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Sample records for identify trpa1 channels

  1. TRPA1 expression levels and excitability brake by KV channels influence cold sensitivity of TRPA1-expressing neurons.

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    Memon, Tosifa; Chase, Kevin; Leavitt, Lee S; Olivera, Baldomero M; Teichert, Russell W

    2017-06-14

    The molecular sensor of innocuous (painless) cold sensation is well-established to be transient receptor potential cation channel, subfamily M, member 8 (TRPM8). However, the role of transient receptor potential cation channel, subfamily A, member 1 (TRPA1) in noxious (painful) cold sensation has been controversial. We find that TRPA1 channels contribute to the noxious cold sensitivity of mouse somatosensory neurons, independent of TRPM8 channels, and that TRPA1-expressing neurons are largely non-overlapping with TRPM8-expressing neurons in mouse dorsal-root ganglia (DRG). However, relatively few TRPA1-expressing neurons (e.g., responsive to allyl isothiocyanate or AITC, a selective TRPA1 agonist) respond overtly to cold temperature in vitro, unlike TRPM8-expressing neurons, which almost all respond to cold. Using somatosensory neurons from TRPM8-/- mice and subtype-selective blockers of TRPM8 and TRPA1 channels, we demonstrate that responses to cold temperatures from TRPA1-expressing neurons are mediated by TRPA1 channels. We also identify two factors that affect the cold-sensitivity of TRPA1-expressing neurons: (1) cold-sensitive AITC-sensitive neurons express relatively more TRPA1 transcripts than cold-insensitive AITC-sensitive neurons and (2) voltage-gated potassium (K V ) channels attenuate the cold-sensitivity of some TRPA1-expressing neurons. The combination of these two factors, combined with the relatively weak agonist-like activity of cold temperature on TRPA1 channels, partially explains why few TRPA1-expressing neurons respond to cold. Blocking K V channels also reveals another subclass of noxious cold-sensitive DRG neurons that do not express TRPM8 or TRPA1 channels. Altogether, the results of this study provide novel insights into the cold-sensitivity of different subclasses of somatosensory neurons. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  2. Activation of the chemosensing transient receptor potential channel A1 (TRPA1) by alkylating agents.

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    Stenger, Bernhard; Zehfuss, Franziska; Mückter, Harald; Schmidt, Annette; Balszuweit, Frank; Schäfer, Eva; Büch, Thomas; Gudermann, Thomas; Thiermann, Horst; Steinritz, Dirk

    2015-09-01

    The transient receptor potential ankyrin 1 (TRPA1) cation channel is expressed in different tissues including skin, lung and neuronal tissue. Recent reports identified TRPA1 as a sensor for noxious substances, implicating a functional role in the molecular toxicology. TRPA1 is activated by various potentially harmful electrophilic substances. The chemical warfare agent sulfur mustard (SM) is a highly reactive alkylating agent that binds to numerous biological targets. Although SM is known for almost 200 years, detailed knowledge about the pathophysiology resulting from exposure is lacking. A specific therapy is not available. In this study, we investigated whether the alkylating agent 2-chloroethyl-ethylsulfide (CEES, a model substance for SM-promoted effects) and SM are able to activate TRPA1 channels. CEES induced a marked increase in the intracellular calcium concentration ([Ca(2+)]i) in TRPA1-expressing but not in TRPA1-negative cells. The TRP-channel blocker AP18 diminished the CEES-induced calcium influx. HEK293 cells permanently expressing TRPA1 were more sensitive toward cytotoxic effects of CEES compared with wild-type cells. At low CEES concentrations, CEES-induced cytotoxicity was prevented by AP18. Proof-of-concept experiments using SM resulted in a pronounced increase in [Ca(2+)]i in HEK293-A1-E cells. Human A549 lung epithelial cells, which express TRPA1 endogenously, reacted with a transient calcium influx in response to CEES exposure. The CEES-dependent calcium response was diminished by AP18. In summary, our results demonstrate that alkylating agents are able to activate TRPA1. Inhibition of TRPA1 counteracted cellular toxicity and could thus represent a feasible approach to mitigate SM-induced cell damage.

  3. TRPA1 channels: expression in non-neuronal murine lung tissues and dispensability for hyperoxia-induced alveolar epithelial hyperplasia.

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    Kannler, Martina; Lüling, Robin; Yildirim, Ali Önder; Gudermann, Thomas; Steinritz, Dirk; Dietrich, Alexander

    2018-05-12

    Transient receptor potential A1 (TRPA1) channels were originally characterized in neuronal tissues but also identified in lung epithelium by staining with fluorescently coupled TRPA1 antibodies. Its exact function in non-neuronal tissues, however, is elusive. TRPA1 is activated in vitro by hypoxia and hyperoxia and is therefore a promising TRP candidate for sensing hyperoxia in pulmonary epithelial cells and for inducing alveolar epithelial hyperplasia. Here, we isolated tracheal, bronchial, and alveolar epithelial cells and show low but detectable TRPA1 mRNA levels in all these cells as well as TRPA1 protein by Western blotting in alveolar type II (AT II) cells. We quantified changes in intracellular Ca 2+ ([Ca 2+ ] i ) levels induced by application of hyperoxic solutions in primary tracheal epithelial, bronchial epithelial, and AT II cells isolated from wild-type (WT) and TRPA1-deficient (TRPA1-/-) mouse lungs. In all cell types, we detected hyperoxia-induced rises in [Ca 2+ ] i levels, which were not significantly different in TRPA1-deficient cells compared to WT cells. We also tested TRPA1 function in a mouse model for hyperoxia-induced alveolar epithelial hyperplasia. A characteristic significant increase in thickening of alveolar tissues was detected in mouse lungs after exposure to hyperoxia, but not in normoxic WT and TRPA1-/- controls. Quantification of changes in lung morphology in hyperoxic WT and TRPA1-/- mice, however, again revealed no significant changes. Therefore, TRPA1 expression does neither appear to be a key player for hyperoxia-induced changes in [Ca 2+ ] i levels in primary lung epithelial cells, nor being essential for the development of hyperoxia-induced alveolar epithelial hyperplasia.

  4. The contribution of TRPM8 and TRPA1 channels to cold allodynia and neuropathic pain.

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    Caspani, Ombretta; Zurborg, Sandra; Labuz, Dominika; Heppenstall, Paul A

    2009-10-08

    Cold allodynia is a common feature of neuropathic pain however the underlying mechanisms of this enhanced sensitivity to cold are not known. Recently the transient receptor potential (TRP) channels TRPM8 and TRPA1 have been identified and proposed to be molecular sensors for cold. Here we have investigated the expression of TRPM8 and TRPA1 mRNA in the dorsal root ganglia (DRG) and examined the cold sensitivity of peripheral sensory neurons in the chronic construction injury (CCI) model of neuropathic pain in mice.In behavioral experiments, chronic constriction injury (CCI) of the sciatic nerve induced a hypersensitivity to both cold and the TRPM8 agonist menthol that developed 2 days post injury and remained stable for at least 2 weeks. Using quantitative RT-PCR and in situ hybridization we examined the expression of TRPM8 and TRPA1 in DRG. Both channels displayed significantly reduced expression levels after injury with no change in their distribution pattern in identified neuronal subpopulations. Furthermore, in calcium imaging experiments, we detected no alterations in the number of cold or menthol responsive neurons in the DRG, or in the functional properties of cold transduction following injury. Intriguingly however, responses to the TRPA1 agonist mustard oil were strongly reduced.Our results indicate that injured sensory neurons do not develop abnormal cold sensitivity after chronic constriction injury and that alterations in the expression of TRPM8 and TRPA1 are unlikely to contribute directly to the pathogenesis of cold allodynia in this neuropathic pain model.

  5. The contribution of TRPM8 and TRPA1 channels to cold allodynia and neuropathic pain.

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    Ombretta Caspani

    Full Text Available Cold allodynia is a common feature of neuropathic pain however the underlying mechanisms of this enhanced sensitivity to cold are not known. Recently the transient receptor potential (TRP channels TRPM8 and TRPA1 have been identified and proposed to be molecular sensors for cold. Here we have investigated the expression of TRPM8 and TRPA1 mRNA in the dorsal root ganglia (DRG and examined the cold sensitivity of peripheral sensory neurons in the chronic construction injury (CCI model of neuropathic pain in mice.In behavioral experiments, chronic constriction injury (CCI of the sciatic nerve induced a hypersensitivity to both cold and the TRPM8 agonist menthol that developed 2 days post injury and remained stable for at least 2 weeks. Using quantitative RT-PCR and in situ hybridization we examined the expression of TRPM8 and TRPA1 in DRG. Both channels displayed significantly reduced expression levels after injury with no change in their distribution pattern in identified neuronal subpopulations. Furthermore, in calcium imaging experiments, we detected no alterations in the number of cold or menthol responsive neurons in the DRG, or in the functional properties of cold transduction following injury. Intriguingly however, responses to the TRPA1 agonist mustard oil were strongly reduced.Our results indicate that injured sensory neurons do not develop abnormal cold sensitivity after chronic constriction injury and that alterations in the expression of TRPM8 and TRPA1 are unlikely to contribute directly to the pathogenesis of cold allodynia in this neuropathic pain model.

  6. Crotalphine desensitizes TRPA1 ion channels to alleviate inflammatory hyperalgesia

    Czech Academy of Sciences Publication Activity Database

    Bressan, E.; Touška, Filip; Vetter, I.; Kistner, K.; Kichko, T. I.; Teixeira, N. B.; Picolo, G.; Cury, Y.; Lewis, R. J.; Fischer, M. J. M.; Zimmermann, K.; Reeh, P. W.

    2016-01-01

    Roč. 157, č. 11 (2016), s. 2504-2516 ISSN 0304-3959 Institutional support: RVO:67985823 Keywords : Crotalphine * desensitization * TRPA1 * CGRP * Ciguatoxin * Bradykinin * Zymosan Subject RIV: ED - Physiology Impact factor: 5.445, year: 2016

  7. TRPA1 channels in Drosophila and honey bee ectoparasitic mites share heat sensitivity and temperature-related physiological functions

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    Guangda Peng

    2016-10-01

    Full Text Available The transient receptor potential cation channel, subfamily A, member 1 (TRPA1 is conserved between many arthropods, and in some has been shown to function as a chemosensor for noxious compounds. Activation of arthropod TRPA1 channels by temperature fluctuations has been tested in only a few insect species, and all of them were shown to be activated by heat. The recent identification of chemosensitive TRPA1 channels from two honey bee ectoparasitic mite species (VdTRPA1 and TmTRPA1 have provided an opportunity to study the temperature-dependent activation and the temperature-associated physiological functions of TRPA1 channels in non-insect arthropods. We found that both mite TRPA1 channels are heat sensitive and capable of rescuing the temperature-related behavioral defects of a Drosophila melanogaster trpA1 mutant. These results suggest that heat-sensitivity of TRPA1 could be conserved between many arthropods despite its amino acid sequence diversity. Nevertheless, the ankyrin repeats (ARs 6 and 7 are well-conserved between six heat-sensitive arthropod TRPA1 channels and have critical roles for the heat activation of VdTRPA1.

  8. The TRPA1 ion channel is expressed in CD4+ T cells and restrains T-cell-mediated colitis through inhibition of TRPV1.

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    Bertin, Samuel; Aoki-Nonaka, Yukari; Lee, Jihyung; de Jong, Petrus R; Kim, Peter; Han, Tiffany; Yu, Timothy; To, Keith; Takahashi, Naoki; Boland, Brigid S; Chang, John T; Ho, Samuel B; Herdman, Scott; Corr, Maripat; Franco, Alessandra; Sharma, Sonia; Dong, Hui; Akopian, Armen N; Raz, Eyal

    2017-09-01

    Transient receptor potential ankyrin-1 (TRPA1) and transient receptor potential vanilloid-1 (TRPV1) are calcium (Ca 2+ )-permeable ion channels mostly known as pain receptors in sensory neurons. However, growing evidence suggests their crucial involvement in the pathogenesis of IBD. We explored the possible contribution of TRPA1 and TRPV1 to T-cell-mediated colitis. We evaluated the role of Trpa1 gene deletion in two models of experimental colitis (ie, interleukin-10 knockout and T-cell-adoptive transfer models). We performed electrophysiological and Ca 2+ imaging studies to analyse TRPA1 and TRPV1 functions in CD4+ T cells. We used genetic and pharmacological approaches to evaluate TRPV1 contribution to the phenotype of Trpa1 -/- CD4+ T cells. We also analysed TRPA1 and TRPV1 gene expression and TRPA1 + TRPV1 + T cell infiltration in colonic biopsies from patients with IBD. We identified a protective role for TRPA1 in T-cell-mediated colitis. We demonstrated the functional expression of TRPA1 on the plasma membrane of CD4+ T cells and identified that Trpa1 -/- CD4+ T cells have increased T-cell receptor-induced Ca 2+ influx, activation profile and differentiation into Th1-effector cells. This phenotype was abrogated upon genetic deletion or pharmacological inhibition of the TRPV1 channel in mouse and human CD4+ T cells. Finally, we found differential regulation of TRPA1 and TRPV1 gene expression as well as increased infiltration of TRPA1 + TRPV1 + T cells in the colon of patients with IBD. Our study indicates that TRPA1 inhibits TRPV1 channel activity in CD4+ T cells, and consequently restrains CD4+ T-cell activation and colitogenic responses. These findings may therefore have therapeutic implications for human IBD. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  9. Activation of the Chemosensory Ion Channels TRPA1 and TRPV1 by Hydroalcohol Extract of Kalopanax pictus Leaves.

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    Son, Hee Jin; Kim, Yiseul; Misaka, Takumi; Noh, Bong Soo; Rhyu, Mee-Ra

    2012-11-01

    TRPA1 and TRPV1 are members of the TRP superfamily of structurally related, nonselective cation channels. TRPA1 and TRPV1 are often co-expressed in sensory neurons and play an important role in somatosense such as cold, pain, and irritants. The first leaves of Kalopanax pictus Nakai (Araliaceae) have long been used as a culinary ingredient in Korea because of their unique chemesthetic flavor. In this study, we observed the intracellular Ca(2+) response to cultured cells expressing human TRPA1 (hTRPA1) and human TRPV1 (hTRPV1) by Ca(2+) imaging analysis to investigate the ability of the first leaves of K. pictus to activate the hTRPA1 and hTRPV1. An 80% ethanol extract of K. pictus (KPEx) increased intracellular Ca(2+) influx in a response time- and concentration-dependent manner via either hTRPA1 or hTRPV1. KPEx-induced response to hTRPA1 was markedly attenuated by ruthenium red, a general blocker of TRP channels, and HC-030031, a specific antagonist of TRPA1. In addition, the intracellular Ca(2+) influx attained with KPEx to hTRPV1 was mostly blocked by ruthenium red, and capsazepine, a specific antagonist of TRPV1. These results indicate that KPEx selectively activates both hTRPA1 and hTRPV1, which may provide evidence that the first leaves of K. pictus primarily activate TRPA1 and TRPV1 to induce their unique chemesthetic sense.

  10. Functional expression of TRPM8 and TRPA1 channels in rat odontoblasts.

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    Maki Tsumura

    Full Text Available Odontoblasts produce dentin during development, throughout life, and in response to pathological conditions by sensing stimulation of exposed dentin. The functional properties and localization patterns of transient receptor potential (TRP melastatin subfamily member 8 (TRPM8 and ankyrin subfamily member 1 (TRPA1 channels in odontoblasts remain to be clarified. We investigated the localization and the pharmacological, biophysical, and mechano-sensitive properties of TRPM8 and TRPA1 channels in rat odontoblasts. Menthol and icilin increased the intracellular free Ca(2+ concentration ([Ca(2+]i. Icilin-, WS3-, or WS12-induced [Ca(2+]i increases were inhibited by capsazepine or 5-benzyloxytriptamine. The increase in [Ca(2+]i elicited by allyl isothiocyanate (AITC was inhibited by HC030031. WS12 and AITC exerted a desensitizing effect on [Ca(2+]i increase. Low-temperature stimuli elicited [Ca(2+]i increases that are sensitive to both 5-benzyloxytriptamine and HC030031. Hypotonic stimulation-induced membrane stretch increased [Ca(2+]i; HC030031 but not 5-benzyloxytriptamine inhibited the effect. The results suggest that TRPM8 channels in rat odontoblasts play a role in detecting low-temperature stimulation of the dentin surface and that TRPA1 channels are involved in sensing membrane stretching and low-temperature stimulation. The results also indicate that odontoblasts act as mechanical and thermal receptor cells, detecting the stimulation of exposed dentin to drive multiple cellular functions, such as sensory transduction.

  11. Activation of mutated TRPA1 ion channel by resveratrol in human prostate cancer associated fibroblasts (CAF).

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    Vancauwenberghe, Eric; Noyer, Lucile; Derouiche, Sandra; Lemonnier, Loïc; Gosset, Pierre; Sadofsky, Laura R; Mariot, Pascal; Warnier, Marine; Bokhobza, Alexandre; Slomianny, Christian; Mauroy, Brigitte; Bonnal, Jean-Louis; Dewailly, Etienne; Delcourt, Philippe; Allart, Laurent; Desruelles, Emilie; Prevarskaya, Natalia; Roudbaraki, Morad

    2017-08-01

    Previous studies showed the effects of resveratrol (RES) on several cancer cells, including prostate cancer (PCa) cell apoptosis without taking into consideration the impact of the tumor microenvironment (TME). The TME is composed of cancer cells, endothelial cells, blood cells, and cancer-associated fibroblasts (CAF), the main source of growth factors. The latter cells might modify in the TME the impact of RES on tumor cells via secreted factors. Recent data clearly show the impact of CAF on cancer cells apoptosis resistance via secreted factors. However, the effects of RES on PCa CAF have not been studied so far. We have investigated here for the first time the effects of RES on the physiology of PCa CAF in the context of TME. Using a prostate cancer CAF cell line and primary cultures of CAF from prostate cancers, we show that RES activates the N-terminal mutated Transient Receptor Potential Ankyrin 1 (TRPA1) channel leading to an increase in intracellular calcium concentration and the expression and secretion of growth factors (HGF and VEGF) without inducing apoptosis in these cells. Interestingly, in the present work, we also show that when the prostate cancer cells were co-cultured with CAF, the RES-induced cancer cell apoptosis was reduced by 40%, an apoptosis reduction canceled in the presence of the TRPA1 channel inhibitors. The present work highlights CAF TRPA1 ion channels as a target for RES and the importance of the channel in the epithelial-stromal crosstalk in the TME leading to resistance to the RES-induced apoptosis. © 2017 Wiley Periodicals, Inc.

  12. Selective blockade of TRPA1 channel attenuates pathological pain without altering noxious cold sensation or body temperature regulation.

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    Chen, Jun; Joshi, Shailen K; DiDomenico, Stanley; Perner, Richard J; Mikusa, Joe P; Gauvin, Donna M; Segreti, Jason A; Han, Ping; Zhang, Xu-Feng; Niforatos, Wende; Bianchi, Bruce R; Baker, Scott J; Zhong, Chengmin; Simler, Gricelda H; McDonald, Heath A; Schmidt, Robert G; McGaraughty, Steve P; Chu, Katharine L; Faltynek, Connie R; Kort, Michael E; Reilly, Regina M; Kym, Philip R

    2011-05-01

    Despite the increasing interest in TRPA1 channel as a pain target, its role in cold sensation and body temperature regulation is not clear; the efficacy and particularly side effects resulting from channel blockade remain poorly understood. Here we use a potent, selective, and bioavailable antagonist to address these issues. A-967079 potently blocks human (IC(50): 51 nmol/L, electrophysiology, 67 nmol/L, Ca(2+) assay) and rat TRPA1 (IC(50): 101 nmol/L, electrophysiology, 289 nmol/L, Ca(2+) assay). It is >1000-fold selective over other TRP channels, and is >150-fold selective over 75 other ion channels, enzymes, and G-protein-coupled receptors. Oral dosing of A-967079 produces robust drug exposure in rodents, and exhibits analgesic efficacy in allyl isothiocyanate-induced nocifensive response and osteoarthritic pain in rats (ED(50): 23.2 mg/kg, p.o.). A-967079 attenuates cold allodynia produced by nerve injury but does not alter noxious cold sensation in naive animals, suggesting distinct roles of TRPA1 in physiological and pathological states. Unlike TRPV1 antagonists, A-967079 does not alter body temperature. It also does not produce locomotor or cardiovascular side effects. Collectively, these data provide novel insights into TRPA1 function and suggest that the selective TRPA1 blockade may present a viable strategy for alleviating pain without untoward side effects. Copyright © 2011 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  13. Using Neurogenetics and the Warmth-Gated Ion Channel TRPA1 to Study the Neural Basis of Behavior in Drosophila.

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    Berni, Jimena; Muldal, Alistair M; Pulver, Stefan R

    2010-01-01

    Here we describe a set of straightforward laboratory exercises that integrate the study of genetics, neuroanatomy, cellular physiology and animal behavior. We use genetic tools in Drosophila for visualizing and remotely activating ensembles of neurons with heat pulses. First, we show how to examine the anatomy of several neuronal populations using genetically encoded green fluorescent protein. Next we demonstrate how to use the warmth gated Drosophila TRPA1 (dTRPA1) cation channel to remotely activate neural circuits in flies. To demonstrate the cellular effects of dTRPA1 activation, we expressed dTRPA1 panneurally and recorded excitatory junctional potentials in muscles in response to warmed (29°C) saline. Finally, we present inexpensive techniques for delivering heat pulses to activate dTRPA1 in the neuronal groups we observed previously while flies are freely behaving. We suggest how to film and quantify resulting behavioral phenotypes with limited resources. Activating all neurons with dTRPA1 caused tetanic paralysis in larvae, while in adults it led to paralysis in males and continuous uncoordinated leg and wing movements in females. Activation of cholinergic neurons produced spasms and writhing in larvae while causing paralysis in adults. When a single class of nociceptive sensory neurons was activated, it caused lateral rolling in larvae, but no discernable effects in adults. Overall, these exercises illustrate principles of modern genetics, neuroanatomy, the ionic basis of neuronal excitability, and quantitative methods in neuroethology. Relatively few research studies have used dTRPA1 to activate neural circuits, so these exercises give students opportunities to test novel hypotheses and make actual contributions to the scientific record.

  14. Wu-Tou Decoction Inhibits Chronic Inflammatory Pain in Mice: Participation of TRPV1 and TRPA1 Ion Channels

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    Chao Wang

    2015-01-01

    Full Text Available Wu-tou decoction (WTD is a classic traditional Chinese medicine formula and has been used effectively to treat joint diseases clinically. Previous reports indicated that WTD possesses anti-inflammatory activity; however, its actions on pain have not been clarified. Here, we investigated the antinociceptive activity of WTD in CFA-induced mice, and its possible mechanism of the action associated with transient receptor potential (TRP ion channels was also explored. Our results showed that 1.58, 3.15, and 6.30 g/kg WTD significantly attenuated mechanical, cold, and heat hypersensitivities. Moreover, WTD effectively inhibited spontaneous nociceptive responses to intraplantar injections of capsaicin and cinnamaldehyde, respectively. WTD also effectively suppressed jumping and wet-dog-shake behaviors to intraperitoneal injection of icilin. Additionally, WTD significantly reduced protein expression of TRPV1 and TRPA1 in dorsal root ganglia and skins of injured paw. Collectively, our data demonstrate firstly that WTD exerts antinociceptive activity in inflammatory conditions by attenuating mechanical, cold, and heat hypersensitivities. This antinociceptive effect may result in part from inhibiting the activities of TRPV1, TRPA1, and TRPM8, and the suppression of TRPV1 and TRPA1 protein by WTD was also highly effective. These findings suggest that WTD might be an attractive and suitable therapeutic agent for the management of chronic inflammatory pain.

  15. Enhanced production of nitric oxide in A549 cells through activation of TRPA1 ion channel by cold stress.

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    Sun, Wenwu; Wang, Zhonghua; Cao, Jianping; Wang, Xu; Han, Yaling; Ma, Zhuang

    2014-08-31

    The respiratory epithelium is exposed to the external environment, and inhalation of cold air is common during the season of winter. In addition, the lung is a major source of nitric oxide (NO). However, the effect of cold stress on the production of NO is still unclear. In the present work, We measured the change of NO in single cell with DACF-DA and the change in cytosolic Ca(2+) concentration ([Ca(2+)]c) in A549 cell. We observed that cold stress (from 20 °C to 5 °C) induced an increase of NO in A549 cell, which was completely abolished by applying an extracellular Ca(2+) free medium. Further experiments showed that cold-sensing transient receptor potential subfamily member 1 (TRPA1) channel agonist (allyl isothiocyanate, AITC) increased the production of NO and the level of [Ca(2+)]c in A549 cell. Additionally, TRPA1 inhibitor, Ruthenium red (RR) and camphor, significantly blocked the enhanced production of NO and the rise of [Ca(2+)]c induced by AITC or cold stimulation, respectively. Taken together, these data indicated that cold-induced TRPA1 activation was responsible for the enhanced production of NO in A549 cell. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Intracellular cavity of sensor domain controls allosteric gating of TRPA1 channel

    Czech Academy of Sciences Publication Activity Database

    Zímová, Lucie; Sinica, Viktor; Kádková, Anna; Vyklická, Lenka; Zíma, Vlastimil; Barvík, I.; Vlachová, Viktorie

    2018-01-01

    Roč. 11, č. 514 (2018), č. článku eaan8621. ISSN 1945-0877 R&D Projects: GA ČR(CZ) GA15-15839S Institutional support: RVO:67985823 Keywords : TRPA1 * gating * sensor domain * open state * transient receptor potential * ankyrin receptor subtype 1 Subject RIV: FH - Neurology OBOR OECD: Neurosciences (including psychophysiology Impact factor: 6.494, year: 2016

  17. Sensitization of TRPA1 by Protein Kinase A.

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    Jannis E Meents

    Full Text Available The TRPA1 ion channel is expressed in nociceptive (pain-sensitive somatosensory neurons and is activated by a wide variety of chemical irritants, such as acrolein in smoke or isothiocyanates in mustard. Here, we investigate the enhancement of TRPA1 function caused by inflammatory mediators, which is thought to be important in lung conditions such as asthma and COPD. Protein kinase A is an important kinase acting downstream of inflammatory mediators to cause sensitization of TRPA1. By using site-directed mutagenesis, patch-clamp electrophysiology and calcium imaging we identify four amino acid residues, S86, S317, S428, and S972, as the principal targets of PKA-mediated phosphorylation and sensitization of TRPA1.

  18. Inhibition of TRPA1 channel activity in sensory neurons by the glial cell line-derived neurotrophic factor family member, artemin

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    Wang Shenglan

    2011-05-01

    Full Text Available Abstract Background The transient receptor potential (TRP channel subtype A1 (TRPA1 is known to be expressed on sensory neurons and respond to changes in temperature, pH and local application of certain noxious chemicals such as allyl isothiocyanate (AITC. Artemin is a neuronal survival and differentiation factor and belongs to the glial cell line-derived neurotrophic factor (GDNF family. Both TRPA1 and artemin have been reported to be involved in pathological pain initiation and maintenance. In the present study, using whole-cell patch clamp recording technique, in situ hybridization and behavioral analyses, we examined the functional interaction between TRPA1 and artemin. Results We found that 85.8 ± 1.9% of TRPA1-expressing neurons also expressed GDNF family receptor alpha 3 (GFR α3, and 87.5 ± 4.1% of GFRα3-expressing neurons were TRPA1-positive. In whole-cell patch clamp analysis, a short-term treatment of 100 ng/ml artemin significantly suppressed the AITC-induced TRPA1 currents. A concentration-response curve of AITC resulting from the effect of artemin showed that this inhibition did not change EC50 but did lower the AITC-induced maximum response. In addition, pre-treatment of artemin significantly suppressed the number of paw lifts induced by intraplantar injection of AITC, as well as the formalin-induced pain behaviors. Conclusions These findings that a short-term application of artemin inhibits the TRPA1 channel's activity and the sequential pain behaviors suggest a role of artemin in regulation of sensory neurons.

  19. Curcumin ((E,E)-1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione) activates and desensitizes the nociceptor ion channel TRPA1.

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    Leamy, Andrew W; Shukla, Praveen; McAlexander, Michael A; Carr, Michael J; Ghatta, Srinivas

    2011-10-10

    The ion channel TRPA1 is activated by a wide variety of noxious stimuli, such as pollutants, products of oxidative tissue damage, and pungent natural products. Many TRPA1 activators are reactive electrophiles that form Michael adducts with cysteine and lysine residues of TRPA1's intracellular N-terminus. Curcumin, the active principle of turmeric root (Curcuma longa), can also form Michael adducts. In order to test the hypothesis that the electrophilic curcumin activates TRPA1, we have performed whole-cell, voltage-clamp analysis on both HEK293 cells expressing human TRPA1 (hTRPA1-HEK) and native mouse vagal neurons. In nominally calcium-free extracellular and intracellular solutions which minimized the chances of calcium-dependent activation of TRPA1, curcumin increased TRPA1 currents in hTRPA1-HEK cells in a concentration-dependent manner (1-30μM) but did not cause block or activation of recombinant TRPM8 and TRPV1. In addition, 7 out of 11 vagal sensory neurons from wild type mice responded to curcumin (30μM) with inward currents (11.6±5.4pA/pF) that were largely reversed by TRPA1 blockers. In marked contrast, neurons from TRPA1-deficient mice did not respond to curcumin (30μM). With physiological levels of calcium added to the external solution to facilitate channel desensitization, curcumin-dependent currents in hTRPA1-HEK cells were completely desensitized and exhibited marked tachyphylaxis upon subsequent application of curcumin. Taken together, these results demonstrate that curcumin causes activation and subsequent desensitization of native and recombinant TRPA1 ion channels of multiple mammalian species. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  20. Comparison of the transport of QX-314 through TRPA1, TRPM8, and TRPV1 channels

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    Nakagawa H

    2013-03-01

    Full Text Available Hiroshi Nakagawa,1 Akio Hiura2 1Dentistry for Persons with Disability, Tokushima University Hospital, Tokushima, Japan; 2Department of Oral Histology, School of Dentistry, University of Tokushima, Tokushima, Japan Background: It has been demonstrated that N-ethyl-lidocaine (QX-314 can target the transient receptor protein vanilloid 1 (TRPV1 nociceptors when coadministered with capsaicin, resulting in a selective block of the nociceptors. Capsaicin is problematic in therapeutic use because it induces firing of nociceptors. The present study aimed to search for substitutes for capsaicin. We also examined the transportability of QX-314 into nociceptive neurons, through the pores of transient receptor potential ankyrin 1 (TRPA1, transient receptor potential melastatin-8 (TRPM8, and TRPV1. Methods: To investigate the effect on TRPA1, injections of a vehicle, allyl isothiocyanate (AITC, QX-314, or AITC/QX-314 were made into the hind paws of rats. The effects of menthol and capsaicin on the opening of TRPM8 and TRPV1 were also examined and compared with the potency of QX-314. To examine inhibition of the antinociceptive effect by capsaicin/QX-314, capsazepine (50 µg/mL; 10 µL was injected 30 minutes prior to capsaicin/QX-314 (10 µL injection. Thermal sensitivity was investigated by the Hargreaves method. 5(6-carboxyfluorescein (FAM-conjugated QX-314 was used as a tracer to examine how many and which kind of dorsal root ganglia accumulate this molecule. QX-314-FAM, capsaicin/QX-314-FAM, AITC/QX-314-FAM, and menthol/QX-314-FAM were injected into the paw. Two weeks after injections, dorsal root ganglia were removed and sectioned with a cryostat. Results: The capsaicin/QX-314 group induced longer withdrawal-response latency at 60 to 300 minutes after injection than the control. Both menthol only and menthol/QX-314 injections showed analgesia 10 to 60 minutes after injection. No significant difference was seen between the capsazepine/capsaicin/QX-314

  1. Plant-Derived Tick Repellents Activate the Honey Bee Ectoparasitic Mite TRPA1

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    Guangda Peng

    2015-07-01

    Full Text Available We have identified and characterized the TRPA1 channel of Varroa destructor (VdTRPA1, a major ectoparasitic mite of honey bee. One of the two VdTRPA1 isoforms, VdTRPA1L, was activated by a variety of plant-derived compounds, including electrophilic compounds, suggesting that chemical activation profiles are mostly shared between arthropod TRPA1 channels. Nevertheless, carvacrol and α-terpineol activated VdTRPA1L but not a honey bee noxious-stimuli-sensitive TRPA, AmHsTRPA, and Drosophila melanogaster TRPA1. Activation of VdTRPA1L in D. melanogaster taste neurons by the above compounds was sufficient to modify the gustatory behaviors. Carvacrol and α-terpineol repelled V. destructor in a laboratory assay, and α-terpineol repressed V. destructor entry for reproduction into the brood cells in hives. Understanding the functions of parasite TRP channels not only gives clues about the evolving molecular and cellular mechanisms of parasitism but also helps in the development of control methods.

