cell lines, while the suspended cell lines transmit these signals via hormones and soluble proteins. This review provides the background information on how reactive oxygen species (ROS act as bystander signals. Although ROS have a very short half-life and have a nanometer-scale sphere of influence, the wide variety of ROS produced via various sources can exert a cumulative effect, not only in forming DNA adducts but also setting up signaling pathways of inflammation, apoptosis, cell-cycle arrest, aging, and even tumorigenesis. This review outlines the sources of the bystander effect linked to ROS in a cell, and provides methods of investigation for researchers who would like to

  12. A stilbene synthase allele from a Chinese wild grapevine confers resistance to powdery mildew by recruiting salicylic acid signalling for efficient defence.

    Science.gov (United States)

    Jiao, Yuntong; Xu, Weirong; Duan, Dong; Wang, Yuejin; Nick, Peter

    2016-10-01

    Stilbenes are central phytoalexins in Vitis, and induction of the key enzyme stilbene synthase (STS) is pivotal for disease resistance. Here, we address the potential for breeding resistance using an STS allele isolated from Chinese wild grapevine Vitis pseudoreticulata (VpSTS) by comparison with its homologue from Vitis vinifera cv. 'Carigane' (VvSTS). Although the coding regions of both alleles are very similar (>99% identity on the amino acid level), the promoter regions are significantly different. By expression in Arabidopsis as a heterologous system, we show that the allele from the wild Chinese grapevine can confer accumulation of stilbenes and resistance against the powdery mildew Golovinomyces cichoracearum, whereas the allele from the vinifera cultivar cannot. To dissect the upstream signalling driving the activation of this promoter, we used a dual-luciferase reporter system in a grapevine cell culture. We show elevated responsiveness of the promoter from the wild grape to salicylic acid (SA) and to the pathogen-associated molecular pattern (PAMP) flg22, equal induction of both alleles by jasmonic acid (JA), and a lack of response to the cell death-inducing elicitor Harpin. This elevated SA response of the VpSTS promoter depends on calcium influx, oxidative burst by RboH, mitogen-activated protein kinase (MAPK) signalling, and JA synthesis. We integrate the data in the context of a model where the resistance of V. pseudoreticulata is linked to a more efficient recruitment of SA signalling for phytoalexin synthesis. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  13. Study of Bioreductive Anticancer Agent RH-1-Induced Signals Leading the Wild-Type p53-Bearing Lung Cancer A549 Cells to Apoptosis.

    Science.gov (United States)

    Stulpinas, Aurimas; Imbrasaitė, Aušra; Krestnikova, Natalija; Šarlauskas, Jonas; Čėnas, Narimantas; Kalvelytė, Audronė Valerija

    2016-01-19

    Aziridinylquinone RH-1 (2,5-diaziridinyl-3-hydroxymethyl-6-methyl-cyclohexa-2,5-diene-1,4-dione) is a potential anticancer agent. RH-1 action is associated with quinone oxidoreductase (NQO1) which reduces this diaziridinylbenzoquinone into DNA-alkylating hydroquinone and is overexpressed in many tumors. Another suggested mechanism of RH-1 toxicity is the formation of reactive oxygen species (ROS) arising from its redox cycling. In order to improve anticancer action of this and similar antitumor quinones, we investigated the involvement of different signaling molecules in cytotoxicity induced by RH-1 by using wild-type tumor suppressor p53 bearing nonsmall cell lung carcinoma A549 cells as a model. Gradual and prolonged increase of mitogen-activated protein kinases (MAPK) ERK, P38, and JNK phosphorylation was observed during 24-h RH-1 treatment. In parallel, activation of DNA damage-sensing ATM kinase, upregulation, and phosphorylation of TP53 (human p53) took place. Inhibition studies revealed that RH-1-induced A549 apoptosis involved the NQO1-ATM-p53 signaling pathway and ROS generation. TP53 participated in ROS- and DNA damage-induced cell death differently. Moreover, MAP kinase JNK was another TP53 activator and death inducer in A549 cells. At the same time, rapid and prolonged activation of AKT kinase during RH-1 treatment was found, and it proved to be antiapoptotic kinase in our model system. Therefore, we identified that different and opposite cell death regulating signaling pathways, which may counteract one another, are induced in cancer cells during chemotherapeutic RH-1 treatment.

  14. Liquid Argon TPC Signal Formation, Signal Processing and Hit Reconstruction

    Energy Technology Data Exchange (ETDEWEB)

    Baller, Bruce [Fermilab

    2017-03-11

    This document describes the early stage of the reconstruction chain that was developed for the ArgoNeuT and MicroBooNE experiments at Fermilab. These experiments study accelerator neutrino interactions that occur in a Liquid Argon Time Projection Chamber. Reconstructing the properties of particles produced in these interactions requires knowledge of the micro-physics processes that affect the creation and transport of ionization electrons to the readout system. A wire signal deconvolution technique was developed to convert wire signals to a standard form for hit reconstruction, to remove artifacts in the electronics chain and to remove coherent noise.

  15. Biomedical signal and image processing.

    Science.gov (United States)

    Cerutti, Sergio; Baselli, Giuseppe; Bianchi, Anna; Caiani, Enrico; Contini, Davide; Cubeddu, Rinaldo; Dercole, Fabio; Rienzo, Luca; Liberati, Diego; Mainardi, Luca; Ravazzani, Paolo; Rinaldi, Sergio; Signorini, Maria; Torricelli, Alessandro

    2011-01-01

    Generally, physiological modeling and biomedical signal processing constitute two important paradigms of biomedical engineering (BME): their fundamental concepts are taught starting from undergraduate studies and are more completely dealt with in the last years of graduate curricula, as well as in Ph.D. courses. Traditionally, these two cultural aspects were separated, with the first one more oriented to physiological issues and how to model them and the second one more dedicated to the development of processing tools or algorithms to enhance useful information from clinical data. A practical consequence was that those who did models did not do signal processing and vice versa. However, in recent years,the need for closer integration between signal processing and modeling of the relevant biological systems emerged very clearly [1], [2]. This is not only true for training purposes(i.e., to properly prepare the new professional members of BME) but also for the development of newly conceived research projects in which the integration between biomedical signal and image processing (BSIP) and modeling plays a crucial role. Just to give simple examples, topics such as brain–computer machine or interfaces,neuroengineering, nonlinear dynamical analysis of the cardiovascular (CV) system,integration of sensory-motor characteristics aimed at the building of advanced prostheses and rehabilitation tools, and wearable devices for vital sign monitoring and others do require an intelligent fusion of modeling and signal processing competences that are certainly peculiar of our discipline of BME.

  16. 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

  17. EGFR Signaling in Liver Diseases

    Directory of Open Access Journals (Sweden)

    Karin Komposch

    2015-12-01

    Full Text Available The epidermal growth factor receptor (EGFR is a transmembrane receptor tyrosine kinase that is activated by several ligands leading to the activation of diverse signaling pathways controlling mainly proliferation, differentiation, and survival. The EGFR signaling axis has been shown to play a key role during liver regeneration following acute and chronic liver damage, as well as in cirrhosis and hepatocellular carcinoma (HCC highlighting the importance of the EGFR in the development of liver diseases. Despite the frequent overexpression of EGFR in human HCC, clinical studies with EGFR inhibitors have so far shown only modest results. Interestingly, a recent study has shown that in human HCC and in mouse HCC models the EGFR is upregulated in liver macrophages where it plays a tumor-promoting function. Thus, the role of EGFR in liver diseases appears to be more complex than what anticipated. Further studies are needed to improve the molecular understanding of the cell-specific signaling pathways that control disease development and progression to be able to develop better therapies targeting major components of the EGFR signaling network in selected cell types. In this review, we compiled the current knowledge of EGFR signaling in different models of liver damage and diseases, mainly derived from the analysis of HCC cell lines and genetically engineered mouse models (GEMMs.

  18. Dialkylresorcinols as bacterial signaling molecules.

    Science.gov (United States)

    Brameyer, Sophie; Kresovic, Darko; Bode, Helge B; Heermann, Ralf

    2015-01-13

    It is well recognized that bacteria communicate via small diffusible molecules, a process termed quorum sensing. The best understood quorum sensing systems are those that use acylated homoserine lactones (AHLs) for communication. The prototype of those systems consists of a LuxI-like AHL synthase and a cognate LuxR receptor that detects the signal. However, many proteobacteria possess LuxR receptors, yet lack any LuxI-type synthase, and thus these receptors are referred to as LuxR orphans or solos. In addition to the well-known AHLs, little is known about the signaling molecules that are sensed by LuxR solos. Here, we describe a novel cell-cell communication system in the insect and human pathogen Photorhabdus asymbiotica. We identified the LuxR homolog PauR to sense dialkylresorcinols (DARs) and cyclohexanediones (CHDs) instead of AHLs as signals. The DarABC synthesis pathway produces the molecules, and the entire system emerged as important for virulence. Moreover, we have analyzed more than 90 different Photorhabdus strains by HPLC/MS and showed that these DARs and CHDs are specific to the human pathogen P. asymbiotica. On the basis of genomic evidence, 116 other bacterial species are putative DAR producers, among them many human pathogens. Therefore, we discuss the possibility of DARs as novel and widespread bacterial signaling molecules and show that bacterial cell-cell communication goes far beyond AHL signaling in nature.

  19. Optical time-lens signal processing

    DEFF Research Database (Denmark)

    Oxenløwe, Leif Katsuo; Galili, Michael; Mulvad, Hans Christian Hansen

    2014-01-01

    This paper describes the use of optical time lenses for optical signal processing of advanced optical data signals. Examples given include 1.28 Tbaud Nyquist channel serial-to-parallel conversion and spectral magnification of OFDM signals.......This paper describes the use of optical time lenses for optical signal processing of advanced optical data signals. Examples given include 1.28 Tbaud Nyquist channel serial-to-parallel conversion and spectral magnification of OFDM signals....

  20. Mathematical model for classification of EEG signals

    Science.gov (United States)

    Ortiz, Victor H.; Tapia, Juan J.

    2015-09-01

    A mathematical model to filter and classify brain signals from a brain machine interface is developed. The mathematical model classifies the signals from the different lobes of the brain to differentiate the signals: alpha, beta, gamma and theta, besides the signals from vision, speech, and orientation. The model to develop further eliminates noise signals that occur in the process of signal acquisition. This mathematical model can be used on different platforms interfaces for rehabilitation of physically handicapped persons.

  1. [Signaling network-based functional cell design].

    Science.gov (United States)

    Ju, Jianqi; Wei, Ping

    2017-03-25

    Cellular signaling networks act as the central processor to deal with environmental signals and regulate cell function, and determine cell fate. Using synthetic biology approach to engineer cell signaling networks is crucial for ultimately constructing man-made "cell machines". Cellular signaling networks can encode sophisticated cell information by processing quantitatively signaling dynamics, which enables multi-dimensional regulation of functional sub-circuits. Here, we first review the research progresses on the signaling coding mechanisms; and then elaborate the methodologies and applications of cells signaling engineering; finally, we envision that signaling-based cell engineering are important for the increasingly-complicated next generation synthetic biology.

  2. Cytokinin signaling during root development.

    Science.gov (United States)

    Bishopp, Anthony; Help, Hanna; Helariutta, Ykä

    2009-01-01

    The cytokinin class of phytohormones regulates division and differentiation of plant cells. They are perceived and signaled by a phosphorelay mechanism similar to those observed in prokaryotes. Research into the components of phosphorelay had previously been marred by genetic redundancy. However, recent studies have addressed this with the creation of high-order mutants. In addition, several new elements regulating cytokinin signaling have been identified. This has uncovered many roles in diverse developmental and physiological processes. In this review, we look at these processes specifically in the context of root development. We focus on the formation and maintenance of the root apical meristem, primary and secondary vascular development, lateral root emergence and development, and root nodulation. We believe that the root is an ideal organ with which to investigate cytokinin signaling in a wider context.

  3. 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.)

  4. The Dynamics of Costly Signaling

    Directory of Open Access Journals (Sweden)

    Elliott O. Wagner

    2013-04-01

    Full Text Available Costly signaling is a mechanism through which the honesty of signals can be secured in equilibrium, even in interactions where communicators have conflicting interests. This paper explores the dynamics of one such signaling game: Spence’s model of education. It is found that separating equilibria are unlikely to emerge under either the replicator or best response dynamics, but that partially communicative mixed equilibria are quite important dynamically. These mixtures are Lyapunov stable in the replicator dynamic and asymptotically stable in the best response dynamic. Moreover, they have large basins of attraction, in fact larger than those of either pooling or separating equilibria. This suggests that these mixtures may play significant, and underappreciated, roles in the explanation of the emergence and stability of information transfer.

  5. Ocean circulation generated magnetic signals

    DEFF Research Database (Denmark)

    Manoj, C.; Kuvshinov, A.; Maus, S.

    2006-01-01

    Conducting ocean water, as it flows through the Earth's magnetic field, generates secondary electric and magnetic fields. An assessment of the ocean-generated magnetic fields and their detectability may be of importance for geomagnetism and oceanography. Motivated by the clear identification...... of ocean tidal signatures in the CHAMP magnetic field data we estimate the ocean magnetic signals of steady flow using a global 3-D EM numerical solution. The required velocity data are from the ECCO ocean circulation experiment and alternatively from the OCCAM model for higher resolution. We assume...... of the magnetic field, as compared to the ECCO simulation. Besides the expected signatures of the global circulation patterns, we find significant seasonal variability of ocean magnetic signals in the Indian and Western Pacific Oceans. Compared to seasonal variation, interannual variations produce weaker signals....

  6. Notch Signaling and Brain Tumors

    DEFF Research Database (Denmark)

    Stockhausen, Marie; Kristoffersen, Karina; Poulsen, Hans Skovgaard

    2011-01-01

    Human brain tumors are a heterogenous group of neoplasms occurring inside the cranium and the central spinal cord. In adults and children, astrocytic glioma and medulloblastoma are the most common subtypes of primary brain tumors. These tumor types are thought to arise from cells in which Notch...... signaling plays a fundamental role during development. Recent findings have shown that Notch signaling is dysregulated, and contributes to the malignant potential of these tumors. Growing evidence point towards an important role for cancer stem cells in the initiation and maintenance of glioma...... and medulloblastoma. In this chapter we will cover the present findings of Notch signaling in human glioma and medulloblastoma and try to create an overall picture of its relevance in the pathogenesis of these tumors....

  7. Wavelets and multiscale signal processing

    CERN Document Server

    Cohen, Albert

    1995-01-01

    Since their appearance in mid-1980s, wavelets and, more generally, multiscale methods have become powerful tools in mathematical analysis and in applications to numerical analysis and signal processing. This book is based on "Ondelettes et Traitement Numerique du Signal" by Albert Cohen. It has been translated from French by Robert D. Ryan and extensively updated by both Cohen and Ryan. It studies the existing relations between filter banks and wavelet decompositions and shows how these relations can be exploited in the context of digital signal processing. Throughout, the book concentrates on the fundamentals. It begins with a chapter on the concept of multiresolution analysis, which contains complete proofs of the basic results. The description of filter banks that are related to wavelet bases is elaborated in both the orthogonal case (Chapter 2), and in the biorthogonal case (Chapter 4). The regularity of wavelets, how this is related to the properties of the filters and the importance of regularity for t...

  8. Hedgehog signaling in the stomach.

    Science.gov (United States)

    Konstantinou, Daniel; Bertaux-Skeirik, Nina; Zavros, Yana

    2016-12-01

    The Hedgehog (Hh) signaling pathway not only plays a key part in controlling embryonic development, but in the adult stomach governs important cellular events such as epithelial cell differentiation, proliferation, gastric disease, and regeneration. In particular, Sonic Hedgehog (Shh) signaling has been well studied for its role in gastric physiology and pathophysiology. Shh is secreted from the gastric parietal cells and contributes to the regeneration of the epithelium in response to injury, or the development of gastritis during Helicobacter pylori infection. Dysregulation of the Shh signaling pathway leads to the disruption of gastric differentiation, loss of gastric acid secretion and the development of cancer. In this chapter, we will review the most recent findings that reveal the role of Shh as a regulator of gastric physiology, regeneration, and disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Multichannel Coding of Applause Signals

    Directory of Open Access Journals (Sweden)

    Jeroen Breebaart

    2007-08-01

    Full Text Available We develop a parametric multichannel audio codec dedicated to coding signals consisting of a dense series of transient-type events. These signals of which applause is a typical example are known to be problematic for such audio codecs. The codec design is based on preservation of both timbre and transient-type event density. It combines a very low complexity and a low parameter bit rate (0.2 kbps. In a formal listening test, we compared the proposed codec to the recently standardised MPEG Surround multichannel codec, with an associated parameter bit rate of 9 kbps. We found the new codec to have a significantly higher audio quality than the MPEG Surround codec for the two multichannel applause signals under test. Though this seems promising, the technique presented is not fully mature, for example, because issues related to integration of the proposed codec in the MPEG Surround codec were not addressed.

  10. Multichannel Coding of Applause Signals

    Science.gov (United States)

    Hotho, Gerard; van de Par, Steven; Breebaart, Jeroen

    2007-12-01

    We develop a parametric multichannel audio codec dedicated to coding signals consisting of a dense series of transient-type events. These signals of which applause is a typical example are known to be problematic for such audio codecs. The codec design is based on preservation of both timbre and transient-type event density. It combines a very low complexity and a low parameter bit rate (0.2 kbps). In a formal listening test, we compared the proposed codec to the recently standardised MPEG Surround multichannel codec, with an associated parameter bit rate of 9 kbps. We found the new codec to have a significantly higher audio quality than the MPEG Surround codec for the two multichannel applause signals under test. Though this seems promising, the technique presented is not fully mature, for example, because issues related to integration of the proposed codec in the MPEG Surround codec were not addressed.

  11. Humanin signal for Alzheimer's disease.

    Science.gov (United States)

    Matsuoka, Masaaki

    2011-01-01

    Despite a bulk of evidence supporting the idea that increased neurotoxic insults lead to Alzheimer's disease (AD), the possibility still remains that insufficiency of an endogenous defense system contributes to the disease progression. Humanin is a bioactive peptide that is likely to inhibit both neuronal death and dysfunction only related to AD by binding to a Humanin receptor on the cell-surface and by activating a STAT3-mediated signal, preventing the onset of dementia. A couple of recent studies presented evidence suggesting that the Humanin signal is decreased in neurons of AD patients. If this is the case, the restoration or activation of the Humanin signal in neurons may change the course of AD.

  12. Signals, systems, transforms, and digital signal processing with Matlab

    CERN Document Server

    Corinthios, Michael

    2009-01-01

    Continuous-Time and Discrete-Time Signals and SystemsIntroductionContinuous-Time SignalsPeriodic FunctionsUnit Step FunctionGraphical Representation of FunctionsEven and Odd Parts of a FunctionDirac-Delta ImpulseBasic Properties of the Dirac-Delta ImpulseOther Important Properties of the ImpulseContinuous-Time SystemsCausality, StabilityExamples of Electrical Continuous-Time SystemsMechanical SystemsTransfer Function and Frequency ResponseConvolution and CorrelationA Right-Sided and a Left-Sided FunctionConvolution with an Impulse and Its DerivativesAdditional Convolution PropertiesCorrelation FunctionProperties of the Correlation FunctionGraphical InterpretationCorrelation of Periodic FunctionsAverage, Energy and Power of Continuous-Time SignalsDiscrete-Time SignalsPeriodicityDifference EquationsEven/Odd DecompositionAverage Value, Energy and Power SequencesCausality, StabilityProblemsAnswers to Selected ProblemsFourier Series ExpansionTrigonometric Fourier SeriesExponential Fourier SeriesExponential versus ...

  13. DMPD: Signal integration between IFNgamma and TLR signalling pathways in macrophages. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 16920490 Signal integration between IFNgamma and TLR signalling pathways in macroph...tml) (.csml) Show Signal integration between IFNgamma and TLR signalling pathways in macrophages. PubmedID 1...6920490 Title Signal integration between IFNgamma and TLR signalling pathways in

  14. "Immunocytochemical expression of P53, PTEN, FAS (CD95), P16INK4A and HPV L1 major capsid proteins in ThinPrep cervical samples with squamous intraepithelial lesions".

    Science.gov (United States)

    Grapsa, D; Frangou-Plemenou, M; Kondi-Pafiti, A; Stergiou, E; Nicolopoulou-Stamati, P; Patsouris, E; Chelidonis, G; Athanassiadou, P

    2014-06-01

    The aim of this study was to further investigate the immunocytochemical expression of p53, PTEN, Fas, p16, and HPV L1 capsid proteins in cervical smears with low and high grade squamous intraepithelial lesions (LSIL and HSIL, respectively). A total of 92 ThinPrep cervical samples, comprising 11 cases of HSIL, 61 cases of LSIL, and 20 negative cases were studied by immunocytochemical methods. The results obtained in LSIL cases were correlated with the available follow up data. Abnormal p53, PTEN, or Fas expression was found in a subset of HSIL cases, while positive expression for p16 was significantly associated with the diagnosis of HSIL (P 0.05). Our results suggest that loss of PTEN or Fas expression and p53 overexpression may be involved in the process of neoplastic transformation of the cervical epithelium. Furthermore, negative or weak immunocytochemical staining for p16 in a Pap smear may strongly argue against the presence of a high grade lesion, while the combined p16/L1 staining pattern may be useful as a diagnostic adjunct for differentiating between LSIL and HSIL. Copyright © 2013 Wiley Periodicals, Inc.

  15. Signal processing for cognitive radios

    CERN Document Server

    Jayaweera, Sudharman K

    2014-01-01

    This book covers power electronics, in depth, by presenting the basic principles and application details, and it can be used both as a textbook and reference book.  Introduces the specific type of CR that has gained the most research attention in recent years: the CR for Dynamic Spectrum Access (DSA). Provides signal processing solutions to each task by relating the tasks to materials covered in Part II. Specialized chapters then discuss specific signal processing algorithms required for DSA and DSS cognitive radios  

  16. PSpice for digital signal processing

    CERN Document Server

    Tobin, Paul

    2007-01-01

    PSpice for Digital Signal Processing is the last in a series of five books using Cadence Orcad PSpice version 10.5 and introduces a very novel approach to learning digital signal processing (DSP). DSP is traditionally taught using Matlab/Simulink software but has some inherent weaknesses for students particularly at the introductory level. The 'plug in variables and play' nature of these software packages can lure the student into thinking they possess an understanding they don't actually have because these systems produce results quicklywithout revealing what is going on. However, it must be

  17. Genomic Signals of Reoriented ORFs

    Directory of Open Access Journals (Sweden)

    Paul Dan Cristea

    2004-01-01

    Full Text Available Complex representation of nucleotides is used to convert DNA sequences into complex digital genomic signals. The analysis of the cumulated phase and unwrapped phase of DNA genomic signals reveals large-scale features of eukaryote and prokaryote chromosomes that result from statistical regularities of base and base-pair distributions along DNA strands. By reorienting the chromosome coding regions, a “hidden” linear variation of the cumulated phase has been revealed, along with the conspicuous almost linear variation of the unwrapped phase. A model of chromosome longitudinal structure is inferred on these bases.

  18. Signal processing for remote sensing

    CERN Document Server

    Chen, CH

    2007-01-01

    Written by leaders in the field, Signal Processing for Remote Sensing explores the data acquisitions segment of remote sensing. Each chapter presents a major research result or the most up to date development of a topic. The book includes a chapter by Dr. Norden Huang, inventor of the Huang-Hilbert transform who, along with and Dr. Steven Long discusses the application of the transform to remote sensing problems. It also contains a chapter by Dr. Enders A. Robinson, who has made major contributions to seismic signal processing for over half a century, on the basic problem of constructing seism

  19. Digital signal processing for NDT

    International Nuclear Information System (INIS)

    Georgel, B.

    1994-01-01

    NDT begins to adapt and use the most recent developments of digital signal and image processing. We briefly sum up the main characteristics of NDT situations (particularly noise and inverse problem formulation) and comment on techniques already used or just emerging (SAFT, split spectrum, adaptive learning network, noise reference filtering, stochastic models, neural networks). This survey is focused on ultrasonics, eddy currents and X-ray radiography. The final objective of end users (availability of automatic diagnosis systems) cannot be achieved only by signal processing algorithms. A close cooperation with other techniques such as artificial intelligence has therefore to be implemented. (author). 20 refs

  20. Multichannel Coding of Applause Signals

    OpenAIRE

    Jeroen Breebaart; Steven van de Par; Gerard Hotho

    2007-01-01

    We develop a parametric multichannel audio codec dedicated to coding signals consisting of a dense series of transient-type events. These signals of which applause is a typical example are known to be problematic for such audio codecs. The codec design is based on preservation of both timbre and transient-type event density. It combines a very low complexity and a low parameter bit rate (0.2 kbps). In a formal listening test, we compared the proposed codec to the recently standardised MPEG Su...