  2. Essential role for the putative S6 inner pore region in the activation gating of the human TRPA1 channel

    Czech Academy of Sciences Publication Activity Database

    Benedikt, Jan; Samad, Abdul; Ettrich, Rüdiger; Teisinger, Jan; Vlachová, Viktorie

    2009-01-01

    Roč. 1793, č. 7 (2009), s. 1279-1288 ISSN 0167-4889 R&D Projects: GA ČR(CZ) GA305/06/0319; GA ČR GA305/09/0081; GA ČR(CZ) GA303/07/0915; GA AV ČR(CZ) IAA600110701; GA MŠk(CZ) 1M0517; GA MŠk(CZ) LC554 Grant - others:EC(XE) LSHM-CT-2007-037765; GA MŠk(CZ) LC06010 Program:LC Institutional research plan: CEZ:AV0Z50110509; CEZ:AV0Z60870520 Keywords : TRPA1 * channel * vanilloid receptor Subject RIV: ED - Physiology Impact factor: 4.374, year: 2009

  3. Molecular Evolution of the Infrared Sensory Gene TRPA1 in Snakes and Implications for Functional Studies

    Science.gov (United States)

    Jiang, Ke; Zhang, Peng

    2011-01-01

    TRPA1 is a calcium ion channel protein recently identified as the infrared receptor in pit organ-containing snakes. Therefore, understanding the molecular evolution of TRPA1 may help to illuminate the origin of “heat vision” in snakes and reveal the molecular mechanism of infrared sensitivity for TRPA1. To this end, we sequenced the infrared sensory gene TRPA1 in 24 snake species, representing nine snake families and multiple non-snake outgroups. We found that TRPA1 is under strong positive selection in the pit-bearing snakes studied, but not in other non-pit snakes and non-snake vertebrates. As a comparison, TRPV1, a gene closely related to TRPA1, was found to be under strong purifying selection in all the species studied, with no difference in the strength of selection between pit-bearing snakes and non-pit snakes. This finding demonstrates that the adaptive evolution of TRPA1 specifically occurred within the pit-bearing snakes and may be related to the functional modification for detecting infrared radiation. In addition, by comparing the TRPA1 protein sequences, we identified 11 amino acid sites that were diverged in pit-bearing snakes but conserved in non-pit snakes and other vertebrates, 21 sites that were diverged only within pit-vipers but conserved in the remaining snakes. These specific amino acid substitutions may be potentially functional important for infrared sensing. PMID:22163322

  4. Expression of the transient receptor potential channels TRPV1, TRPA1 and TRPM8 in mouse trigeminal primary afferent neurons innervating the dura

    Science.gov (United States)

    2012-01-01

    Background Migraine and other headache disorders affect a large percentage of the population and cause debilitating pain. Activation and sensitization of the trigeminal primary afferent neurons innervating the dura and cerebral vessels is a crucial step in the “headache circuit”. Many dural afferent neurons respond to algesic and inflammatory agents. Given the clear role of the transient receptor potential (TRP) family of channels in both sensing chemical stimulants and mediating inflammatory pain, we investigated the expression of TRP channels in dural afferent neurons. Methods We used two fluorescent tracers to retrogradely label dural afferent neurons in adult mice and quantified the abundance of peptidergic and non-peptidergic neuron populations using calcitonin gene-related peptide immunoreactivity (CGRP-ir) and isolectin B4 (IB4) binding as markers, respectively. Using immunohistochemistry, we compared the expression of TRPV1 and TRPA1 channels in dural afferent neurons with the expression in total trigeminal ganglion (TG) neurons. To examine the distribution of TRPM8 channels, we labeled dural afferent neurons in mice expressing farnesylated enhanced green fluorescent protein (EGFPf) from a TRPM8 locus. We used nearest-neighbor measurement to predict the spatial association between dural afferent neurons and neurons expressing TRPA1 or TRPM8 channels in the TG. Results and conclusions We report that the size of dural afferent neurons is significantly larger than that of total TG neurons and facial skin afferents. Approximately 40% of dural afferent neurons exhibit IB4 binding. Surprisingly, the percentage of dural afferent neurons containing CGRP-ir is significantly lower than those of total TG neurons and facial skin afferents. Both TRPV1 and TRPA1 channels are expressed in dural afferent neurons. Furthermore, nearest-neighbor measurement indicates that TRPA1-expressing neurons are clustered around a subset of dural afferent neurons. Interestingly, TRPM

  5. Identification of Natural Compound Carnosol as a Novel TRPA1 Receptor Agonist

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    Chenxi Zhai

    2014-11-01

    Full Text Available The transient receptor potential ankyrin 1 (TRPA1 cation channel is one of the well-known targets for pain therapy. Herbal medicine is a rich source for new drugs and potentially useful therapeutic agents. To discover novel natural TRPA1 agonists, compounds isolated from Chinese herbs were screened using a cell-based calcium mobilization assay. Out of the 158 natural compounds derived from traditional Chinese herbal medicines, carnosol was identified as a novel agonist of TRPA1 with an EC50 value of 12.46 µM. And the agonistic effect of carnosol on TRPA1 could be blocked by A-967079, a selective TRPA1 antagonist. Furthermore, the specificity of carnosol was verified as it showed no significant effects on two other typical targets of TRP family member: TRPM8 and TRPV3. Carnosol exhibited anti-inflammatory and anti-nociceptive properties; the activation of TRPA1 might be responsible for the modulation of inflammatory nociceptive transmission. Collectively, our findings indicate that carnosol is a new anti-nociceptive agent targeting TRPA1 that can be used to explore further biological role in pain therapy.

  6. Five hTRPA1 Agonists Found in Indigenous Korean Mint, Agastache rugosa.

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    Hana Moon

    Full Text Available Transient receptor potential ankyrin1 (TRPA1 and transient receptor potential vanilloid 1 (TRPV1 are members of the TRP superfamily of structurally related, nonselective cation channels and mediators of several signaling pathways. Previously, we identified methyl syringate as an hTRPA1 agonist with efficacy against gastric emptying. The aim of this study was to find hTRPA1 and/or hTRPV1 activators in Agastache rugosa (Fisch. et Meyer O. Kuntze (A.rugosa, commonly known as Korean mint to improve hTRPA1-related phenomena. An extract of the stem and leaves of A.rugosa (Labiatae selectively activated hTRPA1 and hTRPV1. We next investigated the effects of commercially available compounds found in A.rugosa (acacetin, 4-allylanisole, p-anisaldehyde, apigenin 7-glucoside, L-carveol, β-caryophyllene, trans-p-methoxycinnamaldehyde, methyl eugenol, pachypodol, and rosmarinic acid on cultured hTRPA1- and hTRPV1-expressing cells. Of the ten compounds, L-carveol, trans-p-methoxycinnamaldehyde, methyl eugenol, 4-allylanisole, and p-anisaldehyde selectively activated hTRPA1, with EC50 values of 189.1±26.8, 29.8±14.9, 160.2±21.9, 1535±315.7, and 546.5±73.0 μM, respectively. The activities of these compounds were effectively inhibited by the hTRPA1 antagonists, ruthenium red and HC-030031. Although the five active compounds showed weaker calcium responses than allyl isothiocyanate (EC50=7.2±1.4 μM, our results suggest that these compounds from the stem and leaves of A.rugosa are specific and selective agonists of hTRPA1.

  7. Regulation of the transient receptor potential channel TRPA1 by its N-terminal ankyrin repeat domain

    Czech Academy of Sciences Publication Activity Database

    Zayats, Vasilina; Samad, Abdul; Minofar, Babak; Roelofs, K. E.; Stockner, T.; Ettrich, Rüdiger

    2012-01-01

    Roč. 19, č. 11 (2012), s. 4689-4700 ISSN 1610-2940 R&D Projects: GA ČR GAP207/10/1934 Institutional research plan: CEZ:AV0Z60870520 Keywords : ankyrin repeat * EF-hand * familial episodic pain syndrom * TRPA1 Subject RIV: CE - Biochemistry Impact factor: 1.984, year: 2012

  8. Interaction of a peptide derived from C-terminus of human TRPA1 channel with model membranes mimicking the inner leaflet of the plasma membrane.

    Science.gov (United States)

    Witschas, Katja; Jobin, Marie-Lise; Korkut, Dursun Nizam; Vladan, Maria Magdalena; Salgado, Gilmar; Lecomte, Sophie; Vlachova, Viktorie; Alves, Isabel D

    2015-05-01

    The transient receptor potential ankyrin 1 channel (TRPA1) belongs to the TRP cation channel superfamily that responds to a panoply of stimuli such as changes in temperature, calcium levels, reactive oxygen and nitrogen species and lipid mediators among others. The TRP superfamily has been implicated in diverse pathological states including neurodegenerative disorders, kidney diseases, inflammation, pain and cancer. The intracellular C-terminus is an important regulator of TRP channel activity. Studies with this and other TRP superfamily members have shown that the C-terminus association with lipid bilayer alters channel sensitivity and activation, especially interactions occurring through basic residues. Nevertheless, it is not yet clear how this process takes place and which regions in the C-terminus would be responsible for such membrane recognition. With that in mind, herein the first putative membrane interacting region of the C-terminus of human TRPA1, (corresponding to a 29 residue peptide, IAEVQKHASLKRIAMQVELHTSLEKKLPL) named H1 due to its potential helical character was chosen for studies of membrane interaction. The affinity of H1 to lipid membranes, H1 structural changes occurring upon this interaction as well as effects of this interaction in lipid organization and integrity were investigated using a biophysical approach. Lipid models systems composed of zwitterionic and anionic lipids, namely those present in the lipid membrane inner leaflet, where H1 is prone to interact, where used. The study reveals a strong interaction and affinity of H1 as well as peptide structuration especially with membranes containing anionic lipids. Moreover, the interactions and peptide structure adoption are headgroup specific. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. TRPA1 is a polyunsaturated fatty acid sensor in mammals.

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    Arianne L Motter

    Full Text Available Fatty acids can act as important signaling molecules regulating diverse physiological processes. Our understanding, however, of fatty acid signaling mechanisms and receptor targets remains incomplete. Here we show that Transient Receptor Potential Ankyrin 1 (TRPA1, a cation channel expressed in sensory neurons and gut tissues, functions as a sensor of polyunsaturated fatty acids (PUFAs in vitro and in vivo. PUFAs, containing at least 18 carbon atoms and three unsaturated bonds, activate TRPA1 to excite primary sensory neurons and enteroendocrine cells. Moreover, behavioral aversion to PUFAs is absent in TRPA1-null mice. Further, sustained or repeated agonism with PUFAs leads to TRPA1 desensitization. PUFAs activate TRPA1 non-covalently and independently of known ligand binding domains located in the N-terminus and 5(th transmembrane region. PUFA sensitivity is restricted to mammalian (rodent and human TRPA1 channels, as the drosophila and zebrafish TRPA1 orthologs do not respond to DHA. We propose that PUFA-sensing by mammalian TRPA1 may regulate pain and gastrointestinal functions.

  10. TRPA1 gene polymorphisms and childhood asthma.

    Science.gov (United States)

    Gallo, Valentina; Dijk, F Nicole; Holloway, John W; Ring, Susan M; Koppelman, Gerard H; Postma, Dirkje S; Strachan, David P; Granell, Raquel; de Jongste, Johan C; Jaddoe, Vincent W V; den Dekker, Herman T; Duijts, Liesbeth; Henderson, A John; Shaheen, Seif O

    2017-03-01

    Animal data have suggested that the transient receptor potential ankyrin-1 (TRPA1) ion channel plays a key role in promoting airway inflammation in asthma and may mediate effects of paracetamol on asthma, yet confirmatory human data are lacking. To study associations of TRPA1 gene variants with childhood asthma and total IgE concentration, and interactions between TRPA1 and prenatal paracetamol exposure on these outcomes. We analysed associations between 31 TRPA1 single nucleotide polymorphisms (SNPs) and current doctor-diagnosed asthma and total IgE concentration at 7.5 years in the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort. We sought to confirm the most significant associations with comparable outcomes in the Prevention and Incidence of Asthma and Mite Allergy (PIAMA) and Generation R birth cohorts. In ALSPAC, we explored interactions with prenatal paracetamol exposure. In ALSPAC, there was strong evidence for association between six SNPs and asthma: rs959974 and rs1384001 (per-allele odds ratio for both: 1.30 (95% CI: 1.15-1.47), p = 0.00001), rs7010969 (OR 1.28 (1.13-1.46), p = 0.00004), rs3735945 (OR 1.30 (1.09-1.55), p = 0.003), rs920829 (OR 1.30 (1.09-1.54), p = 0.004) and rs4738202 (OR 1.22 (1.07-1.39), p = 0.004). In a meta-analysis across the three cohorts, the pooled effect estimates confirmed that all six SNPs were significantly associated with asthma. In ALSPAC, TRPA1 associations with asthma were not modified by prenatal paracetamol, although associations with IgE concentration were. This study suggests that TRPA1 may play a role in the development of childhood asthma. (249 words). © 2016 The Authors Pediatric Allergy and Immunology Published by John Wiley & Sons Ltd.

  11. TRPV1, TRPA1, and TRPM8 channels in inflammation, energy redirection, and water retention: role in chronic inflammatory diseases with an evolutionary perspective.

    Science.gov (United States)

    Straub, Rainer H

    2014-09-01

    Chronic inflammatory diseases are accompanied by a systemic response of the body, necessary to redirect energy-rich fuels to the activated immune system and to induce volume expansion. The systemic response is switched on by two major pathways: (a) circulating cytokines enter the brain, and (b) signals via sensory nerve fibers are transmitted to the brain. Concerning item b, sensory nerve terminals are equipped with a multitude of receptors that sense temperature, inflammation, osmolality, and pain. Thus, they can be important to inform the brain about peripheral inflammation. Central to these sensory modalities are transient receptor potential channels (TRP channels) on sensory nerve endings. For example, TRP vanilloid 1 (TRPV1) can be activated by heat, inflammatory factors (e.g., protons, bradykinin, anandamide), hyperosmolality, pungent irritants, and others. TRP channels are multimodal switches that transmit peripheral signals to the brain, thereby inducing a systemic response. It is demonstrated how and why these TRP channels (TRPV1, TRP ankyrin type 1 (TRPA1), and TRP melastatin type 8 (TRPM8)) are important to start up a systemic response of energy expenditure, energy allocation, and water retention and how this is linked to a continuously activated immune system in chronic inflammatory diseases.

  12. Transient receptor potential cation channel A1 (TRPA1) mediates changes in heart rate variability following a single exposure to acrolein in mice

    Science.gov (United States)

    The data show that a single exposure to acrolein causes autonomic imbalance in mice through the TRPA1 sensor and subsequent cardiac dysfunction. Human and animal studies have shown that short-term air pollution exposure causes...

  13. Burning Cold: Involvement of TRPA1 in Noxious Cold Sensation

    OpenAIRE

    Kwan, Kelvin Y.; Corey, David P.

    2009-01-01

    Soon after its discovery ten years ago, the ion channel TRPA1 was proposed as a sensor of noxious cold. Evidence for its activation by painfully cold temperatures (below ~15° C) has been mixed, however. Some groups found that cold elicits a nonselective conductance in cells expressing TRPA1; others found no activation, or argued that activation is an indirect effect of elevated \\(Ca^{ 2+}\\) . Sensory cells from the trigeminal and dorsal root ganglia that are activated by cold were sometimes c...

  14. Tear gasses CN, CR, and CS are potent activators of the human TRPA1 receptor

    International Nuclear Information System (INIS)

    Brone, Bert; Peeters, Pieter J.; Marrannes, Roger; Mercken, Marc; Nuydens, Ronny; Meert, Theo; Gijsen, Harrie J.M.

    2008-01-01

    The TRPA1 channel is activated by a number of pungent chemicals, such as allylisothiocyanate, present in mustard oil and thiosulfinates present in garlic. Most of the known activating compounds contain reactive, electrophilic chemical groups, reacting with cysteine residues in the active site of the TRPA1 channel. This covalent modification results in activation of the channel and has been shown to be reversible for several ligands. Commonly used tear gasses CN, CR and CS are also pungent chemicals, and in this study we show that they are extremely potent and selective activators of the human TRPA1 receptor. To our knowledge, these are the most potent TRPA1 agonists known to date. The identification of the molecular target for these tear gasses may open up possibilities to alleviate the effects of tear gasses via treatment with TRPA1 antagonists. In addition these results may contribute to the basic knowledge of the TRPA1 channel that is gaining importance as a pharmacological target

  15. TRPA1 receptor is upregulated in human oral lichen planus.

    Science.gov (United States)

    Kun, J; Perkecz, A; Knie, L; Sétáló, G; Tornóczki, T; Pintér, E; Bán, Á

    2017-03-01

    Oral lichen planus (OLP) is a chronic inflammatory disease of unknown etiology with antigen-specific and non-specific mechanisms. Transient receptor potential ankyrin 1 (TRPA1) is a non-selective cation channel activated by noxious stimuli such as oxidative stress products evoking pain and release of proinflammatory mediators from sensory nerve endings culminating in neurogenic inflammation. Extraneuronal TRPA1s, for example, on immune cells possess yet unknown functions. We studied the buccal mRNA expression (qPCR) and protein localization (immunohistochemistry) of TRPA1 receptors and key OLP mediator transcripts in oral mucosa samples of healthy volunteers (n = 9), OLP patients (n = 43), and OLP-like hyperkeratotic patients (n = 12). We measured 27.7- and 25.5-fold TRPA1 mRNA increase in OLP and OLP-like hyperkeratotic patients compared to healthy controls. TRPA1 transcripts elevated 2.4-fold in hypertensive OLP but not in hyperkeratotic patients compared to counterparts, reduced by 1.6-fold by angiotensin-convertase inhibitor intake. TRPA1 messenger RNA was more coexpressed with transcripts of tumor necrosis factor α than with interferon γ. Keratinocytes, macrophages but not T cells expressed TRPA1. We provided evidence for the extraneuronal presence and upregulation of the proinflammatory TRPA1 receptor in buccal samples of patients with OLP. This may implicate the ion channel in the pathomechanism of OLP. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. Drosophila larvae food intake cessation following exposure to Erwinia contaminated media requires odor perception, Trpa1 channel and evf virulence factor.

    Science.gov (United States)

    Keita, Seydou; Masuzzo, Ambra; Royet, Julien; Kurz, C Leopold

    2017-05-01

    When exposed to microorganisms, animals use several protective strategies. On one hand, as elegantly exemplified in Drosophila melanogaster, the innate immune system recognizes microbial compounds and triggers an antimicrobial response. On the other hand, behaviors preventing an extensive contact with the microbes and thus reducing the risk of infection have been described. However, these reactions ranging from microbes aversion to intestinal transit increase or food intake decrease have been rarely defined at the molecular level. In this study, we set up an experimental system that allowed us to rapidly identify and quantify food intake decreases in Drosophila larvae exposed to media contaminated with bacteria. Specifically, we report a robust dose-dependent food intake decrease following exposure to the bacteria Erwinia carotovora carotovora strain Ecc15. We demonstrate that this response does not require Imd innate immune pathway, but rather the olfactory neuronal circuitry, the Trpa1 receptor and the evf virulence factor. Finally, we show that Ecc15 induce the same behavior in the invasive pest insect Drosophila suzukii. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Mechanosensory and ATP Release Deficits following Keratin14-Cre-Mediated TRPA1 Deletion Despite Absence of TRPA1 in Murine Keratinocytes.

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    Katherine J Zappia

    Full Text Available Keratinocytes are the first cells that come into direct contact with external tactile stimuli; however, their role in touch transduction in vivo is not clear. The ion channel Transient Receptor Potential Ankyrin 1 (TRPA1 is essential for some mechanically-gated currents in sensory neurons, amplifies mechanical responses after inflammation, and has been reported to be expressed in human and mouse skin. Other reports have not detected Trpa1 mRNA transcripts in human or mouse epidermis. Therefore, we set out to determine whether selective deletion of Trpa1 from keratinocytes would impact mechanosensation. We generated K14Cre-Trpa1fl/fl mice lacking TRPA1 in K14-expressing cells, including keratinocytes. Surprisingly, Trpa1 transcripts were very poorly detected in epidermis of these mice or in controls, and detection was minimal enough to preclude observation of Trpa1 mRNA knockdown in the K14Cre-Trpa1fl/fl mice. Unexpectedly, these K14Cre-Trpa1fl/fl mice nonetheless exhibited a pronounced deficit in mechanosensitivity at the behavioral and primary afferent levels, and decreased mechanically-evoked ATP release from skin. Overall, while these data suggest that the intended targeted deletion of Trpa1 from keratin 14-expressing cells of the epidermis induces functional deficits in mechanotransduction and ATP release, these deficits are in fact likely due to factors other than reduction of Trpa1 expression in adult mouse keratinocytes because they express very little, if any, Trpa1.

  18. The First Extracellular Linker Is Important for Several Aspects of the Gating Mechanism of Human TRPA1 Channel

    Czech Academy of Sciences Publication Activity Database

    Maršáková, Lenka; Barvík, I.; Zíma, V.; Zímová, Lucie; Vlachová, Viktorie

    2017-01-01

    Roč. 10, Jan 31 (2017), č. článku 16. ISSN 1662-5099 R&D Projects: GA ČR(CZ) GA15-15839S; GA ČR(CZ) GBP304/12/G069; GA MŠk(CZ) EE2.3.30.0025 Institutional support: RVO:67985823 Keywords : TRP channel * S1-S2 linker * allyl isothiocynate * sensor module Subject RIV: FH - Neurology OBOR OECD: Neuroscience s (including psychophysiology Impact factor: 5.076, year: 2016

  19. In vitro pharmacological characterization of a novel TRPA1 antagonist and proof of mechanism in a human dental pulp model

    Directory of Open Access Journals (Sweden)

    Nyman E

    2013-01-01

    Full Text Available Eva Nyman,1,* Bo Franzén,1,* Andreas Nolting,1 Göran Klement,1 Gang Liu,1 Maria Nilsson,1 Annika Rosén,2 Charlotta Björk,3 Dirk Weigelt,4 Patrik Wollberg,1 Paul Karila,1 Patrick Raboisson11Neuroscience, Innovative Medicines CNS/Pain, AstraZeneca R&D, Södertälje, Sweden; 2Division of Oral and Maxillofacial Surgery, Karolinska Institute/Karolinska University Hospital, Huddinge, Sweden; 3Clinical TA NS Early Development, 4Medicinal Chemistry, Innovative Medicines CNS/Pain, AstraZeneca R&D, Södertälje, Sweden*These authors contributed equally to this workAbstract: AZ465 is a novel selective transient receptor potential cation channel, member A1 (TRPA1 antagonist identified during a focused drug discovery effort. In vitro, AZ465 fully inhibits activation by zinc, O-chlorobenzylidene malononitrile (CS, or cinnamaldehyde of the human TRPA1 channel heterologously expressed in human embryonic kidney cells. Our data using patch-clamp recordings and mouse/human TRPA1 chimeras suggest that AZ465 binds reversibly in the pore region of the human TRPA1 channel. Finally, in an ex vivo model measuring TRPA1 agonist-stimulated release of neuropeptides from human dental pulp biopsies, AZD465 was able to block 50%–60% of CS-induced calcitonin gene-related peptide release, confirming that AZ465 inhibits the native human TRPA1 channel in neuronal tissue.Keywords: pain, pharmacology, antagonist, chimeric proteins, dental pulp, inflammation, neuropeptide, calcitonin gene-related peptide, CGRP

  20. Transient receptor potential cation channel A1 (TRPA1) mediates decrements in cardiac mechanical function and dysrhythmia caused by a single air pollution exposure in mice

    Science.gov (United States)

    This work, which will be presented at SOT 2014, demonstrates that a single exposure to either ozone or acrolein causes decrements in cardiac function and altered electrical activity (i.e. arrhythmia). The results suggest that this effect is mediated by the airway sensor TRPA1. ...

  1. Human TRPA1 is intrinsically cold- and chemosensitive with and without its N-terminal ankyrin repeat domain.

    Science.gov (United States)

    Moparthi, Lavanya; Survery, Sabeen; Kreir, Mohamed; Simonsen, Charlotte; Kjellbom, Per; Högestätt, Edward D; Johanson, Urban; Zygmunt, Peter M

    2014-11-25

    We have purified and reconstituted human transient receptor potential (TRP) subtype A1 (hTRPA1) into lipid bilayers and recorded single-channel currents to understand its inherent thermo- and chemosensory properties as well as the role of the ankyrin repeat domain (ARD) of the N terminus in channel behavior. We report that hTRPA1 with and without its N-terminal ARD (Δ1-688 hTRPA1) is intrinsically cold-sensitive, and thus, cold-sensing properties of hTRPA1 reside outside the N-terminal ARD. We show activation of hTRPA1 by the thiol oxidant 2-((biotinoyl)amino)ethyl methanethiosulfonate (MTSEA-biotin) and that electrophilic compounds activate hTRPA1 in the presence and absence of the N-terminal ARD. The nonelectrophilic compounds menthol and the cannabinoid Δ(9)-tetrahydrocannabiorcol (C16) directly activate hTRPA1 at different sites independent of the N-terminal ARD. The TRPA1 antagonist HC030031 inhibited cold and chemical activation of hTRPA1 and Δ1-688 hTRPA1, supporting a direct interaction with hTRPA1 outside the N-terminal ARD. These findings show that hTRPA1 is an intrinsically cold- and chemosensitive ion channel. Thus, second messengers, including Ca(2+), or accessory proteins are not needed for hTRPA1 responses to cold or chemical activators. We suggest that conformational changes outside the N-terminal ARD by cold, electrophiles, and nonelectrophiles are important in hTRPA1 channel gating and that targeting chemical interaction sites outside the N-terminal ARD provides possibilities to fine tune TRPA1-based drug therapies (e.g., for treatment of pain associated with cold hypersensitivity and cardiovascular disease).

  2. Acrolein relaxes mouse isolated tracheal smooth muscle via a TRPA1-dependent mechanism.

    Science.gov (United States)

    Cheah, Esther Y; Burcham, Philip C; Mann, Tracy S; Henry, Peter J

    2014-05-01

    Airway sensory C-fibres express TRPA1 channels which have recently been identified as a key chemosensory receptor for acrolein, a toxic and highly prevalent component of smoke. TRPA1 likely plays an intermediary role in eliciting a range of effects induced by acrolein including cough and neurogenic inflammation. Currently, it is not known whether acrolein-induced activation of TRPA1 produces other airway effects including relaxation of mouse airway smooth muscle. The aims of this study were to examine the effects of acrolein on airway smooth muscle tone in mouse isolated trachea, and to characterise the cellular and molecular mechanisms underpinning the effects of acrolein. Isometric tension recording studies were conducted on mouse isolated tracheal segments to characterise acrolein-induced relaxation responses. Release of the relaxant PGE₂ was measured by EIA to examine its role in the response. Use of selective antagonists/inhibitors permitted pharmacological characterisation of the molecular and cellular mechanisms underlying this relaxation response. Acrolein induced dose-dependent relaxation responses in mouse isolated tracheal segments. Importantly, these relaxation responses were significantly inhibited by the TRPA1 antagonists AP-18 and HC-030031, an NK₁ receptor antagonist RP-67580, and the EP₂ receptor antagonist PF-04418948, whilst completely abolished by the non-selective COX inhibitor indomethacin. Acrolein also caused rapid PGE₂ release which was suppressed by HC-030031. In summary, acrolein induced a novel bronchodilator response in mouse airways. Pharmacologic studies indicate that acrolein-induced relaxation likely involves interplay between TRPA1-expressing airway sensory C-fibres, NK₁ receptor-expressing epithelial cells, and EP₂-receptor expressing airway smooth muscle cells. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. Role of TRPA1 in acute cardiopulmonary toxicity of inhaled acrolein.

    Science.gov (United States)

    Conklin, Daniel J; Haberzettl, Petra; Jagatheesan, Ganapathy; Kong, Maiying; Hoyle, Gary W

    2017-06-01

    Acrolein is a highly toxic, volatile, unsaturated aldehyde generated during incomplete combustion as in tobacco smoke and indoor fires. Because the transient receptor potential ankyrin 1 (TRPA1) channel mediates tobacco smoke-induced lung injury, we assessed its role in high-level acrolein-induced toxicity in mice. Acrolein (100-275ppm, 10-30min) caused upper airway epithelial sloughing, bradypnea and oral gasping, hypothermia, cardiac depression and mortality. Male wild-type mice (WT, C57BL/6; 5-52weeks) were significantly more sensitive to high-level acrolein than age-matched, female WT mice. Both male and female TRPA1-null mice were more sensitive to acrolein-induced mortality than age- and sex-matched WT mice. Acrolein exposure increased lung weight:body weight ratios and lung albumin and decreased plasma albumin to a greater extent in TRPA1-null than in WT mice. Lung and plasma protein-acrolein adducts were not increased in acrolein-exposed TRPA1-null mice compared with WT mice. To assess TRPA1-dependent protective mechanisms, respiratory parameters were monitored by telemetry. TRPA1-null mice had a slower onset of breathing rate suppression ('respiratory braking') than WT mice suggesting TRPA1 mediates this protective response. Surprisingly, WT male mice treated either with a TRPA1 antagonist (HC030031; 200mg/kg) alone or with combined TRPA1 (100mg/kg) and TRPV1 (capsazepine, 10mg/kg) antagonists at 30min post-acrolein exposure (i.e., "real world" delay in treatment) were significantly protected from acrolein-induced mortality. These data show TRPA1 protects against high-level acrolein-induced toxicity in a sex-dependent manner. Post-exposure TRPA1 antagonism also protected against acrolein-induced mortality attesting to a complex role of TRPA1 in cardiopulmonary injury. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Blocking TRPA1 in Respiratory Disorders: Does It Hold a Promise?

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    Indranil Mukhopadhyay

    2016-11-01

    Full Text Available Transient Receptor Potential Ankyrin 1 (TRPA1 ion channel is expressed abundantly on the C fibers that innervate almost entire respiratory tract starting from oral cavity and oropharynx, conducting airways in the trachea, bronchi, terminal bronchioles, respiratory bronchioles and upto alveolar ducts and alveoli. Functional presence of TRPA1 on non-neuronal cells got recognized recently. TRPA1 plays a well-recognized role of “chemosensor”, detecting presence of exogenous irritants and endogenous pro-inflammatory mediators that are implicated in airway inflammation and sensory symptoms like chronic cough, asthma, chronic obstructive pulmonary disease (COPD, allergic rhinitis and cystic fibrosis. TRPA1 can remain activated chronically due to elevated levels and continued presence of such endogenous ligands and pro-inflammatory mediators. Several selective TRPA1 antagonists have been tested in animal models of respiratory disease and their performance is very promising. Although there is no TRPA1 antagonist in advanced clinical trials or approved on market yet to treat respiratory diseases, however, limited but promising evidences available so far indicate likelihood that targeting TRPA1 may present a new therapy in treatment of respiratory diseases in near future. This review will focus on in vitro, animal and human evidences that strengthen the proposed role of TRPA1 in modulation of specific airway sensory responses and also on preclinical and clinical progress of selected TRPA1 antagonists.

  5. Role of TRPA1 in acute cardiopulmonary toxicity of inhaled acrolein

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    Conklin, Daniel J.; Haberzettl, Petra; Jagatheesan, Ganapathy; Kong, Maiying; Hoyle, Gary W.