  1. Notch Signaling and Brain Tumors

    DEFF Research Database (Denmark)

    Stockhausen, Marie; Kristoffersen, Karina; Poulsen, Hans Skovgaard

    2011-01-01

    Human brain tumors are a heterogenous group of neoplasms occurring inside the cranium and the central spinal cord. In adults and children, astrocytic glioma and medulloblastoma are the most common subtypes of primary brain tumors. These tumor types are thought to arise from cells in which Notch...... signaling plays a fundamental role during development. Recent findings have shown that Notch signaling is dysregulated, and contributes to the malignant potential of these tumors. Growing evidence point towards an important role for cancer stem cells in the initiation and maintenance of glioma...

  2. The Pseudomonas Quinolone Signal (PQS)

    DEFF Research Database (Denmark)

    Sams, Thomas; Baker, Ysobel; Hodgkinson, James

    2015-01-01

    Pseudomonas aeruginosa is an opportunistichuman pathogen that routinely appears near the top ofpublic health threat lists worldwide. P. aeruginosa causes in-fections by secreting a wealth of exceptionally active exo-products, leading to tissue damage. The synthesis of manyof these virulence factors...... is now known to be under the con-trol of the quorum sensing (QS) system. Over the last15 years, the Pseudomonas quinolone signal (PQS) has beenfound to play a crucial role in QS by linking the two seg-ments (las and rhl) of the P. aeruginosa N-acylhomoserinelactone-dependent QS signaling pathways. Herein...

  3. Chaotic signals in digital communications

    CERN Document Server

    Eisencraft, Marcio; Suyama, Ricardo

    2013-01-01

    Chaotic Signals in Digital Communications combines fundamental background knowledge with state-of-the-art methods for using chaotic signals and systems in digital communications. The book builds a bridge between theoretical works and practical implementation to help researchers attain consistent performance in realistic environments. It shows the possible shortcomings of the chaos-based communication systems proposed in the literature, particularly when they are subjected to non-ideal conditions. It also presents a toolbox of techniques for researchers working to actually implement such system

  4. Signal recovery in imaging photoplethysmography

    International Nuclear Information System (INIS)

    Holton, Benjamin D; Mannapperuma, Kavan; Lesniewski, Peter J; Thomas, John C

    2013-01-01

    Imaging photoplethysmography is an emerging technique for the extraction of biometric information from people using video recordings. The focus is on extracting the cardiac heart rate of the subject by analysing the luminance of the colour video signal and identifying periodic components. Advanced signal processing is needed to recover the information required. In this paper, independent component analysis (ICA), principal component analysis, auto- and cross-correlation are investigated and compared with respect to their effectiveness in extracting the relevant information from video recordings. Results obtained are compared with those recorded by a modern commercial finger pulse oximeter. It is found that ICA produces the most consistent results. (paper)

  5. Signal recovery in imaging photoplethysmography.

    Science.gov (United States)

    Holton, Benjamin D; Mannapperuma, Kavan; Lesniewski, Peter J; Thomas, John C

    2013-11-01

    Imaging photoplethysmography is an emerging technique for the extraction of biometric information from people using video recordings. The focus is on extracting the cardiac heart rate of the subject by analysing the luminance of the colour video signal and identifying periodic components. Advanced signal processing is needed to recover the information required. In this paper, independent component analysis (ICA), principal component analysis, auto- and cross-correlation are investigated and compared with respect to their effectiveness in extracting the relevant information from video recordings. Results obtained are compared with those recorded by a modern commercial finger pulse oximeter. It is found that ICA produces the most consistent results.

  6. Subgraph detection using graph signals

    KAUST Repository

    Chepuri, Sundeep Prabhakar

    2017-03-06

    In this paper we develop statistical detection theory for graph signals. In particular, given two graphs, namely, a background graph that represents an usual activity and an alternative graph that represents some unusual activity, we are interested in answering the following question: To which of the two graphs does the observed graph signal fit the best? To begin with, we assume both the graphs are known, and derive an optimal Neyman-Pearson detector. Next, we derive a suboptimal detector for the case when the alternative graph is not known. The developed theory is illustrated with numerical experiments.

  7. Signal processing systems for nuclear reactor

    International Nuclear Information System (INIS)

    Hirano, Kazuo.

    1981-01-01

    Purpose: To carry out the works signal processing, in a nuclear power plant, automatically. Constitution: Neutron flux signal from reactor instruments is inputted into a reactivity meter, and processes in accordance with reactor characteristic equations and, as the result, outputted as a reactivity signal rho. The signal rho, as well as the neutron flux signal and temperature signal are inputted together to a pen recorder and recorded on a record chart. While on the other hand, these signals are inputted into a signal processor, together with a range-switching signal from the reactivity meter and with a control-rod-position signal n from other instrument. In the signal processor, the differentiation and integration values such as Δrho/(n 1 -n 2 ) and ΣΔrho of the control element are conducted automatically. The results are indicated on a graphic display. (J.P.N.)

  8. HIF-1α signaling activation by post-ischemia treatment with astragaloside IV attenuates myocardial ischemia-reperfusion injury.

    Directory of Open Access Journals (Sweden)

    Jingwen Si

    Full Text Available In this study, we evaluated the effect of astragaloside IV (Ast IV post-ischemia treatment on myocardial ischemia-reperfusion (IR injury (IRI. We also examined whether hypoxia inducible factor-1α (HIF-1α and its downstream gene-inducible nitric oxide (NO synthase (iNOS play roles in the cardioprotective effect of Ast IV. Cultured cardiomyocytes and perfused isolated rat hearts were exposed to Ast IV during reperfusion in the presence or absence of the HIF-1α inhibitor 2-methoxyestradiol (2-MeOE2. The post-ischemia treatment with Ast IV protected cardiomyocytes from the apoptosis and death induced by simulated IRI (SIRI. Additionally, in cardiomyocytes, 2-MeOE2 and HIF-1α siRNA treatment each not only abolished the anti-apoptotic effect of post-ischemia treatment with Ast IV but also reversed the upregulation of HIF-1α and iNOS expression. Furthermore, after treatment with Ast IV, post-ischemic cardiac functional recovery and lactate dehydrogenase (LDH release in the coronary flow (CF were improved, and the myocardial infarct size was decreased. Moreover, the number of apoptotic cells was reduced, and the upregulation of the anti-apoptotic protein Bcl2 and downregulation of the pro-apoptotic protein Caspase3 were reversed. 2-MeOE2 reversed these effects of Ast IV on IR-injured hearts. These results suggest that post-ischemia treatment with Ast IV can attenuate IRI by upregulating HIF-1α expression, which transmits a survival signal to the myocardium.

  9. Cell death patterns in Arabidopsis cells subjected to four physiological stressors indicate multiple signalling pathways and cell cycle phase specificity.

    Science.gov (United States)

    Pathirana, Ranjith; West, Phillip; Hedderley, Duncan; Eason, Jocelyn

    2017-03-01

    Corpse morphology, nuclear DNA fragmentation, expression of senescence-associated genes (SAG) and cysteine protease profiles were investigated to understand cell death patterns in a cell cycle-synchronised Arabidopsis thaliana cell suspension culture treated with four physiological stressors in the late G2 phase. Within 4 h of treatment, polyethylene glycol (PEG, 20 %), mannose (100 mM) and hydrogen peroxide (2 mM) caused DNA fragmentation coinciding with cell permeability to Evans Blue (EB) and produced corpse morphology corresponding to apoptosis-like programmed cell death (AL-PCD) with cytoplasmic retraction from the cell wall. Ethylene (8 mL per 250-mL flask) caused permeability of cells to EB without concomitant nuclear DNA fragmentation and cytoplasmic retraction, suggesting necrotic cell death. Mannose inducing glycolysis block and PEG causing dehydration resulted in relatively similar patterns of upregulation of SAG suggesting similar cell death signalling pathways for these two stress factors, whereas hydrogen peroxide caused unique patterns indicating an alternate pathway for cell death induced by oxidative stress. Ethylene did not cause appreciable changes in SAG expression, confirming necrotic cell death. Expression of AtDAD, BoMT1 and AtSAG2 genes, previously shown to be associated with plant senescence, also changed rapidly during AL-PCD in cultured cells. The profiles of nine distinct cysteine protease-active bands ranging in size from ca. 21.5 to 38.5 kDa found in the control cultures were also altered after treatment with the four stressors, with mannose and PEG again producing similar patterns. Results also suggest that cysteine proteases may have a role in necrotic cell death.

  10. Sub-lethal irradiation of human colorectal tumor cells imparts enhanced and sustained susceptibility to multiple death receptor signaling pathways.

    Directory of Open Access Journals (Sweden)

    Victoria Ifeadi

    Full Text Available BACKGROUND: Death receptors (DR of the TNF family function as anti-tumor immune effector molecules. Tumor cells, however, often exhibit DR-signaling resistance. Previous studies indicate that radiation can modify gene expression within tumor cells and increase tumor cell sensitivity to immune attack. The aim of this study is to investigate the synergistic effect of sub-lethal doses of ionizing radiation in sensitizing colorectal carcinoma cells to death receptor-mediated apoptosis. METHODOLOGY/PRINCIPAL FINDINGS: The ability of radiation to modulate the expression of multiple death receptors (Fas/CD95, TRAILR1/DR4, TRAILR2/DR5, TNF-R1 and LTβR was examined in colorectal tumor cells. The functional significance of sub-lethal doses of radiation in enhancing tumor cell susceptibility to DR-induced apoptosis was determined by in vitro functional sensitivity assays. The longevity of these changes and the underlying molecular mechanism of irradiation in sensitizing diverse colorectal carcinoma cells to death receptor-mediated apoptosis were also examined. We found that radiation increased surface expression of Fas, DR4 and DR5 but not LTβR or TNF-R1 in these cells. Increased expression of DRs was observed 2 days post-irradiation and remained elevated 7-days post irradiation. Sub-lethal tumor cell irradiation alone exhibited minimal cell death, but effectively sensitized three of three colorectal carcinoma cells to both TRAIL and Fas-induced apoptosis, but not LTβR-induced death. Furthermore, radiation-enhanced Fas and TRAIL-induced cell death lasted as long as 5-days post-irradiation. Specific analysis of intracellular sensitizers to apoptosis indicated that while radiation did reduce Bcl-X(L and c-FLIP protein expression, this reduction did not correlate with the radiation-enhanced sensitivity to Fas and/or TRAIL mediated apoptosis among the three cell types. CONCLUSIONS/SIGNIFICANCE: Irradiation of tumor cells can overcome Fas and TRAIL

  11. Error signals driving locomotor adaptation

    DEFF Research Database (Denmark)

    Choi, Julia T; Jensen, Peter; Nielsen, Jens Bo

    2016-01-01

    anaesthesia (n = 5) instead of repetitive nerve stimulation. Foot anaesthesia reduced ankle adaptation to external force perturbations during walking. Our results suggest that cutaneous input plays a role in force perception, and may contribute to the 'error' signal involved in driving walking adaptation when...

  12. Syndecans, signaling, and cell adhesion

    DEFF Research Database (Denmark)

    Couchman, J R; Woods, A

    1996-01-01

    structures within the heparan sulfate chains, leaving the roles of chondroitin sulfate chains and extracellular portion of the core proteins to be elucidated. Evidence that syndecans are a class of receptor involved in cell adhesion is mounting, and their small cytoplasmic domains may link...... transmembrane signaling from matrix to cytoskeleton, as proposed for other classes of adhesion receptors....

  13. VLSI mixed signal processing system

    Science.gov (United States)

    Alvarez, A.; Premkumar, A. B.

    1993-01-01

    An economical and efficient VLSI implementation of a mixed signal processing system (MSP) is presented in this paper. The MSP concept is investigated and the functional blocks of the proposed MSP are described. The requirements of each of the blocks are discussed in detail. A sample application using active acoustic cancellation technique is described to demonstrate the power of the MSP approach.

  14. Mathematical Modelling Plant Signalling Networks

    KAUST Repository

    Muraro, D.

    2013-01-01

    During the last two decades, molecular genetic studies and the completion of the sequencing of the Arabidopsis thaliana genome have increased knowledge of hormonal regulation in plants. These signal transduction pathways act in concert through gene regulatory and signalling networks whose main components have begun to be elucidated. Our understanding of the resulting cellular processes is hindered by the complex, and sometimes counter-intuitive, dynamics of the networks, which may be interconnected through feedback controls and cross-regulation. Mathematical modelling provides a valuable tool to investigate such dynamics and to perform in silico experiments that may not be easily carried out in a laboratory. In this article, we firstly review general methods for modelling gene and signalling networks and their application in plants. We then describe specific models of hormonal perception and cross-talk in plants. This mathematical analysis of sub-cellular molecular mechanisms paves the way for more comprehensive modelling studies of hormonal transport and signalling in a multi-scale setting. © EDP Sciences, 2013.

  15. Noisy signaling: theory and experiment

    NARCIS (Netherlands)

    de Haan, T.; Offerman, T.; Sloof, R.

    2009-01-01

    We investigate a noisy signaling game, in which nature adds random noise to the message chosen. Theoretically, with an unfavorable prior the separating equilibrium vanishes for low noise. It reappears for intermediate and high noise, where messages increase with noise. A pooling equilibrium always

  16. Syndecans, signaling, and cell adhesion

    DEFF Research Database (Denmark)

    Couchman, J R; Woods, A

    1996-01-01

    with the microfilament cytoskeleton, thereby mediating signaling events. The molecular details are unknown, but the conservation of regions of syndecan cytoplasmic domains, and a strong tendency for homotypic association, support the idea that the ligand-induced clustering may be a discrete source of specific...

  17. Text Signals Influence Team Artifacts

    Science.gov (United States)

    Clariana, Roy B.; Rysavy, Monica D.; Taricani, Ellen

    2015-01-01

    This exploratory quasi-experimental investigation describes the influence of text signals on team visual map artifacts. In two course sections, four-member teams were given one of two print-based text passage versions on the course-related topic "Social influence in groups" downloaded from Wikipedia; this text had two paragraphs, each…

  18. Maternal health Indicators Signal Optimism

    African Journals Online (AJOL)

    user

    Maternal health Indicators Signal Optimism. Abraham Haileamlak, MD, Professor of Pediatrics and Child Health. Maternal health is a major health priority for international agencies and the Ethiopian. Government. Many low income countries including. Ethiopia, made substantial improvements in maternal health achieving ...

  19. Biophysical Aspects of Transmembrane Signaling

    CERN Document Server

    Damjanovich, Sandor

    2005-01-01

    Transmembrane signaling is one of the most significant cell biological events in the life and death of cells in general and lymphocytes in particular. Until recently biochemists and biophysicists were not accustomed to thinking of these processes from the side of a high number of complex biochemical events and an equally high number of physical changes at molecular and cellular levels at the same time. Both types of researchers were convinced that their findings are the most decisive, having higher importance than the findings of the other scientist population. Both casts were wrong. Life, even at cellular level, has a number of interacting physical and biochemical mechanisms, which finally build up the creation of an "excited" cell that will respond to particular signals from the outer or inner world. This book handles both aspects of the signalling events, and in some cases tries to unify our concepts and help understand the signals that govern the life and death of our cells. Not only the understanding, bu...

  20. Handbook of signal processing systems

    CERN Document Server

    Bhattacharyya, Shuvra S; Leupers, Rainer; Takala, Jarmo

    2010-01-01

    The Handbook is organized in four parts. The first part motivates representative applications that drive and apply state-of-the art methods for design and implementation of signal processing systems; the second part discusses architectures for implementing these applications; the third part focuses on compilers and simulation tools; and the fourth part describes models of computation and their associated design tools and methodologies.

  1. On statistical significance of signal

    International Nuclear Information System (INIS)

    Zhu Yongsheng

    2006-01-01

    A definition for the statistical significance of a signal in an experiment is proposed by establishing a correlation between the observed p-value and the normal distribution integral probability, which is suitable for both counting experiment and continuous test statistics. The explicit expressions to calculate the statistical significance for both cases are given. (author)

  2. Insulin Signalling: The Inside Story.

    Science.gov (United States)

    Posner, Barry I

    2017-02-01

    Insulin signalling begins with binding to its cell surface insulin receptor (IR), which is a tyrosine kinase. The insulin receptor kinase (IRK) is subsequently autophosphorylated and activated to tyrosine phosphorylate key cellular substrates that are essential for entraining the insulin response. Although IRK activation begins at the cell surface, it is maintained and augmented following internalization into the endosomal system (ENS). The peroxovanadium compounds (pVs) were discovered to activate the IRK in the absence of insulin and lead to a full insulin response. Thus, IRK activation is both necessary and sufficient for insulin signalling. Furthermore, this could be shown to occur with activation of only the endosomal IRK. The mechanism of pV action was shown to be the inhibition of IRK-associated phosphotyrosine phosphatases (PTPs). Our studies showed that the duration and intensity of insulin signalling are modulated within ENS by the recruitment of cellular substrates to ENS; intra-endosomal acidification, which promotes dissociation of insulin from the IRK; an endosomal acidic insulinase, which degrades intra-endosomal insulin; and IRK-associated PTPs, which dephosphorylate and, hence, deactivate the IRK. Therefore, the internalization of IRKs is central to insulin signalling and its regulation. Copyright © 2016 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.

  3. VEGF Signaling in Neurological Disorders

    Directory of Open Access Journals (Sweden)

    Joon W. Shim

    2018-01-01

    Full Text Available Vascular endothelial growth factor (VEGF is a potent growth factor playing diverse roles in vasculogenesis and angiogenesis. In the brain, VEGF mediates angiogenesis, neural migration and neuroprotection. As a permeability factor, excessive VEGF disrupts intracellular barriers, increases leakage of the choroid plexus endothelia, evokes edema, and activates the inflammatory pathway. Recently, we discovered that a heparin binding epidermal growth factor like growth factor (HB-EGF—a class of EGF receptor (EGFR family ligands—contributes to the development of hydrocephalus with subarachnoid hemorrhage through activation of VEGF signaling. The objective of this review is to entail a recent update on causes of death due to neurological disorders involving cerebrovascular and age-related neurological conditions and to understand the mechanism by which angiogenesis-dependent pathological events can be treated with VEGF antagonisms. The Global Burden of Disease study indicates that cancer and cardiovascular disease including ischemic and hemorrhagic stroke are two leading causes of death worldwide. The literature suggests that VEGF signaling in ischemic brains highlights the importance of concentration, timing, and alternate route of modulating VEGF signaling pathway. Molecular targets distinguishing two distinct pathways of VEGF signaling may provide novel therapies for the treatment of neurological disorders and for maintaining lower mortality due to these conditions.

  4. Systems theory of Smad signalling.

    Science.gov (United States)

    Clarke, D C; Betterton, M D; Liu, X

    2006-11-01

    Transforming growth factor-beta (TGFbeta) signalling is an important regulator of cellular growth and differentiation. The principal intracellular mediators of TGFbeta signalling are the Smad proteins, which upon TGFbeta stimulation accumulate in the nucleus and regulate the transcription of target genes. To investigate the mechanisms of Smad nuclear accumulation, we developed a simple mathematical model of canonical Smad signalling. The model was built using both published data and our experimentally determined cellular Smad concentrations (isoforms 2, 3 and 4). We found in mink lung epithelial cells that Smad2 (8.5-12 x 10(4) molecules cell(-1)) was present in similar amounts to Smad4 (9.3-12 x 10(4) molecules cell(-1)), whereas both were in excess of Smad3 (1.1-2.0 x 10(4) molecules cell(-1)). Variation of the model parameters and statistical analysis showed that Smad nuclear accumulation is most sensitive to parameters affecting the rates of R-Smad phosphorylation and dephosphorylation and Smad complex formation/ dissociation in the nucleus. Deleting Smad4 from the model revealed that rate-limiting phospho-R-Smad dephosphorylation could be an important mechanism for Smad nuclear accumulation. Furthermore, we observed that binding factors constitutively localised to the nucleus do not efficiently mediate Smad nuclear accumulation, if dephosphorylation is rapid. We therefore conclude that an imbalance in the rates of R-Smad phosphorylation and dephosphorylation is likely an important mechanism of Smad nuclear accumulation during TGFbeta signalling.

  5. A Serpentine Way to Signaling

    Indian Academy of Sciences (India)

    IAS Admin

    coding genome. This article will take you through the years of discovery, experimentation and characterization of the structure and molecular mechanisms of GPCR signaling and how this discovery impacts a vast area of research in health and medicine. History: John Langley, Paul Ehrlich and the birth of the receptor theory.

  6. Robust power detector for wideband signals among many single tone signals

    Energy Technology Data Exchange (ETDEWEB)

    Musgrove, Cameron H.; Thompson, Douglas

    2018-03-06

    Various technologies for isolating a signal of interest from signals received contemporaneously by an antenna are described herein. A time period for which a signal of interest is present in a second signal can be identified based upon ratios of values of the second signal to the mean value of the second signal. When the ratio of the value of the second signal at a particular time to the mean of the second signal exceeds a threshold value, the signal of interest is considered to be present in the second signal.

  7. BPSK Demodulation Using Digital Signal Processing

    Science.gov (United States)

    Garcia, Thomas R.

    1996-01-01

    A digital communications signal is a sinusoidal waveform that is modified by a binary (digital) information signal. The sinusoidal waveform is called the carrier. The carrier may be modified in amplitude, frequency, phase, or a combination of these. In this project a binary phase shift keyed (BPSK) signal is the communication signal. In a BPSK signal the phase of the carrier is set to one of two states, 180 degrees apart, by a binary (i.e., 1 or 0) information signal. A digital signal is a sampled version of a "real world" time continuous signal. The digital signal is generated by sampling the continuous signal at discrete points in time. The rate at which the signal is sampled is called the sampling rate (f(s)). The device that performs this operation is called an analog-to-digital (A/D) converter or a digitizer. The digital signal is composed of the sequence of individual values of the sampled BPSK signal. Digital signal processing (DSP) is the modification of the digital signal by mathematical operations. A device that performs this processing is called a digital signal processor. After processing, the digital signal may then be converted back to an analog signal using a digital-to-analog (D/A) converter. The goal of this project is to develop a system that will recover the digital information from a BPSK signal using DSP techniques. The project is broken down into the following steps: (1) Development of the algorithms required to demodulate the BPSK signal; (2) Simulation of the system; and (3) Implementation a BPSK receiver using digital signal processing hardware.

  8. Signaling Molecules and Pulp Regeneration.

    Science.gov (United States)

    Schmalz, Gottfried; Widbiller, Matthias; Galler, Kerstin M

    2017-09-01

    Signaling molecules play an essential role in tissue engineering because they regulate regenerative processes. Evidence exists from animal studies that single molecules such as members of the transforming growth factor beta superfamily and factors that induce the growth of blood vessels (vascular endothelial growth factor), nerves (brain-derived neurotrophic factor), or fibroblasts (fibroblast growth factor) may induce reparative dentin formation. Mainly the formation of atubular dentin (osteodentin) has been described after the application of single molecules or combinations of recombinant growth factors on healthy exposed pulps or in pulp regeneration. Generally, such preparations have not received regulatory approval on the market so far. Only the use of granulocyte colony-stimulating factors together with cell transplantation is presently tested clinically. Besides approaches with only 1 or few combined molecules, the exploitation of tissue-derived growth factors depicts a third promising way in dental pulp tissue engineering. Preparations such as platelet-rich plasma or platelet-rich fibrin provide a multitude of endogenous signaling molecules, and special regulatory approval for the market does not seem necessary. Furthermore, dentin is a perfect reservoir of signaling molecules that can be mobilized by treatment with demineralizing agents such as EDTA. This conditions the dentin surface and allows for contact differentiation of pulp stem cells into odontoblastlike cells, protects dentin from resorption, and enhances cell growth as well as attachment to dentin. By ultrasonic activation, signaling molecules can be further released from EDTA pretreated dentin into saline, thus avoiding cytotoxic EDTA in the final preparation. The use of dentin-derived growth factors offers a number of advantages because they are locally available and presumably are most fit to induce signaling processes in dental pulp. However, better characterization and standardization of the

  9. 33 CFR 62.47 - Sound signals.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Sound signals. 62.47 Section 62... UNITED STATES AIDS TO NAVIGATION SYSTEM The U.S. Aids to Navigation System § 62.47 Sound signals. (a) Often sound signals are located on or adjacent to aids to navigation. When visual signals are obscured...