    2017-01-01

    Acrolein is a highly toxic, volatile, unsaturated aldehyde generated during incomplete combustion as in tobacco smoke and indoor fires. Because the transient receptor potential ankyrin 1 (TRPA1) channel mediates tobacco smoke-induced lung injury, we assessed its role in high-level acrolein-induced toxicity in mice. Acrolein (100–275 ppm, 10–30 min) caused upper airway epithelial sloughing, bradypnea and oral gasping, hypothermia, cardiac depression and mortality. Male wild-type mice (WT, C57BL/6; 5–52 weeks) were significantly more sensitive to high-level acrolein than age-matched, female WT mice. Both male and female TRPA1-null mice were more sensitive to acrolein-induced mortality than age- and sex-matched WT mice. Acrolein exposure increased lung weight:body weight ratios and lung albumin and decreased plasma albumin to a greater extent in TRPA1-null than in WT mice. Lung and plasma protein-acrolein adducts were not increased in acrolein-exposed TRPA1-null mice compared with WT mice. To assess TRPA1-dependent protective mechanisms, respiratory parameters were monitored by telemetry. TRPA1-null mice had a slower onset of breathing rate suppression (‘respiratory braking’) than WT mice suggesting TRPA1 mediates this protective response. Surprisingly, WT male mice treated either with a TRPA1 antagonist (HC030031; 200 mg/kg) alone or with combined TRPA1 (100 mg/kg) and TRPV1 (capsazepine, 10 mg/kg) antagonists at 30 min post-acrolein exposure (i.e., “real world” delay in treatment) were significantly protected from acrolein-induced mortality. These data show TRPA1 protects against high-level acrolein-induced toxicity in a sex-dependent manner. Post-exposure TRPA1 antagonism also protected against acrolein-induced mortality attesting to a complex role of TRPA1 in cardiopulmonary injury. - Highlights: • TRPA1 protects mice against toxicity and mortality of inhaled high-level acrolein. • TRPA1 protection against inhaled high-level acrolein is sex

  6. Role of TRPA1 in acute cardiopulmonary toxicity of inhaled acrolein

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    Conklin, Daniel J., E-mail: dj.conklin@louisville.edu [Diabetes and Obesity Center, Institute of Molecular Cardiology, Division of Cardiovascular Medicine, Department of Medicine, School of Medicine, University of Louisville, Louisville, KY 40292 (United States); Haberzettl, Petra; Jagatheesan, Ganapathy [Diabetes and Obesity Center, Institute of Molecular Cardiology, Division of Cardiovascular Medicine, Department of Medicine, School of Medicine, University of Louisville, Louisville, KY 40292 (United States); Kong, Maiying [Department of Bioinformatics and Biostatistics, School of Public Health & Information Sciences, University of Louisville, Louisville, KY 40292 (United States); Hoyle, Gary W. [Department of Environmental and Occupational Health Sciences, School of Public Health & Information Sciences, University of Louisville, Louisville, KY 40292 (United States)

    2017-06-01

    Acrolein is a highly toxic, volatile, unsaturated aldehyde generated during incomplete combustion as in tobacco smoke and indoor fires. Because the transient receptor potential ankyrin 1 (TRPA1) channel mediates tobacco smoke-induced lung injury, we assessed its role in high-level acrolein-induced toxicity in mice. Acrolein (100–275 ppm, 10–30 min) caused upper airway epithelial sloughing, bradypnea and oral gasping, hypothermia, cardiac depression and mortality. Male wild-type mice (WT, C57BL/6; 5–52 weeks) were significantly more sensitive to high-level acrolein than age-matched, female WT mice. Both male and female TRPA1-null mice were more sensitive to acrolein-induced mortality than age- and sex-matched WT mice. Acrolein exposure increased lung weight:body weight ratios and lung albumin and decreased plasma albumin to a greater extent in TRPA1-null than in WT mice. Lung and plasma protein-acrolein adducts were not increased in acrolein-exposed TRPA1-null mice compared with WT mice. To assess TRPA1-dependent protective mechanisms, respiratory parameters were monitored by telemetry. TRPA1-null mice had a slower onset of breathing rate suppression (‘respiratory braking’) than WT mice suggesting TRPA1 mediates this protective response. Surprisingly, WT male mice treated either with a TRPA1 antagonist (HC030031; 200 mg/kg) alone or with combined TRPA1 (100 mg/kg) and TRPV1 (capsazepine, 10 mg/kg) antagonists at 30 min post-acrolein exposure (i.e., “real world” delay in treatment) were significantly protected from acrolein-induced mortality. These data show TRPA1 protects against high-level acrolein-induced toxicity in a sex-dependent manner. Post-exposure TRPA1 antagonism also protected against acrolein-induced mortality attesting to a complex role of TRPA1 in cardiopulmonary injury. - Highlights: • TRPA1 protects mice against toxicity and mortality of inhaled high-level acrolein. • TRPA1 protection against inhaled high-level acrolein is sex

  7. A role of TRPA1 in mechanical hyperalgesia is revealed by pharmacological inhibition

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    Huynh Truc

    2007-12-01

    Full Text Available Abstract Mechanical hyperalgesia is a clinically-relevant form of pain sensitization that develops through largely unknown mechanisms. TRPA1, a Transient Receptor Potential ion channel, is a sensor of pungent chemicals that may play a role in acute noxious mechanosensation and cold thermosensation. We have developed a specific small molecule TRPA1 inhibitor (AP18 that can reduce cinnameldehyde-induced nociception in vivo. Interestingly, AP18 is capable of reversing CFA-induced mechanical hyperalgesia in mice. Although TRPA1-deficient mice develop normal CFA-induced hyperalgeisa, AP18 is ineffective in the knockout mice, consistent with an on-target mechanism. Therefore, TRPA1 plays a role in sensitization of nociception, and that compensation in TRPA1-deficient mice masks this requirement.

  8. Plant derived aporphinic alkaloid S-(+-dicentrine induces antinociceptive effect in both acute and chronic inflammatory pain models: evidence for a role of TRPA1 channels.

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    Deise Prehs Montrucchio

    Full Text Available S-(+-dicentrine is an aporphinic alkaloid found in several plant species, mainly from Lauraceae family, which showed significant antinociceptive activity in an acute model of visceral pain in mice. In this work, we extended the knowledge on the antinociceptive properties of S-(+-dicentrine and showed that this alkaloid also attenuates mechanical and cold hypersensitivity associated with cutaneous inflammation induced by Complete Freund's Adjuvant in mice. Given orally, S-(+-dicentrine (100 mg/kg reversed CFA-induced mechanical hypersensitivity, evaluated as the paw withdrawal threshold to von Frey hairs, and this effect lasted up to 2 hours. S-(+-dicentrine also reversed CFA-induced cold hypersensitivity, assessed as the responses to a drop of acetone in the injured paw, but did not reverse the heat hypersensitivity, evaluated as the latency time to paw withdrawal in the hot plate (50°C. Moreover, S-(+-dicentrine (100 mg/kg, p.o. was effective in inhibit nociceptive responses to intraplantar injections of cinnamaldehyde, a TRPA1 activator, but not the responses induced by capsaicin, a TRPV1 activator. When administered either by oral or intraplantar routes, S-(+-dicentrine reduced the licking time (spontaneous nociception and increased the latency time to paw withdrawal in the cold plate (cold hypersensitivity, both induced by the intraplantar injection of cinnamaldehyde. Taken together, our data adds information about antinociceptive properties of S-(+-dicentrine in inflammatory conditions, reducing spontaneous nociception and attenuating mechanical and cold hypersensitivity, probably via a TRPA1-dependent mechanism. It also indicates that S-(+-dicentrine might be potentially interesting in the development of new clinically relevant drugs for the management of persistent pain, especially under inflammatory conditions.

  9. Expression of transient receptor potential ankyrin 1 (TRPA1 and its role in insulin release from rat pancreatic beta cells.

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    De-Shou Cao

    Full Text Available Several transient receptor potential (TRP channels are expressed in pancreatic beta cells and have been proposed to be involved in insulin secretion. However, the endogenous ligands for these channels are far from clear. Here, we demonstrate the expression of the transient receptor potential ankyrin 1 (TRPA1 ion channel in the pancreatic beta cells and its role in insulin release. TRPA1 is an attractive candidate for inducing insulin release because it is calcium permeable and is activated by molecules that are produced during oxidative glycolysis.Immunohistochemistry, RT-PCR, and Western blot techniques were used to determine the expression of TRPA1 channel. Ca²⁺ fluorescence imaging and electrophysiology (voltage- and current-clamp techniques were used to study the channel properties. TRPA1-mediated insulin release was determined using ELISA.TRPA1 is abundantly expressed in a rat pancreatic beta cell line and freshly isolated rat pancreatic beta cells, but not in pancreatic alpha cells. Activation of TRPA1 by allyl isothiocyanate (AITC, hydrogen peroxide (H₂O₂, 4-hydroxynonenal (4-HNE, and cyclopentenone prostaglandins (PGJ₂ and a novel agonist methylglyoxal (MG induces membrane current, depolarization, and Ca²⁺ influx leading to generation of action potentials in a pancreatic beta cell line and primary cultured pancreatic beta cells. Activation of TRPA1 by agonists stimulates insulin release in pancreatic beta cells that can be inhibited by TRPA1 antagonists such as HC030031 or AP-18 and by RNA interference. TRPA1-mediated insulin release is also observed in conditions of voltage-gated Na⁺ and Ca²⁺ channel blockade as well as ATP sensitive potassium (K(ATP channel activation.We propose that endogenous and exogenous ligands of TRPA1 cause Ca²⁺ influx and induce basal insulin release and that TRPA1-mediated depolarization acts synergistically with K(ATP channel blockade to facilitate insulin release.

  10. Inhibition by TRPA1 agonists of compound action potentials in the frog sciatic nerve

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    Matsushita, Akitomo; Ohtsubo, Sena; Fujita, Tsugumi; Kumamoto, Eiichi, E-mail: kumamote@cc.saga-u.ac.jp

    2013-04-26

    Highlights: •TRPA1 agonists inhibited compound action potentials in frog sciatic nerves. •This inhibition was not mediated by TRPA1 channels. •This efficacy was comparable to those of lidocaine and cocaine. •We found for the first time an ability of TRPA1 agonists to inhibit nerve conduction. -- Abstract: Although TRPV1 and TRPM8 agonists (vanilloid capsaicin and menthol, respectively) at high concentrations inhibit action potential conduction, it remains to be unknown whether TRPA1 agonists have a similar action. The present study examined the actions of TRPA1 agonists, cinnamaldehyde (CA) and allyl isothiocyanate (AITC), which differ in chemical structure from each other, on compound action potentials (CAPs) recorded from the frog sciatic nerve by using the air-gap method. CA and AITC concentration-dependently reduced the peak amplitude of the CAP with the IC{sub 50} values of 1.2 and 1.5 mM, respectively; these activities were resistant to a non-selective TRP antagonist ruthenium red or a selective TRPA1 antagonist HC-030031. The CA and AITC actions were distinct in property; the latter but not former action was delayed in onset and partially reversible, and CA but not AITC increased thresholds to elicit CAPs. A CAP inhibition was seen by hydroxy-α-sanshool (by 60% at 0.05 mM), which activates both TRPA1 and TRPV1 channels, a non-vanilloid TRPV1 agonist piperine (by 20% at 0.07 mM) and tetrahydrolavandulol (where the six-membered ring of menthol is opened; IC{sub 50} = 0.38 mM). It is suggested that TRPA1 agonists as well as TRPV1 and TRPM8 agonists have an ability to inhibit nerve conduction without TRP activation, although their agonists are quite different in chemical structure from each other.

  11. TRPA1 is functionally expressed primarily by IB4-binding, non-peptidergic mouse and rat sensory neurons.

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    Marie E Barabas

    Full Text Available Subpopulations of somatosensory neurons are characterized by functional properties and expression of receptor proteins and surface markers. CGRP expression and IB4-binding are commonly used to define peptidergic and non-peptidergic subpopulations. TRPA1 is a polymodal, plasma membrane ion channel that contributes to mechanical and cold hypersensitivity during tissue injury, making it a key target for pain therapeutics. Some studies have shown that TRPA1 is predominantly expressed by peptidergic sensory neurons, but others indicate that TRPA1 is expressed extensively within non-peptidergic, IB4-binding neurons. We used FURA-2 calcium imaging to define the functional distribution of TRPA1 among peptidergic and non-peptidergic adult mouse (C57BL/6J DRG neurons. Approximately 80% of all small-diameter (<27 µm neurons from lumbar 1-6 DRGs that responded to TRPA1 agonists allyl isothiocyanate (AITC; 79% or cinnamaldehyde (84% were IB4-positive. Retrograde labeling via plantar hind paw injection of WGA-Alexafluor594 showed similarly that most (81% cutaneous neurons responding to TRPA1 agonists were IB4-positive. Additionally, we cultured DRG neurons from a novel CGRP-GFP mouse where GFP expression is driven by the CGRPα promoter, enabling identification of CGRP-expressing live neurons. Interestingly, 78% of TRPA1-responsive neurons were CGRP-negative. Co-labeling with IB4 revealed that the majority (66% of TRPA1 agonist responders were IB4-positive but CGRP-negative. Among TRPA1-null DRGs, few small neurons (2-4% responded to either TRPA1 agonist, indicating that both cinnamaldehyde and AITC specifically target TRPA1. Additionally, few large neurons (≥27 µm diameter responded to AITC (6% or cinnamaldehyde (4%, confirming that most large-diameter somata lack functional TRPA1. Comparison of mouse and rat DRGs showed that the majority of TRPA1-responsive neurons in both species were IB4-positive. Together, these data demonstrate that TRPA1 is

  12. TRPA1 Is Functionally Expressed Primarily by IB4-Binding, Non-Peptidergic Mouse and Rat Sensory Neurons

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    Stucky, Cheryl L.

    2012-01-01

    Subpopulations of somatosensory neurons are characterized by functional properties and expression of receptor proteins and surface markers. CGRP expression and IB4-binding are commonly used to define peptidergic and non-peptidergic subpopulations. TRPA1 is a polymodal, plasma membrane ion channel that contributes to mechanical and cold hypersensitivity during tissue injury, making it a key target for pain therapeutics. Some studies have shown that TRPA1 is predominantly expressed by peptidergic sensory neurons, but others indicate that TRPA1 is expressed extensively within non-peptidergic, IB4-binding neurons. We used FURA-2 calcium imaging to define the functional distribution of TRPA1 among peptidergic and non-peptidergic adult mouse (C57BL/6J) DRG neurons. Approximately 80% of all small-diameter (neurons from lumbar 1–6 DRGs that responded to TRPA1 agonists allyl isothiocyanate (AITC; 79%) or cinnamaldehyde (84%) were IB4-positive. Retrograde labeling via plantar hind paw injection of WGA-Alexafluor594 showed similarly that most (81%) cutaneous neurons responding to TRPA1 agonists were IB4-positive. Additionally, we cultured DRG neurons from a novel CGRP-GFP mouse where GFP expression is driven by the CGRPα promoter, enabling identification of CGRP-expressing live neurons. Interestingly, 78% of TRPA1-responsive neurons were CGRP-negative. Co-labeling with IB4 revealed that the majority (66%) of TRPA1 agonist responders were IB4-positive but CGRP-negative. Among TRPA1-null DRGs, few small neurons (2–4%) responded to either TRPA1 agonist, indicating that both cinnamaldehyde and AITC specifically target TRPA1. Additionally, few large neurons (≥27 µm diameter) responded to AITC (6%) or cinnamaldehyde (4%), confirming that most large-diameter somata lack functional TRPA1. Comparison of mouse and rat DRGs showed that the majority of TRPA1-responsive neurons in both species were IB4-positive. Together, these data demonstrate that TRPA1 is functionally expressed

  13. Drosophila TRPA1 isoforms detect UV light via photochemical production of H2O2

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    Guntur, Ananya R.; Gu, Pengyu; Takle, Kendra; Chen, Jingyi; Xiang, Yang; Yang, Chung-Hui

    2015-01-01

    The transient receptor potential A1 (TRPA1) channel is an evolutionarily conserved detector of temperature and irritant chemicals. Here, we show that two specific isoforms of TRPA1 in Drosophila are H2O2 sensitive and that they can detect strong UV light via sensing light-induced production of H2O2. We found that ectopic expression of these H2O2-sensitive Drosophila TRPA1 (dTRPA1) isoforms conferred UV sensitivity to light-insensitive HEK293 cells and Drosophila neurons, whereas expressing the H2O2-insensitive isoform did not. Curiously, when expressed in one specific group of motor neurons in adult flies, the H2O2-sensitive dTRPA1 isoforms were as competent as the blue light-gated channelrhodopsin-2 in triggering motor output in response to light. We found that the corpus cardiacum (CC) cells, a group of neuroendocrine cells that produce the adipokinetic hormone (AKH) in the larval ring gland endogenously express these H2O2-sensitive dTRPA1 isoforms and that they are UV sensitive. Sensitivity of CC cells required dTRPA1 and H2O2 production but not conventional phototransduction molecules. Our results suggest that specific isoforms of dTRPA1 can sense UV light via photochemical production of H2O2. We speculate that UV sensitivity conferred by these isoforms in CC cells may allow young larvae to activate stress response—a function of CC cells—when they encounter strong UV, an aversive stimulus for young larvae. PMID:26443856

  14. TRPA1 controls inflammation and pruritogen responses in allergic contact dermatitis

    Science.gov (United States)

    Liu, Boyi; Escalera, Jasmine; Balakrishna, Shrilatha; Fan, Lu; Caceres, Ana I.; Robinson, Eve; Sui, Aiwei; McKay, M. Craig; McAlexander, M. Allen; Herrick, Christina A.; Jordt, Sven E.

    2013-01-01

    Allergic contact dermatitis is a common skin disease associated with inflammation and persistent pruritus. Transient receptor potential (TRP) ion channels in skin-innervating sensory neurons mediate acute inflammatory and pruritic responses following exogenous stimulation and may contribute to allergic responses. Genetic ablation or pharmacological inhibition of TRPA1, but not TRPV1, inhibited skin edema, keratinocyte hyperplasia, nerve growth, leukocyte infiltration, and antihistamine-resistant scratching behavior in mice exposed to the haptens, oxazolone and urushiol, the contact allergen of poison ivy. Hapten-challenged skin of TRPA1-deficient mice contained diminished levels of inflammatory cytokines, nerve growth factor, and endogenous pruritogens, such as substance P (SP) and serotonin. TRPA1-deficient sensory neurons were defective in SP signaling, and SP-induced scratching behavior was abolished in Trpa1−/− mice. SP receptor antagonists, such as aprepitant inhibited both hapten-induced cutaneous inflammation and scratching behavior. These findings support a central role for TRPA1 and SP in the integration of immune and neuronal mechanisms leading to chronic inflammatory responses and pruritus associated with contact dermatitis.—Liu, B., Escalera, J., Balakrishna, S., Fan, L., Caceres, A. I., Robinson, E., Sui, A., McKay, M. C., McAlexander, M. A., Herrick, C. A., Jordt, S. E. TRPA1 controls inflammation and pruritogen responses in allergic contact dermatitis. PMID:23722916

  15. Bimodal voltage dependence of TRPA1: mutations of a key pore helix residue reveal strong intrinsic voltage-dependent inactivation.

    Science.gov (United States)

    Wan, Xia; Lu, Yungang; Chen, Xueqin; Xiong, Jian; Zhou, Yuanda; Li, Ping; Xia, Bingqing; Li, Min; Zhu, Michael X; Gao, Zhaobing

    2014-07-01

    Transient receptor potential A1 (TRPA1) is implicated in somatosensory processing and pathological pain sensation. Although not strictly voltage-gated, ionic currents of TRPA1 typically rectify outwardly, indicating channel activation at depolarized membrane potentials. However, some reports also showed TRPA1 inactivation at high positive potentials, implicating voltage-dependent inactivation. Here we report a conserved leucine residue, L906, in the putative pore helix, which strongly impacts the voltage dependency of TRPA1. Mutation of the leucine to cysteine (L906C) converted the channel from outward to inward rectification independent of divalent cations and irrespective to stimulation by allyl isothiocyanate. The mutant, but not the wild-type channel, displayed exclusively voltage-dependent inactivation at positive potentials. The L906C mutation also exhibited reduced sensitivity to inhibition by TRPA1 blockers, HC030031 and ruthenium red. Further mutagenesis of the leucine to all natural amino acids individually revealed that most substitutions at L906 (15/19) resulted in inward rectification, with exceptions of three amino acids that dramatically reduced channel activity and one, methionine, which mimicked the wild-type channel. Our data are plausibly explained by a bimodal gating model involving both voltage-dependent activation and inactivation of TRPA1. We propose that the key pore helix residue, L906, plays an essential role in responding to the voltage-dependent gating.

  16. Acrolein contributes to TRPA1 up-regulation in peripheral and central sensory hypersensitivity following spinal cord injury.

    Science.gov (United States)

    Park, Jonghyuck; Zheng, Lingxing; Acosta, Glen; Vega-Alvarez, Sasha; Chen, Zhe; Muratori, Breanne; Cao, Peng; Shi, Riyi

    2015-12-01

    Acrolein, an endogenous aldehyde, has been shown to be involved in sensory hypersensitivity after rat spinal cord injury (SCI), for which the pathogenesis is unclear. Acrolein can directly activate a pro-algesic transient receptor protein ankyrin 1 (TRPA1) channel that exists in sensory neurons. Both acrolein and TRPA1 mRNA are elevated post SCI, which contributes to the activation of TRPA1 by acrolein and consequently, neuropathic pain. In the current study, we further showed that, post-SCI elevation of TRPA1 mRNA exists not only in dorsal root ganglias but also in both peripheral (paw skin) and central endings of primary afferent nerves (dorsal horn of spinal cord). This is the first indication that pain signaling can be over-amplified in the peripheral skin by elevated expressions of TRPA1 following SCI, in addition over-amplification previously seen in the spinal cord and dorsal root ganglia. Furthermore, we show that acrolein alone, in the absence of physical trauma, could lead to the elevation of TRPA1 mRNA at various locations when injected to the spinal cord. In addition, post-SCI elevation of TRPA1 mRNA could be mitigated using acrolein scavengers. Both of these attributes support the critical role of acrolein in elevating TRPA1 expression through gene regulation. Taken together, these data indicate that acrolein is likely a critical causal factor in heightening pain sensation post-SCI, through both the direct binding of TRPA1 receptor, and also by boosting the expression of TRPA1. Finally, our data also further support the notion that acrolein scavenging may be an effective therapeutic approach to alleviate neuropathic pain after SCI. We propose that the trauma-mediated elevation of acrolein causes neuropathic pain through at least two mechanisms: acrolein stimulates the production of transient receptor protein ankyrin 1 (TRPA1) in both central and peripheral locations, and it activates TRPA1 channels directly. Therefore, acrolein appears to be a critical

  17. Involvement of transient receptor potential A1 channel in algesic and analgesic actions of the organic compound limonene.

    Science.gov (United States)

    Kaimoto, T; Hatakeyama, Y; Takahashi, K; Imagawa, T; Tominaga, M; Ohta, T

    2016-08-01

    TRPA1 is a Ca-permeable nonselective cation channel expressed in sensory neurons and acts as a nocisensor. Recent reports show that some monoterpenes, a group of naturally occurring organic compounds, modulate TRP channel activity. Here, we report that limonene, being contained in citrus fruits and mushrooms, shows a unique bimodal action on TRPA1 channel. We examine the effects of limonene on sensory neurons from wild-type, TRPV1- and TRPA1-gene-deficient mice and on heterologously expressed channels in vitro. Molecular determinants were identified with using mutated channels. Cellular excitability is monitored with ratiometric Ca imaging. Nociceptive and analgesic actions of limonene are also examined in vivo. In wild-type mouse sensory neurons, limonene increased the intracellular Ca(2+) concentration ([Ca(2+) ]i ), which was inhibited by selective inhibitors of TRPA1 but not TRPV1. Limonene-responsive neurons highly corresponded to TRPA1 agonist-sensitive ones. Limonene failed to stimulate sensory neurons from the TRPA1 (-/-) mouse. Heterologously expressed mouse TRPA1 was activated by limonene. Intraplantar injection of limonene elicited acute pain, which was significantly less in TRPA1 (-/-) mice. Systemic administration of limonene reduced nociceptive behaviours evoked by H2 O2 . In both heterologously and endogenously expressed TRPA1, a low concentration of limonene significantly inhibited H2 O2 -induced TRPA1 activation. TRPA1 activation by limonene was abolished in H2 O2 -insensitive cysteine-mutated channels. Topically applied limonene stimulates TRPA1, resulting in elicitation of acute pain, but its systemic application inhibits nociception induced by oxidative stress. Because limonene is a safe compound, it may be utilized for pain control due to its inhibition of TRPA1 channels. What does this study add: Limonene, a monoterpene in essential oils of various plants, has been known for its antitumor and anti-inflammatory properties. However, molecular

  18. TrpA1 Regulates Defecation of Food-Borne Pathogens under the Control of the Duox Pathway.

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    Eun Jo Du

    2016-01-01

    Full Text Available Pathogen expulsion from the gut is an important defense strategy against infection, but little is known about how interaction between the intestinal microbiome and host immunity modulates defecation. In Drosophila melanogaster, dual oxidase (Duox kills pathogenic microbes by generating the microbicidal reactive oxygen species (ROS, hypochlorous acid (HOCl in response to bacterially excreted uracil. The physiological function of enzymatically generated HOCl in the gut is, however, unknown aside from its anti-microbial activity. Drosophila TRPA1 is an evolutionarily conserved receptor for reactive chemicals like HOCl, but a role for this molecule in mediating responses to gut microbial content has not been described. Here we identify a molecular mechanism through which bacteria-produced uracil facilitates pathogen-clearing defecation. Ingestion of uracil increases defecation frequency, requiring the Duox pathway and TrpA1. The TrpA1(A transcript spliced with exon10b (TrpA1(A10b that is present in a subset of midgut enteroendocrine cells (EECs is critical for uracil-dependent defecation. TRPA1(A10b heterologously expressed in Xenopus oocytes is an excellent HOCl receptor characterized with elevated sensitivity and fast activation kinetics of macroscopic HOCl-evoked currents compared to those of the alternative TRPA1(A10a isoform. Consistent with TrpA1's role in defecation, uracil-excreting Erwinia carotovora showed higher persistence in TrpA1-deficient guts. Taken together, our results propose that the uracil/Duox pathway promotes bacteria expulsion from the gut through the HOCl-sensitive receptor, TRPA1(A10b, thereby minimizing the chances that bacteria adapt to survive host defense systems.

  19. Consequences of a human TRPA1 genetic variant on the perception of nociceptive and olfactory stimuli.

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    Michael Schütz

    Full Text Available BACKGROUND: TRPA1 ion channels are involved in nociception and are also excited by pungent odorous substances. Based on reported associations of TRPA1 genetics with increased sensitivity to thermal pain stimuli, we therefore hypothesized that this association also exists for increased olfactory sensitivity. METHODS: Olfactory function and nociception was compared between carriers (n = 38 and non-carriers (n = 43 of TRPA1 variant rs11988795 G>A, a variant known to enhance cold pain perception. Olfactory function was quantified by assessing the odor threshold, odor discrimination and odor identification, and by applying 200-ms pulses of H2S intranasal. Nociception was assessed by measuring pain thresholds to experimental nociceptive stimuli (blunt pressure, electrical stimuli, cold and heat stimuli, and 200-ms intranasal pulses of CO2. RESULTS: Among the 11 subjects with moderate hyposmia, carriers of the minor A allele (n = 2 were underrepresented (34 carriers among the 70 normosmic subjects; p = 0.049. Moreover, carriers of the A allele discriminated odors significantly better than non-carriers (13.1±1.5 versus 12.3±1.6 correct discriminations and indicated a higher intensity of the H2S stimuli (29.2±13.2 versus 21±12.8 mm VAS, p = 0.006, which, however, could not be excluded to have involved a trigeminal component during stimulation. Finally, the increased sensitivity to thermal pain could be reproduced. CONCLUSIONS: The findings are in line with a previous association of a human TRPA1 variant with nociceptive parameters and extend the association to the perception of odorants. However, this addresses mainly those stimulants that involve a trigeminal component whereas a pure olfactory effect may remain disputable. Nevertheless, findings suggest that future TRPA1 modulating drugs may modify the perception of odorants.

  20. Intraganglionic signaling as a novel nasal-meningeal pathway for TRPA1-dependent trigeminovascular activation by inhaled environmental irritants.

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    Phillip Edward Kunkler

    Full Text Available Headache is the most common symptom associated with air pollution, but little is understood about the underlying mechanism. Nasal administration of environmental irritants activates the trigeminovascular system by a TRPA1-dependent process. This report addresses questions about the anatomical pathway involved and the function of TRP channels in this pathway. TRPV1 and TRPA1 are frequently co-localized and interact to modulate function in sensory neurons. We demonstrate here that resiniferatoxin ablation of TRPV1 expressing neurons significantly reduces meningeal blood flow responses to nasal administration of both TRPV1 and TRPA1 agonists. Accordingly resiniferatoxin also significantly reduces TRPV1 and CGRP immunostaining and TRPV1 and TRPA1 message levels in trigeminal ganglia. Sensory neurons of the trigeminal ganglia innervate the nasal epithelium and the meninges, but the mechanism and anatomical route by which nasal administration evokes meningeal vasodilatation is unclear. Double retrograde labeling from the nose and meninges reveals no co-localization of fluorescent label, however nasal and meningeal labeled cells are located in close proximity to each other within the trigeminal ganglion. Our data demonstrate that TRPV1 expressing neurons are important for TRPA1 responses in the nasal-meningeal pathway. Our data also suggest that the nasal-meningeal pathway is not primarily by axon reflex, but may instead result from intraganglionic transmission.

  1. TRPA1 activation by lidocaine in nerve terminals results in glutamate release increase

    International Nuclear Information System (INIS)

    Piao, L.-H.; Fujita, Tsugumi; Jiang, C.-Y.; Liu Tao; Yue, H.-Y.; Nakatsuka, Terumasa; Kumamoto, Eiichi

    2009-01-01

    We examined the effects of local anesthetics lidocaine and procaine on glutamatergic spontaneous excitatory transmission in substantia gelatinosa (SG) neurons in adult rat spinal cord slices with whole-cell patch-clamp techniques. Bath-applied lidocaine (1-5 mM) dose-dependently and reversibly increased the frequency but not the amplitude of spontaneous excitatory postsynaptic current (sEPSC) in SG neurons. Lidocaine activity was unaffected by the Na + -channel blocker, tetrodotoxin, and the TRPV1 antagonist, capsazepine, but was inhibited by the TRP antagonist, ruthenium red. In the same neuron, the TRPA1 agonist, allyl isothiocyanate, and lidocaine both increased sEPSC frequency. In contrast, procaine did not produce presynaptic enhancement. These results indicate that lidocaine activates TRPA1 in nerve terminals presynaptic to SG neurons to increase the spontaneous release of L-glutamate.

  2. Differential Contribution of TRPA1, TRPV4 and TRPM8 to Colonic Nociception in Mice.

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    Sonja M Mueller-Tribbensee

    Full Text Available Various transient receptor potential (TRP channels in sensory neurons contribute to the transduction of mechanical stimuli in the colon. Recently, even the cold-sensing menthol receptor TRPM(melastatin8 was suggested to be involved in murine colonic mechano-nociception.To analyze the roles of TRPM8, TRPA1 and TRPV4 in distension-induced colonic nociception and pain, TRP-deficient mice and selective pharmacological blockers in wild-type mice (WT were used. Visceromotor responses (VMR to colorectal distension (CRD in vivo were recorded and distension/pressure-induced CGRP release from the isolated murine colon ex vivo was measured by EIA.Distension-induced colonic CGRP release was markedly reduced in TRPA1-/- and TRPV4-/- mice at 90/150 mmHg compared to WT. In TRPM8-deficient mice the reduction was only distinct at 150 mmHg. Exposure to selective pharmacological antagonists (HC030031, 100 μM; RN1734, 10 μM; AMTB, 10 μM showed corresponding effects. The unselective TRP blocker ruthenium red (RR, 10 μM was as efficient in inhibiting distension-induced CGRP release as the unselective antagonists of mechanogated DEG/ENaC (amiloride, 100 μM and stretch-activated channels (gadolinium, 50 μM. VMR to CRD revealed prominent deficits over the whole pressure range (up to 90 mmHg in TRPA1-/- and TRPV4-/- but not TRPM8-/- mice; the drug effects of the TRP antagonists were again highly consistent with the results from mice lacking the respective TRP receptor gene.TRPA1 and TRPV4 mediate colonic distension pain and CGRP release and appear to govern a wide and congruent dynamic range of distensions. The role of TRPM8 seems to be confined to signaling extreme noxious distension, at least in the healthy colon.

  3. How cold is it? TRPM8 and TRPA1 in the molecular logic of cold sensation

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    McKemy David D

    2005-04-01

    Full Text Available Abstract Recognition of temperature is a critical element of sensory perception and allows us to evaluate both our external and internal environments. In vertebrates, the somatosensory system can discriminate discrete changes in ambient temperature, which activate nerve endings of primary afferent fibers. These thermosensitive nerves can be further segregated into those that detect either innocuous or noxious (painful temperatures; the latter neurons being nociceptors. We now know that thermosensitive afferents express ion channels of the transient receptor potential (TRP family that respond at distinct temperature thresholds, thus establishing the molecular basis for thermosensation. Much is known of those channels mediating the perception of noxious heat; however, those proposed to be involved in cool to noxious cold sensation, TRPM8 and TRPA1, have only recently been described. The former channel is a receptor for menthol, and links the sensations provided by this and other cooling compounds to temperature perception. While TRPM8 almost certainly performs a critical role in cold signaling, its part in nociception is still at issue. The latter channel, TRPA1, is activated by the pungent ingredients in mustard and cinnamon, but has also been postulated to mediate our perception of noxious cold temperatures. However, a number of conflicting reports have suggested that the role of this channel in cold sensation needs to be confirmed. Thus, the molecular logic for the perception of cold-evoked pain remains enigmatic. This review is intended to summarize our current understanding of these cold thermoreceptors, as well as address the current controversy regarding TRPA1 and cold signaling.

  4. TrpA1 activation in peripheral sensory neurons underlies the ionic basis of pain hypersensitivity in response to vinca alkaloids.

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    Nina Boiko

    Full Text Available Chemotherapy induced peripheral neuropathy (CIPN, a side effect of many anti-cancer drugs including the vinca alkaloids, is characterized by a severe pain syndrome that compromises treatment in many patients. Currently there are no effective treatments for this pain syndrome except for the reduction of anti-cancer drug dose. Existing data supports the model that the pain associated with CIPN is the result of anti-cancer drugs augmenting the function of the peripheral sensory nociceptors but the cellular mechanisms underlying the effects of anti-cancer drugs on sensory neuron function are not well described. Studies from animal models have suggested a number of disease etiologies including mitotoxicity, axonal degeneration, immune signaling, and reduced sensory innervations but these outcomes are the result of prolonged treatment paradigms and do not necessarily represent the early formative events associated with CIPN. Here we show that acute exposure to vinca alkaloids results in an immediate pain syndrome in both flies and mice. Furthermore, we demonstrate that exposure of isolated sensory neurons to vinca alkaloids results in the generation of an inward sodium current capable of depolarizing these neurons to threshold resulting in neuronal firing. These neuronal effects of vinca alkaloids require the transient receptor potential ankyrin-1 (TrpA1 channel, and the hypersensitization to painful stimuli in response to the acute exposure to vinca alkaloids is reduced in TrpA1 mutant flies and mice. These findings demonstrate the direct excitation of sensory neurons by CIPN-causing chemotherapy drugs, and identify TrpA1 as an important target during the pathogenesis of CIPN.