  10. Predicting Secretory Proteins with SignalP

    DEFF Research Database (Denmark)

    Nielsen, Henrik

    2017-01-01

    SignalP is the currently most widely used program for prediction of signal peptides from amino acid sequences. Proteins with signal peptides are targeted to the secretory pathway, but are not necessarily secreted. After a brief introduction to the biology of signal peptides and the history...

  11. Empirical mode decomposition for analyzing acoustical signals

    Science.gov (United States)

    Huang, Norden E. (Inventor)

    2005-01-01

    The present invention discloses a computer implemented signal analysis method through the Hilbert-Huang Transformation (HHT) for analyzing acoustical signals, which are assumed to be nonlinear and nonstationary. The Empirical Decomposition Method (EMD) and the Hilbert Spectral Analysis (HSA) are used to obtain the HHT. Essentially, the acoustical signal will be decomposed into the Intrinsic Mode Function Components (IMFs). Once the invention decomposes the acoustic signal into its constituting components, all operations such as analyzing, identifying, and removing unwanted signals can be performed on these components. Upon transforming the IMFs into Hilbert spectrum, the acoustical signal may be compared with other acoustical signals.

  12. 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.

  13. Alternatives to Pyrotechnic Distress Signals; Additional Signal Evaluation

    Science.gov (United States)

    2017-06-01

    stars ” include 3 LEDs pre-soldered to a small aluminum based circuit board/heat sink. For each color, RDC installed 2 stars , yielding six, series...connected LEDS. The Red-Orange color, with a lower maximum current rating required 4 LED stars to achieve the desired luminosity. Figure 5. Signal...Behavioral Sciences: New York, MCGraw- Hill . Young R., Dye D., Brunsman-Johnson C., Locklear C., Amerson T., Lewandowski M., Reubelt V., Rothblum A

  14. SignalPlant: an open signal processing software platform

    Czech Academy of Sciences Publication Activity Database

    Plešinger, Filip; Jurčo, Juraj; Halámek, Josef; Jurák, Pavel

    2016-01-01

    Roč. 37, č. 7 (2016), N38-N48 ISSN 0967-3334 R&D Projects: GA ČR GAP103/11/0933; GA MŠk(CZ) LO1212; GA ČR GAP102/12/2034 Institutional support: RVO:68081731 Keywords : data visualization * software * signal processing * ECG * EEG Subject RIV: FS - Medical Facilities ; Equipment Impact factor: 2.058, year: 2016

  15. Subversion of cell signaling by pathogens.

    Science.gov (United States)

    Alto, Neal M; Orth, Kim

    2012-09-01

    Pathogens exploit several eukaryotic signaling pathways during an infection. They have evolved specific effectors and toxins to hijack host cell machinery for their own benefit. Signaling molecules are preferentially targeted by pathogens because they globally regulate many cellular processes. Both viruses and bacteria manipulate and control pathways that regulate host cell survival and shape, including MAPK signaling, G-protein signaling, signals controlling cytoskeletal dynamics, and innate immune responses.

  16. Signal-to-Signal Ratio Independent Speaker Identification for Co-channel Speech Signals

    DEFF Research Database (Denmark)

    Saeidi, Rahim; Mowlaee, Pejman; Kinnunen, Tomi

    2010-01-01

    In this paper, we consider speaker identification for the co-channel scenario in which speech mixture from speakers is recorded by one microphone only. The goal is to identify both of the speakers from their mixed signal. High recognition accuracies have already been reported when an accurately...

  17. The interplay between biological and physical scenarios of bacterial death induced by non-thermal plasma

    Czech Academy of Sciences Publication Activity Database

    Lunov, O.; Zablotskyy, V.; Churpita, O.; Jäger, A.; Polívka, L.; Syková, Eva; Dejneka, A.; Kubinová, Šárka

    2016-01-01

    Roč. 82, mar. (2016), s. 71-83 ISSN 0142-9612 R&D Projects: GA MŠk(CZ) LO1309 Institutional support: RVO:68378041 Keywords : non-thermal plasma * bacteria * cytotoxicity Subject RIV: FP - Other Medical Disciplines Impact factor: 8.402, year: 2016

  18. Necrotic and apoptotic cell death induced by Captan on Saccharomyces cerevisiae.

    Science.gov (United States)

    Scariot, Fernando J; Jahn, Luciane; Delamare, Ana Paula L; Echeverrigaray, Sergio

    2017-08-01

    Captan is one of the most widely used broad-spectrum fungicide applied to control several early and late diseases of grapes, apples, and other fruits and vegetables, and as other phthalimide fungicides is defined as a multisite compound with thiol-reactivity. Captan can affect non-target organisms as yeasts, modifying microbial populations and fermentation processes. In this study, we asked whether Captan thiol-reactivity and other mechanisms are involved in acute Captan-induced cell death on aerobic growing Saccharomyces cerevisiae. Thus for, we analyze cellular protein and non-protein thiols, cell membrane integrity, reactive oxygen species accumulation, phosphatidylserine externalization, and apoptotic mutants behavior. The results showed that when submitted to acute Captan treatment most cells lost their membrane integrity and died by necrosis due to Captan reaction with thiols. However, part of the cells, even maintaining their membrane integrity, lost their culture ability. These cells showed an apoptotic behavior that may be the result of non-protein thiol depletion and consequent increase of reactive oxygen species (ROS). ROS accumulation triggers a metacaspase-dependent apoptotic cascade, as shown by the higher viability of the yca1-deleted mutant. Together, necrosis and apoptosis are responsible for the high mortality detected after acute Captan treatment of aerobically growing cells of S. cerevisiae.

  19. Mechanisms of cell death induced by the neutrophil antimicrobial peptides alpha-defensins and LL-37.

    NARCIS (Netherlands)

    Aarbiou, J.; Tjabringa, G.S.; Verhoosel, R.M.; Ninaber, D.K.; White, S.R.; Peltenburg, L.T.; Rabe, K.F.; Hiemstra, P.S.

    2006-01-01

    OBJECTIVE: The aim of this study was to investigate the mechanisms of cell death mediated by the antimicrobial peptides neutrophil defensins (human neutrophil peptides 1-3 [HNP1-3]) and LL-37. MATERIALS AND METHODS: HNP1-3- and LL-37-mediated cell death was assessed in human lung epithelial cells

  20. Cell death induced by Bothrops asper snake venom metalloproteinase on endothelial and other cell lines.

    Science.gov (United States)

    Brenes, Oscar; Muñóz, Eduardo; Roldán-Rodríguez, Raquel; Díaz, Cecilia

    2010-06-01

    Two adherent cell lines, BAEC and HeLa, and non-adherent Jurkat, were treated with snake venom metalloproteinase BaP1 to determine whether cytotoxicity, previously reported for this toxin, could be mediated by the process of anoikis. It was observed that there was no correlation between the ability of this toxin to induce loss of adherence, and the cytotoxic effect, since concentrations that do not induce loss of adherence (3-6 microg/mL), were able to trigger 50% of cytotoxicity in BAEC. In the case of HeLa, where toxicity was very low (less than 20% at maximun concentrations and times of exposure), significant detachment and no toxicity was observed at concentrations of 1.5 microg/mL, showing also no correlation between both events. We also observed differences between BAEC toxicity measured by XTT reduction and DNA fragmentation determined by flow cytometry (as an indicator of apoptosis), since concentrations that induce 100% of cytotoxicity barely showed any DNA fragmentation (12% at 24h), suggesting that if apoptosis was involved, DNA damage is still not present, although chromatin condensation, another indicator of apoptosis, is observed in 40% of the cells. Inhibition of BAEC cytotoxicity by caspase inhibitors indicate that apoptosis is playing a role in this process, but other mechanisms of cell death could be participating also. Another way to determine whether the mechanism of cell death was related to anoikis was using a non-adherent cell line, which should show substrate independence. We determined by TUNEL that at 50 microg/ml BaP1 triggered 50% of apoptosis at 96 h, an effect that was seen earlier, suggesting also that if this toxin was inducing apoptosis in a non-adherent cell line, the mechanism could not be related to loss of attachment. Cell cycle arrest in S phase was also observed in Jurkat cells, an effect that could be leading to apoptosis. In conclusion, since there was no correlation between cell detachment and cytotoxicity (and apoptosis) in adherent cell lines and due to the ability of BaP1 to induce apoptosis in a non-adherent cell line, we suggest that this enzyme is toxic by a mechanism not related to anoikis, and that in the case of Jurkat cells, it is likely to be related to its ability to induce cell cycle arrest. Processes other than apoptosis could be also involved in the cell death mechanism mediated by BaP1 on BAEC. Copyright 2010 Elsevier Inc. All rights reserved.

  1. Selective tumor cell death induced by irradiated riboflavin through recognizing DNA G-T mismatch.

    Science.gov (United States)

    Yuan, Yi; Zhao, Yongyun; Chen, Lianqi; Wu, Jiasi; Chen, Gangyi; Li, Sheng; Zou, Jiawei; Chen, Rong; Wang, Jian; Jiang, Fan; Tang, Zhuo

    2017-09-06

    Riboflavin (vitamin B2) has been thought to be a promising antitumoral agent in photodynamic therapy, though the further application of the method was limited by the unclear molecular mechanism. Our work reveals that riboflavin was able to recognize G-T mismatch specifically and induce single-strand breaks in duplex DNA targets efficiently under irradiation. In the presence of riboflavin, the photo-irradiation could induce the death of tumor cells that are defective in mismatch repair system selectively, highlighting the G-T mismatch as potential drug target for tumor cells. Moreover, riboflavin is a promising leading compound for further drug design due to its inherent specific recognition of the G-T mismatch. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  2. Oxidative damage and cell-programmed death induced in Zea mays L. by allelochemical stress.

    Science.gov (United States)

    Ciniglia, Claudia; Mastrobuoni, Francesco; Scortichini, Marco; Petriccione, Milena

    2015-05-01

    The allelochemical stress on Zea mays was analyzed by using walnut husk washing waters (WHWW), a by-product of Juglans regia post-harvest process, which possesses strong allelopathic potential and phytotoxic effects. Oxidative damage and cell-programmed death were induced by WHWW in roots of maize seedlings. Treatment induced ROS burst, with excess of H2O2 content. Enzymatic activities of catalase were strongly increased during the first hours of exposure. The excess in malonildialdehyde following exposure to WHWW confirmed that oxidative stress severely damaged maize roots. Membrane alteration caused a decrease in NADPH oxidase activity along with DNA damage as confirmed by DNA laddering. The DNA instability was also assessed through sequence-related amplified polymorphism assay, thus suggesting the danger of walnut processing by-product and focusing the attention on the necessity of an efficient treatment of WHWW.

  3. Necroptosis modulated by autophagy is a predominant form of melanoma cell death induced by sanguilutine

    Czech Academy of Sciences Publication Activity Database

    Hammerová, J.; Uldrijan, S.; Táborská, E.; Vaculová, Alena; Slaninová, I.

    2012-01-01

    Roč. 393, č. 7 (2012), s. 647-658 ISSN 1431-6730 Grant - others:GA ČR(CZ) GA525/08/0819; GA MŠk(CZ) LC06077; GA MŠk(CZ) LH12176; GA MZd(CZ) NS10236-3/2009 Program:LC; LH Institutional support: RVO:68081707 Keywords : BCL-2 FAMILY PROTEINS * MITOCHONDRIAL APOPTOSIS * GLUTATHIONE DEPLETION Subject RIV: BO - Biophysics Impact factor: 2.683, year: 2012

  4. Cell death induced by GSM 900-MHz and DCS 1800-MHz mobile telephony radiation

    International Nuclear Information System (INIS)

    Panagopoulos, D. J; Chavdoula, E. D.; Nezis, I. P.; Margaritis, L. H.

    2007-01-01

    In the present study, the TUNEL (Terminal deoxynucleotide transferase dUTP Nick End Labeling) assay '' a well known technique widely used for detecting fragmented DNA in various types of cells'' was used to detect cell death (DNA fragmentation) in a biological model, the early and mid stages of oogenesis of the insect Drosophila melanogaster. The flies were exposed in vivo to either GSM 900-MHz (Global System for Mobile telecommunications) or DCS 1800-MHz (Digital Cellular System) radiation from a common digital mobile phone, for few minutes per day during the first 6 days of their adult life. The exposure conditions were similar to those to which a mobile phone user is exposed, and were determined according to previous studies of ours [D.J. Panagopoulos, A. Karabarbounis, L.H. Margaritis, Effect of GSM 900-MHz mobile phone radiation on the reproductive capacity of D. melanogaster, Electromagn. Biol. Med. 23 (1) (2004) 29''43; D.J. Panagopoulos, N. Messini, A. Karabarbounis, A.L. Philippetis, L.H. Margaritis, Radio frequency electromagnetic radiation within ''safety levels'' alters the physiological function of insects, in: P. Kostarakis, P. Stavroulakis (Eds.), Proceedings of the Millennium International Workshop on Biological Effects of Electromagnetic Fields, Heraklion, Crete, Greece, October 17''20, 2000, pp. 169''175, ISBN: 960-86733-0-5; D.J. Panagopoulos, L.H. Margaritis, Effects of electromagnetic fields on the reproductive capacity of D. melanogaster, in: P. Stavroulakis (Ed.), Biological Effects of Electromagnetic Fields, Springer, 2003, pp. 545''578], which had shown a large decrease in the oviposition of the same insect caused by GSM radiation. Our present results suggest that the decrease in oviposition previously reported, is due to degeneration of large numbers of egg chambers after DNA fragmentation of their constituent cells, induced by both types of mobile telephony radiation. Induced cell death is recorded for the first time, in all types of cells constituting an egg chamber (follicle cells, nurse cells and the oocyte) and in all stages of the early and mid-oogenesis, from germarium to stage 10, during which programmed cell death does not physiologically occur. Germarium and stages 7''8 were found to be the most sensitive developmental stages also in response to electromagnetic stress induced by the GSM and DCS fields and, moreover, germarium was found to be even more sensitive than stages 7''8. (Author)

  5. Tualang Honey Promotes Apoptotic Cell Death Induced by Tamoxifen in Breast Cancer Cell Lines

    Directory of Open Access Journals (Sweden)

    Nik Soriani Yaacob

    2013-01-01

    Full Text Available Tualang honey (TH is rich in flavonoids and phenolic acids and has significant anticancer activity against breast cancer cells comparable to the effect of tamoxifen (TAM, in vitro. The current study evaluated the effects of TH when used in combination with TAM on MCF-7 and MDA-MB-231 cells. We observed that TH promoted the anticancer activity of TAM in both the estrogen receptor-(ER-responsive and ER-nonresponsive human breast cancer cell lines. Flow cytometric analyses indicated accelerated apoptosis especially in MDA-MB-231 cells and with the involvement of caspase-3/7, -8 and -9 activation as shown by fluorescence microscopy. Depolarization of the mitochondrial membrane was also increased in both cell lines when TH was used in combination with TAM compared to TAM treatment alone. TH may therefore be a potential adjuvant to be used with TAM for reducing the dose of TAM, hence, reducing TAM-induced adverse effects.

  6. N-Methyl-d-Aspartate (NMDA) Receptor Blockade Prevents Neuronal Death Induced by Zika Virus Infection.

    Science.gov (United States)

    Costa, Vivian V; Del Sarto, Juliana L; Rocha, Rebeca F; Silva, Flavia R; Doria, Juliana G; Olmo, Isabella G; Marques, Rafael E; Queiroz-Junior, Celso M; Foureaux, Giselle; Araújo, Julia Maria S; Cramer, Allysson; Real, Ana Luíza C V; Ribeiro, Lucas S; Sardi, Silvia I; Ferreira, Anderson J; Machado, Fabiana S; de Oliveira, Antônio C; Teixeira, Antônio L; Nakaya, Helder I; Souza, Danielle G; Ribeiro, Fabiola M; Teixeira, Mauro M

    2017-04-25

    Zika virus (ZIKV) infection is a global health emergency that causes significant neurodegeneration. Neurodegenerative processes may be exacerbated by N -methyl-d-aspartate receptor (NMDAR)-dependent neuronal excitoxicity. Here, we have exploited the hypothesis that ZIKV-induced neurodegeneration can be rescued by blocking NMDA overstimulation with memantine. Our results show that ZIKV actively replicates in primary neurons and that virus replication is directly associated with massive neuronal cell death. Interestingly, treatment with memantine or other NMDAR blockers, including dizocilpine (MK-801), agmatine sulfate, or ifenprodil, prevents neuronal death without interfering with the ability of ZIKV to replicate in these cells. Moreover, in vivo experiments demonstrate that therapeutic memantine treatment prevents the increase of intraocular pressure (IOP) induced by infection and massively reduces neurodegeneration and microgliosis in the brain of infected mice. Our results indicate that the blockade of NMDARs by memantine provides potent neuroprotective effects against ZIKV-induced neuronal damage, suggesting it could be a viable treatment for patients at risk for ZIKV infection-induced neurodegeneration. IMPORTANCE Zika virus (ZIKV) infection is a global health emergency associated with serious neurological complications, including microcephaly and Guillain-Barré syndrome. Infection of experimental animals with ZIKV causes significant neuronal damage and microgliosis. Treatment with drugs that block NMDARs prevented neuronal damage both in vitro and in vivo These results suggest that overactivation of NMDARs contributes significantly to the neuronal damage induced by ZIKV infection, and this is amenable to inhibition by drug treatment. Copyright © 2017 Costa et al.

  7. Cell death induced by ozone and various non-thermal plasmas: therapeutic perspectives and limitations

    Czech Academy of Sciences Publication Activity Database

    Lunov, Oleg; Zablotskyy, Vitaliy A.; Churpita, Olexandr; Chánová, Eliška; Syková, Eva; Dejneka, Alexandr; Kubinová, Šárka

    2014-01-01

    Roč. 4, NOV (2014), "7129-1"-"7129-11" ISSN 2045-2322 R&D Projects: GA MŠk LO1309 Grant - others:AV ČR(CZ) M100101219 Institutional support: RVO:68378271 ; RVO:61389013 ; RVO:68378041 Keywords : cell death * non-thermal plasma * therapeutic perspectives Subject RIV: BO - Biophysics; FH - Neurology (UEM-P); CD - Macromolecular Chemistry (UMCH-V) Impact factor: 5.578, year: 2014

  8. Amplitude death induced by mixed attractive and repulsive coupling in the relay system

    Science.gov (United States)

    Zhao, Nannan; Sun, Zhongkui; Xu, Wei

    2018-01-01

    The amplitude death (AD) phenomenon is found in the relay system in the presence of the mixed couplings composed of attractive coupling and repulsive coupling. The generation mechanism of AD is revealed and shows that the middle oscillator achieving AD is a prerequisite to further suppress oscillation of the outermost oscillators for the paradigmatic Stuart-Landau and Rössler models. Moreover, regarding the Stuart-Landau relay system as a small motif of star network, we also observe that the mixed couplings can facilitate AD state of the whole network system. Particularly, the threshold of coupling strength is invariable with the change of network size. Our findings may shed a new insight to explore the effects of hybrid coupling on complex systems, also provide a new strategy to control dynamic behaviors in engineering science and neuroscience fields.

  9. Cell Death Inducing Microbial Protein Phosphatase Inhibitors--Mechanisms of Action.

    Science.gov (United States)

    Kleppe, Rune; Herfindal, Lars; Døskeland, Stein Ove

    2015-10-22

    Okadaic acid (OA) and microcystin (MC) as well as several other microbial toxins like nodularin and calyculinA are known as tumor promoters as well as inducers of apoptotic cell death. Their intracellular targets are the major serine/threonine protein phosphatases. This review summarizes mechanisms believed to be responsible for the death induction and tumor promotion with focus on the interdependent production of reactive oxygen species (ROS) and activation of Ca(2+)/calmodulin kinase II (CaM-KII). New data are presented using inhibitors of specific ROS producing enzymes to curb nodularin/MC-induced liver cell (hepatocyte) death. They indicate that enzymes of the arachidonic acid pathway, notably phospholipase A2, 5-lipoxygenase, and cyclooxygenases, may be required for nodularin/MC-induced (and presumably OA-induced) cell death, suggesting new ways to overcome at least some aspects of OA and MC toxicity.

  10. ATG7 deficiency suppresses apoptosis and cell death induced by lysosomal photodamage

    Science.gov (United States)

    Kessel, David H.; Price, Michael; Reiners, Jr., John J.

    2012-01-01

    Photodynamic therapy (PDT) involves photosensitizing agents that, in the presence of oxygen and light, initiate formation of cytotoxic reactive oxygen species (ROS). PDT commonly induces both apoptosis and autophagy. Previous studies with murine hepatoma 1c1c7 cells indicated that loss of autophagy-related protein 7 (ATG7) inhibited autophagy and enhanced the cytotoxicity of photosensitizers that mediate photodamage to mitochondria or the endoplasmic reticulum. In this study, we examined two photosensitizing agents that target lysosomes: the chlorin NPe6 and the palladium bacteriopheophorbide WST11. Irradiation of wild-type 1c1c7 cultures loaded with either photosensitizer induced apoptosis and autophagy, with a blockage of autophagic flux. An ATG7- or ATG5-deficiency suppressed the induction of autophagy in PDT protocols using either photosensitizer. Whereas ATG5-deficient cells were quantitatively similar to wild-type cultures in their response to NPe6 and WST11 PDT, an ATG7-deficiency suppressed the apoptotic response (as monitored by analyses of chromatin condensation and procaspase-3/7 activation) and increased the LD50 light dose by > 5-fold (as monitored by colony-forming assays). An ATG7-deficiency did not prevent immediate lysosomal photodamage, as indicated by loss of the lysosomal pH gradient. However, unlike wild-type and ATG5-deficient cells, the lysosomes of ATG7-deficient cells recovered this gradient within 4 h of irradiation, and never underwent permeabilization (monitored as release of endocytosed 10-kDa dextran polymers). We propose that the efficacy of lysosomal photosensitizers is in part due to both promotion of autophagic stress and suppression of autophagic prosurvival functions. In addition, an effect of ATG7 unrelated to autophagy appears to modulate lysosomal photodamage. PMID:22889762

  11. Flavonoids of Inula britannica protect cultured cortical cells from necrotic cell death induced by glutamate.

    Science.gov (United States)

    Kim, So Ra; Park, Mi Jung; Lee, Mi Kyeong; Sung, Sang Hyun; Park, Eun Jung; Kim, Jinwoong; Kim, Sun Yeou; Oh, Tae H; Markelonis, George J; Kim, Young Choong

    2002-04-01

    We previously reported 12 antioxidative flavonoids isolated from the n-BuOH extract of Inula britannica (Asteraceae). This prompted us to investigate further whether these flavonoids also showed antioxidative activity upon live cells grown in a culture system. Among the 12 flavonoids tested, only patuletin, nepetin, and axillarin protected primary cultures of rat cortical cells from oxidative stress induced by glutamate. These flavonoids exerted significant neuroprotective activity when they were administered either before or after the glutamate insult. Treatment with these flavonoids maintained the activities of such antioxidant enzymes as catalase, glutathione-peroxidase, and glutathione reductase, all of which play important roles in the antioxidative defense mechanism. Moreover, these three flavonoids also attenuated significant drops in glutathione induced by glutamate which is a routine concomitant of oxidative stress by inhibiting glutathione diminution. Accordingly, these flavonoids did not stimulate the synthesis of glutathione. With regard to structure-activity relationships, our results indicated that the 6-methoxyl group in the A ring and the 3', 4'-hydroxyl groups in the B ring are crucial for the protection against the oxidative stress; glycosylation greatly reduced their protective activities. Collectively, these results indicated that patuletin, nepetin, and axillarin strongly protect primary cultured neurons against glutamate-induced oxidative stress.

  12. Role of mitochondrial permeability transition in human renal tubular epithelial cell death induced by aristolochic acid

    International Nuclear Information System (INIS)

    Qi Xinming; Cai Yan; Gong Likun; Liu Linlin; Chen Fangping; Xiao Ying; Wu Xiongfei; Li Yan; Xue Xiang; Ren Jin

    2007-01-01

    Aristolochic acid (AA), a natural nephrotoxin and carcinogen, can induce a progressive tubulointerstitial nephropathy. However, the mechanism by which AA causes renal injury remains largely unknown. Here we reported that the mitochondrial permeability transition (MPT) plays an important role in the renal injury induced by aristolochic acid I (AAI). We found that in the presence of Ca 2+ , AAI caused mitochondrial swelling, leakage of Ca 2+ , membrane depolarization, and release of cytochrome c in isolated kidney mitochondria. These alterations were suppressed by cyclosporin A (CsA), an agent known to inhibit MPT. Culture of HK-2 cell, a human renal tubular epithelial cell line for 24 h with AAI caused a decrease in cellular ATP, mitochondrial membrane depolarization, cytochrome c release, and increase of caspase 3 activity. These toxic effects of AAI were attenuated by CsA and bongkrekic acid (BA), another specific MPT inhibitor. Furthermore, AAI greatly inhibited the activity of mitochondrial adenine nucleotide translocator (ANT) in isolated mitochondria. We suggested that ANT may mediate, at least in part, the AAI-induced MPT. Taken together, these results suggested that MPT plays a critical role in the pathogenesis of HK-2 cell injury induced by AAI and implied that MPT might contribute to human nephrotoxicity of aristolochic acid

  13. The interplay between biological and physical scenarios of bacterial death induced by non-thermal plasma

    Czech Academy of Sciences Publication Activity Database

    Lunov, Oleg; Zablotskyy, Vitaliy A.; Churpita, Olexandr; Jäger, Aleš; Polívka, Leoš; Syková, E.; Dejneka, Alexandr; Kubinová, Šárka

    2016-01-01

    Roč. 82, Mar (2016), s. 71-83 ISSN 0142-9612 R&D Projects: GA MŠk LO1409; GA MŠk(CZ) LM2011026 Grant - others:FUNBIO(XE) CZ.2.16/3.1.00/21568; AV ČR(CZ) Fellowship J. E. Purkyně Institutional support: RVO:68378271 Keywords : non-thermal plasma * bacteria * cytotoxicity * apoptosis * bacterial inactivation * reactive oxygen species (ROS) Subject RIV: BO - Biophysics Impact factor: 8.402, year: 2016

  14. Azelnidipine inhibits cultured rat aortic smooth muscle cell death induced by cyclic mechanical stretch.

    Directory of Open Access Journals (Sweden)

    Jing Zhao

    Full Text Available Acute aortic dissection is the most common life-threatening vascular disease, with sudden onset of severe pain and a high fatality rate. Clarifying the detailed mechanism for aortic dissection is of great significance for establishing effective pharmacotherapy for this high mortality disease. In the present study, we evaluated the influence of biomechanical stretch, which mimics an acute rise in blood pressure using an experimental apparatus of stretching loads in vitro, on rat aortic smooth muscle cell (RASMC death. Then, we examined the effects of azelnidipine and mitogen-activated protein kinase inhibitors on mechanical stretch-induced RASMC death. The major findings of the present study are as follows: (1 cyclic mechanical stretch on RASMC caused cell death in a time-dependent manner up to 4 h; (2 cyclic mechanical stretch on RASMC induced c-Jun N-terminal kinase (JNK and p38 activation with peaks at 10 min; (3 azelnidipine inhibited RASMC death in a concentration-dependent manner as well as inhibited JNK and p38 activation by mechanical stretch; and (4 SP600125 (a JNK inhibitor and SB203580 (a p38 inhibitor protected against stretch-induced RASMC death; (5 Antioxidants, diphenylene iodonium and tempol failed to inhibit stretch-induced RASMC death. On the basis of the above findings, we propose a possible mechanism where an acute rise in blood pressure increases biomechanical stress on the arterial walls, which induces RASMC death, and thus, may lead to aortic dissection. Azelnidipine may be used as a pharmacotherapeutic agent for prevention of aortic dissection independent of its blood pressure lowering effect.

  15. Coronatine inhibits stomatal closure and delays hypersensitive response cell death induced by nonhost bacterial pathogens

    Directory of Open Access Journals (Sweden)

    Seonghee Lee

    2013-02-01

    Full Text Available Pseudomonas syringae is the most widespread bacterial pathogen in plants. Several strains of P. syringae produce a phytotoxin, coronatine (COR, which acts as a jasmonic acid mimic and inhibits plant defense responses and contributes to disease symptom development. In this study, we found that COR inhibits early defense responses during nonhost disease resistance. Stomatal closure induced by a nonhost pathogen, P. syringae pv. tabaci, was disrupted by COR in tomato epidermal peels. In addition, nonhost HR cell death triggered by P. syringae pv. tabaci on tomato was remarkably delayed when COR was supplemented along with P. syringae pv. tabaci inoculation. Using isochorismate synthase (ICS-silenced tomato plants and transcript profiles of genes in SA- and JA-related defense pathways, we show that COR suppresses SA-mediated defense during nonhost resistance.

  16. Cell death induced by a 131I-labeled monoclonal antibody in ovarian cancer multicell spheroids

    International Nuclear Information System (INIS)

    Filippovich, I.V.; Sorokina, N.; Robillard, N.; Faivre-Chauvet, A.; Bardies, M.; Chatal, J.F.

    1996-01-01

    Treatment of OVCAR-3 spheroids with 131 I-OC125 monoclonal antibody produced a decrease in spheroid volume and a concomitant rise in necrotic cell number. No increase in apoptotic cell number was observed during incubation of spheroids with the labeled antibody. Necrosis began early, reaching a maximum after 3 Gy of accumulated dose delivered at a dose rate of 1.8 cGy/h. Higher accumulated doses induced necrosis for longer incubation times. Thus, dose rate and time are both determinants of ultimate radiation effects when spheroids are incubated with labeled antibodies, although dose rate is the most important factor

  17. Cell death induced by a 131I-labeled monoclonal antibody in ovarian cancer multicell spheroids.

    Science.gov (United States)

    Filippovich, I V; Sorokina, N; Robillard, N; Faivre-Chauvet, A; Bardies, M; Chatal, J F

    1996-07-01

    Treatment of OVCAR-3 spheroids with 131I-OC125 monoclonal antibody produced a decrease in spheroid volume and a concomitant rise in necrotic cell number. No increase in apoptotic cell number was observed during incubation of spheroids with the labeled antibody. Necrosis began early, reaching a maximum after 3 Gy of accumulated dose delivered at a dose rate of 1.8 cGy/h. Higher accumulated doses induced necrosis for longer incubation times. Thus, dose rate and time are both determinants of ultimate radiation effects when spheroids are incubated with labeled antibodies, although dose rate is the most important factor.

  18. Delayed luminescence to monitor programmed cell death induced by berberine on thyroid cancer cells

    Science.gov (United States)

    Scordino, Agata; Campisi, Agata; Grasso, Rosaria; Bonfanti, Roberta; Gulino, Marisa; Iauk, Liliana; Parenti, Rosalba; Musumeci, Francesco

    2014-11-01

    Correlation between apoptosis and UVA-induced ultraweak photon emission delayed luminescence (DL) from tumor thyroid cell lines was investigated. In particular, the effects of berberine, an alkaloid that has been reported to have anticancer activities, on two cancer cell lines were studied. The FTC-133 and 8305C cell lines, as representative of follicular and anaplastic thyroid human cancer, respectively, were chosen. The results show that berberine is able to arrest cell cycle and activate apoptotic pathway as shown in both cell lines by deoxyribonucleic acid fragmentation, caspase-3 cleavage, p53 and p27 protein overexpression. In parallel, changes in DL spectral components after berberine treatment support the hypothesis that DL from human cells originates mainly from mitochondria, since berberine acts especially at the mitochondrial level. The decrease of DL blue component for both cell lines could be related to the decrease of intra-mitochondrial nicotinamide adenine dinucleotide and may be a hallmark of induced apoptosis. In contrast, the response in the red spectral range is different for the two cell lines and may be ascribed to a different iron homeostasis.

  19. Signalling pathways in pemphigus vulgaris.

    Science.gov (United States)

    Li, Xiaoguang; Ishii, Norito; Ohata, Chika; Furumura, Minao; Hashimoto, Takashi

    2014-03-01

    Acantholysis in pemphigus vulgaris is induced by binding of autoantibodies to desmoglein 3 (Dsg3). The roles of signalling pathways on development of acantholysis have recently been extensively studied. In the study by Sayar et al., recently published in Exp Dermatol, epidermal growth factor receptor (EGFR) signalling was activated in both in vivo and in vitro pemphigus vulgaris experimental models. However, while EGFR inhibitors suppressed activity of p38 mitogen-activated protein kinase (p38MAPK) linearly, they suppressed activity of c-Myc and acantholysis in a non-linear, V-shaped relationship. These findings indicated complicated interactions among EGFR, p38MAPK and c-Myc in pemphigus vulgaris pathology. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Low power digital signal processing

    DEFF Research Database (Denmark)

    Paker, Ozgun

    2003-01-01

    This thesis introduces a novel approach to programmable and low power platform design for audio signal processing, in particular hearing aids. The proposed programmable platform is a heterogeneous multiprocessor architecture consisting of small and simple instruction set processors called mini......-cores as well as standard DSP/CPU-cores that communicate using message passing. The work has been based on a study of the algorithm suite covering the application domain. The observation of dominant tasks for certain algorithms (FIR, IIR, correlation, etc.) that require custom computational units and special...... data addressing capabilities lead to the design of low power mini-cores. The algorithm suite also consisted of less demanding and/or irregular algorithms (LMS, compression) that required subsample rate signal processing justifying the use of a DSP/CPU-core. The thesis also contributes to the recent...

  1. Cancer, signal transduction and nanotechnology.

    Science.gov (United States)

    Sengupta, Poulomi; Basu, Sudipta; Sengupta, Shiladitya

    2011-05-01

    Understanding the mechanisms underlying different cellular signaling pathways implicated in the pathogenesis of cancer are leading to the identification of novel drug targets as well as novel drug candidates. Multiple targeted therapeutics that modulate aberrant molecular pathways have already reached the clinic. However, targeted therapeutics can exert mechanism-driven side effects as a result of the implication of the molecular target in normal physiological functions besides tumorigenesis. We hypothesize that targeted therapeutics can be optimized by merging them with nanotechnology, which offers the potential for preferential targeting to the tumor, resulting in increased intratumoral concentrations of the active agent with reduced distribution to other parts of the body. This review will address some of the emerging concepts that integrate these two disciplines to engineer novel nanovectors that target different signaling pathways.

  2. Peroxynitrite: From interception to signaling.

    Science.gov (United States)

    Speckmann, Bodo; Steinbrenner, Holger; Grune, Tilman; Klotz, Lars-Oliver

    2016-04-01

    Peroxynitrite is a strong oxidant and nitrating species that mediates certain biological effects of superoxide and nitrogen monoxide. These biological effects include oxidative damage to proteins as well as the formation of 3-nitrotyrosyl moieties in proteins. As a consequence, such proteins may lose their activity, gain altered function, or become prone to proteolytic degradation - resulting in modulation of cellular protein turnover and in the modulation of signaling cascades. In analogy to hydrogen peroxide, peroxynitrite may be scavenged by selenoproteins like glutathione peroxidase-1 (GPx-1) or by selenocompounds with a GPx-like activity, such as ebselen; in further analogy to H2O2, peroxiredoxins have also been established as contributors to peroxynitrite reduction. This review covers three aspects of peroxynitrite biochemistry, (i) the interaction of selenocompounds/-proteins with peroxynitrite, (ii) peroxynitrite-induced modulation of cellular proteolysis, and (iii) peroxynitrite-induced modulation of cellular signaling. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. ROS signalling - specificity is required

    DEFF Research Database (Denmark)

    Møller, Ian M; Sweetlove, Lee J

    2010-01-01

    Reactive oxygen species (ROS) production increases in plants under stress. ROS can damage cellular components, but they can also act in signal transduction to help the cell counteract the oxidative damage in the stressed compartment. H2O2 might induce a general stress response, but it does not have...... the required specificity to selectively regulate nuclear genes required for dealing with localized stress, e.g. in chloroplasts or mitochondria. Here we argue that peptides deriving from proteolytic breakdown of oxidatively damaged proteins have the requisite specificity to act as secondary ROS messengers...... and regulate source-specific genes and in this way contribute to retrograde ROS signalling during oxidative stress. Likewise, unmodified peptides deriving from the breakdown of redundant proteins could help coordinate organellar and nuclear gene expression...

  4. Contextual predictability shapes signal autonomy.

    Science.gov (United States)

    Winters, James; Kirby, Simon; Smith, Kenny

    2018-03-10

    Aligning on a shared system of communication requires senders and receivers reach a balance between simplicity, where there is a pressure for compressed representations, and informativeness, where there is a pressure to be communicatively functional. We investigate the extent to which these two pressures are governed by contextual predictability: the amount of contextual information that a sender can estimate, and therefore exploit, in conveying their intended meaning. In particular, we test the claim that contextual predictability is causally related to signal autonomy: the degree to which a signal can be interpreted in isolation, without recourse to contextual information. Using an asymmetric communication game, where senders and receivers are assigned fixed roles, we manipulate two aspects of the referential context: (i) whether or not a sender shares access to the immediate contextual information used by the receiver in interpreting their utterance; (ii) the extent to which the relevant solution in the immediate referential context is generalisable to the aggregate set of contexts. Our results demonstrate that contextual predictability shapes the degree of signal autonomy: when the context is highly predictable (i.e., the sender has access to the context in which their utterances will be interpreted, and the semantic dimension which discriminates between meanings in context is consistent across communicative episodes), languages develop which rely heavily on the context to reduce uncertainty about the intended meaning. When the context is less predictable, senders favour systems composed of autonomous signals, where all potentially relevant semantic dimensions are explicitly encoded. Taken together, these results suggest that our pragmatic faculty, and how it integrates information from the context in reducing uncertainty, plays a central role in shaping language structure. Copyright © 2018 Elsevier B.V. All rights reserved.

  5. The IRS-1 signaling system.

    Science.gov (United States)

    Myers, M G; Sun, X J; White, M F

    1994-07-01

    Insulin-receptor substrate 1 (IRS-1) is a principal substrate of the receptor tyrosine kinase for insulin and insulin-like growth factor 1, and a substrate for a tyrosine kinase activated by interleukin 4. IRS-1 undergoes multisite tyrosine phosphorylation and mediates downstream signals by 'docking' various proteins that contain Src homology 2 domains. IRS-1 appears to be a unique molecule; however, 4PS, a protein found mainly in hemopoietic cells, may represent another member of this family.

  6. Signals of Supersymmetric Dark Matter

    OpenAIRE

    Abbas, Afsar

    1999-01-01

    The Lightest Supersymmetric Particle predicted in most of the supersymmetric scenarios is an ideal candidate for the dark matter of cosmology. Their detection is of extreme significance today. Recently there have been intriguing signals of a 59 Gev neutralino dark matter at DAMA in Gran Sasso. We look at other possible signatures of dark matter in astrophysical and geological frameworks. The passage of the earth through dense clumps of dark matter would produce large quantities of heat in the...

  7. Cell signalling and phospholipid metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Boss, W.F.

    1990-01-01

    These studies explored whether phosphoinositide (PI) has a role in plants analogous to its role in animal cells. Although no parallel activity of PI in signal transduction was found in plant cells, activity of inositol phospholipid kinase was found to be modulated by light and by cell wall degrading enzymes. These studies indicate a major role for inositol phospholipids in plant growth and development as membrane effectors but not as a source of second messengers.

  8. Detection of signals in noise

    CERN Document Server

    McDonough, Robert N

    1995-01-01

    The Second Edition is an updated revision to the authors highly successful and widely used introduction to the principles and application of the statistical theory of signal detection. This book emphasizes those theories that have been found to be particularly useful in practice including principles applied to detection problems encountered in digital communications, radar, and sonar.Detection processing based upon the fast Fourier transform

  9. Cytoskeleton in mast cell signaling

    Czech Academy of Sciences Publication Activity Database

    Dráber, Pavel; Sulimenko, Vadym; Dráberová, Eduarda

    2012-01-01

    Roč. 3, May (2012), s. 130 ISSN 1664-3224 R&D Projects: GA ČR GAP302/10/1701; GA ČR GPP302/11/P709; GA ČR GAP302/12/1673 Grant - others:ECST(XE) Action BM1007 Institutional research plan: CEZ:AV0Z50520514 Keywords : cytoskeleton * mast cell activation * signal transduction Subject RIV: EB - Genetics ; Molecular Biology

  10. Signal and image multiresolution analysis

    CERN Document Server

    Ouahabi, Abdelialil

    2012-01-01

    Multiresolution analysis using the wavelet transform has received considerable attention in recent years by researchers in various fields. It is a powerful tool for efficiently representing signals and images at multiple levels of detail with many inherent advantages, including compression, level-of-detail display, progressive transmission, level-of-detail editing, filtering, modeling, fractals and multifractals, etc.This book aims to provide a simple formalization and new clarity on multiresolution analysis, rendering accessible obscure techniques, and merging, unifying or completing

  11. Signalling properties of lysophosphatidic acid.

    Science.gov (United States)

    Durieux, M E; Lynch, K R

    1993-06-01

    Lysophosphatidic acid (LPA) is the simplest natural phospholipid, primarily known as a membrane component and metabolic intermediate. However, a remarkable variety of biological effects of this compound have come to light, seemingly pointing to an additional role for LPA as a signalling molecule. In this review, Marcel Durieux and Kevin Lynch integrate the recent information that indicates that LPA could be an intercellular messenger, possibly acting through a G protein-coupled receptor, and with a role in cell growth and motility.

  12. AR Signaling in Breast Cancer

    Directory of Open Access Journals (Sweden)

    Bilal Rahim

    2017-02-01

    Full Text Available Androgen receptor (AR, a member of the steroid hormone receptor family status has become increasingly important as both a prognostic marker and potential therapeutic target in breast cancer. AR is expressed in up to 90% of estrogen receptor (ER positive breast cancer, and to a lesser degree, human epidermal growth factor 2 (HER2 amplified tumors. In the former, AR signaling has been correlated with a better prognosis given its inhibitory activity in estrogen dependent disease, though conversely has also been shown to increase resistance to anti-estrogen therapies such as tamoxifen. AR blockade can mitigate this resistance, and thus serves as a potential target in ER-positive breast cancer. In HER2 amplified breast cancer, studies are somewhat conflicting, though most show either no effect or are associated with poorer survival. Much of the available data on AR signaling is in triple-negative breast cancer (TNBC, which is an aggressive disease with inferior outcomes comparative to other breast cancer subtypes. At present, there are no approved targeted therapies in TNBC, making study of the AR signaling pathway compelling. Gene expression profiling studies have also identified a luminal androgen receptor (LAR subtype that is dependent on AR signaling in TNBC. Regardless, there seems to be an association between AR expression and improved outcomes in TNBC. Despite lower pathologic complete response (pCR rates with neoadjuvant therapy, patients with AR-expressing TNBC have been shown to have a better prognosis than those that are AR-negative. Clinical studies targeting AR have shown somewhat promising results. In this paper we review the literature on the biology of AR in breast cancer and its prognostic and predictive roles. We also present our thoughts on therapeutic strategies.

  13. Voting as a Signaling Device

    OpenAIRE

    R. Emre Aytimur; Aristotelis Boukouras; Robert Schwager

    2012-01-01

    In this paper, citizens vote in order to influence the election outcome and in order to signal their unobserved characteristics to others. The model is one of rational voting and generates the following predictions: (i) The paradox of not voting does not arise, because the benefit of voting does not vanish with population size. (ii) Turnout in elections is positively related to the size of the local community and the importance of social interactions. (iii) Voting may exhibit bandwagon effect...

  14. Intracellular calcium homeostasis and signaling.

    Science.gov (United States)

    Brini, Marisa; Calì, Tito; Ottolini, Denis; Carafoli, Ernesto

    2013-01-01

    Ca(2+) is a universal carrier of biological information: it controls cell life from its origin at fertilization to its end in the process of programmed cell death. Ca(2+) is a conventional diffusible second messenger released inside cells by the interaction of first messengers with plasma membrane receptors. However, it can also penetrate directly into cells to deliver information without the intermediation of first or second messengers. Even more distinctively, Ca(2+) can act as a first messenger, by interacting with a plasma membrane receptor to set in motion intracellular signaling pathways that involve Ca(2+) itself. Perhaps the most distinctive property of the Ca(2+) signal is its ambivalence: while essential to the correct functioning of cells, Ca(2+) becomes an agent that mediates cell distress, or even (toxic) cell death, if its concentration and movements inside cells are not carefully tuned. Ca(2+) is controlled by reversible complexation to specific proteins, which could be pure Ca(2+) buffers, or which, in addition to buffering Ca(2+), also decode its signal to pass it on to targets. The most important actors in the buffering of cell Ca(2+) are proteins that transport it across the plasma membrane and the membrane of the organelles: some have high Ca(2+) affinity and low transport capacity (e.g., Ca(2+) pumps), others have opposite properties (e.g., the Ca(2+) uptake system of mitochondria). Between the initial event of fertilization, and the terminal event of programmed cell death, the Ca(2+) signal regulates the most important activities of the cell, from the expression of genes, to heart and muscle contraction and other motility processes, to diverse metabolic pathways involved in the generation of cell fuels.

  15. Ketone bodies as signaling metabolites

    OpenAIRE

    Newman, John C.; Verdin, Eric

    2013-01-01

    Traditionally, the ketone body β-hydroxybutyrate (βOHB) has been looked upon as a carrier of energy from liver to peripheral tissues during fasting or exercise. However, βOHB also signals via extracellular receptors and acts as an endogenous inhibitor of histone deacetylases (HDACs). These recent findings support a model in which βOHB functions to link the environment, in this case the diet, and gene expression via chromatin modifications. Here, we review the regulation and functions of keton...

  16. Terminality implies non-signalling

    OpenAIRE

    Coecke, Bob

    2014-01-01

    A 'process theory' is any theory of systems and processes which admits sequential and parallel composition. `Terminality' unifies normalisation of pure states, trace-preservation of CP-maps, and adding up to identity of positive operators in quantum theory, and generalises this to arbitrary process theories. We show that terminality and non-signalling coincide in any process theory, provided one makes causal structure explicit. In fact, making causal structure explicit is necessary to even ma...

  17. Calcium Signals from the Vacuole

    Directory of Open Access Journals (Sweden)

    Gerald Schönknecht

    2013-10-01

    Full Text Available The vacuole is by far the largest intracellular Ca2+ store in most plant cells. Here, the current knowledge about the molecular mechanisms of vacuolar Ca2+ release and Ca2+ uptake is summarized, and how different vacuolar Ca2+ channels and Ca2+ pumps may contribute to Ca2+ signaling in plant cells is discussed. To provide a phylogenetic perspective, the distribution of potential vacuolar Ca2+ transporters is compared for different clades of photosynthetic eukaryotes. There are several candidates for vacuolar Ca2+ channels that could elicit cytosolic [Ca2+] transients. Typical second messengers, such as InsP3 and cADPR, seem to trigger vacuolar Ca2+ release, but the molecular mechanism of this Ca2+ release still awaits elucidation. Some vacuolar Ca2+ channels have been identified on a molecular level, the voltage-dependent SV/TPC1 channel, and recently two cyclic-nucleotide-gated cation channels. However, their function in Ca2+ signaling still has to be demonstrated. Ca2+ pumps in addition to establishing long-term Ca2+ homeostasis can shape cytosolic [Ca2+] transients by limiting their amplitude and duration, and may thus affect Ca2+ signaling.

  18. Purinergic signaling in the airways.

    Science.gov (United States)

    Burnstock, Geoffrey; Brouns, Inge; Adriaensen, Dirk; Timmermans, Jean-Pierre

    2012-10-01

    Evidence for a significant role and impact of purinergic signaling in normal and diseased airways is now beyond dispute. The present review intends to provide the current state of knowledge of the involvement of purinergic pathways in the upper and lower airways and lungs, thereby differentiating the involvement of different tissues, such as the epithelial lining, immune cells, airway smooth muscle, vasculature, peripheral and central innervation, and neuroendocrine system. In addition to the vast number of well illustrated functions for purinergic signaling in the healthy respiratory tract, increasing data pointing to enhanced levels of ATP and/or adenosine in airway secretions of patients with airway damage and respiratory diseases corroborates the emerging view that purines act as clinically important mediators resulting in either proinflammatory or protective responses. Purinergic signaling has been implicated in lung injury and in the pathogenesis of a wide range of respiratory disorders and diseases, including asthma, chronic obstructive pulmonary disease, inflammation, cystic fibrosis, lung cancer, and pulmonary hypertension. These ostensibly enigmatic actions are based on widely different mechanisms, which are influenced by the cellular microenvironment, but especially the subtypes of purine receptors involved and the activity of distinct members of the ectonucleotidase family, the latter being potential protein targets for therapeutic implementation.

  19. Dynamics in atomic signaling games

    KAUST Repository

    Fox, Michael J.