  5. Environmental cold exposure increases blood flow and affects pain sensitivity in the knee joints of CFA-induced arthritic mice in a TRPA1-dependent manner.

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    Fernandes, Elizabeth S; Russell, Fiona A; Alawi, Khadija M; Sand, Claire; Liang, Lihuan; Salamon, Robin; Bodkin, Jennifer V; Aubdool, Aisah A; Arno, Matthew; Gentry, Clive; Smillie, Sarah-Jane; Bevan, Stuart; Keeble, Julie E; Malcangio, Marzia; Brain, Susan D

    2016-01-11

    The effect of cold temperature on arthritis symptoms is unclear. The aim of this study was to investigate how environmental cold affects pain and blood flow in mono-arthritic mice, and examine a role for transient receptor potential ankyrin 1 (TRPA1), a ligand-gated cation channel that can act as a cold sensor. Mono-arthritis was induced by unilateral intra-articular injection of complete Freund's adjuvant (CFA) in CD1 mice, and in mice either lacking TRPA1 (TRPA1 KO) or respective wildtypes (WT). Two weeks later, nociception and joint blood flow were measured following exposure to 10 °C (1 h) or room temperature (RT). Primary mechanical hyperalgesia in the knee was measured by pressure application apparatus; secondary mechanical hyperalgesia by automated von Frey system; thermal hyperalgesia by Hargreaves technique, and weight bearing by the incapacitance test. Joint blood flow was recorded by full-field laser perfusion imager (FLPI) and using clearance of (99m)Technetium. Blood flow was assessed after pretreatment with antagonists of either TRPA1 (HC-030031), substance P neurokinin 1 (NK1) receptors (SR140333) or calcitonin gene-related peptide (CGRP) (CGRP8-37). TRPA1, TAC-1 and CGRP mRNA levels were examined in dorsal root ganglia, synovial membrane and patellar cartilage samples. Cold exposure caused bilateral primary mechanical hyperalgesia 2 weeks after CFA injection, in a TRPA1-dependent manner. In animals maintained at RT, clearance techniques and FLPI showed that CFA-treated joints exhibited lower blood flow than saline-treated joints. In cold-exposed animals, this reduction in blood flow disappears, and increased blood flow in the CFA-treated joint is observed using FLPI. Cold-induced increased blood flow in CFA-treated joints was blocked by HC-030031 and not observed in TRPA1 KOs. Cold exposure increased TRPA1 mRNA levels in patellar cartilage, whilst reducing it in synovial membranes from CFA-treated joints. We provide evidence that environmental

  6. Acute cold hypersensitivity characteristically induced by oxaliplatin is caused by the enhanced responsiveness of TRPA1 in mice

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    Zhao Meng

    2012-07-01

    Full Text Available Abstract Background Oxaliplatin, a platinum-based chemotherapeutic agent, causes an unusual acute peripheral neuropathy. Oxaliplatin-induced acute peripheral neuropathy appears in almost all patients rapidly after infusion, and is triggered or exacerbated by cold, while its mechanisms are poorly understood. In this study, the involvement of thermosensitive transient receptor potential channels (TRPA1, TRPM8 and TRPV1 in oxaliplatin-induced acute hypersensitivity was investigated in mice. Results A single intraperitoneal administration of oxaliplatin (1–10 mg/kg induced cold but not mechanical hypersensitivity within 2 h in a dose-dependent manner. Infusion of the oxaliplatin metabolite, oxalate (1.7 mg/kg, also induced acute cold hypersensitivity, while another platinum-based chemotherapeutic agent, cisplatin (5 mg/kg, or the non-platinum-containing chemotherapeutic agent, paclitaxel (6 mg/kg failed to induce mechanical or cold hypersensitivity. The oxaliplatin-induced acute cold hypersensitivity was abolished by the TRPA1 antagonist HC-030031 (100 mg/kg and by TRPA1 deficiency. The nocifensive behaviors evoked by intraplantar injections of allyl-isothiocyanate (AITC; TRPA1 agonist were significantly enhanced in mice treated for 2 h with oxaliplatin (1–10 mg/kg in a dose-dependent manner, while capsaicin (TRPV1 agonist-evoked nocifensive behaviors were not affected. Menthol (TRPM8/TRPA1 agonist-evoked nocifensive-like behaviors were also enhanced by oxaliplatin pretreatment, which were inhibited by TRPA1 deficiency. Similarly, oxalate enhanced, but neither cisplatin nor paclitaxel affected AITC-evoked nocifensive behaviors. Pretreatment of cultured mouse dorsal root ganglia (DRG neurons with oxaliplatin (30–300 μM for 1, 2, or 4 h significantly increased the number of AITC-sensitive neurons in a concentration-dependent manner whereas there was no change in the number of menthol- or capsaicin-sensitive neurons

  7. Differential Effects of TRPA and TRPV Channels on Behaviors of

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    Jennifer Thies

    2016-01-01

    Full Text Available TRPA and TRPV ion channels are members of the transient receptor potential (TRP cation channel superfamily, which mediates various sensory transductions. In Caenorhabditis elegans , the TRPV channels are known to affect chemosensation, while the TRPA-1 channel is associated with thermosensation and mechanosensation. We examined thermosensation, chemosensation, and osmosensation in strains lacking TRPA-1 or TRPV channels. We found that TRPV channel knockout worms exhibited similar behavioral deficits associated with thermotaxis as the TRPA-1 channel knockout, suggesting a dual role for TRPV channels. In contrast, chemosensation responses, assessed by both avoidance reversal behavior and NaCl osmosensation, were dependent on TRPV channels but seemed independent of TRPA-1 channel. Our findings suggest that, in addition to TRPA-1 channel, TRPV channels are necessary for thermotaxis and may activate, or modulate, the function of TRPA-1 channels. In contrast, TRPA-1 channels do not have a dual responsibility, as they have no functional role in odorant avoidance or osmosensation.

  8. TRPA1 in the spinal dorsal horn is involved in post-inflammatory visceral hypersensitivity: in vivo study using TNBS-treated rat model

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    Li Q

    2016-12-01

    Full Text Available Qian Li,1,* Cheng-Hao Guo,2,* Mohammed Ali Chowdhury,1 Tao-Li Dai,1 Wei Han,1,3 1Department of Gastroenterology, Qilu Hospital of Shandong University, 2Department of Pathology, Medical School of Shandong University, 3Laboratory of Translational Gastroenterology, Shandong University, Qilu Hospital, Jinan, Shandong Province, People’s Republic of China *These authors contributed equally to this work Introduction: The transient receptor potential ankyrin-1 (TRPA1 channel, a pain transducer and amplifier, is drawing increasing attention in the field of visceral hypersensitivity, commonly seen in irritable bowel syndrome and inflammatory bowel disease. However, the role of TRPA1 in visceral nociception during post-inflammatory states is not well defined. Here, we explore the correlation between TRPA1 expression in the spinal dorsal horn (SDH and persistent post-inflammatory visceral hypersensitivity.Methods: We injected rats intracolonically with 2,4,6-trinitrobenzene sulfonic acid (TNBS or vehicle (n=12 per group. Post-inflammatory visceral hypersensitivity was assessed by recording the electromyographic activity of the external oblique muscle in response to colorectal distension. TRPA1 expression and distribution in the spinal cord and colon were examined by Western blotting and immunohistochemistry.Results: Animals exposed to TNBS had more abdominal contractions than vehicle-injected controls (P<0.05, which corresponded to a lower nociceptive threshold. Expression of TRPA1 in the SDH (especially in the substantia gelatinosa and the colon was significantly greater in the TNBS-treated group than in controls (P<0.05. In the SDH, the number of TRPA1-immunopositive neurons was 25.75±5.12 in the control group and 34.25±7.89 in the TNBS-treated group (P=0.023, and integrated optical density values of TRPA1 in the control and TNBS-treated groups were 14,544.63±6,525.54 and 22,532.75±7,608.11, respectively (P=0.041.Conclusion: Our results indicate

  9. Noxious heat threshold temperature and pronociceptive effects of allyl isothiocyanate (mustard oil) in TRPV1 or TRPA1 gene-deleted mice.

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    Tékus, Valéria; Horváth, Ádám; Hajna, Zsófia; Borbély, Éva; Bölcskei, Kata; Boros, Melinda; Pintér, Erika; Helyes, Zsuzsanna; Pethő, Gábor; Szolcsányi, János

    2016-06-01

    To investigate the roles of TRPV1 and TRPA1 channels in baseline and allyl isothiocyanate (AITC)-evoked nociceptive responses by comparing wild-type and gene-deficient mice. In contrast to conventional methods of thermonociception measuring reflex latencies, we used our novel methods to determine the noxious heat threshold. It was revealed that the heat threshold of the tail measured by an increasing-temperature water bath is significantly higher in TRPV1(-/-), but not TRPA1(-/-), mice compared to respective wild-types. There was no difference between the noxious heat thresholds of the hind paw as measured by an increasing-temperature hot plate in TRPV1(-/-), TRPA1(-/-) and the corresponding wild-type mice. The withdrawal latency of the tail from 0°C water was prolonged in TRPA1(-/-), but not TRPV1(-/-), mice compared to respective wild-types. In wild-type animals, dipping the tail or paw into 1% AITC induced an 8-14°C drop of the noxious heat threshold (heat allodynia) of both the tail and paw, and 40-50% drop of the mechanonociceptive threshold (mechanical allodynia) of the paw measured by dynamic plantar esthesiometry. These AITC-evoked responses were diminished in TRPV1(-/-), but not TRPA1(-/-), mice. Tail withdrawal latency to 1% AITC was significantly prolonged in both gene-deleted strains. Different heat sensors determine the noxious heat threshold in distinct areas: a pivotal role for TRPV1 on the tail is contrasted with no involvement of either TRPV1 or TRPA1 on the hind paw. Noxious heat threshold measurement appears appropriate for preclinical screening of TRP channel ligands as novel analgesics. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. TRPV1 and TRPA1 in cutaneous neurogenic and chronic inflammation: pro-inflammatory response induced by their activation and their sensitization

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    Olivier Gouin

    2017-03-01

    Full Text Available ABSTRACT Cutaneous neurogenic inflammation (CNI is inflammation that is induced (or enhanced in the skin by the release of neuropeptides from sensory nerve endings. Clinical manifestations are mainly sensory and vascular disorders such as pruritus and erythema. Transient receptor potential vanilloid 1 and ankyrin 1 (TRPV1 and TRPA1, respectively are non-selective cation channels known to specifically participate in pain and CNI. Both TRPV1 and TRPA1 are co-expressed in a large subset of sensory nerves, where they integrate numerous noxious stimuli. It is now clear that the expression of both channels also extends far beyond the sensory nerves in the skin, occuring also in keratinocytes, mast cells, dendritic cells, and endothelial cells. In these non-neuronal cells, TRPV1 and TRPA1 also act as nociceptive sensors and potentiate the inflammatory process. This review discusses the role of TRPV1 and TRPA1 in the modulation of inflammatory genes that leads to or maintains CNI in sensory neurons and non-neuronal skin cells. In addition, this review provides a summary of current research on the intracellular sensitization pathways of both TRP channels by other endogenous inflammatory mediators that promote the self-maintenance of CNI.

  11. TRPA1 contributes to capsaicin-induced facial cold hyperalgesia in rats.

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    Honda, Kuniya; Shinoda, Masamichi; Furukawa, Akihiko; Kita, Kozue; Noma, Noboru; Iwata, Koichi

    2014-12-01

    Orofacial cold hyperalgesia is known to cause severe persistent pain in the face following trigeminal nerve injury or inflammation, and transient receptor potential (TRP) vanilloid 1 (TRPV1) and TRP ankylin 1 (TRPA1) are thought to be involved in cold hyperalgesia. However, how these two receptors are involved in cold hyperalgesia is not fully understood. To clarify the mechanisms underlying facial cold hyperalgesia, nocifensive behaviors to cold stimulation, the expression of TRPV1 and TRPA1 in trigeminal ganglion (TG) neurons, and TG neuronal excitability to cold stimulation following facial capsaicin injection were examined in rats. The head-withdrawal reflex threshold (HWRT) to cold stimulation of the lateral facial skin was significantly decreased following facial capsaicin injection. This reduction of HWRT was significantly recovered following local injection of TRPV1 antagonist as well as TRPA1 antagonist. Approximately 30% of TG neurons innervating the lateral facial skin expressed both TRPV1 and TRPA1, and about 64% of TRPA1-positive neurons also expressed TRPV1. The TG neuronal excitability to noxious cold stimulation was significantly increased following facial capsaicin injection and this increase was recovered by pretreatment with TRPA1 antagonist. These findings suggest that TRPA1 sensitization via TRPV1 signaling in TG neurons is involved in cold hyperalgesia following facial skin capsaicin injection. © 2014 Eur J Oral Sci.

  12. TRPA1 polymorphisms in chronic and complete spinal cord injury patients with neuropathic pain: a pilot study.

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    Vidal Rodriguez, Sonia; Castillo Aguilar, Inmaculada; Cuesta Villa, Luis; Serrano Saenz de Tejada, Francisco

    2017-01-01

    Pilot study. Single-nucleotide polymorphisms (SNPs) in TRPA1 gene are related to the etiology of chronic pain. The study is a pilot study with the primary objective of analyzing these SNPs in Spanish patients with chronic and complete spinal cord injury (SCI) and neuropathic pain (NPP). Asepeyo Hospital Department of Chronic and Complete SCI. Twelve patients with chronic and complete SCI and NPP, and 12 patients with chronic and complete SCI with no pain were reviewed. International Spinal Cord Injury Pain Classification (LANSS) and visual analog score (VAS) were chosen to classify pain syndrome. SNPs were identified by melting analysis after DNA amplification with real-time fluorescence PCR. There were differences in rs11988795 variant: GG homozygous ( p  = 0.01) and G allele ( p  = 0.001) were more frequent in SCI patients with no pain. There were differences in rs13255063 variant: TT homozygous were prevalent ( p  = 0.03) in patients with NPP. Until now this is the first study to show a description of TRPA1 SNPs in Spanish patients with chronic and complete SCI and NPP. These results suggest that GG genotype in rs11988795 variant and G allele could be protective factors against NPP. TT genotype in rs13255063 variant could be a risk factor for NPP. Neuropathic pain after spinal cord injuries may have genetic contributions.

  13. Gosha-jinki-gan reduced oxaliplatin-induced hypersensitivity to cold sensation and its effect would be related to suppression of the expression of TRPM8 and TRPA1 in rats.

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    Kato, Yoshinori; Tateai, Yoshikazu; Ohkubo, Misao; Saito, Yuka; Amagai, Syun-ya; Kimura, Yu-Suke; Iimura, Naohumi; Okada, Megumi; Matsumoto, Akiko; Mano, Yasunari; Hirosawa, Iori; Ohuchi, Kaori; Tajima, Masataka; Asahi, Mariko; Kotaki, Hajime; Yamada, Harumi

    2014-01-01

    Peripheral neuropathy is a common side effect of the chemotherapeutic agent oxaliplatin (Oxp), and is associated with hypersensitivity to cold sensation in the acute stage. Recently, gosha-jinki-gan (GJG), a Japanese herbal medicine, was reported to improve Oxp-induced cold hypersensitivity. However, the mechanism for this effect was not elucidated. We hypothesized that the effect of GJG on Oxp-induced cold hypersensitivity may be associated with the expression of the transient receptor potential melastatin 8 (TRPM8) and transient receptor potential ankyrin 1 (TRPA1) channels, which are cold-gated ion channels. To assess this hypothesis, we examined alteration of the withdrawal response to cold stimulation following coadministration of GJG and Oxp in rats, and the relationship between this altered withdrawal response and the expression of TRPM8 and TRPA1 mRNA in the dorsal root ganglia (DRG). Assessment of cold hypersensitivity was performed at 4 and 10°C using a cold plate. Compared with Oxp administration alone, coadministration of GJG (oral dose: 1 g/kg/day for 12 days) and Oxp (intraperitoneal dose: 4 mg/kg twice a week) significantly reduced the withdrawal response to cold stimulation. On the 12th day of drug administration, the L4-L6 DRG were removed and the expression of TRPM8 and TRPA1 mRNA was determined using RT-PCR. The expression of TRPM8 and TRPA1 in the DRG of rats that were coadministered GJG and Oxp decreased significantly compared with that in the rats administered Oxp alone. These results suggest that coadministration of GJG may improve Oxp-induced cold hypersensitivity by suppressing the overexpression of TRPM8 and TRPA1 mRNA.

  14. A Comparison of Oral Sensory Effects of Three TRPA1 Agonists in Young Adult Smokers and Non-smokers

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    Hansen, Eva Ø.; Arendt-Nielsen, Lars; Boudreau, Shellie A.

    2017-01-01

    This study profiled intra-oral somatosensory and vasomotor responses to three different transient receptor potential (TRP) channels, subfamily A, member 1 (TRPA1) agonists (menthol, nicotine, and cinnamaldehyde) in smoking and non-smoking young adults. Healthy non-smokers (N = 30) and otherwise healthy smokers (N = 25) participated in a randomized, double-blinded, cross-over study consisting of three experimental sessions in which they received menthol (30 mg), nicotine (4 mg), or cinnamaldehyde (25 mg) chewing gum. Throughout a standardized 10 min chewing regime, burning, cooling, and irritation intensities, and location were recorded. In addition, blood pressure, heart rate and intra-oral temperature were assessed before, during, and after chewing. Basal intra-oral temperature was lower in smokers (35.2°C ± 1.58) as compared to non-smokers (35.9°C ± 1.61) [F(1, 52) = 8.5, P = 0.005, post hoc, p = 0.005]. However, the increase in temperature, heart rate, and blood pressure in response to chewing menthol, nicotine, and cinnamaldehyde gums were similar between smokers and non-smokers. Although smoking status did not influence the intensity of burning, cooling, and irritation, smokers did report nicotine burn more often (92%) than non-smokers (63%) [χ(1, N=55)2 = 6.208, P = 0.013]. Reports of nicotine burn consistently occurred at the back of the throat and cinnamaldehyde burn on the tongue. The cooling sensation of menthol was more widely distributed in the mouth of non-smokers as compared to smokers. Smoking alters thermoregulation, somatosensory, and possibly TRPA1 receptor responsiveness and suggests that accumulated exposure of nicotine by way of cigarette smoke alters oral sensory and vasomotor sensitivity. PMID:28936178

  15. Cold stress increases reactive oxygen species formation via TRPA1 activation in A549 cells.

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    Sun, Wenwu; Wang, Zhonghua; Cao, Jianping; Cui, Haiyang; Ma, Zhuang

    2016-03-01

    Reactive oxygen species (ROS) are responsible for lung damage during inhalation of cold air. However, the mechanism of the ROS production induced by cold stress in the lung is still unclear. In this work, we measured the changes of ROS and the cytosolic Ca(2+) concentration ([Ca(2+)]c) in A549 cell. We observed that cold stress (from 20 to 5 °C) exposure of A549 cell resulted in an increase of ROS and [Ca(2+)]c, which was completely attenuated by removing Ca(2+) from medium. Further experiments showed that cold-sensing transient receptor potential subfamily member 1 (TRPA1) agonist (allyl isothiocyanate, AITC) increased the production of ROS and the level of [Ca(2+)]c in A549 cell. Moreover, HC-030031, a TRPA1 selective antagonist, significantly inhibited the enhanced ROS and [Ca(2+)]c induced by AITC or cold stimulation, respectively. Taken together, these data demonstrated that TRPA1 activation played an important role in the enhanced production of ROS induced by cold stress in A549 cell.

  16. Participation of peripheral TRPV1, TRPV4, TRPA1 and ASIC in a magnesium sulfate-induced local pain model in rat.

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    Srebro, Dragana; Vučković, Sonja; Prostran, Milica

    2016-12-17

    We previously showed that magnesium sulfate (MS) has systemic antinociceptive and local peripheral pronociceptive effects. The role of transient receptor potential (TRP) channels and acid-sensing ion channels (ASICs) in the mechanism of action of MS has not been investigated in detail. The aim of this study was to explore the participation of TRP channels in the pronociceptive action of MS in rats after its intraplantar injection. The paw withdrawal threshold (PWT) to mechanical stimuli was measured by the electronic von Frey test. Drugs that were tested were either co-administered with an isotonic pH-unadjusted or pH-adjusted solution of MS intraplantarily, or to the contralateral paw to exclude systemic effects. We found that the subcutaneous administration of both pH-adjusted (7.4) and pH-unadjusted (about 6.0) isotonic (6.2% w/v in water) solutions of MS induce the pain at the injection site. The pH-unadjusted MS solution-induced mechanical hyperalgesia decreased in a dose-dependent manner as a consequence of co-injection of capsazepine, a selective TRPV1 antagonist (20, 100 and 500pmol/paw), RN-1734, a selective TRPV4 antagonist (1.55, 3.1 and 6.2μmol/paw), HC-030031, a selective TRPA1 antagonist (5.6, 28.1 and 140nmol/paw), and amiloride hydrochloride, a non-selective ASIC inhibitor (0.83, 2.5 and 7.55μmol/paw). In pH-adjusted MS-induced hyperalgesia, the highest doses of TRPV1, TRPV4 and TRPA1 antagonists displayed effects that were, respectively, either similar, less pronounced or delayed in comparison to the effect induced by administration of the pH-unadjusted MS solution; the ASIC antagonist did not have any effect. These results suggest that the MS-induced local peripheral mechanical hyperalgesia is mediated via modulation of the activity of peripheral TRPV1, TRPV4, TRPA1 and ASICs. Specific local inhibition of TRP channels represents a novel approach to treating local injection-related pain. Copyright © 2016 IBRO. Published by Elsevier Ltd. All

  17. Loss of Transient Receptor Potential Ankyrin 1 Channel Deregulates Emotion, Learning and Memory, Cognition, and Social Behavior in Mice.

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    Lee, Kuan-I; Lin, Hui-Ching; Lee, Hsueh-Te; Tsai, Feng-Chuan; Lee, Tzong-Shyuan

    2017-07-01

    The transient receptor potential ankyrin 1 (TRPA1) channel is a non-selective cation channel that helps regulate inflammatory pain sensation and nociception and the development of inflammatory diseases. However, the potential role of the TRPA1 channel and the underlying mechanism in brain functions are not fully resolved. In this study, we demonstrated that genetic deletion of the TRPA1 channel in mice or pharmacological inhibition of its activity increased neurite outgrowth. In vivo study in mice provided evidence of the TRPA1 channel as a negative regulator in hippocampal functions; functional ablation of the TRPA1 channel in mice enhanced hippocampal functions, as evidenced by less anxiety-like behavior, and enhanced fear-related or spatial learning and memory, and novel location recognition as well as social interactions. However, the TRPA1 channel appears to be a prerequisite for motor function; functional loss of the TRPA1 channel in mice led to axonal bundle fragmentation, downregulation of myelin basic protein, and decreased mature oligodendrocyte population in the brain, for impaired motor function. The TRPA1 channel may play a crucial role in neuronal development and oligodendrocyte maturation and be a potential regulator in emotion, cognition, learning and memory, and social behavior.

  18. High concentrations of morphine sensitize and activate mouse dorsal root ganglia via TRPV1 and TRPA1 receptors

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    Messlinger Karl

    2009-04-01

    Full Text Available Abstract Background Morphine and its derivatives are key drugs in pain control. Despite its well-known analgesic properties morphine at high concentrations may be proalgesic. Particularly, short-lasting painful sensations have been reported upon dermal application of morphine. To study a possible involvement of TRP receptors in the pro-nociceptive effects of morphine (0.3 – 10 mM, two models of nociception were employed using C57BL/6 mice and genetically related TRPV1 and TRPA1 knockout animals, which were crossed and generated double knockouts. Hindpaw skin flaps were used to investigate the release of calcitonin gene-related peptide indicative of nociceptive activation. Results Morphine induced release of calcitonin gene-related peptide and sensitized the release evoked by heat or the TRPA1 agonist acrolein. Morphine activated HEK293t cells transfected with TRPV1 or TRPA1. Activation of C57BL/6 mouse dorsal root ganglion neurons in culture was investigated with calcium imaging. Morphine induced a dose-dependent rise in intracellular calcium in neurons from wild-type animals. In neurons from TRPV1 and TRPA1 knockout animals activation by morphine was markedly reduced, in the TRPV1/A1 double knockout animals this morphine effect was abrogated. Naloxone induced an increase in calcium levels similar to morphine. The responses to both morphine and naloxone were sensitized by bradykinin. Conclusion Nociceptor activation and sensitization by morphine is conveyed by TRPV1 and TRPA1.

  19. TRPA1-dependent reversible opening of tight junction by natural compounds with an α,β-unsaturated moiety and capsaicin.

    Science.gov (United States)

    Kanda, Yusuke; Yamasaki, Youhei; Sasaki-Yamaguchi, Yoshie; Ida-Koga, Noriko; Kamisuki, Shinji; Sugawara, Fumio; Nagumo, Yoko; Usui, Takeo

    2018-02-02

    The delivery of hydrophilic macromolecules runs into difficulties such as penetration of the cell membrane lipid bilayer. Our prior experiment demonstrated that capsaicin induces the reversible opening of tight junctions (TJs) and enhances the delivery of hydrophilic macromolecules through a paracellular route. Herein, we screened paracellular permeability enhancers other than capsaicin. As TJ opening by capsaicin is associated with Ca 2+ influx, we first screened the compounds that induce Ca 2+ influx in layered MDCK II cells, and then we determined the compounds' abilities to open TJs. Our results identified several natural compounds with α,β-unsaturated moiety. A structure-activity relationship (SAR) analysis and the results of pretreatment with reducing reagent DTT suggested the importance of α,β-unsaturated moiety. We also examined the underlying mechanisms, and our findings suggest that the actin reorganization seen in capsaicin treatment is important for the reversibility of TJ opening. Furthermore, our analyses revealed that TRPA1 is involved in the Ca 2+ influx and TJ permeability increase not only by an α,β-unsaturated compound but also by capsaicin. Our results indicate that the α,β-unsaturated moiety can be a potent pharmacophore for TJ opening.

  20. Transient receptor potential channel ankyrin-1 is not a cold sensor for autonomic thermoregulation in rodents.

    Science.gov (United States)

    de Oliveira, Cristiane; Garami, Andras; Lehto, Sonya G; Pakai, Eszter; Tekus, Valeria; Pohoczky, Krisztina; Youngblood, Beth D; Wang, Weiya; Kort, Michael E; Kym, Philip R; Pinter, Erika; Gavva, Narender R; Romanovsky, Andrej A

    2014-03-26

    The rodent transient receptor potential ankyrin-1 (TRPA1) channel has been hypothesized to serve as a temperature sensor for thermoregulation in the cold. We tested this hypothesis by using deletion of the Trpa1 gene in mice and pharmacological blockade of the TRPA1 channel in rats. In both Trpa1(-/-) and Trpa1(+/+) mice, severe cold exposure (8°C) resulted in decreases of skin and deep body temperatures to ∼8°C and 13°C, respectively, both temperatures being below the reported 17°C threshold temperature for TRPA1 activation. Under these conditions, Trpa1(-/-) mice had the same dynamics of body temperature as Trpa1(+/+) mice and showed no weakness in the tail skin vasoconstriction response or thermogenic response to cold. In rats, the effects of pharmacological blockade were studied by using two chemically unrelated TRPA1 antagonists: the highly potent and selective compound A967079, which had been characterized earlier, and the relatively new compound 43 ((4R)-1,2,3,4-tetrahydro-4-[3-(3-methoxypropoxy)phenyl]-2-thioxo-5H-indeno[1,2-d]pyrimidin-5-one), which we further characterized in the present study and found to be highly potent (IC50 against cold of ∼8 nm) and selective. Intragastric administration of either antagonist at 30 mg/kg before severe (3°C) cold exposure did not affect the thermoregulatory responses (deep body and tail skin temperatures) of rats, even though plasma concentrations of both antagonists well exceeded their IC50 value at the end of the experiment. In the same experimental setup, blocking the melastatin-8 (TRPM8) channel with AMG2850 (30 mg/kg) attenuated cold-defense mechanisms and led to hypothermia. We conclude that TRPA1 channels do not drive autonomic thermoregulatory responses to cold in rodents.

  1. Transient receptor potential ankyrin 1 channel localized to non-neuronal airway cells promotes non-neurogenic inflammation

    DEFF Research Database (Denmark)

    Nassini, Romina; Pedretti, Pamela; Moretto, Nadia

    2012-01-01

    The transient receptor potential ankyrin 1 (TRPA1) channel, localized to airway sensory nerves, has been proposed to mediate airway inflammation evoked by allergen and cigarette smoke (CS) in rodents, via a neurogenic mechanism. However the limited clinical evidence for the role of neurogenic...... inflammation in asthma or chronic obstructive pulmonary disease raises an alternative possibility that airway inflammation is promoted by non-neuronal TRPA1.By using Real-Time PCR and calcium imaging, we found that cultured human airway cells, including fibroblasts, epithelial and smooth muscle cells express...... functional TRPA1 channels. By using immunohistochemistry, TRPA1 staining was observed in airway epithelial and smooth muscle cells in sections taken from human airways and lung, and from airways and lung of wild-type, but not TRPA1-deficient mice. In cultured human airway epithelial and smooth muscle cells...