    2015-04-08

    We study an atomic signaling game under stochastic evolutionary dynamics. There are a finite number of players who repeatedly update from a finite number of available languages/signaling strategies. Players imitate the most fit agents with high probability or mutate with low probability. We analyze the long-run distribution of states and show that, for sufficiently small mutation probability, its support is limited to efficient communication systems. We find that this behavior is insensitive to the particular choice of evolutionary dynamic, a property that is due to the game having a potential structure with a potential function corresponding to average fitness. Consequently, the model supports conclusions similar to those found in the literature on language competition. That is, we show that efficient languages eventually predominate the society while reproducing the empirical phenomenon of linguistic drift. The emergence of efficiency in the atomic case can be contrasted with results for non-atomic signaling games that establish the non-negligible possibility of convergence, under replicator dynamics, to states of unbounded efficiency loss.

  20. Method for acoustic signal detection

    International Nuclear Information System (INIS)

    Blalock, S.E.

    1980-01-01

    The disclosure relates to a method and apparatus for acoustic signal detection, adapted for use in acoustic velocity well logging to measure the difference in transit times of an acoustic signal between a transmitter and two or more receivers. In a preferred embodiment of the present invention two timing measurements of the signal arriving at each of two receivers may be made by activating zero crossing detectors at the arrival of the first negative and first positive half-cycles at each receiver. A transit time is calculated from the zero crossing times following the first negative half-cycle. This first transit time may be checked for accuracy by comparing the first transit time with a second transit time calculated from zero crossing times following the first positive half-cycles, by comparing the first transit time to a previously measured transit time and/or by detecting the order of arrival of the negative and positive half-cycles to determine whether the half-cycles have been detected out of sequence at either receiver. Should the first transit time be determined to be inaccurate, the previously measured transit time or the second transit time may be substituted therefor

  1. Characterization of arsenic trioxide resistant clones derived from Jurkat leukemia T cell line: focus on PI3K/Akt signaling pathway.

    Science.gov (United States)

    Roszak, Joanna; Smok-Pieniążek, Anna; Nocuń, Marek; Stępnik, Maciej

    2013-10-05

    In this study the role of PI3K/Akt signaling pathway in arsenic trioxide (ATO)-treated parental Jurkat cells and also in derived ATO-resistant clones grown in the presence of given ATO concentration was investigated. ATO-resistant clones (cultured for 8-12weeks in the presence of 1, 2.5 and 5μM ATO) were characterized by high viability in the presence of ATO but slower growth rate compared to the parental cells. Morphological and functional characterization of derived ATO-resistant clones revealed that they did not differ fundamentally from parental Jurkat cells in terms of cell size, level of GSH, the lysosomal fluorescence or CD95/Fas surface antigen expression. However, a slight increase in the mitochondrial potential (JC-1 staining) was detected in the clones compared to parental Jurkat cells. Side population analysis (Vybrant DyeCycle Violet™ staining) in ATO resistant clones did not indicate any enrichment withcancer stem cells. Akt1/2, AktV or wortmannin inhibitors decreased viability of ATO-resistant clones grown in the presence of ATO, with no effect on ATO-treated parental cells. Flow cytometry analysis showed that ATO decreased the level of p-Akt in ATO-treated parental cells, while the resistant clones exhibited higher levels of p-Akt immunostaining than parental Jurkat cells. Expression analysis of 84 genes involved in the PI3K/Akt pathway revealed that this pathway was predominantly active in ATO-resistant clones. c-JUN seems to play a key role in the induction of cell death in ATO-treated parental Jurkat cells, as dose-dependent strong up-regulation of JUN was specific for the ATO-treated parental Jurkat cells. On the other hand, changes in expression of cyclin D1 (CCND1), insulin receptor substrate 1 (IRS1) and protein kinase C isoforms (PRKCZ,PRKCB and PRKCA) may be responsible for the induction of resistance to ATO. The changes in expression of growth factor receptor-bound protein 10 (GRB10) observed in ATO-resistant clones suggest a

  2. Regulation of TGF-β Signal Transduction.

    Science.gov (United States)

    Zhao, Bing; Chen, Ye-Guang

    2014-01-01

    Transforming growth factor-β (TGF-β) signaling regulates diverse cellular processes, including cell proliferation, differentiation, apoptosis, cell plasticity, and migration. TGF-β signaling can be mediated by Smad proteins or other signaling proteins such as MAP kinases and Akt. TGF-β signaling is tightly regulated at different levels along the pathways to ensure its proper physiological functions in different cells and tissues. Deregulation of TGF-β signaling has been associated with various kinds of diseases, such as cancer and tissue fibrosis. This paper focuses on our recent work on regulation of TGF-β signaling.

  3. Advanced digital signal processing and noise reduction

    CERN Document Server

    Vaseghi, Saeed V

    2008-01-01

    Digital signal processing plays a central role in the development of modern communication and information processing systems. The theory and application of signal processing is concerned with the identification, modelling and utilisation of patterns and structures in a signal process. The observation signals are often distorted, incomplete and noisy and therefore noise reduction, the removal of channel distortion, and replacement of lost samples are important parts of a signal processing system. The fourth edition of Advanced Digital Signal Processing and Noise Reduction updates an

  4. Detection of Noise in Composite Step Signal Pattern by Visualizing Signal Waveforms

    Directory of Open Access Journals (Sweden)

    Chaman Verma

    2018-03-01

    Full Text Available The Step Composite Signals is the combination of vital informative signals that are compressed and coded to produce a predefined test image on a display device. It carries the desired sequence of information from source to destination. This information may be transmitted as digital signal, video information or data signal required as an input for the destination module. For testing of display panels, Composite Test Signals are the most important attribute of test signal transmission system. In the current research paper we present an approach for the noise detection in Composite Step Signal by analysing Composite Step Signal waveforms. The analysis of the signal waveforms reveals that the noise affected components of the signal and subsequently noise reduction process is initiated which targets noisy signal component only. Thus the quality of signal is not compromised during noise reduction process.

  5. Thermoregulation constrains effective warning signal expression.

    Science.gov (United States)

    Lindstedt, Carita; Lindström, Leena; Mappes, Johanna

    2009-02-01

    Evolution of conspicuous signals may be constrained if animal coloration has nonsignaling as well as signaling functions. In aposematic wood tiger moth (Parasemia plantaginis) larvae, the size of a warning signal (orange patch on black body) varies phenotypically and genetically. Although a large warning signal is favored as an antipredator defense, we hypothesized that thermoregulation may constrain the signal size in colder habitats. To test this hypothesis, we conducted a factorial rearing experiment with two selection lines for larval coloration (small and large signal) and with two temperature manipulations (high and low temperature environment). Temperature constrained the size and brightness of the warning signal. Larvae with a small signal had an advantage in the colder environment, which was demonstrated by a faster development time and growth rate in the low temperature treatment, compared to larvae with a large signal. Interestingly, the larvae with a small signal were found more often on the plant than the ones with a large signal, suggesting higher basking activity of the melanic (small signal) individuals in the low temperature. We conclude that the expression of aposematic display is not only defined by its efficacy against predators; variation in temperature may constrain evolution of a conspicuous warning signal and maintain variation in it.

  6. Silicon Photonics for Signal Processing of Tbit/s Serial Data Signals

    DEFF Research Database (Denmark)

    Oxenløwe, Leif Katsuo; Ji, Hua; Galili, Michael

    2012-01-01

    In this paper, we describe our recent work on signal processing of terabit per second optical serial data signals using pure silicon waveguides. We employ nonlinear optical signal processing in nanoengineered silicon waveguides to perform demultiplexing and optical waveform sampling of 1.28-Tbit....../s data signals as well as wavelength conversion of up to 320-Gbit/s data signals. We demonstrate that the silicon waveguides are equally useful for amplitude and phase-modulated data signals....

  7. Neutrino signals from dark matter

    Science.gov (United States)

    Erkoca, Arif Emre

    Large-scale neutrino telescopes will be powerful tools to observe multitude of mysterious phenomena happening in the Universe. The dark matter puzzle is listed as one of them. In this study, indirect detection of dark matter via neutrino signals is presented. The upward muon, the contained muon and the hadronic shower fluxes are calculated, assuming annihilation/decay of the dark matter in the core of the astrophysical objects and in the Galactic center. Direct neutrino production and secondary neutrino production from the decay of Standard Model particles produced in the annihilation/decay of dark matter are studied. The results are contrasted to the ones previously obtained in the literature, illustrating the importance of properly treating muon propagation and energy loss for the upward muon flux. The dependence of the dark matter signals on the density profile, the dark matter mass and the detector threshold are discussed. Different dark matter models (gravitino, Kaluza-Klein and leptophilic) which can account for recent observations of some indirect searches are analyzed regarding their detection in the kilometer size neutrino detectors in the near future. Muon and shower rates and the minimum observation times in order to reach 2sigma detection significance are evaluated, with the result suggesting that the optimum cone half angles chosen about the Galactic center are about 10° (50°) for the muon (shower) events. A detailed analysis shows that for the annihilating dark matter models such as the leptophilic and Kaluza-Klein models, upward and contained muon as well as showers yield promising signals for dark matter detection in just a few years of observation, whereas for decaying dark matter models, the same observation times can only be reached with showers. The analytical results for the final fluxes are also obtained as well as parametric forms for the muon and shower fluxes for the dark matter models considered in this study.

  8. Biomedical signals, imaging, and informatics

    CERN Document Server

    Bronzino, Joseph D

    2014-01-01

    Known as the bible of biomedical engineering, The Biomedical Engineering Handbook, Fourth Edition, sets the standard against which all other references of this nature are measured. As such, it has served as a major resource for both skilled professionals and novices to biomedical engineering.Biomedical Signals, Imaging, and Informatics, the third volume of the handbook, presents material from respected scientists with diverse backgrounds in biosignal processing, medical imaging, infrared imaging, and medical informatics.More than three dozen specific topics are examined, including biomedical s

  9. Fixed-point signal processing

    CERN Document Server

    Padgett, Wayne T

    2009-01-01

    This book is intended to fill the gap between the ""ideal precision"" digital signal processing (DSP) that is widely taught, and the limited precision implementation skills that are commonly required in fixed-point processors and field programmable gate arrays (FPGAs). These skills are often neglected at the university level, particularly for undergraduates. We have attempted to create a resource both for a DSP elective course and for the practicing engineer with a need to understand fixed-point implementation. Although we assume a background in DSP, Chapter 2 contains a review of basic theory

  10. New shaper of scintillation signals

    International Nuclear Information System (INIS)

    Brovchenko, V.G.

    2001-01-01

    Summation of the exponential shape pulse (abrupt front, exponential fall-off) with the pulse, proportional to its integral (the integration time constant is equal to the exponent fall-off constant), results in the pulse, the apex whereof is horizontal (parallel to the base line). Such a pulse is suitable for registration through standard analog-to-digital converters of the consecutive binary approximation, The described scheme is accomplished for verification of the basic principle of the shaper action. The parameters of the scheme are approximated to those ones, necessary for processing scintillation signals NaI(Tl) [ru

  11. Small signal microwave amplifier design

    CERN Document Server

    Grosch, Theodore

    2000-01-01

    This book explains techniques and examples for designing stable amplifiers for high-frequency applications in which the signal is small and the amplifier circuit is linear. An in-depth discussion of linear network theory provides the foundation needed to develop actual designs. Examples throughout the book will show you how to apply the knowledge gained in each chapter leading to the complex design of low noise amplifiers. Many exercises at the end of each chapter will help students to practice their skills. The solutions to these design problems are available in an accompanying solutions book

  12. Expert AE signal arrival detection

    Czech Academy of Sciences Publication Activity Database

    Chlada, Milan; Převorovský, Zdeněk

    2011-01-01

    Roč. 6, 3/4 (2011), s. 191-205 ISSN 1741-8410. [NDT in PROGRESS /4./. Praha, 05.11.2007-07.11.2007] R&D Projects: GA MPO(CZ) FR-TI1/274; GA ČR GA101/07/1518 Institutional research plan: CEZ:AV0Z20760514 Keywords : acoustic emission * signal arrival detection Subject RIV: BI - Acoustics http://www.inderscience.com/search/index.php?mainAction=search&action=record&rec_id=43215&prevQuery=&ps=10&m=or

  13. Signaling and the Education Premium

    OpenAIRE

    Gregory Kurtzon

    2004-01-01

    A large portion of the rise in the education premium can be explained by a signaling theory of education which predicts that in the future, increases in the education level of the workforce will actually cause the education premium to rise, simply because different workers are being labeled as “highly educated†. This prediction is supported by past behavior of the high school education premium. It runs counter to the view that increases in the relative supply of high education workers wil...

  14. Digital Signal Processing Based Biotelemetry Receivers

    Science.gov (United States)

    Singh, Avtar; Hines, John; Somps, Chris

    1997-01-01

    This is an attempt to develop a biotelemetry receiver using digital signal processing technology and techniques. The receiver developed in this work is based on recovering signals that have been encoded using either Pulse Position Modulation (PPM) or Pulse Code Modulation (PCM) technique. A prototype has been developed using state-of-the-art digital signal processing technology. A Printed Circuit Board (PCB) is being developed based on the technique and technology described here. This board is intended to be used in the UCSF Fetal Monitoring system developed at NASA. The board is capable of handling a variety of PPM and PCM signals encoding signals such as ECG, temperature, and pressure. A signal processing program has also been developed to analyze the received ECG signal to determine heart rate. This system provides a base for using digital signal processing in biotelemetry receivers and other similar applications.

  15. Circuit processing pulsed signals from nuclear detector

    International Nuclear Information System (INIS)

    Kalfod Nielsen, H.

    1990-01-01

    A circuit for processing signals from a detector and occuring at random time intervals has a pulse-shaper, a delay and a processing circuit. The signal path is divided over part of its extent into parallel part-signal paths, each including an electronic switch and signal modifying circuits, a discriminator to detect a signal in the path and a control circuit for the switches and controlled by the discriminator being connected to the path ahead of the delay. The parallel paths are identical and the switch in each is ahead of the modifying circuits. When the discriminator detects a signal in the path the switch in on part path is made to conduct for at least as long as the duration of the signal as detected by the discriminator. The switches are preferable made to conduct cyclically. Processes increased number of signals, with quality of results not dependent on pulse rate and risk of errors substantially reduced. (au)

  16. Surface Weather, Signal Service and Weather Bureau

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Surface Weather, Signal Service and Weather Bureau (SWSSWB) Records primarily created by the United States Army Signal Service from 1819 until the paid and voluntary...

  17. Extracellular matrix component signaling in cancer

    DEFF Research Database (Denmark)

    Multhaupt, Hinke A. B.; Leitinger, Birgit; Gullberg, Donald

    2016-01-01

    Cell responses to the extracellular matrix depend on specific signaling events. These are important from early development, through differentiation and tissue homeostasis, immune surveillance, and disease pathogenesis. Signaling not only regulates cell adhesion cytoskeletal organization...

  18. 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

  19. A fully reconfigurable photonic integrated signal processor

    Science.gov (United States)

    Liu, Weilin; Li, Ming; Guzzon, Robert S.; Norberg, Erik J.; Parker, John S.; Lu, Mingzhi; Coldren, Larry A.; Yao, Jianping

    2016-03-01

    Photonic signal processing has been considered a solution to overcome the inherent electronic speed limitations. Over the past few years, an impressive range of photonic integrated signal processors have been proposed, but they usually offer limited reconfigurability, a feature highly needed for the implementation of large-scale general-purpose photonic signal processors. Here, we report and experimentally demonstrate a fully reconfigurable photonic integrated signal processor based on an InP-InGaAsP material system. The proposed photonic signal processor is capable of performing reconfigurable signal processing functions including temporal integration, temporal differentiation and Hilbert transformation. The reconfigurability is achieved by controlling the injection currents to the active components of the signal processor. Our demonstration suggests great potential for chip-scale fully programmable all-optical signal processing.

  20. Seafloor backscatter signal simulation and classification

    Digital Repository Service at National Institute of Oceanography (India)

    Mahale, V.; El Dine, W.G.; Chakraborty, B.

    In this paper, simulation study is initiated to observe the interaction effect of the sound signal with different seafloors types and its classification. Simulation of the echo envelope signal is done by accurately formulating a mathematical model...

  1. Optical unmasking of spectrally overlapping RF signals.

    Science.gov (United States)

    Loh, William; Yegnanarayanan, Siva; Kolodziej, Kenneth E; Juodawlkis, Paul W

    2017-10-30

    When two signals having overlapping frequency content are received at the same time, they interfere to obstruct detection of the information carried by each individual signal. We introduce here a new nonlinear optoelectronic filtering technique that enables the ability to individually detect two concurrent and spectrally overlapping signals, even when the amplitude ratio between the signals is as high as 100,000. We demonstrate our system for application in steganography where we unveil the information carried by a hidden desired RF signal, while a dominant interferer signal is intentionally transmitted nearby and at the same frequency. Our signal recovery technique, which operates assuming no a priori knowledge of either signal, presents an additional pathway that can be used to control how information can be processed and communicated.

  2. Molecular deregulation of signaling in lymphoid tumors.

    Science.gov (United States)

    Spina, Valeria; Martuscelli, Lavinia; Rossi, Davide

    2015-10-01

    Genomic studies have led to a significant impact both on the pace and the nature of understanding the molecular and biological bases of a variety of lymphoid tumors. An increasingly emerging aspect from genomic studies is that malignant lymphoid cells manipulate signaling pathways that are central to the homeostasis of their normal counterpart, including B- and T-cell receptor signaling, NF-κB signaling, Toll-like receptor signaling, cytokine signaling, MAP kinase signaling, and NOTCH signaling. This review aims at covering the signaling pathways that are affected by mutations in lymphoid tumors, and how genetic alteration of these pathways may contribute to disease pathogenesis and management. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  3. Detection of Transient Signals in Doppler Spectra

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Signal processing is used to detect transient signals in the presence of noise. Two embodiments are disclosed. In both embodiments, the time series from a remote...

  4. Computer derivation of some dolphin echolocation signals.

    Science.gov (United States)

    Altes, R A

    1971-09-03

    Recent advances in radar theory have given rise to a straightforward method of sonar signal design. The method involves computer maximization of a signal-to-interference ratio. The procedure has been used to derive sonar signals that can accurately measure target velocity. When two dolphins were placed in a situation conducive to the utilization of such signals, their waveforms were similar to those that had been theoretically derived.

  5. Generation of medium frequency electrotherapeutic signals

    Science.gov (United States)

    Płaza, Mirosław; Szcześniak, Zbigniew; Dudek, Jolanta

    2017-08-01

    In this paper, generation methods of sinusoidal medium frequency electrotherapeutic signals have been studied. Signals of this type are increasingly used in electrotherapy owing to the development of both physical medicine and engineering sciences. The article presents analysis and comparison of analogue and digital methods of generation therapeutic signals. Analysis presented in the paper attempts to answer the question which technique of medium frequency signal generation can be most broadly applied in electrotherapy methods.

  6. A Recognition Method for MIMO DUSTC Signals

    Directory of Open Access Journals (Sweden)

    Qian Bo

    2017-01-01

    Full Text Available For recognizing the MIMO DUSTC signals without a priori knowledge, a blind recognition method is presented. By estimating the number of transmitting antennas, separating the mixed signals, and recognizing modulation, the unitary matrices S is estimated by statistics and DUSTC signals are recognized. The simulation results showed that the method was effectively to recognize DUSTC signals with the SNR no less than 4dB.

  7. Bistability in biochemical signaling models.

    Science.gov (United States)

    Sobie, Eric A

    2011-09-20

    This Teaching Resource provides lecture notes, slides, and a student assignment for a two-part lecture on the principles underlying bistability in biochemical signaling networks, which are illustrated with examples from the literature. The lectures cover analog, or graded, versus digital, all-or-none, responses in cells, with examples from different types of biological processes requiring each. Rate-balance plots are introduced as a method for determining whether generic one-variable systems exhibit one or several stable steady states. Bifurcation diagrams are presented as a more general method for detecting the presence of bistability in biochemical signaling networks. The examples include an artificial toggle switch, the lac operon in bacteria, and the mitogen-activated protein kinase cascade in both Xenopus oocytes and mammalian cells. The second part of the lecture links the concepts of bistability more closely to the mathematical tools provided by dynamical systems analysis. The examples from the first part of the lecture are analyzed with phase-plane techniques and bifurcation analysis, using the scientific programming language MATLAB. Using these programs as a template, the assignment requires the students to implement a model from the literature and analyze the stability of this model's steady states.

  8. Motion signals bias localization judgments

    Science.gov (United States)

    Eagleman, David M.; Sejnowski, Terrence J.

    2008-01-01

    In the flash-lag illusion, a moving object aligned with a flash is perceived to be offset in the direction of motion following the flash. In the “flash-drag” illusion, a flash is mislocalized in the direction of nearby motion. In the “flash-jump” illusion, a transient change in the appearance of a moving object (e.g., color) is mislocalized in the direction of subsequent motion. Finally, in the Frohlich illusion, the starting position of a suddenly appearing moving object is mislocalized in the direction of the subsequent motion. We demonstrate, in a series of experiments, a unified explanation for all these illusions: Perceptual localization is influenced by motion signals collected over ∼80 ms after a query is triggered. These demonstrations rule out “latency difference” and asynchronous feature binding models, in which objects appear in their real positions but misaligned in time. Instead, the illusions explored here are best understood as biases in localization caused by motion signals. We suggest that motion biasing exists because it allows the visual system to account for neural processing delays by retrospectively “pushing” an object closer to its true physical location, and we propose directions for exploring the neural mechanisms underlying the dynamic updating of location by the activity of motion-sensitive neurons. PMID:17461687

  9. Redox signaling in acute pancreatitis

    Science.gov (United States)

    Pérez, Salvador; Pereda, Javier; Sabater, Luis; Sastre, Juan

    2015-01-01

    Acute pancreatitis is an inflammatory process of the pancreatic gland that eventually may lead to a severe systemic inflammatory response. A key event in pancreatic damage is the intracellular activation of NF-κB and zymogens, involving also calcium, cathepsins, pH disorders, autophagy, and cell death, particularly necrosis. This review focuses on the new role of redox signaling in acute pancreatitis. Oxidative stress and redox status are involved in the onset of acute pancreatitis and also in the development of the systemic inflammatory response, being glutathione depletion, xanthine oxidase activation, and thiol oxidation in proteins critical features of the disease in the pancreas. On the other hand, the release of extracellular hemoglobin into the circulation from the ascitic fluid in severe necrotizing pancreatitis enhances lipid peroxidation in plasma and the inflammatory infiltrate into the lung and up-regulates the HIF–VEGF pathway, contributing to the systemic inflammatory response. Therefore, redox signaling and oxidative stress contribute to the local and systemic inflammatory response during acute pancreatitis. PMID:25778551

  10. Signal Incongruence and its Consequences

    DEFF Research Database (Denmark)

    Vergne, Jean-Philippe; Wernicke, Maria Stokholm; Brenner, Steffen

    2018-01-01

    We draw on the signaling and infomediary literatures to examine how media evaluations of CEO overcompensation (a negative cue associated with selfishness and greed) are affected by the presence of corporate philanthropy (a positive cue associated with altruism and generosity). In line with our th...... and damage media evaluations of firms and CEOs. Taken together, these findings shed new light on the media as agents of external corporate governance for firms and open new avenues for research on executive compensation.......We draw on the signaling and infomediary literatures to examine how media evaluations of CEO overcompensation (a negative cue associated with selfishness and greed) are affected by the presence of corporate philanthropy (a positive cue associated with altruism and generosity). In line with our...... incongruence, and to infomediary and corporate governance research by showing that media disapproval can lead to lower executive compensation. We also reconcile two conflicting views on firm prosocial behavior by showing that, in the presence of incongruent cues, philanthropy can simultaneously enhance...

  11. Simulation of Silicon Photomultiplier Signals

    Science.gov (United States)

    Seifert, Stefan; van Dam, Herman T.; Huizenga, Jan; Vinke, Ruud; Dendooven, Peter; Lohner, Herbert; Schaart, Dennis R.

    2009-12-01

    In a silicon photomultiplier (SiPM), also referred to as multi-pixel photon counter (MPPC), many Geiger-mode avalanche photodiodes (GM-APDs) are connected in parallel so as to combine the photon counting capabilities of each of these so-called microcells into a proportional light sensor. The discharge of a single microcell is relatively well understood and electronic models exist to simulate this process. In this paper we introduce an extended model that is able to simulate the simultaneous discharge of multiple cells. This model is used to predict the SiPM signal in response to fast light pulses as a function of the number of fired cells, taking into account the influence of the input impedance of the SiPM preamplifier. The model predicts that the electronic signal is not proportional to the number of fired cells if the preamplifier input impedance is not zero. This effect becomes more important for SiPMs with lower parasitic capacitance (which otherwise is a favorable property). The model is validated by comparing its predictions to experimental data obtained with two different SiPMs (Hamamatsu S10362-11-25u and Hamamatsu S10362-33-25c) illuminated with ps laser pulses. The experimental results are in good agreement with the model predictions.