  2. TRPA1 mediates changes in heart rate variability and cardiac mechanical function in mice exposed to acrolein

    Energy Technology Data Exchange (ETDEWEB)

    Kurhanewicz, Nicole [Curriculum in Toxicology, School of Medicine, University of North Carolina, Chapel Hill, NC 27599 (United States); McIntosh-Kastrinsky, Rachel [Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC 27599 (United States); Tong, Haiyan; Ledbetter, Allen; Walsh, Leon; Farraj, Aimen [Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, Research Triangle Park, NC 27711 (United States); Hazari, Mehdi, E-mail: hazari.mehdi@epa.gov [Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, Research Triangle Park, NC 27711 (United States)

    2017-06-01

    Short-term exposure to ambient air pollution is linked with adverse cardiovascular effects. While previous research focused primarily on particulate matter-induced responses, gaseous air pollutants also contribute to cause short-term cardiovascular effects. Mechanisms underlying such effects have not been adequately described, however the immediate nature of the response suggests involvement of irritant neural activation and downstream autonomic dysfunction. Thus, this study examines the role of TRPA1, an irritant sensory receptor found in the airways, in the cardiac response of mice to acrolein and ozone. Conscious unrestrained wild-type C57BL/6 (WT) and TRPA1 knockout (KO) mice implanted with radiotelemeters were exposed once to 3 ppm acrolein, 0.3 ppm ozone, or filtered air. Heart rate (HR) and electrocardiogram (ECG) were recorded continuously before, during and after exposure. Analysis of ECG morphology, incidence of arrhythmia and heart rate variability (HRV) were performed. Cardiac mechanical function was assessed using a Langendorff perfusion preparation 24 h post-exposure. Acrolein exposure increased HRV independent of HR, as well as incidence of arrhythmia. Acrolein also increased left ventricular developed pressure in WT mice at 24 h post-exposure. Ozone did not produce any changes in cardiac function. Neither gas produced ECG effects, changes in HRV, arrhythmogenesis, or mechanical function in KO mice. These data demonstrate that a single exposure to acrolein causes cardiac dysfunction through TRPA1 activation and autonomic imbalance characterized by a shift toward parasympathetic modulation. Furthermore, it is clear from the lack of ozone effects that although gaseous irritants are capable of eliciting immediate cardiac changes, gas concentration and properties play important roles. - Highlights: • Acute acrolein exposure causes autonomic imbalance and altered CV function in mice. • TRPA1 mediates acrolein-induced autonomic nervous system cardiac

  3. TRPA1 mediates changes in heart rate variability and cardiac mechanical function in mice exposed to acrolein

    International Nuclear Information System (INIS)

    Kurhanewicz, Nicole; McIntosh-Kastrinsky, Rachel; Tong, Haiyan; Ledbetter, Allen; Walsh, Leon; Farraj, Aimen; Hazari, Mehdi

    2017-01-01

    Short-term exposure to ambient air pollution is linked with adverse cardiovascular effects. While previous research focused primarily on particulate matter-induced responses, gaseous air pollutants also contribute to cause short-term cardiovascular effects. Mechanisms underlying such effects have not been adequately described, however the immediate nature of the response suggests involvement of irritant neural activation and downstream autonomic dysfunction. Thus, this study examines the role of TRPA1, an irritant sensory receptor found in the airways, in the cardiac response of mice to acrolein and ozone. Conscious unrestrained wild-type C57BL/6 (WT) and TRPA1 knockout (KO) mice implanted with radiotelemeters were exposed once to 3 ppm acrolein, 0.3 ppm ozone, or filtered air. Heart rate (HR) and electrocardiogram (ECG) were recorded continuously before, during and after exposure. Analysis of ECG morphology, incidence of arrhythmia and heart rate variability (HRV) were performed. Cardiac mechanical function was assessed using a Langendorff perfusion preparation 24 h post-exposure. Acrolein exposure increased HRV independent of HR, as well as incidence of arrhythmia. Acrolein also increased left ventricular developed pressure in WT mice at 24 h post-exposure. Ozone did not produce any changes in cardiac function. Neither gas produced ECG effects, changes in HRV, arrhythmogenesis, or mechanical function in KO mice. These data demonstrate that a single exposure to acrolein causes cardiac dysfunction through TRPA1 activation and autonomic imbalance characterized by a shift toward parasympathetic modulation. Furthermore, it is clear from the lack of ozone effects that although gaseous irritants are capable of eliciting immediate cardiac changes, gas concentration and properties play important roles. - Highlights: • Acute acrolein exposure causes autonomic imbalance and altered CV function in mice. • TRPA1 mediates acrolein-induced autonomic nervous system cardiac

  4. Distinct Mechanism of Cysteine Oxidation-Dependent Activation and Cold Sensitization of Human Transient Receptor Potential Ankyrin 1 Channel by High and Low Oxaliplatin

    Directory of Open Access Journals (Sweden)

    Takahito Miyake

    2017-11-01

    Full Text Available Oxaliplatin, a third-generation platinum-based chemotherapeutic agent, displays unique acute peripheral neuropathy triggered or enhanced by cold, and accumulating evidence suggests that transient receptor potential ankyrin 1 (TRPA1 is responsible. TRPA1 is activated by oxaliplatin via a glutathione-sensitive mechanism. However, oxaliplatin interrupts hydroxylation of a proline residue located in the N-terminal region of TRPA1 via inhibition of prolyl hydroxylase (PHD, which causes sensitization of TRPA1 to reactive oxygen species (ROS. Furthermore, PHD inhibition endows cold-insensitive human TRPA1 (hTRPA1 with ROS-dependent cold sensitivity. Since cysteine oxidation and proline hydroxylation regulate its activity, their association with oxaliplatin-induced TRPA1 activation and acquirement of cold sensitivity were investigated in the present study. A high concentration of oxaliplatin (1 mM induced outward-rectifier whole-cell currents and increased the intracellular Ca2+ concentration in hTRPA1-expressing HEK293 cells, but did not increase the probability of hTRPA1 channel opening in the inside-out configuration. Oxaliplatin also induced the rapid generation of hydrogen peroxide, and the resultant Ca2+ influx was prevented in the presence of glutathione and in cysteine-mutated hTRPA1 (Cys641Ser-expressing cells, whereas proline-mutated hTRPA1 (Pro394Ala-expressing cells showed similar whole-cell currents and Ca2+ influx. By contrast, a lower concentration of oxaliplatin (100 μM did not increase the intracellular Ca2+ concentration but did confer cold sensitivity on hTRPA1-expressing cells, and this was inhibited by PHD2 co-overexpression. Cold sensitivity was abolished by the mitochondria-targeting ROS scavenger mitoTEMPO and was minimal in cysteine-mutated hTRPA1 (Cys641Ser or Cys665Ser-expressing cells. Thus, high oxaliplatin evokes ROS-mediated cysteine oxidation-dependent hTRPA1 activation independent of PHD activity, while a lower

  5. Transient receptor potential A1 channel contributes to activation of the muscle reflex.

    Science.gov (United States)

    Koba, Satoshi; Hayes, Shawn G; Sinoway, Lawrence I

    2011-01-01

    This study was undertaken to elucidate the role played by transient receptor potential A1 channels (TRPA1) in activating the muscle reflex, a sympathoexcitatory drive originating in contracting muscle. First, we tested the hypothesis that stimulation of the TRPA1 located on muscle afferents reflexly increases sympathetic nerve activity. In decerebrate rats, allyl isothiocyanate, a TRPA1 agonist, was injected intra-arterially into the hindlimb muscle circulation. This led to a 33% increase in renal sympathetic nerve activity (RSNA). The effect of allyl isothiocyanate was a reflex because the response was prevented by sectioning the sciatic nerve. Second, we tested the hypothesis that blockade of TRPA1 reduces RSNA response to contraction. Thirty-second continuous static contraction of the hindlimb muscles, induced by electrical stimulation of the peripheral cut ends of L(4) and L(5) ventral roots, increased RSNA and blood pressure. The integrated RSNA during contraction was reduced by HC-030031, a TRPA1 antagonist, injected intra-arterially (163 ± 24 vs. 95 ± 21 arbitrary units, before vs. after HC-030031, P reflex. Increases in RSNA in response to injection into the muscle circulation of arachidonic acid, bradykinin, and diprotonated phosphate, which are metabolic by-products of contraction and stimulants of muscle afferents during contraction, were reduced by HC-030031. These observations suggest that the TRPA1 located on muscle afferents is part of the muscle reflex and further support the notion that arachidonic acid metabolites, bradykinin, and diprotonated phosphate are candidates for endogenous agonists of TRPA1.

  6. Characterization of Transient Receptor Potential Vanilloid-1 (TRPV1) Variant Activation by Coal Fly Ash Particles and Associations with Altered Transient Receptor Potential Ankyrin-1 (TRPA1) Expression and Asthma.

    Science.gov (United States)

    Deering-Rice, Cassandra E; Stockmann, Chris; Romero, Erin G; Lu, Zhenyu; Shapiro, Darien; Stone, Bryan L; Fassl, Bernhard; Nkoy, Flory; Uchida, Derek A; Ward, Robert M; Veranth, John M; Reilly, Christopher A

    2016-11-25

    Transient receptor potential (TRP) channels are activated by environmental particulate materials. We hypothesized that polymorphic variants of transient receptor potential vanilloid-1 (TRPV1) would be uniquely responsive to insoluble coal fly ash compared with the prototypical soluble agonist capsaicin. Furthermore, these changes would manifest as differences in lung cell responses to these agonists and perhaps correlate with changes in asthma symptom control. The TRPV1-I315M and -T469I variants were more responsive to capsaicin and coal fly ash. The I585V variant was less responsive to coal fly ash particles due to reduced translation of protein and an apparent role for Ile-585 in activation by particles. In HEK-293 cells, I585V had an inhibitory effect on wild-type TRPV1 expression, activation, and internalization/agonist-induced desensitization. In normal human bronchial epithelial cells, IL-8 secretion in response to coal fly ash treatment was reduced for cells heterozygous for TRPV1-I585V. Finally, both the I315M and I585V variants were associated with worse asthma symptom control with the effects of I315M manifesting in mild asthma and those of the I585V variant manifesting in severe, steroid-insensitive individuals. This effect may be due in part to increased transient receptor potential ankyrin-1 (TRPA1) expression by lung epithelial cells expressing the TRPV1-I585V variant. These findings suggest that specific molecular interactions control TRPV1 activation by particles, differential activation, and desensitization of TRPV1 by particles and/or other agonists, and cellular changes in the expression of TRPA1 as a result of I585V expression could contribute to variations in asthma symptom control. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  7. Environmental toxin acrolein alters levels of endogenous lipids, including TRP agonists: A potential mechanism for headache driven by TRPA1 activation

    Directory of Open Access Journals (Sweden)

    Emma Leishman

    2017-01-01

    Full Text Available Exposure to airborne toxins can trigger headaches, but the mechanisms are not well understood. Some environmental toxins, such as acrolein, activate transient receptor potential ankyrin 1 (TRPA1, a receptor involved in pain sensation that is highly expressed in the trigeminovascular system. It has been shown in rat models that repeated exposure to acrolein induces trigeminovascular sensitization to both TRPA1 and TRP vanilloid 1 (TRPV1 agonists, a phenomenon linked to headache. In this study, we test the hypothesis that the sensitization of trigeminovascular responses in rats after acrolein exposure via inhalation is associated with changes in levels of endogenous lipids, including TRPV1 agonists, in the trigeminal ganglia, trigeminal nucleus, and cerebellum. Lipidomics analysis of 80 lipids was performed on each tissue after acute acrolein, chronic acrolein, or room air control. Both acute and chronic acrolein exposure drove widespread alterations in lipid levels. After chronic acrolein exposure, levels of all 6 N-acyl ethanolamines in the screening library, including the endogenous cannabinoid and TRPV1 agonist, N-arachidonoyl ethanolamine, were elevated in trigeminal tissue and in the cerebellum. This increase in TRPV1 ligands by acrolein exposure may indicate further downstream signaling, in that we also show here that a combination of these TRPV1 endogenous agonists increases the potency of the individual ligands in TRPV1-HEK cells. In addition to these TRPV1 agonists, 3 TRPV3 antagonists, 4 TRPV4 agonists, and 25 orphan lipids were up and down regulated after acrolein exposure. These data support the hypothesis that lipid signaling may represent a mechanism by which repeated exposure to the TRPA1 agonist and environmental toxin, acrolein, drives trigeminovascular sensitization. Keywords: Lipidomics, Endogenous cannabinoid, TRPA1, TRPV1, Lipoamine, Acrolein, Migraine

  8. Seismic stochastic inversion identify river channel sand body

    Science.gov (United States)

    He, Z.

    2015-12-01

    The technology of seismic inversion is regarded as one of the most important part of geophysics. By using the technology of seismic inversion and the theory of stochastic simulation, the concept of seismic stochastic inversion is proposed.Seismic stochastic inversion can play an significant role in the identifying river channel sand body. Accurate sand body description is a crucial parameter to measure oilfield development and oilfield stimulation during the middle and later periods. Besides, rational well spacing density is an essential condition for efficient production. Based on the geological knowledge of a certain oilfield, in line with the use of seismic stochastic inversion, the river channel sand body in the work area is identified. In this paper, firstly, the single river channel body from the composite river channel body is subdivided. Secondly, the distribution of river channel body is ascertained in order to ascertain the direction of rivers. Morever, the superimposed relationship among the sand body is analyzed, especially among the inter-well sand body. The last but not at the least, via the analysis of inversion results of first vacuating the wells and continuous infilling later, it is meeted the most needs well spacing density that can obtain the optimal inversion result. It would serve effective guidance for oilfield stimulation.

  9. N-terminal tetrapeptide T/SPLH motifs contribute to multimodal activation of human TRPA1 channel

    Czech Academy of Sciences Publication Activity Database

    Hynková, Anna; Maršáková, Lenka; Vašková, Jana; Vlachová, Viktorie

    2016-01-01

    Roč. 6, Jun 27 (2016), s. 28700 ISSN 2045-2322 R&D Projects: GA ČR(CZ) GA15-15839S Institutional support: RVO:67985823 Keywords : ankyrin receptor subtype 1 * transient receptor potential * gating * ankyrin repeat * whole-cell electrophysiology * N-terminus * mutagenesis Subject RIV: FH - Neurology Impact factor: 4.259, year: 2016

  10. Essential role for the putative S6 inner pore region in the activation gating of the human TRPA1 channel

    Czech Academy of Sciences Publication Activity Database

    Samad, Abdul

    2009-01-01

    Roč. 7, č. 1793 (2009), s. 1279-1288 ISSN 0167-4889 R&D Projects: GA MŠk(CZ) LC06010 Institutional research plan: CEZ:AV0Z60870520 Keywords : TRPA family * RESIDUES * VOLTAGE Subject RIV: CE - Biochemistry Impact factor: 4.374, year: 2009

  11. Review article: transient receptor potential channels as possible therapeutic targets in irritable bowel syndrome.

    Science.gov (United States)

    Beckers, A B; Weerts, Z Z R M; Helyes, Z; Masclee, A A M; Keszthelyi, D

    2017-11-01

    Abdominal pain in irritable bowel syndrome (IBS) remains challenging to treat effectively. Researchers have attempted to elucidate visceral nociceptive processes in order to guide treatment development. Transient receptor potential (TRP) channels have been implied in the generation (TRPV1, TRPV4, TRPA1) and inhibition (TRPM8) of visceral pain signals. Pathological changes in their functioning have been demonstrated in inflammatory conditions, and appear to be present in IBS as well. To provide a comprehensive review of the current literature on TRP channels involved in visceral nociception. In particular, we emphasise the clinical implications of these nociceptors in the treatment of IBS. Evidence to support this review was obtained from an electronic database search via PubMed using the search terms "visceral nociception," "visceral hypersensitivity," "irritable bowel syndrome" and "transient receptor potential channels." After screening the abstracts the articles deemed relevant were cross-referenced for additional manuscripts. Recent studies have resulted in significant advances in our understanding of TRP channel mediated visceral nociception. The diversity of TRP channel sensitization pathways is increasingly recognised. Endogenous TRP agonists, including poly-unsaturated fatty acid metabolites and hydrogen sulphide, have been implied in augmented visceral pain generation in IBS. New potential targets for treatment development have been identified (TRPA1 and TRPV4,) and alternative means of affecting TRP channel signalling (partial antagonists, downstream targeting and RNA-based therapy) are currently being explored. The improved understanding of mechanisms involved in visceral nociception provides a solid basis for the development of new treatment strategies for abdominal pain in IBS. © 2017 John Wiley & Sons Ltd.

  12. Multimode Interference: Identifying Channels and Ridges in Quantum Probability Distributions

    OpenAIRE

    O'Connell, Ross C.; Loinaz, Will

    2004-01-01

    The multimode interference technique is a simple way to study the interference patterns found in many quantum probability distributions. We demonstrate that this analysis not only explains the existence of so-called "quantum carpets," but can explain the spatial distribution of channels and ridges in the carpets. With an understanding of the factors that govern these channels and ridges we have a limited ability to produce a particular pattern of channels and ridges by carefully choosing the ...

  13. Identifying cochlear implant channels with poor electrode-neuron interface: partial tripolar, single-channel thresholds and psychophysical tuning curves.

    Science.gov (United States)

    Bierer, Julie Arenberg; Faulkner, Kathleen F

    2010-04-01

    The goal of this study was to evaluate the ability of a threshold measure, made with a restricted electrode configuration, to identify channels exhibiting relatively poor spatial selectivity. With a restricted electrode configuration, channel-to-channel variability in threshold may reflect variations in the interface between the electrodes and auditory neurons (i.e., nerve survival, electrode placement, and tissue impedance). These variations in the electrode-neuron interface should also be reflected in psychophysical tuning curve (PTC) measurements. Specifically, it is hypothesized that high single-channel thresholds obtained with the spatially focused partial tripolar (pTP) electrode configuration are predictive of wide or tip-shifted PTCs. Data were collected from five cochlear implant listeners implanted with the HiRes90k cochlear implant (Advanced Bionics Corp., Sylmar, CA). Single-channel thresholds and most comfortable listening levels were obtained for stimuli that varied in presumed electrical field size by using the pTP configuration for which a fraction of current (sigma) from a center-active electrode returns through two neighboring electrodes and the remainder through a distant indifferent electrode. Forward-masked PTCs were obtained for channels with the highest, lowest, and median tripolar (sigma = 1 or 0.9) thresholds. The probe channel and level were fixed and presented with either the monopolar (sigma = 0) or a more focused pTP (sigma > or = 0.55) configuration. The masker channel and level were varied, whereas the configuration was fixed to sigma = 0.5. A standard, three-interval, two-alternative forced choice procedure was used for thresholds and masked levels. Single-channel threshold and variability in threshold across channels systematically increased as the compensating current, sigma, increased and the presumed electrical field became more focused. Across subjects, channels with the highest single-channel thresholds, when measured with a

  14. Chemo-nociceptive signalling from the colon is enhanced by mild colitis and blocked by inhibition of transient receptor potential ankyrin 1 channels

    DEFF Research Database (Denmark)

    Mitrovic, Martina; Shahbazian, Anaid; Bock, Elisabeth

    2010-01-01

    Transient receptor potential ankyrin 1 (TRPA1) channels are expressed by primary afferent neurones and activated by irritant chemicals including allyl isothiocyanate (AITC). Here we investigated whether intracolonic AITC causes afferent input to the spinal cord and whether this response is modifi...

  15. Role of Transient Receptor Potential Ankyrin 1 Ion Channel and Somatostatin sst4 Receptor in the Antinociceptive and Anti-inflammatory Effects of Sodium Polysulfide and Dimethyl Trisulfide

    Directory of Open Access Journals (Sweden)

    István Z. Bátai

    2018-02-01

    Full Text Available Transient receptor potential ankyrin 1 (TRPA1 non-selective ligand-gated cation channels are mostly expressed in primary sensory neurons. Polysulfides (POLYs are Janus-faced substances interacting with numerous target proteins and associated with both protective and detrimental processes. Activation of TRPA1 in sensory neurons, consequent somatostatin (SOM liberation and action on sst4 receptors have recently emerged as mediators of the antinociceptive effect of organic trisulfide dimethyl trisulfide (DMTS. In the frame of the present study, we set out to compare the participation of this mechanism in antinociceptive and anti-inflammatory effects of inorganic sodium POLY and DMTS in carrageenan-evoked hind-paw inflammation. Inflammation of murine hind paws was induced by intraplantar injection of carrageenan (3% in 30 µL saline. Animals were treated intraperitoneally with POLY (17 µmol/kg or DMTS (250 µmol/kg or their respective vehicles 30 min prior paw challenge and six times afterward every 60 min. Mechanical pain threshold and swelling of the paws were measured by dynamic plantar aesthesiometry and plethysmometry at 2, 4, and 6 h after initiation of inflammation. Myeloperoxidase (MPO activity in the hind paws were detected 6 h after challenge by luminescent imaging. Mice genetically lacking TRPA1 ion channels, sst4 receptors and their wild-type counterparts were used to examine the participation of these proteins in POLY and DMTS effects. POLY counteracted carrageenan-evoked mechanical hyperalgesia in a TRPA1 and sst4 receptor-dependent manner. POLY did not influence paw swelling and MPO activity. DMTS ameliorated all examined inflammatory parameters. Mitigation of mechanical hyperalgesia and paw swelling by DMTS were mediated through sst4 receptors. These effects were present in TRPA1 knockout animals, too. DMTS inhibited MPO activity with no participation of the sensory neuron–SOM axis. While antinociceptive effects of

  16. Structural modeling and patch-clamp analysis of pain-related mutation TRPA1-N855S reveal inter-subunit salt bridges stabilizing the channel open state

    Czech Academy of Sciences Publication Activity Database

    Zíma, V.; Witschas, Katja; Hynková, Anna; Zímová, Lucie; Barvík, I.; Vlachová, Viktorie

    2015-01-01

    Roč. 93, Jun (2015), s. 294-307 ISSN 0028-3908 R&D Projects: GA ČR(CZ) GA305/09/0081; GA ČR(CZ) GBP304/12/G069; GA MŠk(CZ) EE2.3.30.0025; GA ČR(CZ) GA15-15839S Institutional support: RVO:67985823 Keywords : ankyrin receptor subtype 1 * S4-S5-linker * mutagenesis Subject RIV: ED - Physiology Impact factor: 4.936, year: 2015

  17. Ciguatoxins Evoke Potent CGRP Release by Activation of Voltage-Gated Sodium Channel Subtypes Na(V)1.9, Na(V)1.7 and Na(V)1.1

    Czech Academy of Sciences Publication Activity Database

    Touška, Filip; Sattler, S.; Malsch, P.; Lewis, R. J.; Reeh, P. W.; Zimmermann, K.

    2017-01-01

    Roč. 15, č. 9 (2017), č. článku 269. ISSN 1660-3397 Institutional support: RVO:67985823 Keywords : voltage-gated calcium channels * calcitonin-gene related peptide * tetrodotoxin * TTX * P-CTX-1 * TRPA1 * TRPC5 * neuropathic pain * neurogenic inflammation Subject RIV: FH - Neurology OBOR OECD: Neurosciences (including psychophysiology Impact factor: 3.503, year: 2016

  18. Auricular Electroacupuncture Reduced Inflammation-Related Epilepsy Accompanied by Altered TRPA1, pPKCα, pPKCε, and pERk1/2 Signaling Pathways in Kainic Acid-Treated Rats

    Directory of Open Access Journals (Sweden)

    Yi-Wen Lin

    2014-01-01

    Full Text Available Background. Inflammation is often considered to play a crucial role in epilepsy by affecting iron status and metabolism. In this study, we investigated the curative effect of auricular acupuncture and somatic acupuncture on kainic acid- (KA- induced epilepsy in rats. Methods. We established an epileptic seizure model in rats by KA (12 mg, ip. The 2 Hz electroacupuncture (EA was applied at auricular and applied at Zusanli and Shangjuxu (ST36-ST37 acupoints for 20 min for 3 days/week for 6 weeks beginning on the day following the KA injection. Results. The electrophysiological results indicated that neuron overexcitation occurred in the KA-treated rats. This phenomenon could be reversed among either the auricular EA or ST36-ST37 EA treatment, but not in the sham-control rats. The Western blot results revealed that TRPA1, but not TRPV4, was upregulated by injecting KA and could be attenuated by administering auricular or ST36-ST37 EA, but not in the sham group. In addition, potentiation of TRPA1 was accompanied by increased PKCα and reduced PKCε. Furthermore, pERK1/2, which is indicated in inflammation, was also increased by KA. Furthermore, the aforementioned mechanisms could be reversed by administering auricular EA and could be partially reversed by ST36-ST37 EA. Conclusions. These results indicate a novel mechanism for treating inflammation-associated epilepsy and can be translated into clinical therapy.

  19. Functional TRP and ASIC-like channels in cultured urothelial cells from the rat.

    Science.gov (United States)

    Kullmann, F Aura; Shah, M A; Birder, L A; de Groat, W C

    2009-04-01

    Transient receptor potential (TRP) and acid-sensing ion channels (ASIC) are molecular detectors of chemical, mechanical, thermal, and nociceptive stimuli in sensory neurons. They have been identified in the urothelium, a tissue considered part of bladder sensory pathways, where they might play a role in bladder function. This study investigated functional properties of TRP and ASIC channels in cultured urothelial cells from the rat using patch-clamp and fura 2 Ca(2+) imaging techniques. The TRPV4 agonist 4alpha-phorbol-12,13 didecanoate (4alpha-PDD; 1-5 microM) and the TRPA1/TRPM8 agonist icilin (50-100 microM) elicited transient currents in a high percentage of cells (>70%). 4alpha-PDD responses were suppressed by the TRPV4 antagonist HC-010961 (10 microM). The TRPV1 agonist capsaicin (1-100 microM) and the TRPA1/TRPM8 agonist menthol (5-200 microM) elicited transient currents in a moderate percentage of cells ( approximately 25%). All of these agonists increased intracellular calcium concentration ([Ca(2+)](i)). Most cells responded to more than one TRP agonist (e.g., capsaicin and 4alpha-PDD), indicating coexpression of different TRP channels. In the presence of the TRPV1 antagonist capsazepine (10 microM), changes in pH induced by HCl elicited ionic currents (pH 5.5) and increased [Ca(2+)](i) (pH 6.5) in approximately 50% of cells. Changes in pH using acetic acid (pH 5.5) elicited biphasic-like currents. Responses induced by acid were sensitive to amiloride (10 microM). In summary, urothelial cells express multiple TRP and ASIC channels, whose activation elicits ionic currents and Ca(2+) influx. These "neuron-like" properties might be involved in transmitter release, such as ATP, that can act on afferent nerves or smooth muscle to modulate their responses to different stimuli.

  20. Space-Time Coded MC-CDMA: Blind Channel Estimation, Identifiability, and Receiver Design

    Directory of Open Access Journals (Sweden)

    Li Hongbin

    2002-01-01

    Full Text Available Integrating the strengths of multicarrier (MC modulation and code division multiple access (CDMA, MC-CDMA systems are of great interest for future broadband transmissions. This paper considers the problem of channel identification and signal combining/detection schemes for MC-CDMA systems equipped with multiple transmit antennas and space-time (ST coding. In particular, a subspace based blind channel identification algorithm is presented. Identifiability conditions are examined and specified which guarantee unique and perfect (up to a scalar channel estimation when knowledge of the noise subspace is available. Several popular single-user based signal combining schemes, namely the maximum ratio combining (MRC and the equal gain combining (EGC, which are often utilized in conventional single-transmit-antenna based MC-CDMA systems, are extended to the current ST-coded MC-CDMA (STC-MC-CDMA system to perform joint combining and decoding. In addition, a linear multiuser minimum mean-squared error (MMSE detection scheme is also presented, which is shown to outperform the MRC and EGC at some increased computational complexity. Numerical examples are presented to evaluate and compare the proposed channel identification and signal detection/combining techniques.

  1. Plant-derived cannabinoids modulate the activity of transient receptor potential channels of ankyrin type-1 and melastatin type-8.

    Science.gov (United States)

    De Petrocellis, Luciano; Vellani, Vittorio; Schiano-Moriello, Aniello; Marini, Pietro; Magherini, Pier Cosimo; Orlando, Pierangelo; Di Marzo, Vincenzo

    2008-06-01

    The plant cannabinoids (phytocannabinoids), cannabidiol (CBD), and Delta(9)-tetrahydrocannabinol (THC) were previously shown to activate transient receptor potential channels of both vanilloid type 1 (TRPV1) and ankyrin type 1 (TRPA1), respectively. Furthermore, the endocannabinoid anandamide is known to activate TRPV1 and was recently found to antagonize the menthol- and icilin-sensitive transient receptor potential channels of melastatin type 8 (TRPM8). In this study, we investigated the effects of six phytocannabinoids [i.e., CBD, THC, CBD acid, THC acid, cannabichromene (CBC), and cannabigerol (CBG)] on TRPA1- and TRPM8-mediated increase in intracellular Ca2+ in either HEK-293 cells overexpressing the two channels or rat dorsal root ganglia (DRG) sensory neurons. All of the compounds tested induced TRPA1-mediated Ca2+ elevation in HEK-293 cells with efficacy comparable with that of mustard oil isothiocyanates (MO), the most potent being CBC (EC(50) = 60 nM) and the least potent being CBG and CBD acid (EC(50) = 3.4-12.0 microM). CBC also activated MO-sensitive DRG neurons, although with lower potency (EC(50) = 34.3 microM). Furthermore, although none of the compounds tested activated TRPM8-mediated Ca2+ elevation in HEK-293 cells, they all, with the exception of CBC, antagonized this response when it was induced by either menthol or icilin. CBD, CBG, THC, and THC acid were equipotent (IC(50) = 70-160 nM), whereas CBD acid was the least potent compound (IC(50) = 0.9-1.6 microM). CBG inhibited Ca2+ elevation also in icilin-sensitive DRG neurons with potency (IC(50) = 4.5 microM) similar to that of anandamide (IC(50) = 10 microM). Our findings suggest that phytocannabinoids and cannabis extracts exert some of their pharmacological actions also by interacting with TRPA1 and TRPM8 channels, with potential implications for the treatment of pain and cancer.

  2. Evolutionary conservation and changes in insect TRP channels.

    Science.gov (United States)

    Matsuura, Hironori; Sokabe, Takaaki; Kohno, Keigo; Tominaga, Makoto; Kadowaki, Tatsuhiko

    2009-09-10

    TRP (Transient Receptor Potential) channels respond to diverse stimuli and thus function as the primary integrators of varied sensory information. They are also activated by various compounds and secondary messengers to mediate cell-cell interactions as well as to detect changes in the local environment. Their physiological roles have been primarily characterized only in mice and fruit flies, and evolutionary studies are limited. To understand the evolution of insect TRP channels and the mechanisms of integrating sensory inputs in insects, we have identified and compared TRP channel genes in Drosophila melanogaster, Bombyx mori, Tribolium castaneum, Apis mellifera, Nasonia vitripennis, and Pediculus humanus genomes as part of genome sequencing efforts. All the insects examined have 2 TRPV, 1 TRPN, 1 TRPM, 3 TRPC, and 1 TRPML subfamily members, demonstrating that these channels have the ancient origins in insects. The common pattern also suggests that the mechanisms for detecting mechanical and visual stimuli and maintaining lysosomal functions may be evolutionarily well conserved in insects. However, a TRPP channel, the most ancient TRP channel, is missing in B. mori, A. mellifera, and N. vitripennis. Although P. humanus and D. melanogaster contain 4 TRPA subfamily members, the other insects have 5 TRPA subfamily members. T. castaneum, A. mellifera, and N. vitripennis contain TRPA5 channels, which have been specifically retained or gained in Coleoptera and Hymenoptera. Furthermore, TRPA1, which functions for thermotaxis in Drosophila, is missing in A. mellifera and N. vitripennis; however, they have other Hymenoptera-specific TRPA channels (AmHsTRPA and NvHsTRPA). NvHsTRPA expressed in HEK293 cells is activated by temperature increase, demonstrating that HsTRPAs function as novel thermal sensors in Hymenoptera. The total number of insect TRP family members is 13-14, approximately half that of mammalian TRP family members. As shown for mammalian TRP channels, this

  3. Evolutionary conservation and changes in insect TRP channels

    Directory of Open Access Journals (Sweden)

    Tominaga Makoto

    2009-09-01

    Full Text Available Abstract Background TRP (Transient Receptor Potential channels respond to diverse stimuli and thus function as the primary integrators of varied sensory information. They are also activated by various compounds and secondary messengers to mediate cell-cell interactions as well as to detect changes in the local environment. Their physiological roles have been primarily characterized only in mice and fruit flies, and evolutionary studies are limited. To understand the evolution of insect TRP channels and the mechanisms of integrating sensory inputs in insects, we have identified and compared TRP channel genes in Drosophila melanogaster, Bombyx mori, Tribolium castaneum, Apis mellifera, Nasonia vitripennis, and Pediculus humanus genomes as part of genome sequencing efforts. Results All the insects examined have 2 TRPV, 1 TRPN, 1 TRPM, 3 TRPC, and 1 TRPML subfamily members, demonstrating that these channels have the ancient origins in insects. The common pattern also suggests that the mechanisms for detecting mechanical and visual stimuli and maintaining lysosomal functions may be evolutionarily well conserved in insects. However, a TRPP channel, the most ancient TRP channel, is missing in B. mori, A. mellifera, and N. vitripennis. Although P. humanus and D. melanogaster contain 4 TRPA subfamily members, the other insects have 5 TRPA subfamily members. T. castaneum, A. mellifera, and N. vitripennis contain TRPA5 channels, which have been specifically retained or gained in Coleoptera and Hymenoptera. Furthermore, TRPA1, which functions for thermotaxis in Drosophila, is missing in A. mellifera and N. vitripennis; however, they have other Hymenoptera-specific TRPA channels (AmHsTRPA and NvHsTRPA. NvHsTRPA expressed in HEK293 cells is activated by temperature increase, demonstrating that HsTRPAs function as novel thermal sensors in Hymenoptera. Conclusion The total number of insect TRP family members is 13-14, approximately half that of mammalian TRP

  4. Transient receptor potential (TRP) channels as drug targets for diseases of the digestive system

    Science.gov (United States)

    Holzer, Peter

    2011-01-01

    Approximately 20 of the 30 mammalian transient receptor potential (TRP) channel subunits are expressed by specific neurons and cells within the alimentary canal. They subserve important roles in taste, chemesthesis, mechanosensation, pain and hyperalgesia and contribute to the regulation of gastrointestinal motility, absorptive and secretory processes, blood flow, and mucosal homeostasis. In a cellular perspective, TRP channels operate either as primary detectors of chemical and physical stimuli, as secondary transducers of ionotropic or metabotropic receptors, or as ion transport channels. The polymodal sensory function of TRPA1, TRPM5, TRPM8, TRPP2, TRPV1, TRPV3 and TRPV4 enables the digestive system to survey its physical and chemical environment, which is relevant to all processes of digestion. TRPV5 and TRPV6 as well as TRPM6 and TRPM7 contribute to the absorption of Ca2+ and Mg2+, respectively. TRPM7 participates in intestinal pacemaker activity, and TRPC4 transduces muscarinic acetylcholine receptor activation to smooth muscle contraction. Changes in TRP channel expression or function are associated with a variety of diseases/disorders of the digestive system, notably gastro-esophageal reflux disease, inflammatory bowel disease, pain and hyperalgesia in heartburn, functional dyspepsia and irritable bowel syndrome, cholera, hypomagnesemia with secondary hypocalcemia, infantile hypertrophic pyloric stenosis, esophageal, gastrointestinal and pancreatic cancer, and polycystic liver disease. These implications identify TRP channels as promising drug targets for the management of a number of gastrointestinal pathologies. As a result, major efforts are put into the development of selective TRP channel agonists and antagonists and the assessment of their therapeutic potential. PMID:21420431

  5. Immunolocalization and distribution of functional temperature-sensitive TRP channels in salivary glands.

    Science.gov (United States)

    Sobhan, Ubaidus; Sato, Masaki; Shinomiya, Takashi; Okubo, Migiwa; Tsumura, Maki; Muramatsu, Takashi; Kawaguchi, Mitsuru; Tazaki, Masakazu; Shibukawa, Yoshiyuki

    2013-11-01

    Transient receptor potential (TRP) cation channels are unique cellular sensors involved in multiple cellular functions. Their role in salivary secretion remains to be elucidated. The expression and localization of temperature-sensitive TRP channels in salivary (submandibular, sublingual and parotid) glands were analyzed by immunohistochemistry and quantitative real-time reverse transcription plus the polymerase chain reaction (RT-PCR). The effects of various TRP channel agonists on carbachol (CCh)-induced salivary secretion in the submandibular gland and on the intracellular Ca(2+) concentration ([Ca(2+)]i) in a submandibular epithelial cell line were also investigated. Immunohistochemistry revealed the expression of TRP-melastatin subfamily member 8 (TRPM8) and TRP-ankyrin subfamily member 1 (TRPA1) in myoepithelial, acinar and ductal cells in the sublingual, submandibular and parotid glands. In addition, TRP-vanilloid subfamily member 1 (TRPV1), TRPV3 and TRPV4 were also expressed in myoepithelial, acinar and ductal cells in all three types of gland. Quantitative real-time RT-PCR results demonstrated the mRNA expression of TRPV1, TRPV3, TRPV4, TRPM8 and TRPA1 in acinar and ductal cells in these salivary glands. Perfusion of the entire submandibular gland with the TRPV1 agonist capsaicin (1 μM) via the submandibular artery significantly increased CCh-induced salivation, whereas perfusion with TRPM8 and TRPA1 agonists (0.5 μM WS12 and 100 μM allyl isothiocyanate) decreased it. Application of agonists for each of the thermosensitive TRP channels increased [Ca(2+)]i in a submandibular epithelial cell line. These results indicate that temperature-sensitive TRP channels are localized and distributed in acinar, ductal and myoepithelial cells in salivary glands and that they play a functional role in the regulation and/or modulation of salivary secretion.

  6. Identifying transition rates of ionic channels via observations at a single state

    CERN Document Server

    Deng Ying Chun; Qian Min Ping; Feng Jian Feng

    2003-01-01

    We consider how to determine all transition rates of an ion channel when it can be described by a birth-death chain or a Markov chain on a star-graph with continuous time. It is found that all transition rates are uniquely determined by the distribution of its lifetime and death-time histograms at a single state. An algorithm to calculate the transition rates exactly, based on the statistics of the lifetime and death-time of the Markov chain at the state, is provided. Examples to illustrate how an ion channel activity is fully determined by the observation of a single state of the ion channel are included.

  7. Identifying transition rates of ionic channels via observations at a single state

    International Nuclear Information System (INIS)

    Deng Yingchun; Peng Shenglun; Qian Minping; Feng Jianfeng

    2003-01-01

    We consider how to determine all transition rates of an ion channel when it can be described by a birth-death chain or a Markov chain on a star-graph with continuous time. It is found that all transition rates are uniquely determined by the distribution of its lifetime and death-time histograms at a single state. An algorithm to calculate the transition rates exactly, based on the statistics of the lifetime and death-time of the Markov chain at the state, is provided. Examples to illustrate how an ion channel activity is fully determined by the observation of a single state of the ion channel are included

  8. Identifying transition rates of ionic channels via observations at a single state

    Energy Technology Data Exchange (ETDEWEB)

    Deng Yingchun [School of Mathematics, Peking University, Beijing (China); Peng Shenglun [School of Mathematics, Peking University, Beijing (China); Qian Minping [School of Mathematics, Peking University, Beijing (China); Feng Jianfeng [COGS, Sussex University, Brighton (United Kingdom)

    2003-02-07

    We consider how to determine all transition rates of an ion channel when it can be described by a birth-death chain or a Markov chain on a star-graph with continuous time. It is found that all transition rates are uniquely determined by the distribution of its lifetime and death-time histograms at a single state. An algorithm to calculate the transition rates exactly, based on the statistics of the lifetime and death-time of the Markov chain at the state, is provided. Examples to illustrate how an ion channel activity is fully determined by the observation of a single state of the ion channel are included.

  9. Selection of Inhibitor-Resistant Viral Potassium Channels Identifies a Selectivity Filter Site that Affects Barium and Amantadine Block

    Science.gov (United States)

    Fujiwara, Yuichiro; Arrigoni, Cristina; Domigan, Courtney; Ferrara, Giuseppina; Pantoja, Carlos; Thiel, Gerhard; Moroni, Anna; Minor, Daniel L.

    2009-01-01

    Background Understanding the interactions between ion channels and blockers remains an important goal that has implications for delineating the basic mechanisms of ion channel function and for the discovery and development of ion channel directed drugs. Methodology/Principal Findings We used genetic selection methods to probe the interaction of two ion channel blockers, barium and amantadine, with the miniature viral potassium channel Kcv. Selection for Kcv mutants that were resistant to either blocker identified a mutant bearing multiple changes that was resistant to both. Implementation of a PCR shuffling and backcrossing procedure uncovered that the blocker resistance could be attributed to a single change, T63S, at a position that is likely to form the binding site for the inner ion in the selectivity filter (site 4). A combination of electrophysiological and biochemical assays revealed a distinct difference in the ability of the mutant channel to interact with the blockers. Studies of the analogous mutation in the mammalian inward rectifier Kir2.1 show that the T→S mutation affects barium block as well as the stability of the conductive state. Comparison of the effects of similar barium resistant mutations in Kcv and Kir2.1 shows that neighboring amino acids in the Kcv selectivity filter affect blocker binding. Conclusions/Significance The data support the idea that permeant ions have an integral role in stabilizing potassium channel structure, suggest that both barium and amantadine act at a similar site, and demonstrate how genetic selections can be used to map blocker binding sites and reveal mechanistic features. PMID:19834614

  10. TRP channel blamed for burning cold after a tropical fish meal

    Science.gov (United States)

    Voets, Thomas

    2012-01-01

    EMBO J (2012) 31 19, 3795–3808 doi:10.1038/emboj.2012.207; published online 07312012 Ciguatera is one of the most common forms of food poisoning, occurring after consumption of fish contaminated with ciguatoxins. New work by Vetter et al (2012) reveals the key molecular players that underlie the altered temperature sensation associated with ciguatera. In particular, they show that ciguatoxins act on sensory neurons that express TRPA1, an ion channel implicated in the detection of noxious cold. PMID:22960637

  11. Path lumping: An efficient algorithm to identify metastable path channels for conformational dynamics of multi-body systems

    Science.gov (United States)

    Meng, Luming; Sheong, Fu Kit; Zeng, Xiangze; Zhu, Lizhe; Huang, Xuhui

    2017-07-01

    Constructing Markov state models from large-scale molecular dynamics simulation trajectories is a promising approach to dissect the kinetic mechanisms of complex chemical and biological processes. Combined with transition path theory, Markov state models can be applied to identify all pathways connecting any conformational states of interest. However, the identified pathways can be too complex to comprehend, especially for multi-body processes where numerous parallel pathways with comparable flux probability often coexist. Here, we have developed a path lumping method to group these parallel pathways into metastable path channels for analysis. We define the similarity between two pathways as the intercrossing flux between them and then apply the spectral clustering algorithm to lump these pathways into groups. We demonstrate the power of our method by applying it to two systems: a 2D-potential consisting of four metastable energy channels and the hydrophobic collapse process of two hydrophobic molecules. In both cases, our algorithm successfully reveals the metastable path channels. We expect this path lumping algorithm to be a promising tool for revealing unprecedented insights into the kinetic mechanisms of complex multi-body processes.

  12. Identifying the mechanism : is there a bank lending channel of monetary transmission in the Netherlands?

    NARCIS (Netherlands)

    Kakes, J

    The paper investigates the role of bank lending in the monetary transmission process in the Netherlands. The Johansen approach is used to identify supply and demand relationships in the credit market, and it is concluded from the short-run dynamics that this market is demand-determined. In this way,

  13. Extracts and compounds active on TRP ion channels from Waldheimia glabra, a ritual medicinal plant from Himalaya.

    Science.gov (United States)

    Giorgi, Annamaria; Bassoli, Angela; Borgonovo, Gigliola; Panseri, Sara; Manzo, Alessandra; Pentimalli, Daniela; Schiano Moriello, Aniello; De Petrocellis, Luciano

    2017-08-15

    Waldheimia glabra (Decne.) Regel is a wild plant from the Himalayan Mountains, commonly known as Smooth Ground Daisy. This plant is traditionally used by local populations in religious rituals (incense) or in traditional herbal medicine to treat skin diseases, headache, joint pain and fever. In literature few data are available on the investigation of this aromatic plant. The present work aims at deepening knowledge about the chemical composition of W. glabra extracts and incense, as well as its activity on TRP ion channels. Extracts and incense of W. glabra were analyzed by using HS-SPME GC/MS, GC/MS and NMR analysis. Tests on the activity of W. glabra extracts and isolated compounds (+)-ludartin 1 and B-ring-homo-tonghaosu 2 on TRP channels were also performed. Some extracts and pure compounds from W. glabra showed an interesting activity in terms of efficacy and potency on rat TRPA1, an ion channel involved in several sensory mechanisms, including pungency, environmental irritation and pain perception. Activity is discussed and compared with that of other known TRPA1 natural agonists with different chemical structures. All compounds showed only a negligible inhibition activity on rat TRPM8 ion channel. Our findings demonstrate that W. glabra is involved in the receptor activation mechanism and therefore represents a new natural product potentially useful in pharmaceutical and agrifood research. Copyright © 2017 Elsevier GmbH. All rights reserved.

  14. Elevated peritoneal expression and estrogen regulation of nociceptive ion channels in endometriosis.

    Science.gov (United States)

    Greaves, Erin; Grieve, Kelsey; Horne, Andrew W; Saunders, Philippa T K

    2014-09-01

    Ovarian suppression is a common treatment for endometriosis-associated pelvic pain. Its exact mechanism of action is poorly understood, although it is assumed to reflect reduced production/action of estrogens. The objective of the study was to measure the expression of mRNAs encoded by nociceptive genes in the peritoneum of women with chronic pelvic pain (CPP) with or without endometriosis and to investigate whether estrogens alter nociceptive gene expression in human sensory neurons. The study was performed using human tissue analysis and cell culture. The study was conducted at a university research institute. Peritoneal biopsies were obtained from women with CPP and endometriosis (n = 12), CPP and no endometriosis (n = 10), and no pain or endometriosis (n = 5). Endometriosis lesions were obtained from women with endometriosis (n = 18). mRNAs encoding ion channels (P2RX3, SCN9A, SCN11A, TRPA1, TRPV1) and the neurotransmitter TAC1 were measured in human tissue samples and in human embryonic stem cell-derived sensory neurons treated with estrogens. TRPV1, TRPA1, and SCN11A mRNAs were significantly higher in the peritoneum from women with endometriosis (P endometriosis lesions (P endometriosis (P endometriosis-associated pain. Strategies directly targeting ion channels may offer an alternative option for the management of CPP.

  15. Modulation of TRP channels by resveratrol and other stilbenoids

    Directory of Open Access Journals (Sweden)

    Yu Lina

    2013-02-01

    Full Text Available Abstract Background Resveratrol (3,5,4’ - trihydroxy-trans-stilbene, a widely distributed natural stilbenoid, was proposed to account for the unique effects of red wine on life span and health. It has been reported to possess various biological and pharmacological activities, such as anti-oxidant, anti-inflammatory, and anti-carcinogenic effects. Here, using whole-cell patch-clamp techniques and behavioral analyses, we investigated whether resveratrol and other stilbenoids can modulate TRP channels in sensory neurons in vitro, and have analgesic effects in vivo. Results We found that resveratrol dose-dependently suppressed the allyl isothiocyanate (AITC-induced currents (IAITC in HEK293 cells that express TRPA1, as well as in rat dorsal root ganglion (DRG neurons. Instead, pinosylvin methyl ether (PME, another derivate of stilbene which has a similar structure to resveratrol, dose-dependently blocked the capsaicin-induced currents (ICAP in HEK293 cells that express TRPV1 as well as in DRG neurons. Interestingly, resveratrol had no inhibitory effect on the ICAP, and PME had no effect on the IAITC. Otherwise, trans-stilbene showed no any effect on IAITC or ICAP. The concentration response curve of AITC showed that resveratrol inhibited the action of TRPA1 not by changing the EC50, but by suppressing the AITC-induced maximum response. By contrast, the inhibition of TRPV1 by PME did not change the capsaicin-induced maximum response but did cause a right shift of the EC50. Moreover, pre-administration of resveratrol suppressed intraplantar injections of AITC-evoked nocifensive behaviors, as well as that PME suppressed capsaicin-evoked one. Conclusions These data suggest that resveratrol and other stilbenoids may have an inhibitory effect on TRP channels. In addition, these stilbenoids modulate TRP channel activity in different ways.

  16. Phosphorylation of the Transient Receptor Potential Ankyrin 1 by Cyclin-dependent Kinase 5 affects Chemo-nociception

    OpenAIRE

    Hall, Bradford E.; Prochazkova, Michaela; Sapio, Matthew R.; Minetos, Paul; Kurochkina, Natalya; Binukumar, B. K.; Amin, Niranjana D.; Terse, Anita; Joseph, John; Raithel, Stephen J.; Mannes, Andrew J.; Pant, Harish C.; Chung, Man-Kyo; Iadarola, Michael J.; Kulkarni, Ashok B.

    2018-01-01

    Cyclin-dependent kinase 5 (Cdk5) is a key neuronal kinase that is upregulated during inflammation, and can subsequently modulate sensitivity to nociceptive stimuli. We conducted an in silico screen for Cdk5 phosphorylation sites within proteins whose expression was enriched in nociceptors and identified the chemo-responsive ion channel Transient Receptor Potential Ankyrin 1 (TRPA1) as a possible Cdk5 substrate. Immunoprecipitated full length TRPA1 was shown to be phosphorylated by Cdk5 and th...

  17. Citral sensing by Transient [corrected] receptor potential channels in dorsal root ganglion neurons.

    Directory of Open Access Journals (Sweden)

    Stephanie C Stotz

    2008-05-01

    Full Text Available Transient receptor potential (TRP ion channels mediate key aspects of taste, smell, pain, temperature sensation, and pheromone detection. To deepen our understanding of TRP channel physiology, we require more diverse pharmacological tools. Citral, a bioactive component of lemongrass, is commonly used as a taste enhancer, as an odorant in perfumes, and as an insect repellent. Here we report that citral activates TRP channels found in sensory neurons (TRPV1 and TRPV3, TRPM8, and TRPA1, and produces long-lasting inhibition of TRPV1-3 and TRPM8, while transiently blocking TRPV4 and TRPA1. Sustained citral inhibition is independent of internal calcium concentration, but is state-dependent, developing only after TRP channel opening. Citral's actions as a partial agonist are not due to cysteine modification of the channels nor are they a consequence of citral's stereoisoforms. The isolated aldehyde and alcohol cis and trans enantiomers (neral, nerol, geranial, and geraniol each reproduce citral's actions. In juvenile rat dorsal root ganglion neurons, prolonged citral inhibition of native TRPV1 channels enabled the separation of TRPV2 and TRPV3 currents. We find that TRPV2 and TRPV3 channels are present in a high proportion of these neurons (94% respond to 2-aminoethyldiphenyl borate, consistent with our immunolabeling experiments and previous in situ hybridization studies. The TRPV1 activation requires residues in transmembrane segments two through four of the voltage-sensor domain, a region previously implicated in capsaicin activation of TRPV1 and analogous menthol activation of TRPM8. Citral's broad spectrum and prolonged sensory inhibition may prove more useful than capsaicin for allodynia, itch, or other types of pain involving superficial sensory nerves and skin.

  18. Citral Sensing by TRANSient Receptor Potential Channels in Dorsal Root Ganglion Neurons

    Science.gov (United States)

    Stotz, Stephanie C.; Vriens, Joris; Martyn, Derek; Clardy, Jon; Clapham, David E.

    2008-01-01

    Transient receptor potential (TRP) ion channels mediate key aspects of taste, smell, pain, temperature sensation, and pheromone detection. To deepen our understanding of TRP channel physiology, we require more diverse pharmacological tools. Citral, a bioactive component of lemongrass, is commonly used as a taste enhancer, as an odorant in perfumes, and as an insect repellent. Here we report that citral activates TRP channels found in sensory neurons (TRPV1 and TRPV3, TRPM8, and TRPA1), and produces long-lasting inhibition of TRPV1–3 and TRPM8, while transiently blocking TRPV4 and TRPA1. Sustained citral inhibition is independent of internal calcium concentration, but is state-dependent, developing only after TRP channel opening. Citral's actions as a partial agonist are not due to cysteine modification of the channels nor are they a consequence of citral's stereoisoforms. The isolated aldehyde and alcohol cis and trans enantiomers (neral, nerol, geranial, and geraniol) each reproduce citral's actions. In juvenile rat dorsal root ganglion neurons, prolonged citral inhibition of native TRPV1 channels enabled the separation of TRPV2 and TRPV3 currents. We find that TRPV2 and TRPV3 channels are present in a high proportion of these neurons (94% respond to 2-aminoethyldiphenyl borate), consistent with our immunolabeling experiments and previous in situ hybridization studies. The TRPV1 activation requires residues in transmembrane segments two through four of the voltage-sensor domain, a region previously implicated in capsaicin activation of TRPV1 and analogous menthol activation of TRPM8. Citral's broad spectrum and prolonged sensory inhibition may prove more useful than capsaicin for allodynia, itch, or other types of pain involving superficial sensory nerves and skin. PMID:18461159

  19. Citral sensing by Transient [corrected] receptor potential channels in dorsal root ganglion neurons.

    Science.gov (United States)

    Stotz, Stephanie C; Vriens, Joris; Martyn, Derek; Clardy, Jon; Clapham, David E

    2008-05-07

    Transient receptor potential (TRP) ion channels mediate key aspects of taste, smell, pain, temperature sensation, and pheromone detection. To deepen our understanding of TRP channel physiology, we require more diverse pharmacological tools. Citral, a bioactive component of lemongrass, is commonly used as a taste enhancer, as an odorant in perfumes, and as an insect repellent. Here we report that citral activates TRP channels found in sensory neurons (TRPV1 and TRPV3, TRPM8, and TRPA1), and produces long-lasting inhibition of TRPV1-3 and TRPM8, while transiently blocking TRPV4 and TRPA1. Sustained citral inhibition is independent of internal calcium concentration, but is state-dependent, developing only after TRP channel opening. Citral's actions as a partial agonist are not due to cysteine modification of the channels nor are they a consequence of citral's stereoisoforms. The isolated aldehyde and alcohol cis and trans enantiomers (neral, nerol, geranial, and geraniol) each reproduce citral's actions. In juvenile rat dorsal root ganglion neurons, prolonged citral inhibition of native TRPV1 channels enabled the separation of TRPV2 and TRPV3 currents. We find that TRPV2 and TRPV3 channels are present in a high proportion of these neurons (94% respond to 2-aminoethyldiphenyl borate), consistent with our immunolabeling experiments and previous in situ hybridization studies. The TRPV1 activation requires residues in transmembrane segments two through four of the voltage-sensor domain, a region previously implicated in capsaicin activation of TRPV1 and analogous menthol activation of TRPM8. Citral's broad spectrum and prolonged sensory inhibition may prove more useful than capsaicin for allodynia, itch, or other types of pain involving superficial sensory nerves and skin.

  20. Using Remote Sensing and High-Resolution Digital Elevation Models to Identify Potential Erosional Hotspots Along River Channels During High Discharge Storm Events

    Science.gov (United States)

    Orland, E. D.; Amidon, W. H.

    2017-12-01

    As global warming intensifies, large precipitation events and associated floods are becoming increasingly common. Channel adjustments during floods can occur by both erosion and deposition of sediment, often damaging infrastructure in the process. There is thus a need for predictive models that can help managers identify river reaches that are most prone to adjustment during storms. Because rivers in post-glacial landscapes often flow over a mixture of bedrock and alluvial substrates, the identification of bedrock vs. alluvial channel reaches is an important first step in predicting vulnerability to channel adjustment during flood events, especially because bedrock channels are unlikely to adjust significantly, even during floods. This study develops a semi-automated approach to predicting channel substrate using a high-resolution LiDAR-derived digital elevation model (DEM). The study area is the Middlebury River in Middlebury, VT-a well-studied watershed with a wide variety of channel substrates, including reaches with documented channel adjustments during recent flooding events. Multiple metrics were considered for reference—such as channel width and drainage area—but the study utilized channel slope as a key parameter for identifying morphological variations within the Middlebury River. Using data extracted from the DEM, a power law was fit to selected slope and drainage area values for each branch in order to model idealized slope-drainage area relationships, which were then compared with measured slope-drainage area relationships. Differences in measured slope minus predicted slope (called delta-slope) are shown to help predict river channel substrate. Compared with field observations, higher delta-slope values correlate with more stable, boulder rich channels or bedrock gorges; conversely the lowest delta-slope values correlate with flat, sediment rich alluvial channels. The delta-slope metric thus serves as a reliable first-order predictor of channel

  1. A Novel KCNJ2 Mutation Identified in an Autistic Proband Affects the Single Channel Properties of Kir2.1

    Directory of Open Access Journals (Sweden)

    Anna Binda

    2018-03-01

    Full Text Available Inwardly rectifying potassium channels (Kir have been historically associated to several cardiovascular disorders. In particular, loss-of-function mutations in the Kir2.1 channel have been reported in cases affected by Andersen-Tawil syndrome while gain-of-function mutations in the same channel cause the short QT3 syndrome. Recently, a missense mutation in Kir2.1, as well as mutations in the Kir4.1, were reported to be involved in autism spectrum disorders (ASDs suggesting a role of potassium channels in these diseases and introducing the idea of the existence of K+ channel ASDs. Here, we report the identification in an Italian affected family of a novel missense mutation (p.Phe58Ser in the KCNJ2 gene detected in heterozygosity in a proband affected by autism and borderline for short QT syndrome type 3. The mutation is located in the N-terminal region of the gene coding for the Kir2.1 channel and in particular in a very conserved domain. In vitro assays demonstrated that this mutation results in an increase of the channel conductance and in its open probability. This gain-of-function of the protein is consistent with the autistic phenotype, which is normally associated to an altered neuronal excitability.

  2. TRP channel functions in the gastrointestinal tract.

    Science.gov (United States)

    Yu, Xiaoyun; Yu, Mingran; Liu, Yingzhe; Yu, Shaoyong

    2016-05-01

    Transient receptor potential (TRP) channels are predominantly distributed in both somatic and visceral sensory nervous systems and play a crucial role in sensory transduction. As the largest visceral organ system, the gastrointestinal (GI) tract frequently accommodates external inputs, which stimulate sensory nerves to initiate and coordinate sensory and motor functions in order to digest and absorb nutrients. Meanwhile, the sensory nerves in the GI tract are also able to detect potential tissue damage by responding to noxious irritants. This nocifensive function is mediated through specific ion channels and receptors expressed in a subpopulation of spinal and vagal afferent nerve called nociceptor. In the last 18 years, our understanding of TRP channel expression and function in GI sensory nervous system has been continuously improved. In this review, we focus on the expressions and functions of TRPV1, TRPA1, and TRPM8 in primary extrinsic afferent nerves innervated in the esophagus, stomach, intestine, and colon and briefly discuss their potential roles in relevant GI disorders.

  3. Acid-sensing ion channels and transient-receptor potential ion channels in zebrafish taste buds.

    Science.gov (United States)

    Levanti, M; Randazzo, B; Viña, E; Montalbano, G; Garcia-Suarez, O; Germanà, A; Vega, J A; Abbate, F

    2016-09-01

    Sensory information from the environment is required for life and survival, and it is detected by specialized cells which together make up the sensory system. The fish sensory system includes specialized organs that are able to detect mechanical and chemical stimuli. In particular, taste buds are small organs located on the tongue in terrestrial vertebrates that function in the perception of taste. In fish, taste buds occur on the lips, the flanks, and the caudal (tail) fins of some species and on the barbels of others. In fish taste receptor cells, different classes of ion channels have been detected which, like in mammals, presumably participate in the detection and/or transduction of chemical gustatory signals. However, since some of these ion channels are involved in the detection of additional sensory modalities, it can be hypothesized that taste cells sense stimuli other than those specific for taste. This mini-review summarizes current knowledge on the presence of transient-receptor potential (TRP) and acid-sensing (ASIC) ion channels in the taste buds of teleosts, especially adult zebrafish. Up to now ASIC4, TRPC2, TRPA1, TRPV1 and TRPV4 ion channels have been found in the sensory cells, while ASIC2 was detected in the nerves supplying the taste buds. Copyright © 2016 Elsevier GmbH. All rights reserved.

  4. The stress protein heat shock cognate 70 (Hsc70) inhibits the Transient Receptor Potential Vanilloid type 1 (TRPV1) channel.

    Science.gov (United States)

    Iftinca, Mircea; Flynn, Robyn; Basso, Lilian; Melo, Helvira; Aboushousha, Reem; Taylor, Lauren; Altier, Christophe

    2016-01-01

    Specialized cellular defense mechanisms prevent damage from chemical, biological, and physical hazards. The heat shock proteins have been recognized as key chaperones that maintain cell survival against a variety of exogenous and endogenous stress signals including noxious temperature. However, the role of heat shock proteins in nociception remains poorly understood. We carried out an expression analysis of the constitutively expressed 70 kDa heat-shock cognate protein, a member of the stress-induced HSP70 family in lumbar dorsal root ganglia from a mouse model of Complete Freund's Adjuvant-induced chronic inflammatory pain. We used immunolabeling of dorsal root ganglion neurons, behavioral analysis and patch clamp electrophysiology in both dorsal root ganglion neurons and HEK cells transfected with Hsc70 and Transient Receptor Potential Channels to examine their functional interaction in heat shock stress condition. We report an increase in protein levels of Hsc70 in mouse dorsal root ganglia, 3 days post Complete Freund's Adjuvant injection in the hind paw. Immunostaining of Hsc70 was observed in most of the dorsal root ganglion neurons, including the small size nociceptors immunoreactive to the TRPV1 channel. Standard whole-cell patch-clamp technique was used to record Transient Receptor Potential Vanilloid type 1 current after exposure to heat shock. We found that capsaicin-evoked currents are inhibited by heat shock in dorsal root ganglion neurons and transfected HEK cells expressing Hsc70 and TRPV1. Blocking Hsc70 with matrine or spergualin compounds prevented heat shock-induced inhibition of the channel. We also found that, in contrast to TRPV1, both the cold sensor channels TRPA1 and TRPM8 were unresponsive to heat shock stress. Finally, we show that inhibition of TRPV1 depends on the ATPase activity of Hsc70 and involves the rho-associated protein kinase. Our work identified Hsc70 and its ATPase activity as a central cofactor of TRPV1 channel function

  5. Phytochemicals from Ruta graveolens Activate TAS2R Bitter Taste Receptors and TRP Channels Involved in Gustation and Nociception

    Directory of Open Access Journals (Sweden)

    Giuseppe Mancuso

    2015-10-01

    Full Text Available Ruta graveolens (rue is a spontaneous plant in the Mediterranean area with a strong aroma and a very intense bitter taste, used in gastronomy and in folk medicine. From the leaves, stems and fruits of rue, we isolated rutin, rutamarin, three furanocoumarins, two quinolinic alkaloids, a dicoumarin and two long chain ketones. Bitter taste and chemesthetic properties have been evaluated by in vitro assays with twenty receptors of the TAS2R family and four TRP ion channels involved in gustation and nociception. Among the alkaloids, skimmianine was active as a specific agonist of T2R14, whereas kokusaginin did not activate any of the tested receptors. The furanocoumarins activates TAS2R10, 14, and 49 with different degrees of selectivity, as well as the TRPA1 somatosensory ion channel. Rutamarin is an agonist of TRPM5 and TRPV1 and a strong antagonist of TRPM8 ion channels.

  6. Phytochemicals from Ruta graveolens Activate TAS2R Bitter Taste Receptors and TRP Channels Involved in Gustation and Nociception.

    Science.gov (United States)

    Mancuso, Giuseppe; Borgonovo, Gigliola; Scaglioni, Leonardo; Bassoli, Angela

    2015-10-16

    Ruta graveolens (rue) is a spontaneous plant in the Mediterranean area with a strong aroma and a very intense bitter taste, used in gastronomy and in folk medicine. From the leaves, stems and fruits of rue, we isolated rutin, rutamarin, three furanocoumarins, two quinolinic alkaloids, a dicoumarin and two long chain ketones. Bitter taste and chemesthetic properties have been evaluated by in vitro assays with twenty receptors of the TAS2R family and four TRP ion channels involved in gustation and nociception. Among the alkaloids, skimmianine was active as a specific agonist of T2R14, whereas kokusaginin did not activate any of the tested receptors. The furanocoumarins activates TAS2R10, 14, and 49 with different degrees of selectivity, as well as the TRPA1 somatosensory ion channel. Rutamarin is an agonist of TRPM5 and TRPV1 and a strong antagonist of TRPM8 ion channels.

  7. Identifying cochlear implant channels with poor electrode-neuron interface: electrically-evoked auditory brainstem responses measured with the partial tripolar configuration

    Science.gov (United States)

    Bierer, Julie Arenberg; Faulkner, Kathleen F.; Tremblay, Kelly L.

    2011-01-01

    obtained with both the monopolar and partial tripolar configurations. The Wave V amplitude growth functions with increasing stimulus level showed the predicted effect of shallower growth for the partial tripolar than for the monopolar configuration, but this was observed only for the low threshold channel. In contrast, high-threshold channels showed the opposite effect; steeper growth functions were seen for the partial tripolar configuration. Conclusions These results suggest that behavioral thresholds or EABRs measured with a restricted stimulus can be used to identify potentially impaired cochlear implant channels. Channels having high thresholds and steep growth functions would likely not activate the appropriate spatially restricted region of the cochlea, leading to suboptimal perception. As a clinical tool, quick identification of impaired channels could lead to patient-specific mapping strategies and result in improved speech and music perception. PMID:21178633

  8. Identifying cochlear implant channels with poor electrode-neuron interfaces: electrically evoked auditory brain stem responses measured with the partial tripolar configuration.

    Science.gov (United States)

    Bierer, Julie Arenberg; Faulkner, Kathleen F; Tremblay, Kelly L

    2011-01-01

    tripolar configurations. The Wave V amplitude growth functions with increasing stimulus level showed the predicted effect of shallower growth for the partial tripolar than for the monopolar configuration, but this was observed only for the low-threshold channels. In contrast, high-threshold channels showed the opposite effect; steeper growth functions were seen for the partial tripolar configuration. These results suggest that behavioral thresholds or EABRs measured with a restricted stimulus can be used to identify potentially impaired cochlear implant channels. Channels having high thresholds and steep growth functions would likely not activate the appropriate spatially restricted region of the cochlea, leading to suboptimal perception. As a clinical tool, quick identification of impaired channels could lead to patient-specific mapping strategies and result in improved speech and music perception.

  9. A structural view of ligand-dependent activation in thermoTRP channels

    Directory of Open Access Journals (Sweden)

    Ximena eSteinberg

    2014-05-01

    Full Text Available Transient Receptor Potential (TRP proteins are a large family of ion channels, grouped intoseven sub-families. Although great advances have been made regarding the activation andmodulation of TRP channel activity, detailed molecular mechanisms governing TRPchannel gating are still needed. Sensitive to electric, chemical, mechanical, and thermalcues, TRP channels are tightly associated with the detection and integration of sensoryinput, emerging as a model to study the polymodal activation of ion channel proteins.Among TRP channels, the temperature-activated kind constitute a subgroup by itself,formed by Vanilloid receptors 1-4, Melastatin receptors 2, 4, 5 and 8, TRPC5, and TRPA1.Some of the so-called thermoTRP channels participate in the detection of noxious stimulimaking them an interesting pharmacological target for the treatment of pain. However, thepoor specificity of the compounds available in the market represents an important obstacleto overcome. Understanding the molecular mechanics underlying ligand-dependentmodulation of TRP channels may help with the rational design of novel syntheticanalgesics. The present review focuses on the structural basis of ligand-dependentactivation of TRPV1 and TRPM8 channels. Special attention is drawn to the dissection ofligand-binding sites within TRPV1, PIP 2 -dependent modulation of TRP channels, and thestructure of natural and synthetic ligands.

  10. Purification and subunit structure of a putative K sup + -channel protein identified by its binding properties for dendrotoxin I

    Energy Technology Data Exchange (ETDEWEB)

    Rehm, H.; Lazdunski, M. (Centre National de la Recherche Scientifique, Nice (France))

    1988-07-01

    The binding protein for the K{sup +}-channel toxin dendrotoxin I was purified from a detergent extract of rat brain membranes. The purification procedure utilized chromatography on DEAE-Trisacryl, affinity chromatography on a dendrotoxin-I-Aca 22 column, and wheat germ agglutinin-Affigel 10 with a final 3,800- to 4,600-fold enrichment and a recovery of 8-16%. The high affinity (K{sub d}, 40-100 pM) and specificity of the binding site are retained throughout the purification procedure. Analysis of the purified material on silver-stained NaDodSO{sub 4}/polyacrylamide gel revealed three bands of M{sub r} 76,000-80,000, 38,000 and 35,000. Interestingly, the binding site for {sup 125}I-labeled mast cell degranulating peptide, another putative K{sup +}-channel ligand from bee venom, which induces long-term potentiation in hippocampus, seems to reside on the same protein complex, as both binding sites copurify through the entire purification protocol.

  11. Purification and subunit structure of a putative K+-channel protein identified by its binding properties for dendrotoxin I

    International Nuclear Information System (INIS)

    Rehm, H.; Lazdunski, M.