  12. Interfering signals and digital measurements

    International Nuclear Information System (INIS)

    Stulik, P.; Pilat, M.

    1976-01-01

    The possible occurrence was studied of unweighted voltage interference in measuring channels and the effect of the voltage on the measuring system where digital technology is used in the WWR-S reactor experimental loops. Various types of voltmeters were evaluated in the gas loop during measurements of the output signals of a Ni-NiCr jacket thermocouple, this both with an insulated and a noninsulated end. Also studied was digital measurement in measuring channels with vanadium SPN detectors. Two identical detectors were installed in the middle of the core and, assuming an identical neutron flux for both detectors, the effects were investigated of a different cable route design, of the combination of the connection of measuring central input circuits on the size of fluctuations of the measured output signal of both detectors, etc. The optimal value was also studied of the loading resistor incorporated in the measuring circuit. The relation was derived for digital measurement accuracy. It was confirmed experimentally and by calculation that unweighted voltage in series has the greatest effect on measurement accuracy. (Z.M.)

  13. Cytoskeleton in Mast Cell Signaling

    Science.gov (United States)

    Dráber, Pavel; Sulimenko, Vadym; Dráberová, Eduarda

    2012-01-01

    Mast cell activation mediated by the high affinity receptor for IgE (FcεRI) is a key event in allergic response and inflammation. Other receptors on mast cells, as c-Kit for stem cell factor and G protein-coupled receptors (GPCRs) synergistically enhance the FcεRI-mediated release of inflammatory mediators. Activation of various signaling pathways in mast cells results in changes in cell morphology, adhesion to substrate, exocytosis, and migration. Reorganization of cytoskeleton is pivotal in all these processes. Cytoskeletal proteins also play an important role in initial stages of FcεRI and other surface receptors induced triggering. Highly dynamic microtubules formed by αβ-tubulin dimers as well as microfilaments build up from polymerized actin are affected in activated cells by kinases/phosphatases, Rho GTPases and changes in concentration of cytosolic Ca2+. Also important are nucleation proteins; the γ-tubulin complexes in case of microtubules or Arp 2/3 complex with its nucleation promoting factors and formins in case of microfilaments. The dynamic nature of microtubules and microfilaments in activated cells depends on many associated/regulatory proteins. Changes in rigidity of activated mast cells reflect changes in intermediate filaments build up from vimentin. This review offers a critical appraisal of current knowledge on the role of cytoskeleton in mast cells signaling. PMID:22654883

  14. Polyphenol compounds and PKC signaling.

    Science.gov (United States)

    Das, Joydip; Ramani, Rashmi; Suraju, M Olufemi

    2016-10-01

    Naturally occurring polyphenols found in food sources provide huge health benefits. Several polyphenolic compounds are implicated in the prevention of disease states, such as cancer. One of the mechanisms by which polyphenols exert their biological actions is by interfering in the protein kinase C (PKC) signaling pathways. PKC belongs to a superfamily of serine-threonine kinase and are primarily involved in phosphorylation of target proteins controlling activation and inhibition of many cellular processes directly or indirectly. Despite the availability of substantial literature data on polyphenols' regulation of PKC, no comprehensive review article is currently available on this subject. This article reviews PKC-polyphenol interactions and its relevance to various disease states. In particular, salient features of polyphenols, PKC, interactions of naturally occurring polyphenols with PKC, and future perspective of research on this subject are discussed. Some polyphenols exert their antioxidant properties by regulating the transcription of the antioxidant enzyme genes through PKC signaling. Regulation of PKC by polyphenols is isoform dependent. The activation or inhibition of PKC by polyphenols has been found to be dependent on the presence of membrane, Ca(2+) ion, cofactors, cell and tissue types etc. Two polyphenols, curcumin and resveratrol are in clinical trials for the treatment of colon cancer. The fact that 74% of the cancer drugs are derived from natural sources, naturally occurring polyphenols or its simple analogs with improved bioavailability may have the potential to be cancer drugs in the future. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Prostaglandin Receptor Signaling in Disease

    Directory of Open Access Journals (Sweden)

    Toshiyuki Matsuoka

    2007-01-01

    Full Text Available Prostanoids, consisting of the prostaglandins (PGs and the thromboxanes (TXs, are a group of lipid mediators formed in response to various stimuli. They include PGD2, PGE2, PGF2α, PGI2, and TXA2. They are released outside of the cells immediately after synthesis, and exert their actions by binding to a G-protein coupled rhodopsin-type receptor on the surface of target cells. There are eight types of the prostanoid receptors conserved in mammals from mouse to human. They are the PGD receptor (DP, four subtypes of the PGE receptor (EP1, EP2, EP3, and EP4, the PGF receptor (FP, PGI receptor (IP, and TXA receptor (TP. Recently, mice deficient in each of these prostanoid receptors were generated and subjected to various experimental models of disease. These studies have revealed the roles of PG receptor signaling in various pathological conditions, and suggest that selective manipulation of the prostanoid receptors may be beneficial in treatment of the pathological conditions. Here we review these recent findings of roles of prostanoid receptor signaling and their therapeutic implications.

  16. TOR Signaling and Nutrient Sensing.

    Science.gov (United States)

    Dobrenel, Thomas; Caldana, Camila; Hanson, Johannes; Robaglia, Christophe; Vincentz, Michel; Veit, Bruce; Meyer, Christian

    2016-04-29

    All living organisms rely on nutrients to sustain cell metabolism and energy production, which in turn need to be adjusted based on available resources. The evolutionarily conserved target of rapamycin (TOR) protein kinase is a central regulatory hub that connects environmental information about the quantity and quality of nutrients to developmental and metabolic processes in order to maintain cellular homeostasis. TOR is activated by both nitrogen and carbon metabolites and promotes energy-consuming processes such as cell division, mRNA translation, and anabolism in times of abundance while repressing nutrient remobilization through autophagy. In animals and yeasts, TOR acts antagonistically to the starvation-induced AMP-activated kinase (AMPK)/sucrose nonfermenting 1 (Snf1) kinase, called Snf1-related kinase 1 (SnRK1) in plants. This review summarizes the immense knowledge on the relationship between TOR signaling and nutrients in nonphotosynthetic organisms and presents recent findings in plants that illuminate the crucial role of this pathway in conveying nutrient-derived signals and regulating many aspects of metabolism and growth.

  17. Extracellular nucleotide signaling in plants

    Energy Technology Data Exchange (ETDEWEB)

    Stacey, Gary [Univ. of Missouri, Columbia, MO (United States)

    2016-09-08

    Over the life of this funded project, our research group identified and characterized two key receptor proteins in plants; one mediating the innate immunity response to chitin and the other elucidating the key receptor for extracellular ATP. In the case of chitin recognition, we recently described the quaternary structure of this receptor, shedding light on how the receptor functions. Perhaps more importantly, we demonstrated that all plants have the ability to recognize both chitin oligomers and lipochitooligosacchardes, fundamentally changing how the community views the evolution of these systems and strategies that might be used, for example, to extend symbiotic nitrogen fixation to non-legumes. Our discovery of DORN1 opens a new chapter in plant physiology documenting conclusively that eATP is an important extracellular signal in plants, as it is in animals. At this point, we cannot predict just how far reaching this discovery may prove to be but we are convinced that eATP signaling is fundamental to plant growth and development and, hence, we believe that the future will be very exciting for the study of DORN1 and its overall function in plants.

  18. Signals of lepton number violation

    CERN Document Server

    Panella, O; Srivastava, Y N

    1999-01-01

    The production of like-sign-dileptons (LSD), in the high energy lepton number violating ( Delta L=+2) reaction, pp to 2jets+l/sup +/l /sup +/, (l=e, mu , tau ), of interest for the experiments to be performed at the forthcoming Large Hadron Collider (LHC), is reported, taking up a composite model scenario in which the exchanged virtual composite neutrino is assumed to be a Majorana particle. Numerical estimates of the corresponding signal cross-section that implement kinematical cuts needed to suppress the standard model background, are presented which show that in some regions of the parameter space the total number of LSD events is well above the background. Assuming non-observation of the LSD signal it is found that LHC would exclude a composite Majorana neutrino up to 700 GeV (if one requires 10 events for discovery). The sensitivity of LHC experiments to the parameter space is then compared to that of the next generation of neutrinoless double beta decay ( beta beta /sub 0 nu /) experiment, GENIUS, and i...

  19. 40 CFR 156.64 - Signal word.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Signal word. 156.64 Section 156.64... REQUIREMENTS FOR PESTICIDES AND DEVICES Human Hazard and Precautionary Statements § 156.64 Signal word. (a... signal word, reflecting the highest Toxicity Category (Category I is the highest toxicity category) to...

  20. METHOD AND DEVICE FOR PROCESSING A SIGNAL

    NARCIS (Netherlands)

    Van Nee, D.J.R.

    1995-01-01

    Abstract of CA 2109759 (A1) A method and device for processing a signal are described, wherein an estimate of a multipath-induced contribution to a demodulated navigation signal is calculated and subtracted from said demodulated navigation signal to obtain an estimated line of sight contribution to

  1. The intraflagellar transport machinery in ciliary signaling

    DEFF Research Database (Denmark)

    Mourão, André; Christensen, Søren Tvorup; Lorentzen, Esben

    2016-01-01

    environmental cues necessary for organ development and maintenance of human health. Pathways reported to rely on the cilium organelle include Hedgehog, TGF-β, Wnt, PDGFRα, integrin and DNA damage repair signaling. An emerging theme in ciliary signaling is the requirement for active transport of signaling...

  2. Next Steps in Signaling (NSIS): Framework

    NARCIS (Netherlands)

    Hancock, R.; Loughney, J.; van den Bosch, S.; Hancock, R.; Karagiannis, Georgios; Loughney, J.; van den Bosch, S.

    The Next Steps in Signaling (NSIS) working group is considering protocols for signaling information about a data flow along its path in the network. The NSIS suite of protocols is envisioned to support various signaling applications that need to install and/or manipulate such state in the network.

  3. Light signal perception in Arabidopsis rosettes

    NARCIS (Netherlands)

    Evers, J.B.; Pierik, R.; Krol, van der A.R.

    2013-01-01

    Light signals are important signals for future and present competition. We used an architectural model of Arabidopsis development to show that vertical growth of neighboring vegetation is more important than proximity for early detection of competition. Self-signaling is greatly enhanced when own

  4. Nonstationary weak signal detection based on normalization ...

    Indian Academy of Sciences (India)

    ... than the traditional stochastic resonance. The method develops the area of time-varying signal detection with stochastic resonance and presents new strategy for detection and denoising of a time-varying signal. It can be expected to be widely used in the areas of aperiodic signal processing, radar communication,etc ...

  5. Simulated evolution of signal transduction networks.

    Directory of Open Access Journals (Sweden)

    Mohammad Mobashir

    Full Text Available Signal transduction is the process of routing information inside cells when receiving stimuli from their environment that modulate the behavior and function. In such biological processes, the receptors, after receiving the corresponding signals, activate a number of biomolecules which eventually transduce the signal to the nucleus. The main objective of our work is to develop a theoretical approach which will help to better understand the behavior of signal transduction networks due to changes in kinetic parameters and network topology. By using an evolutionary algorithm, we designed a mathematical model which performs basic signaling tasks similar to the signaling process of living cells. We use a simple dynamical model of signaling networks of interacting proteins and their complexes. We study the evolution of signaling networks described by mass-action kinetics. The fitness of the networks is determined by the number of signals detected out of a series of signals with varying strength. The mutations include changes in the reaction rate and network topology. We found that stronger interactions and addition of new nodes lead to improved evolved responses. The strength of the signal does not play any role in determining the response type. This model will help to understand the dynamic behavior of the proteins involved in signaling pathways. It will also help to understand the robustness of the kinetics of the output response upon changes in the rate of reactions and the topology of the network.

  6. Proteomics insights into plant signaling and development.

    NARCIS (Netherlands)

    Kaufmann, K.; Smaczniak, C.D.; Vries, de S.C.; Angenent, G.C.; Karlova, R.B.

    2011-01-01

    Mass spectrometry-based proteomics is used to gain insight into the abundance and subcellular localization of cellular signaling components, the composition of molecular complexes and the regulation of signaling pathways. Multicellular organisms have evolved signaling networks and fast responses to

  7. 78 FR 55648 - Signal Booster Rules

    Science.gov (United States)

    2013-09-11

    ... facilitate review of wireless providers' behavior regarding Consumer Signal Boosters, the R&O requires that... regarding consent for each Consumer Signal Booster that has received FCC certification as listed in a Public... each listed Consumer Signal Booster, wireless providers should publicly indicate whether they (1...

  8. Radar signal analysis and processing using Matlab

    CERN Document Server

    Mahafza, Bassem R

    2008-01-01

    Offering radar-related software for the analysis and design of radar waveform and signal processing, this book provides comprehensive coverage of radar signals and signal processing techniques and algorithms. It contains numerous graphical plots, common radar-related functions, table format outputs, and end-of-chapter problems. The complete set of MATLAB[registered] functions and routines are available for download online.

  9. Cost Discrepancy, Signaling, and Risk Taking

    Science.gov (United States)

    Lemon, Jim

    2005-01-01

    If risk taking is in some measure a signal to others by the person taking risks, the model of "costly signaling" predicts that the more the apparent cost of the risk to others exceeds the perceived cost of the risk to the risk taker, the more attractive that risk will be as a signal. One hundred and twelve visitors to youth…

  10. Syndecan signaling: when, where and why?

    DEFF Research Database (Denmark)

    Multhaupt, H A B; Yoneda, A; Whiteford, J R

    2009-01-01

    make important interactions and/or signalling contributions. It has been established that all syndecans can interact with proteins of the actin-associated cytoskeleton, but details of signalling have been harder to ascertain. However, it appears that Syndecans can signal, primarily to the cytoskeleton...

  11. Temporal expectation weights visual signals over auditory signals.

    Science.gov (United States)

    Menceloglu, Melisa; Grabowecky, Marcia; Suzuki, Satoru

    2017-04-01

    Temporal expectation is a process by which people use temporally structured sensory information to explicitly or implicitly predict the onset and/or the duration of future events. Because timing plays a critical role in crossmodal interactions, we investigated how temporal expectation influenced auditory-visual interaction, using an auditory-visual crossmodal congruity effect as a measure of crossmodal interaction. For auditory identification, an incongruent visual stimulus produced stronger interference when the crossmodal stimulus was presented with an expected rather than an unexpected timing. In contrast, for visual identification, an incongruent auditory stimulus produced weaker interference when the crossmodal stimulus was presented with an expected rather than an unexpected timing. The fact that temporal expectation made visual distractors more potent and visual targets less susceptible to auditory interference suggests that temporal expectation increases the perceptual weight of visual signals.

  12. Signal trend identification with fuzzy methods

    International Nuclear Information System (INIS)

    Reifman, J.; Tsoukalas, L. H.; Wang, X.; Wei, T. Y. C.

    1999-01-01

    A fuzzy-logic-based methodology for on-line signal trend identification is introduced. Although signal trend identification is complicated by the presence of noise, fuzzy logic can help capture important features of on-line signals and classify incoming power plant signals into increasing, decreasing and steady-state trend categories. In order to verify the methodology, a code named PROTREN is developed and tested using plant data. The results indicate that the code is capable of detecting transients accurately, identifying trends reliably, and not misinterpreting a steady-state signal as a transient one

  13. Structure and dynamics of GPCR signaling complexes.

    Science.gov (United States)

    Hilger, Daniel; Masureel, Matthieu; Kobilka, Brian K

    2018-01-01

    G-protein-coupled receptors (GPCRs) relay numerous extracellular signals by triggering intracellular signaling through coupling with G proteins and arrestins. Recent breakthroughs in the structural determination of GPCRs and GPCR-transducer complexes represent important steps toward deciphering GPCR signal transduction at a molecular level. A full understanding of the molecular basis of GPCR-mediated signaling requires elucidation of the dynamics of receptors and their transducer complexes as well as their energy landscapes and conformational transition rates. Here, we summarize current insights into the structural plasticity of GPCR-G-protein and GPCR-arrestin complexes that underlies the regulation of the receptor's intracellular signaling profile.

  14. A signal theoretic introduction to random processes

    CERN Document Server

    Howard, Roy M

    2015-01-01

    A fresh introduction to random processes utilizing signal theory By incorporating a signal theory basis, A Signal Theoretic Introduction to Random Processes presents a unique introduction to random processes with an emphasis on the important random phenomena encountered in the electronic and communications engineering field. The strong mathematical and signal theory basis provides clarity and precision in the statement of results. The book also features:  A coherent account of the mathematical fundamentals and signal theory that underpin the presented material Unique, in-depth coverage of

  15. Notch signaling in cerebrovascular diseases (Review).

    Science.gov (United States)

    Cai, Zhiyou; Zhao, Bin; Deng, Yanqing; Shangguan, Shouqin; Zhou, Faming; Zhou, Wenqing; Li, Xiaoli; Li, Yanfeng; Chen, Guanghui

    2016-10-01

    The Notch signaling pathway is a crucial regulator of numerous fundamental cellular processes. Increasing evidence suggests that Notch signaling is involved in inflammation and oxidative stress, and thus in the progress of cerebrovascular diseases. In addition, Notch signaling in cerebrovascular diseases is associated with apoptosis, angiogenesis and the function of blood‑brain barrier. Despite the contradictory results obtained to date as to whether Notch signaling is harmful or beneficial, the regulation of Notch signaling may provide a novel strategy for the treatment of cerebrovascular diseases.

  16. Deletion of apoptosis signal-regulating kinase 1 (ASK1 protects pancreatic beta-cells from stress-induced death but not from glucose homeostasis alterations under pro-inflammatory conditions.

    Directory of Open Access Journals (Sweden)

    Emilie Pepin

    Full Text Available Type 2 diabetes is characterized by pancreatic beta-cell dysfunction and is associated with low-grade inflammation. Recent observations suggest that apoptosis signal-regulating kinase 1 (ASK1 is involved in beta-cell death in response to different stressors. In this study, we tested whether ASK1 deficiency protects beta-cells from glucolipotoxic conditions and cytokines treatment or from glucose homeostasis alteration induced by endotoxemia.Insulin secretion was neither affected upon shRNA-mediated downregulation of ASK1 in MIN6 cells nor in islets from ASK1-deficient mice. ASK1 silencing in MIN6 cells and deletion in islets did not prevent the deleterious effect of glucolipotoxic conditions or cytokines on insulin secretion. However, it protected MIN6 cells from death induced by ER stress or palmitate and islets from short term caspase activation in response to cytokines. Moreover, endotoxemia induced by LPS infusion increased insulin secretion during hyperglycemic clamps but the response was similar in wild-type and ASK1-deficient mice. Finally, insulin sensitivity in the presence of LPS was not affected by ASK1-deficiency.Our study demonstrates that ASK1 is not involved in beta-cell function and dysfunction but controls stress-induced beta-cell death.

  17. 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.

  18. Optical Processing of High Dimensionality Signals

    DEFF Research Database (Denmark)

    Da Ros, Francesco

    signal processing, including wavelength conversion, optical phase conjugation (OPC), and signal regeneration. This project focuses precisely on the applications of OPAs for all-optical signal processing with a two-fold focus: on the one hand, processing the advanced modulation formats required......) waveguides, are investigated. The limits of parametric amplification for 16-quadrature amplitude modulation (QAM) signals are first characterized. The acquired knowledge is then applied to the design of a black-box OPC-device used to provide Kerr nonlinearity compensation for a 5-channel polarization......-division multiplexing (PDM) 16-QAM signal at 1.12 Tbps with significant improvements in received signal quality. Furthermore, the first demonstration of phase regeneration for binary phase-shift keying (BPSK) signals using the silicon platform is presented. The silicon-based OPA relies on a novel design where a reverse...

  19. Subaperture clutter filter with CFAR signal detection

    Science.gov (United States)

    Ormesher, Richard C.; Naething, Richard M.

    2016-08-30

    The various technologies presented herein relate to the determination of whether a received signal comprising radar clutter further comprises a communication signal. The communication signal can comprise of a preamble, a data symbol, communication data, etc. A first portion of the radar clutter is analyzed to determine a radar signature of the first portion of the radar clutter. A second portion of the radar clutter can be extracted based on the radar signature of the first portion. Following extraction, any residual signal can be analyzed to retrieve preamble data, etc. The received signal can be based upon a linear frequency modulation (e.g., a chirp modulation) whereby the chirp frequency can be determined and the frequency of transmission of the communication signal can be based accordingly thereon. The duration and/or bandwidth of the communication signal can be a portion of the duration and/or the bandwidth of the radar clutter.

  20. Opposed turns at signalized intersections

    Energy Technology Data Exchange (ETDEWEB)

    Akcelik, R.

    1989-06-01

    The 1985 Highway Capacity Manual (HCM) brought the U.S. and Australian methodologies for signalized intersections closer together. An important element in this methodology is the techniques used for the estimation of opposed (permissive) turn saturation flows. Although the basic modeling philosophies of the HCM and Australian methods are similar, there are significant differences in the procedures used and therefore in the results from the two methods. In particular, the latest methodology employed in the SIDRA software has eliminated the use of opposed turn adjustment factors for lane groups and adopted an explicit and direct method of modeling individual lanes. The purpose of this paper is to bring these new methods to the attention of the U.S. researchers since it is understood that efforts are being made to improve the 1985 HCM method.

  1. Signal propagation along the axon.

    Science.gov (United States)

    Rama, Sylvain; Zbili, Mickaël; Debanne, Dominique

    2018-03-08

    Axons link distant brain regions and are usually considered as simple transmission cables in which reliable propagation occurs once an action potential has been generated. Safe propagation of action potentials relies on specific ion channel expression at strategic points of the axon such as nodes of Ranvier or axonal branch points. However, while action potentials are generally considered as the quantum of neuronal information, their signaling is not entirely digital. In fact, both their shape and their conduction speed have been shown to be modulated by activity, leading to regulations of synaptic latency and synaptic strength. We report here newly identified mechanisms of (1) safe spike propagation along the axon, (2) compartmentalization of action potential shape in the axon, (3) analog modulation of spike-evoked synaptic transmission and (4) alteration in conduction time after persistent regulation of axon morphology in central neurons. We discuss the contribution of these regulations in information processing. Copyright © 2018 Elsevier Ltd. All rights reserved.

  2. Calcium signaling and cell proliferation.

    Science.gov (United States)

    Pinto, Mauro Cunha Xavier; Kihara, Alexandre Hiroaki; Goulart, Vânia A M; Tonelli, Fernanda M P; Gomes, Katia N; Ulrich, Henning; Resende, Rodrigo R

    2015-11-01

    Cell proliferation is orchestrated through diverse proteins related to calcium (Ca(2+)) signaling inside the cell. Cellular Ca(2+) influx that occurs first by various mechanisms at the plasma membrane, is then followed by absorption of Ca(2+) ions by mitochondria and endoplasmic reticulum, and, finally, there is a connection of calcium stores to the nucleus. Experimental evidence indicates that the fluctuation of Ca(2+) from the endoplasmic reticulum provides a pivotal and physiological role for cell proliferation. Ca(2+) depletion in the endoplasmatic reticulum triggers Ca(2+) influx across the plasma membrane in an phenomenon called store-operated calcium entries (SOCEs). SOCE is activated through a complex interplay between a Ca(2+) sensor, denominated STIM, localized in the endoplasmic reticulum and a Ca(2+) channel at the cell membrane, denominated Orai. The interplay between STIM and Orai proteins with cell membrane receptors and their role in cell proliferation is discussed in this review. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Molecular basis for mitochondrial signaling

    CERN Document Server

    2017-01-01

    This book covers recent advances in the study of structure, function, and regulation of metabolite, protein and ion translocating channels, and transporters in mitochondria. A wide array of cutting-edge methods are covered, ranging from electrophysiology and cell biology to bioinformatics, as well as structural, systems, and computational biology. At last, the molecular identity of two important channels in the mitochondrial inner membrane, the mitochondrial calcium uniporter and the mitochondrial permeability transition pore have been established. After years of work on the physiology and structure of VDAC channels in the mitochondrial outer membrane, there have been multiple discoveries on VDAC permeation and regulation by cytosolic proteins. Recent breakthroughs in structural studies of the mitochondrial cholesterol translocator reveal a set of novel unexpected features and provide essential clues for defining therapeutic strategies. Molecular Basis for Mitochondrial Signaling covers these and many more re...