    1988-01-01

    The binding protein for the K + -channel toxin dendrotoxin I was purified from a detergent extract of rat brain membranes. The purification procedure utilized chromatography on DEAE-Trisacryl, affinity chromatography on a dendrotoxin-I-Aca 22 column, and wheat germ agglutinin-Affigel 10 with a final 3,800- to 4,600-fold enrichment and a recovery of 8-16%. The high affinity (K d , 40-100 pM) and specificity of the binding site are retained throughout the purification procedure. Analysis of the purified material on silver-stained NaDodSO 4 /polyacrylamide gel revealed three bands of M r 76,000-80,000, 38,000 and 35,000. Interestingly, the binding site for 125 I-labeled mast cell degranulating peptide, another putative K + -channel ligand from bee venom, which induces long-term potentiation in hippocampus, seems to reside on the same protein complex, as both binding sites copurify through the entire purification protocol

  12. Application of amphipols for structure-functional analysis of TRP channels.

    Science.gov (United States)

    Huynh, Kevin W; Cohen, Matthew R; Moiseenkova-Bell, Vera Y

    2014-10-01

    Amphipathic polymers (amphipols), such as A8-35 and SApol, are a new tool for stabilizing integral membrane proteins in detergent-free conditions for structural and functional studies. Transient receptor potential (TRP) ion channels function as tetrameric protein complexes in a diverse range of cellular processes including sensory transduction. Mammalian TRP channels share ~20 % sequence similarity and are categorized into six subfamilies: TRPC (canonical), TRPV (vanilloid), TRPA (ankyrin), TRPM (melastatin), TRPP (polycystin), and TRPML (mucolipin). Due to the inherent difficulties in purifying eukaryotic membrane proteins, structural studies of TRP channels have been limited. Recently, A8-35 was essential in resolving the molecular architecture of the nociceptor TRPA1 and led to the determination of a high-resolution structure of the thermosensitive TRPV1 channel by cryo-EM. Newly developed maltose-neopentyl glycol (MNG) detergents have also proven to be useful in stabilizing TRP channels for structural analysis. In this review, we will discuss the impacts of amphipols and MNG detergents on structural studies of TRP channels by cryo-EM. We will compare how A8-35 and MNG detergents interact with the hydrophobic transmembrane domains of TRP channels. In addition, we will discuss what these cryo-EM studies reveal on the importance of screening different types of surfactants toward determining high-resolution structures of TRP channels.

  13. Substrate Trapping in Crystals of the Thiolase OleA Identifies Three Channels That Enable Long Chain Olefin Biosynthesis

    Energy Technology Data Exchange (ETDEWEB)

    Goblirsch, Brandon R.; Jensen, Matthew R.; Mohamed, Fatuma A.; Wackett, Lawrence P.; Wilmot, Carrie M.

    2016-11-04

    Phylogenetically diverse microbes that produce long chain, olefinic hydrocarbons have received much attention as possible sources of renewable energy biocatalysts. One enzyme that is critical for this process is OleA, a thiolase superfamily enzyme that condenses two fatty acyl-CoA substrates to produce a β-ketoacid product and initiates the biosynthesis of long chain olefins in bacteria. Thiolases typically utilize a ping-pong mechanism centered on an active site cysteine residue. Reaction with the first substrate produces a covalent cysteine-thioester tethered acyl group that is transferred to the second substrate through formation of a carbon-carbon bond. Although the basics of thiolase chemistry are precedented, the mechanism by which OleA accommodates two substrates with extended carbon chains and a coenzyme moiety—unusual for a thiolase—are unknown. Gaining insights into this process could enable manipulation of the system for large scale olefin production with hydrocarbon chains lengths equivalent to those of fossil fuels. In this study, mutagenesis of the active site cysteine in Xanthomonas campestris OleA (Cys143) enabled trapping of two catalytically relevant species in crystals. In the resulting structures, long chain alkyl groups (C12 and C14) and phosphopantetheinate define three substrate channels in a T-shaped configuration, explaining how OleA coordinates its two substrates and product. The C143A OleA co-crystal structure possesses a single bound acyl-CoA representing the Michaelis complex with the first substrate, whereas the C143S co-crystal structure contains both acyl-CoA and fatty acid, defining how a second substrate binds to the acyl-enzyme intermediate. An active site glutamate (Gluβ117) is positioned to deprotonate bound acyl-CoA and initiate carbon-carbon bond formation.

  14. Substrate Trapping in Crystals of the Thiolase OleA Identifies Three Channels That Enable Long Chain Olefin Biosynthesis.

    Science.gov (United States)

    Goblirsch, Brandon R; Jensen, Matthew R; Mohamed, Fatuma A; Wackett, Lawrence P; Wilmot, Carrie M

    2016-12-23

    Phylogenetically diverse microbes that produce long chain, olefinic hydrocarbons have received much attention as possible sources of renewable energy biocatalysts. One enzyme that is critical for this process is OleA, a thiolase superfamily enzyme that condenses two fatty acyl-CoA substrates to produce a β-ketoacid product and initiates the biosynthesis of long chain olefins in bacteria. Thiolases typically utilize a ping-pong mechanism centered on an active site cysteine residue. Reaction with the first substrate produces a covalent cysteine-thioester tethered acyl group that is transferred to the second substrate through formation of a carbon-carbon bond. Although the basics of thiolase chemistry are precedented, the mechanism by which OleA accommodates two substrates with extended carbon chains and a coenzyme moiety-unusual for a thiolase-are unknown. Gaining insights into this process could enable manipulation of the system for large scale olefin production with hydrocarbon chains lengths equivalent to those of fossil fuels. In this study, mutagenesis of the active site cysteine in Xanthomonas campestris OleA (Cys 143 ) enabled trapping of two catalytically relevant species in crystals. In the resulting structures, long chain alkyl groups (C 12 and C 14 ) and phosphopantetheinate define three substrate channels in a T-shaped configuration, explaining how OleA coordinates its two substrates and product. The C143A OleA co-crystal structure possesses a single bound acyl-CoA representing the Michaelis complex with the first substrate, whereas the C143S co-crystal structure contains both acyl-CoA and fatty acid, defining how a second substrate binds to the acyl-enzyme intermediate. An active site glutamate (Gluβ 117 ) is positioned to deprotonate bound acyl-CoA and initiate carbon-carbon bond formation. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  15. Substrate Trapping in Crystals of the Thiolase OleA Identifies Three Channels That Enable Long Chain Olefin Biosynthesis*

    Science.gov (United States)

    Goblirsch, Brandon R.; Jensen, Matthew R.; Mohamed, Fatuma A.; Wackett, Lawrence P.; Wilmot, Carrie M.

    2016-01-01

    Phylogenetically diverse microbes that produce long chain, olefinic hydrocarbons have received much attention as possible sources of renewable energy biocatalysts. One enzyme that is critical for this process is OleA, a thiolase superfamily enzyme that condenses two fatty acyl-CoA substrates to produce a β-ketoacid product and initiates the biosynthesis of long chain olefins in bacteria. Thiolases typically utilize a ping-pong mechanism centered on an active site cysteine residue. Reaction with the first substrate produces a covalent cysteine-thioester tethered acyl group that is transferred to the second substrate through formation of a carbon-carbon bond. Although the basics of thiolase chemistry are precedented, the mechanism by which OleA accommodates two substrates with extended carbon chains and a coenzyme moiety—unusual for a thiolase—are unknown. Gaining insights into this process could enable manipulation of the system for large scale olefin production with hydrocarbon chains lengths equivalent to those of fossil fuels. In this study, mutagenesis of the active site cysteine in Xanthomonas campestris OleA (Cys143) enabled trapping of two catalytically relevant species in crystals. In the resulting structures, long chain alkyl groups (C12 and C14) and phosphopantetheinate define three substrate channels in a T-shaped configuration, explaining how OleA coordinates its two substrates and product. The C143A OleA co-crystal structure possesses a single bound acyl-CoA representing the Michaelis complex with the first substrate, whereas the C143S co-crystal structure contains both acyl-CoA and fatty acid, defining how a second substrate binds to the acyl-enzyme intermediate. An active site glutamate (Gluβ117) is positioned to deprotonate bound acyl-CoA and initiate carbon-carbon bond formation. PMID:27815501

  16. Evidence for the functional involvement of members of the TRP channel family in the uptake of Na(+) and NH4 (+) by the ruminal epithelium.

    Science.gov (United States)

    Rosendahl, Julia; Braun, Hannah S; Schrapers, Katharina T; Martens, Holger; Stumpff, Friederike

    2016-08-01

    Large quantities of protein are degraded in the fermentative parts of the gut to ammonia, which is absorbed, detoxified to urea, and excreted, leading to formation of nitrogenous compounds such as N2O that are associated with global warming. In ruminants, channel-mediated uptake of NH4 (+) from the rumen predominates. The molecular identity of these channels remains to be clarified. Ruminal cells and epithelia from cows and sheep were investigated using patch clamp, Ussing chamber, microelectrode techniques, and qPCR. In patch clamp experiments, bovine ruminal epithelial cells expressed a conductance for NH4 (+) that could be blocked in a voltage-dependent manner by divalent cations. In the native epithelium, NH4 (+) depolarized the apical potential, acidified the cytosol and induced a rise in short-circuit current (I sc) that persisted after the removal of Na(+), was blocked by verapamil, enhanced by the removal of divalent cations, and was sensitive to certain transient receptor potential (TRP) channel modulators. Menthol or thymol stimulated the I sc in Na(+) or NH4 (+) containing solutions in a dose-dependent manner and modulated transepithelial Ca(2+) fluxes. On the level of messenger RNA (mRNA), ovine and bovine ruminal epithelium expressed TRPA1, TRPV3, TRPV4, TRPM6, and TRPM7, with any expression of TRPV6 marginal. No bands were detected for TRPV1, TRPV5, or TRPM8. Functional and molecular biological data suggest that the transport of NH4 (+), Na(+), and Ca(2+) across the rumen involves TRP channels, with TRPV3 and TRPA1 emerging as prime candidate genes. TRP channels may also contribute to the transport of NH4 (+) across other epithelia.

  17. Genetic and bibliographic information: Trpa1 [GenLibi

    Lifescience Database Archive (English)

    Full Text Available l Conditions, Signs and Symptoms (C23) > Signs and Symptoms (C23.888) > Neurologic Manifestations (C23.888.5...92) > Pain (C23.888.592.612) Pathological Conditions, Signs and Symptoms (C23) > Signs and Symptoms (C23.888) > Pain (C23.888.646) 06A0151869 ...

  18. Distribution of Ordinary High Water Mark (OHWM) Indicators and Their Reliability in Identifying the Limits of "Waters of the United States" in Arid Southwestern Channels

    National Research Council Canada - National Science Library

    Lichvar, Robert W; Finnegan, David C; Ericsson, Michael P; Ochs, Walter

    2006-01-01

    .... COE hydrologic models require detailed site information for rainfall and stream flow characteristics, as well as on-site surveys to determine channel morphology, width, fluvial patterns, slope...

  19. Functional Properties of a Newly Identified C-terminal Splice Variant of Cav1.3 L-type Ca2+ Channels*

    Science.gov (United States)

    Bock, Gabriella; Gebhart, Mathias; Scharinger, Anja; Jangsangthong, Wanchana; Busquet, Perrine; Poggiani, Chiara; Sartori, Simone; Mangoni, Matteo E.; Sinnegger-Brauns, Martina J.; Herzig, Stefan; Striessnig, Jörg; Koschak, Alexandra

    2011-01-01

    An intramolecular interaction between a distal (DCRD) and a proximal regulatory domain (PCRD) within the C terminus of long Cav1.3 L-type Ca2+ channels (Cav1.3L) is a major determinant of their voltage- and Ca2+-dependent gating kinetics. Removal of these regulatory domains by alternative splicing generates Cav1.342A channels that activate at a more negative voltage range and exhibit more pronounced Ca2+-dependent inactivation. Here we describe the discovery of a novel short splice variant (Cav1.343S) that is expressed at high levels in the brain but not in the heart. It lacks the DCRD but, in contrast to Cav1.342A, still contains PCRD. When expressed together with α2δ1 and β3 subunits in tsA-201 cells, Cav1.343S also activated at more negative voltages like Cav1.342A but Ca2+-dependent inactivation was less pronounced. Single channel recordings revealed much higher channel open probabilities for both short splice variants as compared with Cav1.3L. The presence of the proximal C terminus in Cav1.343S channels preserved their modulation by distal C terminus-containing Cav1.3- and Cav1.2-derived C-terminal peptides. Removal of the C-terminal modulation by alternative splicing also induced a faster decay of Ca2+ influx during electrical activities mimicking trains of neuronal action potentials. Our findings extend the spectrum of functionally diverse Cav1.3 L-type channels produced by tissue-specific alternative splicing. This diversity may help to fine tune Ca2+ channel signaling and, in the case of short variants lacking a functional C-terminal modulation, prevent excessive Ca2+ accumulation during burst firing in neurons. This may be especially important in neurons that are affected by Ca2+-induced neurodegenerative processes. PMID:21998310

  20. Functional properties of a newly identified C-terminal splice variant of Cav1.3 L-type Ca2+ channels.

    Science.gov (United States)

    Bock, Gabriella; Gebhart, Mathias; Scharinger, Anja; Jangsangthong, Wanchana; Busquet, Perrine; Poggiani, Chiara; Sartori, Simone; Mangoni, Matteo E; Sinnegger-Brauns, Martina J; Herzig, Stefan; Striessnig, Jörg; Koschak, Alexandra

    2011-12-09

    An intramolecular interaction between a distal (DCRD) and a proximal regulatory domain (PCRD) within the C terminus of long Ca(v)1.3 L-type Ca(2+) channels (Ca(v)1.3(L)) is a major determinant of their voltage- and Ca(2+)-dependent gating kinetics. Removal of these regulatory domains by alternative splicing generates Ca(v)1.3(42A) channels that activate at a more negative voltage range and exhibit more pronounced Ca(2+)-dependent inactivation. Here we describe the discovery of a novel short splice variant (Ca(v)1.3(43S)) that is expressed at high levels in the brain but not in the heart. It lacks the DCRD but, in contrast to Ca(v)1.3(42A), still contains PCRD. When expressed together with α2δ1 and β3 subunits in tsA-201 cells, Ca(v)1.3(43S) also activated at more negative voltages like Ca(v)1.3(42A) but Ca(2+)-dependent inactivation was less pronounced. Single channel recordings revealed much higher channel open probabilities for both short splice variants as compared with Ca(v)1.3(L). The presence of the proximal C terminus in Ca(v)1.3(43S) channels preserved their modulation by distal C terminus-containing Ca(v)1.3- and Ca(v)1.2-derived C-terminal peptides. Removal of the C-terminal modulation by alternative splicing also induced a faster decay of Ca(2+) influx during electrical activities mimicking trains of neuronal action potentials. Our findings extend the spectrum of functionally diverse Ca(v)1.3 L-type channels produced by tissue-specific alternative splicing. This diversity may help to fine tune Ca(2+) channel signaling and, in the case of short variants lacking a functional C-terminal modulation, prevent excessive Ca(2+) accumulation during burst firing in neurons. This may be especially important in neurons that are affected by Ca(2+)-induced neurodegenerative processes.

  1. TRP channels and traffic-related environmental pollution-induced pulmonary disease.

    Science.gov (United States)

    Akopian, Armen N; Fanick, E Robert; Brooks, Edward G

    2016-05-01

    Environmental pollutant exposures are major risk factors for adverse health outcomes, with increased morbidity and mortality in humans. Diesel exhaust (DE) is one of the major harmful components of traffic-related air pollution. Exposure to DE affects several physiological systems, including the airways, and pulmonary diseases are increased in highly populated urban areas. Hence, there are urgent needs to (1) create newer and lesser polluting fuels, (2) improve exhaust aftertreatments and reduce emissions, and (3) understand mechanisms of actions for toxic effects of both conventional and cleaner diesel fuels on the lungs. These steps could aid the development of diagnostics and interventions to prevent the negative impact of traffic-related air pollution on the pulmonary system. Exhaust from conventional, and to a lesser extent, clean fuels, contains particulate matter (PM) and more than 400 additional chemical constituents. The major toxic constituents are nitrogen oxides (NOx) and polycyclic aromatic hydrocarbons (PAHs). PM and PAHs could potentially act via transient receptor potential (TRP) channels. In this review, we will first discuss the associations between DE from conventional as well as clean fuel technologies and acute and chronic airway inflammation. We will then review possible activation and/or potentiation of TRP vanilloid type 1 (TRPV1) and ankyrin 1 (TRPA1) channels by PM and PAHs. Finally, we will discuss and summarize recent findings on the mechanisms whereby TRPs could control the link between DE and airway inflammation, which is a primary determinant leading to pulmonary disease.

  2. TRP and ASIC channels mediate the antinociceptive effect of citronellyl acetate.

    Science.gov (United States)

    Rios, Emiliano Ricardo Vasconcelos; Rocha, Nayrton Flávio Moura; Carvalho, Alyne Mara Rodrigues; Vasconcelos, Leonardo Freire; Dias, Marília Leite; de Sousa, Damião Pergentino; de Sousa, Francisca Cléa Florenço; Fonteles, Marta Maria de França

    2013-05-25

    Citronellyl acetate (CAT), a monoterpene product of the secondary metabolism of plants, has been shown in the literature to possess several different biological activities. However, no antinociceptive abilities have yet been discussed. Here, we used acute pain animal models to describe the antinociceptive action of CAT. The acetic acid-induced writhing test and the paw-licking test, in which paw licking was induced by glutamate and formalin, were performed to evaluate the antinociceptive action of CAT and to determine the involvement of PKC, PKA, TRPV1, TRPA1, TRPM8 and ASIC in its antinociceptive mechanism. To do so, we induced paw-linking using agonists. CAT was administered intragastrically (25, 50, 75, 100 and 200 mg/kg), and the two higher doses caused antinociceptive effects in the acetic acid model; the highest dose reduced pain for 4h after it was administered (200 mg/kg). In the formalin test, two doses of CAT promoted antinociception in both the early and later phases of the test. The glutamate test showed that its receptors are involved in the antinociceptive mechanism of CAT. Pretreatment with CAT did not alter locomotor activity or motor coordination. In an investigation into the participation of TRP channels and ASICs in CAT's antinociceptive mechanism, we used capsaicin (2.2 μg/paw), cinnamaldehyde (10 mmol/paw), menthol (1.2 mmol/paw) and acidified saline (2% acetic acid, pH 1.98). The results showed that TRPV1, TRPM8 and ASIC, but not TRPA1, are involved in the antinociceptive mechanism. Finally, the involvement of PKC and PKA was also studied, and we showed that both play a role in the antinociceptive mechanism of CAT. The results of this work contribute information regarding the antinociceptive properties of CAT on acute pain and show that, at least in part, TRPV1, TRPM8, ASIC, glutamate receptors, PKC and PKA participate in CAT's antinociceptive mechanism. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  3. Transient receptor potential channels encode volatile chemicals sensed by rat trigeminal ganglion neurons.

    Directory of Open Access Journals (Sweden)

    Matthias Lübbert

    Full Text Available Primary sensory afferents of the dorsal root and trigeminal ganglia constantly transmit sensory information depicting the individual's physical and chemical environment to higher brain regions. Beyond the typical trigeminal stimuli (e.g. irritants, environmental stimuli comprise a plethora of volatile chemicals with olfactory components (odorants. In spite of a complete loss of their sense of smell, anosmic patients may retain the ability to roughly discriminate between different volatile compounds. While the detailed mechanisms remain elusive, sensory structures belonging to the trigeminal system seem to be responsible for this phenomenon. In order to gain a better understanding of the mechanisms underlying the activation of the trigeminal system by volatile chemicals, we investigated odorant-induced membrane potential changes in cultured rat trigeminal neurons induced by the odorants vanillin, heliotropyl acetone, helional, and geraniol. We observed the dose-dependent depolarization of trigeminal neurons upon application of these substances occurring in a stimulus-specific manner and could show that distinct neuronal populations respond to different odorants. Using specific antagonists, we found evidence that TRPA1, TRPM8, and/or TRPV1 contribute to the activation. In order to further test this hypothesis, we used recombinantly expressed rat and human variants of these channels to investigate whether they are indeed activated by the odorants tested. We additionally found that the odorants dose-dependently inhibit two-pore potassium channels TASK1 and TASK3 heterologously expressed In Xenopus laevis oocytes. We suggest that the capability of various odorants to activate different TRP channels and to inhibit potassium channels causes neuronal depolarization and activation of distinct subpopulations of trigeminal sensory neurons, forming the basis for a specific representation of volatile chemicals in the trigeminal ganglia.

  4. Systematic and quantitative mRNA expression analysis of TRP channel genes at the single trigeminal and dorsal root ganglion level in mouse

    Directory of Open Access Journals (Sweden)

    Vandewauw Ine

    2013-02-01

    Full Text Available Abstract Background Somatosensory nerve fibres arising from cell bodies within the trigeminal ganglia (TG in the head and from a string of dorsal root ganglia (DRG located lateral to the spinal cord convey endogenous and environmental stimuli to the central nervous system. Although several members of the transient receptor potential (TRP superfamily of cation channels have been implicated in somatosensation, the expression levels of TRP channel genes in the individual sensory ganglia have never been systematically studied. Results Here, we used quantitative real-time PCR to analyse and compare mRNA expression of all TRP channels in TG and individual DRGs from 27 anatomically defined segments of the spinal cord of the mouse. At the mRNA level, 17 of the 28 TRP channel genes, TRPA1, TRPC1, TRPC3, TRPC4, TRPC5, TRPM2, TRPM3, TRPM4, TRPM5, TRPM6, TRPM7, TRPM8, TRPV1, TRPV2, TRPV4, TRPML1 and TRPP2, were detectable in every tested ganglion. Notably, four TRP channels, TRPC4, TRPM4, TRPM8 and TRPV1, showed statistically significant variation in mRNA levels between DRGs from different segments, suggesting ganglion-specific regulation of TRP channel gene expression. These ganglion-to-ganglion differences in TRP channel transcript levels may contribute to the variability in sensory responses in functional studies. Conclusions We developed, compared and refined techniques to quantitatively analyse the relative mRNA expression of all TRP channel genes at the single ganglion level. This study also provides for the first time a comparative mRNA distribution profile in TG and DRG along the entire vertebral column for the mammalian TRP channel family.

  5. Measurement of the Top Quark Pair Production Cross-Section in the Dilepton Channel Using Lepton Plus Track Selection and Identified B-Jets

    Energy Technology Data Exchange (ETDEWEB)

    Spreitzer, Teresa [Univ. of Toronto, ON (Canada)

    2008-01-01

    Using 1.0 fb-1 of data collected by the collider detector at fermilab (CDF) from run II of the fermilab tevatron, we measure the t$\\bar{t}$ production cross-section in events with two leptons, significant missing transverse energy, and ≥ 2 jets, at least one of which is identified as a b-jet.

  6. Ion channels in plants.

    Science.gov (United States)

    Hedrich, Rainer

    2012-10-01

    Since the first recordings of single potassium channel activities in the plasma membrane of guard cells more than 25 years ago, patch-clamp studies discovered a variety of ion channels in all cell types and plant species under inspection. Their properties differed in a cell type- and cell membrane-dependent manner. Guard cells, for which the existence of plant potassium channels was initially documented, advanced to a versatile model system for studying plant ion channel structure, function, and physiology. Interestingly, one of the first identified potassium-channel genes encoding the Shaker-type channel KAT1 was shown to be highly expressed in guard cells. KAT1-type channels from Arabidopsis thaliana and its homologs from other species were found to encode the K(+)-selective inward rectifiers that had already been recorded in early patch-clamp studies with guard cells. Within the genome era, additional Arabidopsis Shaker-type channels appeared. All nine members of the Arabidopsis Shaker family are localized at the plasma membrane, where they either operate as inward rectifiers, outward rectifiers, weak voltage-dependent channels, or electrically silent, but modulatory subunits. The vacuole membrane, in contrast, harbors a set of two-pore K(+) channels. Just very recently, two plant anion channel families of the SLAC/SLAH and ALMT/QUAC type were identified. SLAC1/SLAH3 and QUAC1 are expressed in guard cells and mediate Slow- and Rapid-type anion currents, respectively, that are involved in volume and turgor regulation. Anion channels in guard cells and other plant cells are key targets within often complex signaling networks. Here, the present knowledge is reviewed for the plant ion channel biology. Special emphasis is drawn to the molecular mechanisms of channel regulation, in the context of model systems and in the light of evolution.

  7. Transient receptor potential ankyrin 1 antagonists block the noxious effects of toxic industrial isocyanates and tear gases.

    Science.gov (United States)

    Bessac, Bret F; Sivula, Michael; von Hehn, Christian A; Caceres, Ana I; Escalera, Jasmine; Jordt, Sven-Eric

    2009-04-01

    The release of methyl isocyanate in Bhopal, India, caused the worst industrial accident in history. Exposures to industrial isocyanates induce lacrimation, pain, airway irritation, and edema. Similar responses are elicited by chemicals used as tear gases. Despite frequent exposures, the biological targets of isocyanates and tear gases in vivo have not been identified, precluding the development of effective countermeasures. We use Ca(2+) imaging and electrophysiology to show that the noxious effects of isocyanates and those of all major tear gas agents are caused by activation of Ca(2+) influx and membrane currents in mustard oil-sensitive sensory neurons. These responses are mediated by transient receptor potential ankyrin 1 (TRPA1), an ion channel serving as a detector for reactive chemicals. In mice, genetic ablation or pharmacological inhibition of TRPA1 dramatically reduces isocyanate- and tear gas-induced nocifensive behavior after both ocular and cutaneous exposures. We conclude that isocyanates and tear gas agents target the same neuronal receptor, TRPA1. Treatment with TRPA1 antagonists may prevent and alleviate chemical irritation of the eyes, skin, and airways and reduce the adverse health effects of exposures to a wide range of toxic noxious chemicals.

  8. Transient receptor potential ankyrin 1 activation enhances hapten sensitization in a T-helper type 2-driven fluorescein isothiocyanate-induced contact hypersensitivity mouse model

    International Nuclear Information System (INIS)

    Shiba, Takahiro; Tamai, Takuma; Sahara, Yurina; Kurohane, Kohta; Watanabe, Tatsuo; Imai, Yasuyuki

    2012-01-01

    Some chemicals contribute to the development of allergies by increasing the immunogenicity of other allergens. We have demonstrated that several phthalate esters, including dibutyl phthalate (DBP), enhance skin sensitization to fluorescein isothiocyanate (FITC) in a mouse contact hypersensitivity model, in which the T-helper type 2 (Th2) response is essential. On the other hand, some phthalate esters were found to activate transient receptor potential ankyrin 1 (TRPA1) cation channels on sensory neurons. We then found a positive correlation between the enhancing effects of several types of phthalate esters on skin sensitization to FITC and their ability to activate TRPA1. Here we examined the involvement of TRPA1 in sensitization to FITC by using TRPA1 agonists other than phthalate esters. During skin sensitization to FITC, the TRPA1 agonists (menthol, carvacrol, cinnamaldehyde and DBP) augmented the ear-swelling response as well as trafficking of FITC-presenting dendritic cells to draining lymph nodes. We confirmed that these TRPA1 agonists induced calcium influx into TRPA1-expressing Chinese hamster ovary (CHO) cells. We also found that TRPA1 antagonist HC-030031 inhibited DBP-induced calcium influx into TRPA1-expressing CHO cells. After pretreatment with this antagonist upon skin sensitization to FITC, the enhancing effect of DBP on sensitization was suppressed. These results suggest that TRPA1 activation will become a useful marker to find chemicals that facilitate sensitization in combination with other immunogenic haptens. -- Highlights: ► Role of TRPA1 activation was revealed in a mouse model of skin sensitization to FITC. ► TRPA1 agonists enhanced skin sensitization as well as dendritic cell trafficking. ► Dibutyl phthalate (DBP) has been shown to enhance skin sensitization to FITC. ► TRPA1 activation by DBP was inhibited by a selective antagonist, HC-030031. ► HC-030031 inhibited the enhancing effect of DBP on skin sensitization to FITC.

  9. Transient receptor potential ankyrin 1 activation enhances hapten sensitization in a T-helper type 2-driven fluorescein isothiocyanate-induced contact hypersensitivity mouse model

    Energy Technology Data Exchange (ETDEWEB)

    Shiba, Takahiro; Tamai, Takuma; Sahara, Yurina; Kurohane, Kohta [Laboratory of Microbiology and Immunology, School of Pharmaceutical Sciences, University of Shizuoka, 52‐1 Yada, Suruga-ku, Shizuoka City, Shizuoka 422‐8526 (Japan); Watanabe, Tatsuo [Laboratory of Food Chemistry, School of Food and Nutritional Sciences, University of Shizuoka, 52‐1 Yada, Suruga-ku, Shizuoka City, Shizuoka 422‐8526 (Japan); Imai, Yasuyuki, E-mail: imai@u-shizuoka-ken.ac.jp [Laboratory of Microbiology and Immunology, School of Pharmaceutical Sciences, University of Shizuoka, 52‐1 Yada, Suruga-ku, Shizuoka City, Shizuoka 422‐8526 (Japan)

    2012-11-01

    Some chemicals contribute to the development of allergies by increasing the immunogenicity of other allergens. We have demonstrated that several phthalate esters, including dibutyl phthalate (DBP), enhance skin sensitization to fluorescein isothiocyanate (FITC) in a mouse contact hypersensitivity model, in which the T-helper type 2 (Th2) response is essential. On the other hand, some phthalate esters were found to activate transient receptor potential ankyrin 1 (TRPA1) cation channels on sensory neurons. We then found a positive correlation between the enhancing effects of several types of phthalate esters on skin sensitization to FITC and their ability to activate TRPA1. Here we examined the involvement of TRPA1 in sensitization to FITC by using TRPA1 agonists other than phthalate esters. During skin sensitization to FITC, the TRPA1 agonists (menthol, carvacrol, cinnamaldehyde and DBP) augmented the ear-swelling response as well as trafficking of FITC-presenting dendritic cells to draining lymph nodes. We confirmed that these TRPA1 agonists induced calcium influx into TRPA1-expressing Chinese hamster ovary (CHO) cells. We also found that TRPA1 antagonist HC-030031 inhibited DBP-induced calcium influx into TRPA1-expressing CHO cells. After pretreatment with this antagonist upon skin sensitization to FITC, the enhancing effect of DBP on sensitization was suppressed. These results suggest that TRPA1 activation will become a useful marker to find chemicals that facilitate sensitization in combination with other immunogenic haptens. -- Highlights: ► Role of TRPA1 activation was revealed in a mouse model of skin sensitization to FITC. ► TRPA1 agonists enhanced skin sensitization as well as dendritic cell trafficking. ► Dibutyl phthalate (DBP) has been shown to enhance skin sensitization to FITC. ► TRPA1 activation by DBP was inhibited by a selective antagonist, HC-030031. ► HC-030031 inhibited the enhancing effect of DBP on skin sensitization to FITC.

  10. Channelized Streams in Iowa

    Data.gov (United States)

    Iowa State University GIS Support and Research Facility — This draft dataset consists of all ditches or channelized pieces of stream that could be identified using three input datasets; namely the1:24,000 National...

  11. Potassium channels in brain mitochondria.

    Science.gov (United States)

    Bednarczyk, Piotr

    2009-01-01

    Potassium channels are the most widely distributed class of ion channels. These channels are transmembrane proteins known to play important roles in both normal and pathophysiological functions in all cell types. Various potassium channels are recognised as potential therapeutic targets in the treatment of Parkinson's disease, Alzheimer's disease, brain/spinal cord ischaemia and sepsis. In addition to their importance as therapeutic targets, certain potassium channels are known for their beneficial roles in anaesthesia, cardioprotection and neuroprotection. Some types of potassium channels present in the plasma membrane of various cells have been found in the inner mitochondrial membrane as well. Potassium channels have been proposed to regulate mitochondrial membrane potential, respiration, matrix volume and Ca(+) ion homeostasis. It has been proposed that mitochondrial potassium channels mediate ischaemic preconditioning in various tissues. However, the specificity of a pharmacological agents and the mechanisms underlying their effects on ischaemic preconditioning remain controversial. The following potassium channels from various tissues have been identified in the inner mitochondrial membrane: ATP-regulated (mitoK(ATP)) channel, large conductance Ca(2+)-regulated (mitoBK(Ca)) channel, intermediate conductance Ca(2+)-regulated (mitoIK(Ca)) channel, voltage-gated (mitoKv1.3 type) channel, and twin-pore domain (mitoTASK-3) channel. It has been shown that increased potassium flux into brain mitochondria induced by either the mitoK(ATP) channel or mitoBK(Ca) channel affects the beneficial effects on neuronal cell survival under pathological conditions. Recently, differential distribution of mitoBK(Ca) channels has been observed in neuronal mitochondria. These findings may suggest a neuroprotective role for the mitoBK(Ca) channel in specific brain structures. This minireview summarises current data on brain mitochondrial potassium channels and the efforts to identify

  12. Cl- channels in apoptosis

    DEFF Research Database (Denmark)

    Wanitchakool, Podchanart; Ousingsawat, Jiraporn; Sirianant, Lalida

    2016-01-01

    A remarkable feature of apoptosis is the initial massive cell shrinkage, which requires opening of ion channels to allow release of K(+), Cl(-), and organic osmolytes to drive osmotic water movement and cell shrinkage. This article focuses on the role of the Cl(-) channels LRRC8, TMEM16/anoctamin......, and cystic fibrosis transmembrane conductance regulator (CFTR) in cellular apoptosis. LRRC8A-E has been identified as a volume-regulated anion channel expressed in many cell types. It was shown to be required for regulatory and apoptotic volume decrease (RVD, AVD) in cultured cell lines. Its presence also......(-) channels or as regulators of other apoptotic Cl(-) channels, such as LRRC8. CFTR has been known for its proapoptotic effects for some time, and this effect may be based on glutathione release from the cell and increase in cytosolic reactive oxygen species (ROS). Although we find that CFTR is activated...

  13. Ion channeling

    International Nuclear Information System (INIS)

    Erramli, H.; Blondiaux, G.