  4. Fundamentals of adaptive signal processing

    CERN Document Server

    Uncini, Aurelio

    2015-01-01

    This book is an accessible guide to adaptive signal processing methods that equips the reader with advanced theoretical and practical tools for the study and development of circuit structures and provides robust algorithms relevant to a wide variety of application scenarios. Examples include multimodal and multimedia communications, the biological and biomedical fields, economic models, environmental sciences, acoustics, telecommunications, remote sensing, monitoring, and, in general, the modeling and prediction of complex physical phenomena. The reader will learn not only how to design and implement the algorithms but also how to evaluate their performance for specific applications utilizing the tools provided. While using a simple mathematical language, the employed approach is very rigorous. The text will be of value both for research purposes and for courses of study.

  5. Digital signal processing using MATLAB

    CERN Document Server

    Schilling, Robert L

    2016-01-01

    Focus on the development, implementation, and application of modern DSP techniques with DIGITAL SIGNAL PROCESSING USING MATLAB(R), 3E. Written in an engaging, informal style, this edition immediately captures your attention and encourages you to explore each critical topic. Every chapter starts with a motivational section that highlights practical examples and challenges that you can solve using techniques covered in the chapter. Each chapter concludes with a detailed case study example, a chapter summary with learning outcomes, and practical homework problems cross-referenced to specific chapter sections for your convenience. DSP Companion software accompanies each book to enable further investigation. The DSP Companion software operates with MATLAB(R) and provides intriguing demonstrations as well as interactive explorations of analysis and design concepts.

  6. Wnt signaling in ankylosing spondylitis.

    Science.gov (United States)

    Corr, Maripat

    2014-06-01

    The mechanisms that lead to bony fusion in ankylosing spondylitis (AS) are yet to be fully defined. In recent years, there have been several advances in our understanding of this complex disease. Here, the potential impact of the Wnt signaling pathway will be discussed. This pathway is involved in bone morphogenesis and homeostasis. Perturbations in the normal regulation have been implicated in abnormal bone formation (e.g., osteophytes). Levels of Wnt regulatory proteins like Dickkopf have been investigated as potential biomarkers of disease. This pathway might be involved in other aspects of this disease including T cell activation and differentiation, and in bone marrow adipogenesis. The pathways leading to the unique pathology and bony fusion in AS are complex and the Wnt pathway might play a critical contributing role.

  7. Ocean circulation generated magnetic signals

    DEFF Research Database (Denmark)

    Manoj, C.; Kuvshinov, A.; Maus, S.

    2006-01-01

    of ocean tidal signatures in the CHAMP magnetic field data we estimate the ocean magnetic signals of steady flow using a global 3-D EM numerical solution. The required velocity data are from the ECCO ocean circulation experiment and alternatively from the OCCAM model for higher resolution. We assume......Conducting ocean water, as it flows through the Earth's magnetic field, generates secondary electric and magnetic fields. An assessment of the ocean-generated magnetic fields and their detectability may be of importance for geomagnetism and oceanography. Motivated by the clear identification...... an Earth's conductivity model with a surface thin shell of variable conductance with a realistic ID mantle underneath. Simulations using both models predict an amplitude range of +/-2 nT at Swarm altitude (430 km). However at sea level, the higher resolution simulation predicts a higher strength...

  8. Biologically-based signal processing system applied to noise removal for signal extraction

    Science.gov (United States)

    Fu, Chi Yung; Petrich, Loren I.

    2004-07-13

    The method and system described herein use a biologically-based signal processing system for noise removal for signal extraction. A wavelet transform may be used in conjunction with a neural network to imitate a biological system. The neural network may be trained using ideal data derived from physical principles or noiseless signals to determine to remove noise from the signal.

  9. Phantom phone signals: An investigation into the prevalence and predictors of imagined cell phone signals

    NARCIS (Netherlands)

    Tanis, M.A.; Beukeboom, C.J.; Hartmann, T.; Vermeulen, I.E.

    2015-01-01

    This paper aims to elucidate the peculiar phenomenon of imagined cell phone signals, or Phantom Phone Signals (PPS), which is defined as an individual's perception of a phone signal, indicating an incoming call, message, or social media notification, when in fact no such signal was transmitted. A

  10. Validation of signal impact assessment tool in order to explore pharmacovigilance signals' follow-up actions

    NARCIS (Netherlands)

    Rolfes, Leàn; Kolfschoten, Judith; Van Hunsel, Florence; Van Puijenbroek, Eugene; van Grootheest, Kees

    2014-01-01

    Background: To determine which actions are advisable for signals arising from a spontaneous reporting system, the Netherlands Pharmacovigilance Centre Lareb uses a Signal Impact Assessment Tool (SIAT). It categorizes signals into one of four categories: strong/moderate signal strength and similarly

  11. Process hypercube comparison for signal validation

    International Nuclear Information System (INIS)

    Holbert, K.E.

    1991-01-01

    The optimal control and safe operation of a nuclear power plant requires reliable information concerning the state of the process. Signal validation is the detection, isolation, and characterization of faulty signals. Properly validated process signals are beneficial from the standpoint of increased plant availability and reliability of operator actions. This paper reports on a signal validation technique utilizing a process hypercube comparison (PHC) originated during this research. The hypercube is merely a multidimensional joint histogram of the process conditions. The hypercube is created off-line during a learning phase using operational plant data. In the event that a newly observed plant state does not match with those in the learned hypercube, the PHV algorithm performs signal validation by progressively hypothesizing that one or more signals is in error. This assumption is then either substantiated or denied. In the case where many signals are found to be in error, a conclusion that the process conditions are abnormal is reached. The global data base contained within the hypercube provides a best estimate of the process conditions in the event a signal is deemed failed. The hypercube signal validation methodology was tested using operational data from a commercial pressurized water reactor (PWR) and the Experimental Breeder Reactor II (EBR-II). This research was part of a larger project aimed at the development of a comprehensive signal validation software system for application to nuclear power plants

  12. Strigolactone versus gibberellin signaling: reemerging concepts?

    Science.gov (United States)

    Wallner, Eva-Sophie; López-Salmerón, Vadir; Greb, Thomas

    2016-06-01

    In this review, we compare knowledge about the recently discovered strigolactone signaling pathway and the well established gibberellin signaling pathway to identify gaps of knowledge and putative research directions in strigolactone biology. Communication between and inside cells is integral for the vitality of living organisms. Hormonal signaling cascades form a large part of this communication and an understanding of both their complexity and interactive nature is only beginning to emerge. In plants, the strigolactone (SL) signaling pathway is the most recent addition to the classically acting group of hormones and, although fundamental insights have been made, knowledge about the nature and impact of SL signaling is still cursory. This narrow understanding is in spite of the fact that SLs influence a specific spectrum of processes, which includes shoot branching and root system architecture in response, partly, to environmental stimuli. This makes these hormones ideal tools for understanding the coordination of plant growth processes, mechanisms of long-distance communication and developmental plasticity. Here, we summarize current knowledge about SL signaling and employ the well-characterized gibberellin (GA) signaling pathway as a scaffold to highlight emerging features as well as gaps in our knowledge in this context. GA signaling is particularly suitable for this comparison because both signaling cascades share key features of hormone perception and of immediate downstream events. Therefore, our comparative view demonstrates the possible level of complexity and regulatory interfaces of SL signaling.

  13. Prediction of twin-arginine signal peptides

    Directory of Open Access Journals (Sweden)

    Widdick David

    2005-07-01

    Full Text Available Abstract Background Proteins carrying twin-arginine (Tat signal peptides are exported into the periplasmic compartment or extracellular environment independently of the classical Sec-dependent translocation pathway. To complement other methods for classical signal peptide prediction we here present a publicly available method, TatP, for prediction of bacterial Tat signal peptides. Results We have retrieved sequence data for Tat substrates in order to train a computational method for discrimination of Sec and Tat signal peptides. The TatP method is able to positively classify 91% of 35 known Tat signal peptides and 84% of the annotated cleavage sites of these Tat signal peptides were correctly predicted. This method generates far less false positive predictions on various datasets than using simple pattern matching. Moreover, on the same datasets TatP generates less false positive predictions than a complementary rule based prediction method. Conclusion The method developed here is able to discriminate Tat signal peptides from cytoplasmic proteins carrying a similar motif, as well as from Sec signal peptides, with high accuracy. The method allows filtering of input sequences based on Perl syntax regular expressions, whereas hydrophobicity discrimination of Tat- and Sec-signal peptides is carried out by an artificial neural network. A potential cleavage site of the predicted Tat signal peptide is also reported. The TatP prediction server is available as a public web server at http://www.cbs.dtu.dk/services/TatP/.

  14. Selection-Mutation Dynamics of Signaling Games

    Directory of Open Access Journals (Sweden)

    Josef Hofbauer

    2015-01-01

    Full Text Available We study the structure of the rest points of signaling games and their dynamic behavior under selection-mutation dynamics by taking the case of three signals as our canonical example. Many rest points of the replicator dynamics of signaling games are not isolated and, therefore, not robust under perturbations. However, some of them attract open sets of initial conditions. We prove the existence of certain rest points of the selection-mutation dynamics close to Nash equilibria of the signaling game and show that all but the perturbed rest points close to strict Nash equilibria are dynamically unstable. This is an important result for the evolution of signaling behavior, since it shows that the second-order forces that are governed by mutation can increase the chances of successful signaling.

  15. Digital signal processing with kernel methods

    CERN Document Server

    Rojo-Alvarez, José Luis; Muñoz-Marí, Jordi; Camps-Valls, Gustavo

    2018-01-01

    A realistic and comprehensive review of joint approaches to machine learning and signal processing algorithms, with application to communications, multimedia, and biomedical engineering systems Digital Signal Processing with Kernel Methods reviews the milestones in the mixing of classical digital signal processing models and advanced kernel machines statistical learning tools. It explains the fundamental concepts from both fields of machine learning and signal processing so that readers can quickly get up to speed in order to begin developing the concepts and application software in their own research. Digital Signal Processing with Kernel Methods provides a comprehensive overview of kernel methods in signal processing, without restriction to any application field. It also offers example applications and detailed benchmarking experiments with real and synthetic datasets throughout. Readers can find further worked examples with Matlab source code on a website developed by the authors. * Presents the necess...

  16. Reconfigurable Analog Signal Processing by Living Cells.

    Science.gov (United States)

    Lewis, Daniel D; Chavez, Michael; Chiu, Kwan Lun; Tan, Cheemeng

    2018-01-19

    Living cells are known for their capacity for versatile signal processing, particularly the ability to respond differently to the same stimuli using biochemical networks that integrate environmental signals and reconfigure their dynamic responses. However, the complexity of natural biological networks confounds the discovery of fundamental mechanisms behind versatile signaling. Here, we study one specific aspect of reconfigurable signal processing in which a minimal biological network integrates two signals, using one to reconfigure the network's transfer function with respect to the other, producing an emergent switch between induction and repression. In contrast to known mechanisms, the new mechanism reconfigures transfer functions through genetic networks without extensive protein-protein interactions. These results provide a novel explanation for the versatility of genetic programs, and suggest a new mechanism of signal integration that may govern flexibility and plasticity of gene expression.

  17. Compressive sensing and entropy in seismic signals

    Science.gov (United States)

    Marinho, Eberton S.; Rocha, Tiago C.; Corso, Gilberto; Lucena, Liacir S.

    2017-09-01

    This work analyzes the correlation between the seismic signal entropy and the Compressive Sensing (CS) recovery index. The recovery index measures the quality of a signal reconstructed by the CS method. We analyze the performance of two CS algorithms: the ℓ1-MAGIC and the Fast Bayesian Compressive Sensing (BCS). We have observed a negative correlation between the performance of CS and seismic signal entropy. Signals with low entropy have small recovery index in their reconstruction by CS. The rationale behind our finding is: a sparse signal is easy to recover by CS and, besides, a sparse signal has low entropy. In addition, ℓ1-MAGIC shows a more significant correlation between entropy and CS performance than Fast BCS.

  18. Seizure detection algorithms based on EMG signals

    DEFF Research Database (Denmark)

    Conradsen, Isa

    Background: the currently used non-invasive seizure detection methods are not reliable. Muscle fibers are directly connected to the nerves, whereby electric signals are generated during activity. Therefore, an alarm system on electromyography (EMG) signals is a theoretical possibility. Objective......: to show whether medical signal processing of EMG data is feasible for detection of epileptic seizures. Methods: EMG signals during generalised seizures were recorded from 3 patients (with 20 seizures in total). Two possible medical signal processing algorithms were tested. The first algorithm was based...... the frequency-based algorithm was efficient for detecting the seizures in the third patient. Conclusion: Our results suggest that EMG signals could be used to develop an automatic seizuredetection system. However, different patients might require different types of algorithms /approaches....

  19. Signal detection by means of orthogonal decomposition

    Science.gov (United States)

    Hajdu, C. F.; Dabóczi, T.; Péceli, G.; Zamantzas, C.

    2018-03-01

    Matched filtering is a well-known method frequently used in digital signal processing to detect the presence of a pattern in a signal. In this paper, we suggest a time variant matched filter, which, unlike a regular matched filter, maintains a given alignment between the input signal and the template carrying the pattern, and can be realized recursively. We introduce a method to synchronize the two signals for presence detection, usable in case direct synchronization between the signal generator and the receiver is not possible or not practical. We then propose a way of realizing and extending the same filter by modifying a recursive spectral observer, which gives rise to orthogonal filter channels and also leads to another way to synchronize the two signals.

  20. Modified BTC Algorithm for Audio Signal Coding

    Directory of Open Access Journals (Sweden)

    TOMIC, S.

    2016-11-01

    Full Text Available This paper describes modification of a well-known image coding algorithm, named Block Truncation Coding (BTC and its application in audio signal coding. BTC algorithm was originally designed for black and white image coding. Since black and white images and audio signals have different statistical characteristics, the application of this image coding algorithm to audio signal presents a novelty and a challenge. Several implementation modifications are described in this paper, while the original idea of the algorithm is preserved. The main modifications are performed in the area of signal quantization, by designing more adequate quantizers for audio signal processing. The result is a novel audio coding algorithm, whose performance is presented and analyzed in this research. The performance analysis indicates that this novel algorithm can be successfully applied in audio signal coding.

  1. Prediction of twin-arginine signal peptides

    DEFF Research Database (Denmark)

    Bendtsen, Jannick Dyrløv; Nielsen, Henrik; Widdick, D.

    2005-01-01

    a publicly available method, TatP, for prediction of bacterial Tat signal peptides. Results: We have retrieved sequence data for Tat substrates in order to train a computational method for discrimination of Sec and Tat signal peptides. The TatP method is able to positively classify 91% of 35 known Tat signal...... peptides and 84% of the annotated cleavage sites of these Tat signal peptides were correctly predicted. This method generates far less false positive predictions on various datasets than using simple pattern matching. Moreover, on the same datasets TatP generates less false positive predictions than...... expressions, whereas hydrophobicity discrimination of Tat- and Sec- signal peptides is carried out by an artificial neural network. A potential cleavage site of the predicted Tat signal peptide is also reported. The TatP prediction server is available as a public web server at http://www.cbs.dtu.dk/services/TatP/....

  2. Signal-to-noise ratio determination circuit

    Science.gov (United States)

    Deerkoski, L. F. (Inventor)

    1973-01-01

    A signal-to-noise ratio (SNR) determination of an input is described, having signal components within a given frequency range and noise components, without actual measurement of the noise components. Bandpass limiter having a constant signal plus noise output level is connected to the output of the first filter, the signal-to-noise ratio of the input to the bandpass limiter being linearly related to the dbm level of signal components at the output. Calibration is connected to the bandpass limiter and is responsive to the signal components at the output to derive the SNR of the input to the determination circuit. The SNR determination circuit is disclosed for use in a diversity receiver having a plurality of input channels.

  3. Advances in thermographic signal reconstruction

    Science.gov (United States)

    Shepard, Steven M.; Frendberg Beemer, Maria

    2015-05-01

    Since its introduction in 2001, the Thermographic Signal Reconstruction (TSR) method has emerged as one of the most widely used methods for enhancement and analysis of thermographic sequences, with applications extending beyond industrial NDT into biomedical research, art restoration and botany. The basic TSR process, in which a noise reduced replica of each pixel time history is created, yields improvement over unprocessed image data that is sufficient for many applications. However, examination of the resulting logarithmic time derivatives of each TSR pixel replica provides significant insight into the physical mechanisms underlying the active thermography process. The deterministic and invariant properties of the derivatives have enabled the successful implementation of automated defect recognition and measurement systems. Unlike most approaches to analysis of thermography data, TSR does not depend on flawbackground contrast, so that it can also be applied to characterization and measurement of thermal properties of flaw-free samples. We present a summary of recent advances in TSR, a review of the underlying theory and examples of its implementation.

  4. Tyrosine phosphorylation in signal transduction

    International Nuclear Information System (INIS)

    Roberts, T.M.; Kaplan, D.; Morgan, W.; Keller, T.; Mamon, H.; Piwnica-Worms, H.; Druker, B.; Whitman, M.; Morrison, D.; Cohen, B.; Schaffhausen, B.; Cantley, L.; Rapp, U.

    1988-01-01

    Recent work has focused on the elucidation of the mechanisms by which membrane-bound tyrosine kinases transmit signals within the cell. To examine the role of tyrosine phosphorylation the authors have employed the following strategy. First, they have utilized antibodies to phosphotyrosine (anti-P.Tyr) to identify candidate substrates of various tyrosine kinases, such as pp60 c-src , the CSF- receptor, or the platelet-derived growth factor (PDGF) receptor. Second, they have attempted to characterize the biochemical properties of the putative substrates and to determine in what manner these properties are modified by phosphorylation on tyrosine residues. In this endeavor, they are recapitulating the classic biochemical analysis used to study the effect of kinases on metabolism. The final portion of our work consists of using modern molecular biological strategies to clone the genes or cDNAs for the substrates and overproduce the relevant proteins for studies in vitro in defined systems. This paper describes the first and second aspects of this strategy, the identification and characterization of novel substrate molecules

  5. Huntington's Disease and Striatal Signaling

    Directory of Open Access Journals (Sweden)

    Emmanuel eRoze

    2011-08-01

    Full Text Available Huntington’s Disease (HD is the most frequent neurodegenerative disease caused by an expansion of polyglutamines (CAG. The main clinical manifestations of HD are chorea, cognitive impairment and psychiatric disorders. The transmission of HD is autosomal dominant with a complete penetrance. HD has a single genetic cause, a well-defined neuropathology, and informative pre-manifest genetic testing of the disease is available. Striatal atrophy begins as early as 15 years before disease onset and continues throughout the period of manifest illness. Therefore, patients could theoretically benefit from therapy at early stages of the disease. One important characteristic of HD is the striatal vulnerability to neurodegeneration, despite similar expression of the protein in other brain areas. Aggregation of the mutated Huntingtin (HTT, impaired axonal transport, excitotoxicity, transcriptional dysregulation as well as mitochondrial dysfunction and energy deficits, are all part of the cellular events that underlie neuronal dysfunction and striatal death. Among these non-exclusive mechanisms, an alteration of striatal signaling is thought to orchestrate the downstream events involved in the cascade of striatal dysfunction.

  6. High Frequency Components Recovery in Music Signals

    Directory of Open Access Journals (Sweden)

    V. Sebesta

    1999-04-01

    Full Text Available A new technique is presented which improves the subjective quality of band-limited music by recovery of high frequency components. Sequences of harmonics are found in the band-limited signal and these sequences are expanded to the high frequency band to estimate the lost part of spectrum. High frequency signal is generated to match this estimation and is added to the band-limited signal.

  7. SIGNAL PROCESSING UTILIZING RADIO FREQUENCY PHOTONICS

    Science.gov (United States)

    2017-09-07

    AFRL-RY-WP-TR-2017-0172 SIGNAL PROCESSING UTILIZING RADIO FREQUENCY PHOTONICS Preetpaul S. Devgan RF/EO Subsystems Branch Aerospace Components...4. TITLE AND SUBTITLE SIGNAL PROCESSING UTILIZING RADIO FREQUENCY PHOTONICS 5a. CONTRACT NUMBER In-house 5b. GRANT NUMBER N/A 5c. PROGRAM ELEMENT...can be used for multiple signal processing applications. Down conversion, oscillators analog to digital conversion and waveform generation are

  8. Promotion Signal: Proxy for a Price Cut?

    OpenAIRE

    Inman, J Jeffrey; McAlister, Leigh; Hoyer, Wayne D

    1990-01-01

    Evidence suggests that some consumers react to promotion signals without considering relative price information. We adopt Petty and Cacioppo's Elaboration Likelihood Model (ELM) to explain this behavior in terms of the ELM's peripheral route to pursuasion in which the promotion signal is taken as a cue for a price cut. Experimental results show that low need for cognition individuals react to the simple presence of a promotion signal whether or not the price of the promoted brand is reduced, ...

  9. Integrated Microwave Photonics for Wideband Signal Processing

    Directory of Open Access Journals (Sweden)

    Xiaoke Yi

    2017-11-01

    Full Text Available We describe recent progress in integrated microwave photonics in wideband signal processing applications with a focus on the key signal processing building blocks, the realization of monolithic integration, and cascaded photonic signal processing for analog radio frequency (RF photonic links. New developments in integration-based microwave photonic techniques, that have high potentialities to be used in a variety of sensing applications for enhanced resolution and speed are also presented.

  10. ANALYSIS AND PROCESSING OF ELECTROMYOGRAM SIGNALS

    Directory of Open Access Journals (Sweden)

    K. A. Zimenko

    2013-01-01

    Full Text Available A method of electromyogram signals processing and identification for implementation in rehabilitation devices control is given. The method is based on the high-frequency components filtration which improves the signal/noise ratio; also it is based on the wavelet analysis for signal preprocessing and motion type classification by taught artificial neural network. Obtained accuracy of motion type classification is 94%.

  11. Photoacoustic signal amplification through plasmonic nanoparticle aggregation

    OpenAIRE

    Bayer, Carolyn L.; Nam, Seung Yun; Chen, Yun-Sheng; Emelianov, Stanislav Y.

    2013-01-01

    Photoacoustic imaging, using targeted plasmonic metallic nanoparticles, is a promising noninvasive molecular imaging method. Analysis of the photoacoustic signal generated by plasmonic metallic nanoparticles is complex because of the dependence upon physical properties of both the nanoparticle and the surrounding environment. We studied the effect of the aggregation of gold nanoparticles on the photoacoustic signal amplitude. We found that the photoacoustic signal from aggregated silica-coate...

  12. Advances and current challenges in calcium signaling.

    Science.gov (United States)

    Kudla, Jörg; Becker, Dirk; Grill, Erwin; Hedrich, Rainer; Hippler, Michael; Kummer, Ursula; Parniske, Martin; Romeis, Tina; Schumacher, Karin

    2018-04-01

    Content Summary 414 I. Introduction 415 II. Ca 2+ importer and exporter in plants 415 III. The Ca 2+ decoding toolkit in plants 415 IV. Mechanisms of Ca 2+ signal decoding 417 V. Immediate Ca 2+ signaling in the regulation of ion transport 418 VI. Ca 2+ signal integration into long-term ABA responses 419 VII Integration of Ca 2+ and hormone signaling through dynamic complex modulation of the CCaMK/CYCLOPS complex 420 VIII Ca 2+ signaling in mitochondria and chloroplasts 422 IX A view beyond recent advances in Ca 2+ imaging 423 X Modeling approaches in Ca 2+ signaling 424 XI Conclusions: Ca 2+ signaling a still young blooming field of plant research 424 Acknowledgements 425 ORCID 425 References 425 SUMMARY: Temporally and spatially defined changes in Ca 2+ concentration in distinct compartments of cells represent a universal information code in plants. Recently, it has become evident that Ca 2+ signals not only govern intracellular regulation but also appear to contribute to long distance or even organismic signal propagation and physiological response regulation. Ca 2+ signals are shaped by an intimate interplay of channels and transporters, and during past years important contributing individual components have been identified and characterized. Ca 2+ signals are translated by an elaborate toolkit of Ca 2+ -binding proteins, many of which function as Ca 2+ sensors, into defined downstream responses. Intriguing progress has been achieved in identifying specific modules that interconnect Ca 2+ decoding proteins and protein kinases with downstream target effectors, and in characterizing molecular details of these processes. In this review, we reflect on recent major advances in our understanding of Ca 2+ signaling and cover emerging concepts and existing open questions that should be informative also for scientists that are currently entering this field of ever-increasing breath and impact. © 2018 The Authors. New Phytologist © 2018 New Phytologist Trust.

  13. Pseudo random signal processing theory and application

    CERN Document Server

    Zepernick, Hans-Jurgen

    2013-01-01

    In recent years, pseudo random signal processing has proven to be a critical enabler of modern communication, information, security and measurement systems. The signal's pseudo random, noise-like properties make it vitally important as a tool for protecting against interference, alleviating multipath propagation and allowing the potential of sharing bandwidth with other users. Taking a practical approach to the topic, this text provides a comprehensive and systematic guide to understanding and using pseudo random signals. Covering theoretical principles, design methodologies and applications

  14. Signal and image processing in medical applications

    CERN Document Server

    Kumar, Amit; Rahim, B Abdul; Kumar, D Sravan

    2016-01-01

    This book highlights recent findings on and analyses conducted on signals and images in the area of medicine. The experimental investigations involve a variety of signals and images and their methodologies range from very basic to sophisticated methods. The book explains how signal and image processing methods can be used to detect and forecast abnormalities in an easy-to-follow manner, offering a valuable resource for researchers, engineers, physicians and bioinformatics researchers alike.

  15. Digital Signal Processor For GPS Receivers

    Science.gov (United States)

    Thomas, J. B.; Meehan, T. K.; Srinivasan, J. M.

    1989-01-01

    Three innovative components combined to produce all-digital signal processor with superior characteristics: outstanding accuracy, high-dynamics tracking, versatile integration times, lower loss-of-lock signal strengths, and infrequent cycle slips. Three components are digital chip advancer, digital carrier downconverter and code correlator, and digital tracking processor. All-digital signal processor intended for use in receivers of Global Positioning System (GPS) for geodesy, geodynamics, high-dynamics tracking, and ionospheric calibration.

  16. Advanced Methods of Biomedical Signal Processing

    CERN Document Server

    Cerutti, Sergio

    2011-01-01

    This book grew out of the IEEE-EMBS Summer Schools on Biomedical Signal Processing, which have been held annually since 2002 to provide the participants state-of-the-art knowledge on emerging areas in biomedical engineering. Prominent experts in the areas of biomedical signal processing, biomedical data treatment, medicine, signal processing, system biology, and applied physiology introduce novel techniques and algorithms as well as their clinical or physiological applications. The book provides an overview of a compelling group of advanced biomedical signal processing techniques, such as mult

  17. Radar signal processing and its applications

    CERN Document Server

    Hummel, Robert; Stoica, Petre; Zelnio, Edmund

    2003-01-01

    Radar Signal Processing and Its Applications brings together in one place important contributions and up-to-date research results in this fast-moving area. In twelve selected chapters, it describes the latest advances in architectures, design methods, and applications of radar signal processing. The contributors to this work were selected from the leading researchers and practitioners in the field. This work, originally published as Volume 14, Numbers 1-3 of the journal, Multidimensional Systems and Signal Processing, will be valuable to anyone working or researching in the field of radar signal processing. It serves as an excellent reference, providing insight into some of the most challenging issues being examined today.

  18. Signals and systems primer with Matlab

    CERN Document Server

    Poularikas, Alexander D

    2006-01-01

    Signals and Systems Primer with MATLAB® equally emphasizes the fundamentals of both analog and digital signals and systems. To ensure insight into the basic concepts and methods, the text presents a variety of examples that illustrate a wide range of applications, from microelectromechanical to worldwide communication systems. It also provides MATLAB functions and procedures for practice and verification of these concepts.Taking a pedagogical approach, the author builds a solid foundation in signal processing as well as analog and digital systems. The book first introduces orthogonal signals,

  19. Bistatic SAR: Signal Processing and Image Formation.

    Energy Technology Data Exchange (ETDEWEB)

    Wahl, Daniel E.; Yocky, David A.

    2014-10-01

    This report describes the significant processing steps that were used to take the raw recorded digitized signals from the bistatic synthetic aperture RADAR (SAR) hardware built for the NCNS Bistatic SAR project to a final bistatic SAR image. In general, the process steps herein are applicable to bistatic SAR signals that include the direct-path signal and the reflected signal. The steps include preprocessing steps, data extraction to for a phase history, and finally, image format. Various plots and values will be shown at most steps to illustrate the processing for a bistatic COSMO SkyMed collection gathered on June 10, 2013 on Kirtland Air Force Base, New Mexico.

  20. Digital signal processing an experimental approach

    CERN Document Server

    Engelberg, Shlomo

    2008-01-01

    Digital Signal Processing is a mathematically rigorous but accessible treatment of digital signal processing that intertwines basic theoretical techniques with hands-on laboratory instruction. Divided into three parts, the book covers various aspects of the digital signal processing (DSP) ""problem."" It begins with the analysis of discrete-time signals and explains sampling and the use of the discrete and fast Fourier transforms. The second part of the book???covering digital to analog and analog to digital conversion???provides a practical interlude in the mathematical content before Part II

  1. Send mixed signals : earn more, work less

    DEFF Research Database (Denmark)

    Miltersen, Peter Bro; Sheffet, Or

    2012-01-01

    Emek et al presented a model of probabilistic single-item second price auctions where an auctioneer who is informed about the type of an item for sale, broadcasts a signal about this type to uninformed bidders. They proved that finding the optimal (for the purpose of generating revenue) pure...... that a mixed signaling scheme can in some cases generate twice as much revenue as the best pure signaling scheme and we prove a generally applicable lower bound on the revenue generated by the best mixed signaling scheme....

  2. Random signals and noise a mathematical introduction

    CERN Document Server

    Engelberg, Shlomo

    2011-01-01

    Understanding the nature of random signals and noise is critically important for detecting signals and for reducing and minimizing the effects of noise in applications such as communications and control systems. Outlining a variety of techniques and explaining when and how to use them, Random Signals and Noise: A Mathematical Introduction focuses on applications and practical problem solving rather than probability theory.A Firm FoundationBefore launching into the particulars of random signals and noise, the author outlines the elements of probability that are used throughout the book and incl

  3. Plant monitoring and signal validation at HFIR

    International Nuclear Information System (INIS)

    Mullens, J.A.

    1991-01-01

    This paper describes a monitoring system for the Oak Ridge National Laboratory's (ORNL'S) High Flux Isotope Reactor (HFIR). HFIR is an 85 MW pressurized water reactor designed to produce isotopes and intense neutron beams. The monitoring system is described with respect to plant signals and computer system; monitoring overview; data acquisition, logging and network distribution; signal validation; status displays; reactor condition monitoring; reactor operator aids. Future work will include the addition of more plant signals, more signal validation and diagnostic capabilities, improved status display, integration of the system with the RELAP plant simulation and graphical interface, improved operator aids, and an alarm filtering system. 8 refs., 7 figs. (MB)

  4. Abiotic stress signaling and responses in plants

    Science.gov (United States)

    Zhu, Jian-Kang

    2016-01-01

    Summary As sessile organisms, plants must cope with abiotic stress such as soil salinity, drought, and extreme temperatures. Core stress signaling pathways involve protein kinases related to the yeast SNF1 and mammalian AMPK, suggesting that stress signaling in plants evolved from energy sensing. Stress signaling regulates proteins critical for ion and water transport and for metabolic and gene-expression reprogramming to bring about ionic and water homeostasis and cellular stability under stress conditions. Understanding stress signaling and responses will increase our ability to improve stress resistance in crops to achieve agricultural sustainability and food security for a growing world population. PMID:27716505

  5. Computing angle of arrival of radio signals

    Science.gov (United States)

    Borchardt, John J.; Steele, David K.

    2017-11-07

    Various technologies pertaining to computing angle of arrival of radio signals are described. A system that is configured for computing the angle of arrival of a radio signal includes a cylindrical sheath wrapped around a cylindrical object, where the cylindrical sheath acts as a ground plane. The system further includes a plurality of antennas that are positioned about an exterior surface of the cylindrical sheath, and receivers respectively coupled to the antennas. The receivers output measurements pertaining to the radio signal. A processing circuit receives the measurements and computes the angle of arrival of the radio signal based upon the measurements.

  6. 4-hydroxynonenal-mediated signaling and aging.

    Science.gov (United States)

    Zhang, Hongqiao; Forman, Henry Jay

    2017-10-01

    4-Hydroxy-2-nonenal (HNE), one of the major α, β-unsaturated aldehydes produced during lipid peroxidation, is a potent messenger in mediating signaling pathways. Lipid peroxidation and HNE production appear to increase with aging. Although the cause and effect relation remains arguable, aging is associated with significant changes in diverse signaling events, characterized by enhanced or diminished responses of specific signaling pathways. In this review we will discuss how HNE may contribute to aging-related alterations of signaling pathways. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Endocannabinoid Signaling Regulates Sleep Stability.

    Directory of Open Access Journals (Sweden)

    Matthew J Pava

    Full Text Available The hypnogenic properties of cannabis have been recognized for centuries, but endogenous cannabinoid (endocannabinoid regulation of vigilance states is poorly characterized. We report findings from a series of experiments in mice measuring sleep with polysomnography after various systemic pharmacological manipulations of the endocannabinoid system. Rapid, unbiased scoring of vigilance states was achieved using an automated algorithm that we devised and validated. Increasing endocannabinoid tone with a selective inhibitor of monoacyglycerol lipase (JZL184 or fatty acid amide hydrolase (AM3506 produced a transient increase in non-rapid eye movement (NREM sleep due to an augmentation of the length of NREM bouts (NREM stability. Similarly, direct activation of type 1 cannabinoid (CB1 receptors with CP47,497 increased NREM stability, but both CP47,497 and JZL184 had a secondary effect that reduced NREM sleep time and stability. This secondary response to these drugs was similar to the early effect of CB1 blockade with the antagonist/inverse agonist AM281, which fragmented NREM sleep. The magnitude of the effects produced by JZL184 and AM281 were dependent on the time of day this drug was administered. While activation of CB1 resulted in only a slight reduction in gamma power, CB1 blockade had dramatic effects on broadband power in the EEG, particularly at low frequencies. However, CB1 blockade did not significantly reduce the rebound in NREM sleep following total sleep deprivation. These results support the hypothesis that endocannabinoid signaling through CB1 is necessary for NREM stability but it is not necessary for sleep homeostasis.

  8. Endocannabinoid Signaling Regulates Sleep Stability.

    Science.gov (United States)

    Pava, Matthew J; Makriyannis, Alexandros; Lovinger, David M

    2016-01-01

    The hypnogenic properties of cannabis have been recognized for centuries, but endogenous cannabinoid (endocannabinoid) regulation of vigilance states is poorly characterized. We report findings from a series of experiments in mice measuring sleep with polysomnography after various systemic pharmacological manipulations of the endocannabinoid system. Rapid, unbiased scoring of vigilance states was achieved using an automated algorithm that we devised and validated. Increasing endocannabinoid tone with a selective inhibitor of monoacyglycerol lipase (JZL184) or fatty acid amide hydrolase (AM3506) produced a transient increase in non-rapid eye movement (NREM) sleep due to an augmentation of the length of NREM bouts (NREM stability). Similarly, direct activation of type 1 cannabinoid (CB1) receptors with CP47,497 increased NREM stability, but both CP47,497 and JZL184 had a secondary effect that reduced NREM sleep time and stability. This secondary response to these drugs was similar to the early effect of CB1 blockade with the antagonist/inverse agonist AM281, which fragmented NREM sleep. The magnitude of the effects produced by JZL184 and AM281 were dependent on the time of day this drug was administered. While activation of CB1 resulted in only a slight reduction in gamma power, CB1 blockade had dramatic effects on broadband power in the EEG, particularly at low frequencies. However, CB1 blockade did not significantly reduce the rebound in NREM sleep following total sleep deprivation. These results support the hypothesis that endocannabinoid signaling through CB1 is necessary for NREM stability but it is not necessary for sleep homeostasis.

  9. Nitric oxide signaling in hypoxia.

    Science.gov (United States)

    Ho, J J David; Man, H S Jeffrey; Marsden, Philip A

    2012-03-01

    Endothelial-derived nitric oxide (NO) is classically viewed as a regulator of vasomotor tone. NO plays an important role in regulating O(2) delivery through paracrine control of vasomotor tone locally and cardiovascular and respiratory responses centrally. Very soon after the cloning and functional characterization of the endothelial nitric oxide synthase (eNOS), studies on the interaction between O(2) and NO made the paradoxical finding that hypoxia led to decreases in eNOS expression and function. Why would decreases in O(2) content in tissues elicit a loss of a potent endothelial-derived vasodilator? We now know that restricting our view of NO as a regulator of vasomotor tone or blood pressure limited deeper levels of mechanistic insight. Exciting new studies indicate that functional interactions between NO and O(2) exhibit profound complexity and are relevant to diseases states, especially those associated with hypoxia in tissues. NOS isoforms catalytically require O(2). Hypoxia regulates steady-state expression of the mRNA and protein abundance of the NOS enzymes. Animals genetically deficient in NOS isoforms have perturbations in their ability to adapt to changes in O(2) supply or demand. Most interestingly, the intracellular pathways for O(2) sensing that evolved to ensure an appropriate balance of O(2) delivery and utilization intersect with NO signaling networks. Recent studies demonstrate that hypoxia-inducible factor (HIF) stabilization and transcriptional activity is achieved through two parallel pathways: (1) a decrease in O(2)-dependent prolyl hydroxylation of HIF and (2) S-nitrosylation of HIF pathway components. Recent findings support a role for S-nitrosothiols as hypoxia-mimetics in certain biological and/or disease settings, such as living at high altitude, exposure to small molecules that can bind NO, or anemia.

  10. [Glutamate signaling and neural plasticity].

    Science.gov (United States)

    Watanabe, Masahiko

    2013-07-01

    Proper functioning of the nervous system relies on the precise formation of neural circuits during development. At birth, neurons have redundant synaptic connections not only to their proper targets but also to other neighboring cells. Then, functional neural circuits are formed during early postnatal development by the selective strengthening of necessary synapses and weakening of surplus connections. Synaptic connections are also modified so that projection fields of active afferents expand at the expense of lesser ones. We have studied the molecular mechanisms underlying these activity-dependent prunings and the plasticity of synaptic circuitry using gene-engineered mice defective in the glutamatergic signaling system. NMDA-type glutamate receptors are critically involved in the establishment of the somatosensory pathway ascending from the brainstem trigeminal nucleus to the somatosensory cortex. Without NMDA receptors, whisker-related patterning fails to develop, whereas lesion-induced plasticity occurs normally during the critical period. In contrast, mice lacking the glutamate transporters GLAST or GLT1 are selectively impaired in the lesion-induced critical plasticity of cortical barrels, although whisker-related patterning itself develops normally. In the developing cerebellum, multiple climbing fibers initially innervating given Purkinje cells are eliminated one by one until mono-innervation is achieved. In this pruning process, P/Q-type Ca2+ channels expressed on Purkinje cells are critically involved by the selective strengthening of single main climbing fibers against other lesser afferents. Therefore, the activation of glutamate receptors that leads to an activity-dependent increase in the intracellular Ca2+ concentration plays a key role in the pruning of immature synaptic circuits into functional circuits. On the other hand, glutamate transporters appear to control activity-dependent plasticity among afferent fields, presumably through adjusting

  11. Endocannabinoid Signaling Regulates Sleep Stability

    Science.gov (United States)

    Pava, Matthew J.; Makriyannis, Alexandros; Lovinger, David M.

    2016-01-01

    The hypnogenic properties of cannabis have been recognized for centuries, but endogenous cannabinoid (endocannabinoid) regulation of vigilance states is poorly characterized. We report findings from a series of experiments in mice measuring sleep with polysomnography after various systemic pharmacological manipulations of the endocannabinoid system. Rapid, unbiased scoring of vigilance states was achieved using an automated algorithm that we devised and validated. Increasing endocannabinoid tone with a selective inhibitor of monoacyglycerol lipase (JZL184) or fatty acid amide hydrolase (AM3506) produced a transient increase in non-rapid eye movement (NREM) sleep due to an augmentation of the length of NREM bouts (NREM stability). Similarly, direct activation of type 1 cannabinoid (CB1) receptors with CP47,497 increased NREM stability, but both CP47,497 and JZL184 had a secondary effect that reduced NREM sleep time and stability. This secondary response to these drugs was similar to the early effect of CB1 blockade with the antagonist/inverse agonist AM281, which fragmented NREM sleep. The magnitude of the effects produced by JZL184 and AM281 were dependent on the time of day this drug was administered. While activation of CB1 resulted in only a slight reduction in gamma power, CB1 blockade had dramatic effects on broadband power in the EEG, particularly at low frequencies. However, CB1 blockade did not significantly reduce the rebound in NREM sleep following total sleep deprivation. These results support the hypothesis that endocannabinoid signaling through CB1 is necessary for NREM stability but it is not necessary for sleep homeostasis. PMID:27031992

  12. Phase synchronization of instrumental music signals

    Science.gov (United States)

    Mukherjee, Sayan; Palit, Sanjay Kumar; Banerjee, Santo; Ariffin, M. R. K.; Bhattacharya, D. K.

    2014-06-01

    Signal analysis is one of the finest scientific techniques in communication theory. Some quantitative and qualitative measures describe the pattern of a music signal, vary from one to another. Same musical recital, when played by different instrumentalists, generates different types of music patterns. The reason behind various patterns is the psycho-acoustic measures - Dynamics, Timber, Tonality and Rhythm, varies in each time. However, the psycho-acoustic study of the music signals does not reveal any idea about the similarity between the signals. For such cases, study of synchronization of long-term nonlinear dynamics may provide effective results. In this context, phase synchronization (PS) is one of the measures to show synchronization between two non-identical signals. In fact, it is very critical to investigate any other kind of synchronization for experimental condition, because those are completely non identical signals. Also, there exists equivalence between the phases and the distances of the diagonal line in Recurrence plot (RP) of the signals, which is quantifiable by the recurrence quantification measure τ-recurrence rate. This paper considers two nonlinear music signals based on same raga played by two eminent sitar instrumentalists as two non-identical sources. The psycho-acoustic study shows how the Dynamics, Timber, Tonality and Rhythm vary for the two music signals. Then, long term analysis in the form of phase space reconstruction is performed, which reveals the chaotic phase spaces for both the signals. From the RP of both the phase spaces, τ-recurrence rate is calculated. Finally by the correlation of normalized tau-recurrence rate of their 3D phase spaces and the PS of the two music signals has been established. The numerical results well support the analysis.

  13. A comb filter based signal processing method to effectively reduce motion artifacts from photoplethysmographic signals.

    Science.gov (United States)

    Peng, Fulai; Liu, Hongyun; Wang, Weidong

    2015-10-01

    A photoplethysmographic (PPG) signal can provide very useful information about a subject's cardiovascular status. Motion artifacts (MAs), which usually deteriorate the waveform of a PPG signal, severely obstruct its applications in the clinical diagnosis and healthcare area. To reduce the MAs from a PPG signal, in the present study we present a comb filter based signal processing method. Firstly, wavelet de-noising was implemented to preliminarily suppress a part of the MAs. Then, the PPG signal in the time domain was transformed into the frequency domain by a fast Fourier transform (FFT). Thirdly, the PPG signal period was estimated from the frequency domain by tracking the fundamental frequency peak of the PPG signal. Lastly, the MAs were removed by the comb filter which was designed based on the obtained PPG signal period. Experiments with synthetic and real-world datasets were implemented to validate the performance of the method. Results show that the proposed method can effectively restore the PPG signals from the MA corrupted signals. Also, the accuracy of blood oxygen saturation (SpO2), calculated from red and infrared PPG signals, was significantly improved after the MA reduction by the proposed method. Our study demonstrates that the comb filter can effectively reduce the MAs from a PPG signal provided that the PPG signal period is obtained.

  14. Spectral Correlation of Multicarrier Modulated Signals and Its Application for Signal Detection

    Directory of Open Access Journals (Sweden)

    Zhang Haijian

    2010-01-01

    Full Text Available Spectral correlation theory for cyclostationary time-series signals has been studied for decades. Explicit formulas of spectral correlation function for various types of analog-modulated and digital-modulated signals are already derived. In this paper, we investigate and exploit the cyclostationarity characteristics for two kinds of multicarrier modulated (MCM signals: conventional OFDM and filter bank based multicarrier (FBMC signals. The spectral correlation characterization of MCM signal can be described by a special linear periodic time-variant (LPTV system. Using this LPTV description, we have derived the explicit theoretical formulas of nonconjugate and conjugate cyclic autocorrelation function (CAF and spectral correlation function (SCF for OFDM and FBMC signals. According to theoretical spectral analysis, Cyclostationary Signatures (CS are artificially embedded into MCM signal and a low-complexity signature detector is, therefore, presented for detecting MCM signal. Theoretical analysis and simulation results demonstrate the efficiency and robustness of this CS detector compared to traditionary energy detector.

  15. Blood and Wall Signal Simulator for Doppler Ultrasound Signal Analysis Algorithm Development

    National Research Council Canada - National Science Library

    Fish, P

    2001-01-01

    Doppler ultrasound instruments, used for the detection and monitoring of vascular disease, require a means of separating the large, low frequency Doppler signal from the vessel wall from the signal...

  16. Multi-Modal Intelligent Traffic Signal Systems Signal Plans for Roadside Equipment

    Data.gov (United States)

    Department of Transportation — Data were collected during the Multi-Modal Intelligent Transportation Signal Systems (MMITSS) study. MMITSS is a next-generation traffic signal system that seeks to...

  17. Laser heterodyne interferometric signal processing method based on rising edge locking with high frequency clock signal.

    Science.gov (United States)

    Zhang, Enzheng; Chen, Benyong; Yan, Liping; Yang, Tao; Hao, Qun; Dong, Wenjun; Li, Chaorong

    2013-02-25

    A novel phase measurement method composed of the rising-edge locked signal processing and the digital frequency mixing is proposed for laser heterodyne interferometer. The rising-edge locked signal processing, which employs a high frequency clock signal to lock the rising-edges of the reference and measurement signals, not only can improve the steepness of the rising-edge, but also can eliminate the error counting caused by multi-rising-edge phenomenon in fringe counting. The digital frequency mixing is realized by mixing the digital interference signal with a digital base signal that is different from conventional frequency mixing with analogue signals. These signal processing can improve the measurement accuracy and enhance anti-interference and measurement stability. The principle and implementation of the method are described in detail. An experimental setup was constructed and a series of experiments verified the feasibility of the method in large displacement measurement with high speed and nanometer resolution.

  18. Frequency domain laser velocimeter signal processor: A new signal processing scheme

    Science.gov (United States)

    Meyers, James F.; Clemmons, James I., Jr.

    1987-01-01

    A new scheme for processing signals from laser velocimeter systems is described. The technique utilizes the capabilities of advanced digital electronics to yield a smart instrument that is able to configure itself, based on the characteristics of the input signals, for optimum measurement accuracy. The signal processor is composed of a high-speed 2-bit transient recorder for signal capture and a combination of adaptive digital filters with energy and/or zero crossing detection signal processing. The system is designed to accept signals with frequencies up to 100 MHz with standard deviations up to 20 percent of the average signal frequency. Results from comparative simulation studies indicate measurement accuracies 2.5 times better than with a high-speed burst counter, from signals with as few as 150 photons per burst.

  19. Signaling within Allosteric Machines: Signal Transmission Pathways Inside G Protein-Coupled Receptors.

    Science.gov (United States)

    Bartuzi, Damian; Kaczor, Agnieszka A; Matosiuk, Dariusz

    2017-07-15

    In recent years, our understanding of function of G protein-coupled receptors (GPCRs) has changed from a picture of simple signal relays, transmitting only a particular signal to a particular G protein heterotrimer, to versatile machines, capable of various responses to different stimuli and being modulated by various factors. Some recent reports provide not only the data on ligands/modulators and resultant signals induced by them, but also deeper insights into exact pathways of signal migration and mechanisms of signal transmission through receptor structure. Combination of these computational and experimental data sheds more light on underlying mechanisms of signal transmission and signaling bias in GPCRs. In this review we focus on available clues on allosteric pathways responsible for complex signal processing within GPCRs structures, with particular emphasis on linking compatible in silico- and in vitro-derived data on the most probable allosteric connections.

  20. Atmospheric signals produced by cavity rebound

    International Nuclear Information System (INIS)

    Jones, E.M.; App, F.N.; Whitaker, R.W.

    1993-01-01

    An analysis of the atmospheric acoustic signals produced by a class of low-yield tests conducted just below the base of the alluvial cover in Yucca Flat of the Nevada Test Site (NTS), has revealed a clear manifestation of an elastic, cavity rebound signal. We use modeling as the basis for understanding the observed phenomena