    1994-01-01

    Channeling phenomenon was predicted, many years ago, by stark. The first channeling experiments were performed in 1963 by Davies and his coworkers. Parallely Robinson and Oen have investigated this process by simulating trajectories of ions in monocrystals. This technique has been combined with many methods like Rutherford Backscattering Spectrometry (R.B.S.), Particles Induced X-rays Emission (P.I.X.E) and online Nuclear Reaction (N.R.A.) to localize trace elements in the crystal or to determine crystalline quality. To use channeling for material characterization we need data about the stopping power of the incident particle in the channeled direction. The ratios of channeled to random stopping powers of silicon for irradiation in the direction have been investigated and compared to the available theoretical results. We describe few applications of ion channeling in the field of materials characterization. Special attention is given to ion channeling combined with Charged Particle Activation Analysis (C.P.A.A.) for studying the behaviour of oxygen atoms in Czochralski silicon lattices under the influence of internal gettering and in different gaseous atmospheres. Association between ion channeling and C.P.A.A was also utilised for studying the influence of the growing conditions on concentration and position of carbon atoms at trace levels in the MOVPE Ga sub (1-x) Al sub x lattice. 6 figs., 1 tab., 32 refs. (author)

  14. Channel box

    International Nuclear Information System (INIS)

    Tanabe, Akira.

    1993-01-01

    In a channel box of a BWR type reactor, protruding pads are disposed in axial position on the lateral side of a channel box opposing to a control rod and facing the outer side portion of the control rod in a reactor core loaded state. In the initial loading stage of fuel assemblies, channel fasteners and spacer pads are abutted against each other in the upper portion between the channel boxes sandwiching the control rod therebetween. Further, in the lower portion, a gap as a channel for the movement of the control rod is ensured by the support of fuel support metals. If the channel box is bent toward the control rod along with reactor operation, the pads are abutted against each other to always ensure the gap through which the control rod can move easily. Further, when the pads are brought into contact with each other, the bending deformation of the channel box is corrected by urging to each other. Thus, the control rod can always be moved smoothly to attain reactor safety operation. (N.H.)

  15. Surface channeling

    International Nuclear Information System (INIS)

    Sizmann, R.; Varelas, C.

    1976-01-01

    There is experimental evidence that swift light ions incident at small angles towards single crystalline surfaces can lose an appreciable fraction of their kinetic energy during reflection. It is shown that these projectiles penetrate into the bulk surface region of the crystal. They can travel as channeled particles along long paths through the solid (surface channeling). The angular distribution and the depth history of the re-emerged projectiles are investigated by computer simulations. A considerable fraction of the penetrating projectiles re-emerges from the crystal with constant transverse energy if the angle of incidence is smaller than the critical angle for axial channeling. Analytical formulae are derived based on a diffusion model for surface channeling. A comparison with experimental data exhibits the relevance of the analytical solutions. (Auth.)

  16. Spark Channels

    Energy Technology Data Exchange (ETDEWEB)

    Haydon, S. C. [Department of Physics, University of New England, Armidale, NSW (Australia)

    1968-04-15

    A brief summary is given of the principal methods used for initiating spark channels and the various highly time-resolved techniques developed recently for studies with nanosecond resolution. The importance of the percentage overvoltage in determining the early history and subsequent development of the various phases of the growth of the spark channel is discussed. An account is then given of the recent photographic, oscillographic and spectroscopic investigations of spark channels initiated by co-axial cable discharges of spark gaps at low [{approx} 1%] overvoltages. The phenomena observed in the development of the immediate post-breakdown phase, the diffuse glow structure, the growth of the luminous filament and the final formation of the spark channel in hydrogen are described. A brief account is also given of the salient features emerging from corresponding studies of highly overvolted spark gaps in which the spark channel develops from single avalanche conditions. The essential differences between the two types of channel formation are summarized and possible explanations of the general features are indicated. (author)

  17. Electrophysiological characterisation of KCNQ channel modulators

    DEFF Research Database (Denmark)

    Schrøder, R.L

    Potassium (K+) ion channels are ubiquitously expressed in mammalian cells, and each channel serves a precise physiological role due to its specific biophysical characteristics and expression pattern. A few K+ channels are targets for certain drugs, and in this thesis it is suggested that the KCNQ K......+ channels may be targets for neuroprotective, anti-epileptic and anti-nociceptive compounds. The importance of these channels is underscored by the fact that four out of five KCNQ channel subtypes are involved in severe human diseases. However, the pharmacology of the KCNQ channels is yet poorly understood...... as these channels were identified only recently. Therefore, there is a need for understanding the biophysical behavior and pharmacology of these ion channels. KCNQ channels belong to the group of voltage-activated K+ channels. The subfamily consists of KCNQ1-5, which is primarily expressed in the CNS, heart, ear...

  18. Pharmacological modulation of SK3 channels

    DEFF Research Database (Denmark)

    Grunnet, M; Jespersen, Thomas; Angelo, K

    2001-01-01

    Small-conductance, calcium-activated K+ channels (SK channels) are voltage-insensitive channels that have been identified molecularly within the last few years. As SK channels play a fundamental role in most excitable cells and participate in afterhyperpolarization (AHP) and spike-frequency adapt...... at concentrations of 3 microM and above. Amitriptyline, a tricyclic antidepressive widely used clinically, inhibits SK3 channels with an IC50 of 39.1 +/- 10 microM (n=6)....

  19. MARKETING CHANNELS

    Directory of Open Access Journals (Sweden)

    Ljiljana Stošić Mihajlović

    2014-07-01

    Full Text Available Marketing channel is a set of entities and institutions, completion of distribution and marketing activities, attend the efficient and effective networking of producers and consumers. Marketing channels include the total flows of goods, money and information taking place between the institutions in the system of marketing, establishing a connection between them. The functions of the exchange, the physical supply and service activities, inherent in the system of marketing and trade. They represent paths which products and services are moving after the production, which will ultimately end up buying and eating by the user.

  20. Molecular Basis of TRPA1 Regulation in Nociceptive Neurons. A Review

    Czech Academy of Sciences Publication Activity Database

    Kádková, Anna; Synytsya, Viktor; Krůšek, Jan; Zímová, Lucie; Vlachová, Viktorie

    2017-01-01

    Roč. 66, č. 3 (2017), s. 425-439 ISSN 0862-8408 R&D Projects: GA ČR(CZ) GA15-15839S; GA MZd(CZ) NV16-28784A Institutional support: RVO:67985823 Keywords : transient receptor potential ankyrin 1 * bradykinin * structure- function * nociception * post-translational modifications * signaling pathways Subject RIV: FH - Neurology OBOR OECD: Neurosciences (including psychophysiology Impact factor: 1.461, year: 2016

  1. Examining the role of TRPA1 in air pollution-induced cardiac arrhythmias and autonomic imbalance

    Science.gov (United States)

    Here we describe how air pollution causes cardiac arrhythmogenesis through sensory irritation in the airways. Time-series studies show the risk of adverse cardiac events increases significantly in the hours to days after expos...

  2. Optical Communications Channel Combiner

    Science.gov (United States)

    Quirk, Kevin J.; Quirk, Kevin J.; Nguyen, Danh H.; Nguyen, Huy

    2012-01-01

    NASA has identified deep-space optical communications links as an integral part of a unified space communication network in order to provide data rates in excess of 100 Mb/s. The distances and limited power inherent in a deep-space optical downlink necessitate the use of photon-counting detectors and a power-efficient modulation such as pulse position modulation (PPM). For the output of each photodetector, whether from a separate telescope or a portion of the detection area, a communication receiver estimates a log-likelihood ratio for each PPM slot. To realize the full effective aperture of these receivers, their outputs must be combined prior to information decoding. A channel combiner was developed to synchronize the log-likelihood ratio (LLR) sequences of multiple receivers, and then combines these into a single LLR sequence for information decoding. The channel combiner synchronizes the LLR sequences of up to three receivers and then combines these into a single LLR sequence for output. The channel combiner has three channel inputs, each of which takes as input a sequence of four-bit LLRs for each PPM slot in a codeword via a XAUI 10 Gb/s quad optical fiber interface. The cross-correlation between the channels LLR time series are calculated and used to synchronize the sequences prior to combining. The output of the channel combiner is a sequence of four-bit LLRs for each PPM slot in a codeword via a XAUI 10 Gb/s quad optical fiber interface. The unit is controlled through a 1 Gb/s Ethernet UDP/IP interface. A deep-space optical communication link has not yet been demonstrated. This ground-station channel combiner was developed to demonstrate this capability and is unique in its ability to process such a signal.

  3. Channel Power in Multi-Channel Environments

    NARCIS (Netherlands)

    M.G. Dekimpe (Marnik); B. Skiera (Bernd)

    2004-01-01

    textabstractIn the literature, little attention has been paid to instances where companies add an Internet channel to their direct channel portfolio. However, actively managing multiple sales channels requires knowing the customers’ channel preferences and the resulting channel power. Two key

  4. Channel Identification Machines

    Directory of Open Access Journals (Sweden)

    Aurel A. Lazar

    2012-01-01

    Full Text Available We present a formal methodology for identifying a channel in a system consisting of a communication channel in cascade with an asynchronous sampler. The channel is modeled as a multidimensional filter, while models of asynchronous samplers are taken from neuroscience and communications and include integrate-and-fire neurons, asynchronous sigma/delta modulators and general oscillators in cascade with zero-crossing detectors. We devise channel identification algorithms that recover a projection of the filter(s onto a space of input signals loss-free for both scalar and vector-valued test signals. The test signals are modeled as elements of a reproducing kernel Hilbert space (RKHS with a Dirichlet kernel. Under appropriate limiting conditions on the bandwidth and the order of the test signal space, the filter projection converges to the impulse response of the filter. We show that our results hold for a wide class of RKHSs, including the space of finite-energy bandlimited signals. We also extend our channel identification results to noisy circuits.

  5. Channel identification machines.

    Science.gov (United States)

    Lazar, Aurel A; Slutskiy, Yevgeniy B

    2012-01-01

    We present a formal methodology for identifying a channel in a system consisting of a communication channel in cascade with an asynchronous sampler. The channel is modeled as a multidimensional filter, while models of asynchronous samplers are taken from neuroscience and communications and include integrate-and-fire neurons, asynchronous sigma/delta modulators and general oscillators in cascade with zero-crossing detectors. We devise channel identification algorithms that recover a projection of the filter(s) onto a space of input signals loss-free for both scalar and vector-valued test signals. The test signals are modeled as elements of a reproducing kernel Hilbert space (RKHS) with a Dirichlet kernel. Under appropriate limiting conditions on the bandwidth and the order of the test signal space, the filter projection converges to the impulse response of the filter. We show that our results hold for a wide class of RKHSs, including the space of finite-energy bandlimited signals. We also extend our channel identification results to noisy circuits.

  6. Mechanosensitive Channels: In Touch with Piezo

    OpenAIRE

    Xiao, Rui; Xu, X.Z. Shawn

    2010-01-01

    Mechanosensory transduction underlies touch, hearing and proprioception and requires mechanosensitive channels that are directly gated by forces; however, the molecular identities of these channels remain largely elusive. A new study has identified Piezo1 and Piezo2 as a novel class of mechanosensitive channels.

  7. Channelling and electromagnetic radiation of channelling particles

    International Nuclear Information System (INIS)

    Kalashnikov, N.

    1983-01-01

    A brief description is presented of the channelling of charged particles between atoms in the crystal lattice. The specificities are discussed of the transverse motion of channelling particles as are the origin and properties of quasi-characteristic radiation of channelling particles which accompany transfers from one band of permissible energies of the transverse motion of channelling particles to the other. (B.S.)

  8. Channel Modeling

    Science.gov (United States)

    Schmitz, Arne; Schinnenburg, Marc; Gross, James; Aguiar, Ana

    For any communication system the Signal-to-Interference-plus-Noise-Ratio of the link is a fundamental metric. Recall (cf. Chapter 9) that the SINR is defined as the ratio between the received power of the signal of interest and the sum of all "disturbing" power sources (i.e. interference and noise). From information theory it is known that a higher SINR increases the maximum possible error-free transmission rate (referred to as Shannon capacity [417] of any communication system and vice versa). Conversely, the higher the SINR, the lower will be the bit error rate in practical systems. While one aspect of the SINR is the sum of all distracting power sources, another issue is the received power. This depends on the transmitted power, the used antennas, possibly on signal processing techniques and ultimately on the channel gain between transmitter and receiver.

  9. Channeling experiment

    International Nuclear Information System (INIS)

    Abelin, H.; Birgersson, L.; Widen, H.; Aagren, T.; Moreno, L.; Neretnieks, I.

    1990-07-01

    Channeling of water flow and tracer transport in real fractures in a granite body at Stripa have been investigated experimentally. The experimental site was located 360 m below the ground level. Two kinds of experiments were performed. In the single hole experiments, 20 cm diameter holes were drilled about 2.5 m into the rock in the plane of the fracture. Specially designed packers were used to inject water into the fracture in 5 cm intervals all along the fracture trace in the hole. The variation of the injection flowrates along the fracture were used to determine the transmissivity variations in the fracture plane. Detailed photographs were taken from inside the hole and the visual fracture aperture was compared with the injection flowrates in the same locations. Geostatistical methods were used to evaluate the results. Five holes were measured in great detail. In addition 7 holes were drilled and scanned by simpler packer systems. A double hole experiment was performed where two parallel holes were drilled in the same fracture plane at nearly 2 m distance. Pressure pulse tests were made between the holes in both directions. Tracers were injected in 5 locations in one hole and monitored for in many locations in the other hole. The single hole experiment and the double hole experiment show that most of the fracture planes are tight but that there are open sections which form connected channels over distances of at least 2 meters. It was also found in the double hole experiment that the investigated fracture was intersected by at least one fracture between the two holes which diverted a large amount of the injected tracers to several distant locations at the tunnel wall. (authours)

  10. Ciguatoxins activate specific cold pain pathways to elicit burning pain from cooling.

    Science.gov (United States)

    Vetter, Irina; Touska, Filip; Hess, Andreas; Hinsbey, Rachel; Sattler, Simon; Lampert, Angelika; Sergejeva, Marina; Sharov, Anastasia; Collins, Lindon S; Eberhardt, Mirjam; Engel, Matthias; Cabot, Peter J; Wood, John N; Vlachová, Viktorie; Reeh, Peter W; Lewis, Richard J; Zimmermann, Katharina

    2012-10-03

    Ciguatoxins are sodium channel activator toxins that cause ciguatera, the most common form of ichthyosarcotoxism, which presents with peripheral sensory disturbances, including the pathognomonic symptom of cold allodynia which is characterized by intense stabbing and burning pain in response to mild cooling. We show that intraplantar injection of P-CTX-1 elicits cold allodynia in mice by targeting specific unmyelinated and myelinated primary sensory neurons. These include both tetrodotoxin-resistant, TRPA1-expressing peptidergic C-fibres and tetrodotoxin-sensitive A-fibres. P-CTX-1 does not directly open heterologously expressed TRPA1, but when co-expressed with Na(v) channels, sodium channel activation by P-CTX-1 is sufficient to drive TRPA1-dependent calcium influx that is responsible for the development of cold allodynia, as evidenced by a large reduction of excitatory effect of P-CTX-1 on TRPA1-deficient nociceptive C-fibres and of ciguatoxin-induced cold allodynia in TRPA1-null mutant mice. Functional MRI studies revealed that ciguatoxin-induced cold allodynia enhanced the BOLD (Blood Oxygenation Level Dependent) signal, an effect that was blunted in TRPA1-deficient mice, confirming an important role for TRPA1 in the pathogenesis of cold allodynia.

  11. Comparative immunohistochemical characterization of interstitial cells in the urinary bladder of human, guinea pig and pig.

    Science.gov (United States)

    Steiner, Clara; Gevaert, Thomas; Ganzer, Roman; De Ridder, Dirk; Neuhaus, Jochen

    2018-05-01

    Interstitial cells (ICs) are thought to play a functional role in urinary bladder. Animal models are commonly used to elucidate bladder physiology and pathophysiology. However, inter-species comparative studies on ICs are rare. We therefore analyzed ICs and their distribution in the upper lamina propria (ULP), the deeper lamina propria (DLP) and the detrusor muscular layer (DET) of human, guinea pig (GP) and pig. Paraffin slices were examined by immunohistochemistry and 3D confocal immunofluorescence of the mesenchymal intermediate filament vimentin (VIM), alpha-smooth muscle actin (αSMA), platelet-derived growth factor receptor alpha (PDGFRα) and transient receptor potential cation channel A1 (TRPA1). Image stacks were processed for analysis using Huygens software; quantitative analysis was performed with Fiji macros. ICs were identified by immunoreactivity for VIM (excluding blood vessels). In all species ≥ 75% of ULP ICs were VIM + /PDGFRα + and ≥ 90% were VIM + /TRPA1 + . In human and pig ≥ 74% of ULP ICs were VIM + /αSMA + , while in GP the percentage differed significantly with only 37% VIM + /αSMA + ICs. Additionally, over 90% of αSMA + ICs were also TRPA1 + and PDGFRα + in human, GP and pig. In all three species, TRPA1 + and PDGFRα + ICs point to an active role for these cells in bladder physiology, regarding afferent signaling processes and signal modification. We hypothesize that decline in αSMA-positivity in GP reflects adaptation of bladder histology to smaller bladder size. In our experiments, pig bladder proved to be highly comparable to human urinary bladder and seems to provide safer interpretation of experimental findings than GP.

  12. Role of Ca++ Influx via Epidermal TRP Ion Channels

    Science.gov (United States)

    2017-12-01

    manuscript and helpful discussions. References 1. Burkhart, C. G., and Burkhart, H. R. (2003) Contact irritant dermatitis and anti-pruritic agents...E. (2013) TRPA1 controls inflammation and pruritogen responses in allergic contact dermatitis . FASEB J. 27, 3549–3563 64. Yoshioka, T., Imura, K...allergic   contact   dermatitis ,   including   contact   dermatitis   elicited  by  the  poison  ivy  allergen,  urushiol  [75,  126].     Similarly

  13. Beyond the Manual Channel

    DEFF Research Database (Denmark)

    , the main focus there is on spoken languages in their written and spoken forms. This series of workshops, however, offers a forum for researchers focussing on sign languages. For the fourth time, the workshop had sign language corpora as its main topic. This time, the focus was on any aspect beyond...... the manual channel. Not surprisingly, most papers deal with non-manuals on the face. Once again, the papers at this workshop clearly identify the potentials of even closer cooperation between sign linguists and sign language engineers, and we think it is events like this that contribute a lot to a better...

  14. Post-Translational Modifications of TRP Channels

    Directory of Open Access Journals (Sweden)

    Olaf Voolstra

    2014-04-01

    Full Text Available Transient receptor potential (TRP channels constitute an ancient family of cation channels that have been found in many eukaryotic organisms from yeast to human. TRP channels exert a multitude of physiological functions ranging from Ca2+ homeostasis in the kidney to pain reception and vision. These channels are activated by a wide range of stimuli and undergo covalent post-translational modifications that affect and modulate their subcellular targeting, their biophysical properties, or channel gating. These modifications include N-linked glycosylation, protein phosphorylation, and covalent attachment of chemicals that reversibly bind to specific cysteine residues. The latter modification represents an unusual activation mechanism of ligand-gated ion channels that is in contrast to the lock-and-key paradigm of receptor activation by its agonists. In this review, we summarize the post-translational modifications identified on TRP channels and, when available, explain their physiological role.

  15. Anion channels: master switches of stress responses.

    Science.gov (United States)

    Roelfsema, M Rob G; Hedrich, Rainer; Geiger, Dietmar

    2012-04-01

    During stress, plant cells activate anion channels and trigger the release of anions across the plasma membrane. Recently, two new gene families have been identified that encode major groups of anion channels. The SLAC/SLAH channels are characterized by slow voltage-dependent activation (S-type), whereas ALMT genes encode rapid-activating channels (R-type). Both S- and R-type channels are stimulated in guard cells by the stress hormone ABA, which leads to stomatal closure. Besides their role in ABA-dependent stomatal movement, anion channels are also activated by biotic stress factors such as microbe-associated molecular patterns (MAMPs). Given that anion channels occur throughout the plant kingdom, they are likely to serve a general function as master switches of stress responses. Copyright © 2012 Elsevier Ltd. All rights reserved.

  16. Citizens and service channels: channel choice and channel management implications

    NARCIS (Netherlands)

    Pieterson, Willem Jan

    2010-01-01

    The arrival of electronic channels in the 1990s has had a huge impact on governmental service delivery. The new channels have led to many new opportunities to improve public service delivery, not only in terms of citizen satisfaction, but also in cost reduction for governmental agencies. However,

  17. Quantum privacy and Schur product channels

    Science.gov (United States)

    Levick, Jeremy; Kribs, David W.; Pereira, Rajesh

    2017-12-01

    We investigate the quantum privacy properties of an important class of quantum channels, by making use of a connection with Schur product matrix operations and associated correlation matrix structures. For channels implemented by mutually commuting unitaries, which cannot privatise qubits encoded directly into subspaces, we nevertheless identify private algebras and subsystems that can be privatised by the channels. We also obtain further results by combining our analysis with tools from the theory of quasi-orthogonal operator algebras and graph theory.

  18. Quantum incompatibility of channels with general outcome operator algebras

    Science.gov (United States)

    Kuramochi, Yui

    2018-04-01

    A pair of quantum channels is said to be incompatible if they cannot be realized as marginals of a single channel. This paper addresses the general structure of the incompatibility of completely positive channels with a fixed quantum input space and with general outcome operator algebras. We define a compatibility relation for such channels by identifying the composite outcome space as the maximal (projective) C*-tensor product of outcome algebras. We show theorems that characterize this compatibility relation in terms of the concatenation and conjugation of channels, generalizing the recent result for channels with quantum outcome spaces. These results are applied to the positive operator valued measures (POVMs) by identifying each of them with the corresponding quantum-classical (QC) channel. We also give a characterization of the maximality of a POVM with respect to the post-processing preorder in terms of the conjugate channel of the QC channel. We consider another definition of compatibility of normal channels by identifying the composite outcome space with the normal tensor product of the outcome von Neumann algebras. We prove that for a given normal channel, the class of normally compatible channels is upper bounded by a special class of channels called tensor conjugate channels. We show the inequivalence of the C*- and normal compatibility relations for QC channels, which originates from the possibility and impossibility of copying operations for commutative von Neumann algebras in C*- and normal compatibility relations, respectively.

  19. Oral treatment with essential oil of Hyptis spicigera Lam. (Lamiaceae) reduces acute pain and inflammation in mice: Potential interactions with transient receptor potential (TRP) ion channels.

    Science.gov (United States)

    Simões, Róli Rodrigues; Coelho, Igor Dos Santos; Junqueira, Stella Célio; Pigatto, Glauce Regina; Salvador, Marcos José; Santos, Adair Roberto Soares; de Faria, Felipe Meira

    2017-03-22

    The genus Hyptis comprehends almost 400 species widespread in tropical and temperate regions of America. The use of Hyptis spicigera Lam. (Lamiaceae) is reported in traditional medicine due to its gastroprotective, anti-inflammatory and analgesic properties. The rationale of this study was to investigate the potential use of the essential oil of H. spicigera (EOHs) as analgesic. The antinociceptive effect of EOHs was verified analyzing acute nocifensive behavior of mice induced by chemical noxious stimuli [i.e., formalin and transient receptor potential (TRP) channels agonists]. We also verified the effects of EOHs on locomotor activity and motor performance in mice. Finally, we investigate the involvement of central afferent C-fibers with EOHs analgesic effect. EOHs presented antinociceptive effect at 300 and 1000mg/kg on formalin-induced pain behavior model, presenting 50% and 72% of inhibition during the first phase (ED 50 =292mg/kg), and 85% and 100% during de second phase (ED 50 =205mg/kg), respectively. Temperature of the hind paw was reduced by EOHs treatment in a dose-dependent manner; oedema was diminished only by EOHs 1000mg/kg. EOHs does not impaired locomotor activity or motor performance. For mice injected with capsaicin, a TRPV1 activator, EOHs (1000mg/kg, ED 50 =660mg/kg) showed decreased (63%) nociceptive behavior. When injected with cinnamaldehyde (TRPA1 activator), mice treated with EOHs showed 23%, 43% and 66% inhibition on nociceptive behavior (100, 300 and 1000mg/kg, respectively; ED 50 402mg/kg). When mice were injected with menthol (TRPM8 activator), EOHs showed 29%, 59% and 98% inhibition of nociceptive behavior (100, 300 and 1000mg/kg, respectively; with ED 50 =198mg/kg. Finally, when desensitized mice were injected with menthol, EOHs (300mg/kg) does not show antinociceptive effect. This study demonstrated the efficacy of EOHs on experimental models of nociception. We have found the involvement of TRP channels V1, A1 and M8 with EOHs

  20. Comparative Study between Sequential Automatic and Manual Home Respiratory Polygraphy Scoring Using a Three-Channel Device: Impact of the Manual Editing of Events to Identify Severe Obstructive Sleep Apnea

    Directory of Open Access Journals (Sweden)

    Glenda Ernst

    2015-01-01

    Full Text Available Objective. According to current guidelines, autoscoring of respiratory events in respiratory polygraphy requires manual scoring. The aim of this study was to evaluate the agreement between automatic analysis and manual scoring to identify patients with suspected OSA. Methods. This retrospective study analyzed 791 records from respiratory polygraphy (RP performed at home. The association grade between automatic scoring and manual scoring was evaluated using Kappa coefficient and the agreement using Bland and Altman test and intraclass correlation coefficient (CCI. To determine the accuracy in the identification of AHI≥30 eV/h, the ROC curve analysis was used. Results. The population analyzed consisted of 493 male (62.3% and 298 female patients, with an average age of 54.7±14.20 years and BMI of 32.7±8.21 kg/m2. There was no significant difference between automatic and manual apnea/hypopnea indexes (aAHI, mAHI: aAHI 17.25 (SD: 17.42 versus mAHI 21.20±7.96 (p; NS. The agreement between mAHI and aAHI to AHI≥30 was 94%, with a Kappa coefficient of 0.83 (p<0.001 and a CCI of 0.83. The AUC-ROC, sensitivity, and specificity were 0.99 (CI 95%: 0.98-0.99, p<0.001, 86% (CI 95%: 78.7–91.4, and 97% (CI 95%: 96–98.3, respectively. Conclusions. We observed good agreement between automatic scoring and sequential manual scoring to identify subjects with AHI≥30 eV/h.

  1. ASIC3 channels in multimodal sensory perception.

    Science.gov (United States)

    Li, Wei-Guang; Xu, Tian-Le

    2011-01-19

    Acid-sensing ion channels (ASICs), which are members of the sodium-selective cation channels belonging to the epithelial sodium channel/degenerin (ENaC/DEG) family, act as membrane-bound receptors for extracellular protons as well as nonproton ligands. At least five ASIC subunits have been identified in mammalian neurons, which form both homotrimeric and heterotrimeric channels. The highly proton sensitive ASIC3 channels are predominantly distributed in peripheral sensory neurons, correlating with their roles in multimodal sensory perception, including nociception, mechanosensation, and chemosensation. Different from other ASIC subunit composing ion channels, ASIC3 channels can mediate a sustained window current in response to mild extracellular acidosis (pH 7.3-6.7), which often occurs accompanied by many sensory stimuli. Furthermore, recent evidence indicates that the sustained component of ASIC3 currents can be enhanced by nonproton ligands including the endogenous metabolite agmatine. In this review, we first summarize the growing body of evidence for the involvement of ASIC3 channels in multimodal sensory perception and then discuss the potential mechanisms underlying ASIC3 activation and mediation of sensory perception, with a special emphasis on its role in nociception. We conclude that ASIC3 activation and modulation by diverse sensory stimuli represent a new avenue for understanding the role of ASIC3 channels in sensory perception. Furthermore, the emerging implications of ASIC3 channels in multiple sensory dysfunctions including nociception allow the development of new pharmacotherapy.

  2. VKCDB: Voltage-gated potassium channel database

    Directory of Open Access Journals (Sweden)

    Gallin Warren J

    2004-01-01

    Full Text Available Abstract Background The family of voltage-gated potassium channels comprises a functionally diverse group of membrane proteins. They help maintain and regulate the potassium ion-based component of the membrane potential and are thus central to many critical physiological processes. VKCDB (Voltage-gated potassium [K] Channel DataBase is a database of structural and functional data on these channels. It is designed as a resource for research on the molecular basis of voltage-gated potassium channel function. Description Voltage-gated potassium channel sequences were identified by using BLASTP to search GENBANK and SWISSPROT. Annotations for all voltage-gated potassium channels were selectively parsed and integrated into VKCDB. Electrophysiological and pharmacological data for the channels were collected from published journal articles. Transmembrane domain predictions by TMHMM and PHD are included for each VKCDB entry. Multiple sequence alignments of conserved domains of channels of the four Kv families and the KCNQ family are also included. Currently VKCDB contains 346 channel entries. It can be browsed and searched using a set of functionally relevant categories. Protein sequences can also be searched using a local BLAST engine. Conclusions VKCDB is a resource for comparative studies of voltage-gated potassium channels. The methods used to construct VKCDB are general; they can be used to create specialized databases for other protein families. VKCDB is accessible at http://vkcdb.biology.ualberta.ca.

  3. Mechanosensitive Piezo Channels in the Gastrointestinal Tract.

    Science.gov (United States)

    Alcaino, C; Farrugia, G; Beyder, A

    2017-01-01

    Sensation of mechanical forces is critical for normal function of the gastrointestinal (GI) tract and abnormalities in mechanosensation are linked to GI pathologies. In the GI tract there are several mechanosensitive cell types-epithelial enterochromaffin cells, intrinsic and extrinsic enteric neurons, smooth muscle cells and interstitial cells of Cajal. These cells use mechanosensitive ion channels that respond to mechanical forces by altering transmembrane ionic currents in a process called mechanoelectrical coupling. Several mechanosensitive ionic conductances have been identified in the mechanosensory GI cells, ranging from mechanosensitive voltage-gated sodium and calcium channels to the mechanogated ion channels, such as the two-pore domain potassium channels K2P (TREK-1) and nonselective cation channels from the transient receptor potential family. The recently discovered Piezo channels are increasingly recognized as significant contributors to cellular mechanosensitivity. Piezo1 and Piezo2 are nonselective cationic ion channels that are directly activated by mechanical forces and have well-defined biophysical and pharmacologic properties. The role of Piezo channels in the GI epithelium is currently under investigation and their role in the smooth muscle syncytium and enteric neurons is still not known. In this review, we outline the current state of knowledge on mechanosensitive ion channels in the GI tract, with a focus on the known and potential functions of the Piezo channels. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. TRPV6 channels.

    Science.gov (United States)

    Fecher-Trost, Claudia; Weissgerber, Petra; Wissenbach, Ulrich

    2014-01-01

    TRPV6 (former synonyms ECAC2, CaT1, CaT-like) displays several specific features which makes it unique among the members of the mammalian Trp gene family (1) TRPV6 (and its closest relative, TRPV5) are the only highly Ca(2+)-selective channels of the entire TRP superfamily (Peng et al. 1999; Wissenbach et al. 2001; Voets et al. 2004). (2) Translation of Trpv6 initiates at a non-AUG codon, at ACG, located upstream of the annotated AUG, which is not used for initiation (Fecher-Trost et al. 2013). The ACG codon is nevertheless decoded by methionine. Not only a very rare event in eukaryotic biology, the full-length TRPV6 protein existing in vivo comprises an amino terminus extended by 40 amino acid residues compared to the annotated truncated TRPV6 protein which has been used in most studies on TRPV6 channel activity so far. (In the following numbering occurs according to this full-length protein, with the numbers of the so far annotated truncated protein in brackets). (3) Only in humans a coupled polymorphism of Trpv6 exists causing three amino acid exchanges and resulting in an ancestral Trpv6 haplotype and a so-called derived Trpv6 haplotype (Wissenbach et al. 2001). The ancestral allele encodes the amino acid residues C197(157), M418(378) and M721(681) and the derived alleles R197(157), V418(378) and T721(681). The ancestral haplotype is found in all species, the derived Trpv6 haplotype has only been identified in humans, and its frequency increases with the distance to the African continent. Apparently the Trpv6 gene has been a strong target for selection in humans, and its derived variant is one of the few examples showing consistently differences to the orthologues genes of other primates (Akey et al. 2004, 2006; Stajich and Hahn 2005; Hughes et al. 2008). (4) The Trpv6 gene expression is significantly upregulated in several human malignancies including the most common cancers, prostate and breast cancer (Wissenbach et al. 2001; Zhuang et al. 2002; Fixemer et al

  5. USACE Navigation Channels 2012

    Data.gov (United States)

    California Natural Resource Agency — This dataset represents both San Francisco and Los Angeles District navigation channel lines. All San Francisco District channel lines were digitized from CAD files...

  6. Calcium channel blocker overdose

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/002580.htm Calcium-channel blocker overdose To use the sharing features on this page, please enable JavaScript. Calcium-channel blockers are a type of medicine used ...

  7. Quantum Channels With Memory

    International Nuclear Information System (INIS)

    Rybar, T.

    2012-01-01

    Quantum memory channels represent a very general, yet simple and comprehensible model for causal processes. As such they have attracted considerable research interest, mostly aimed on their transfer capabilities and structure properties. Most notably it was shown that memory channels can be implemented via physically naturally motivated collision models. We also define the concept of repeatable channels and show that only unital channels can be implemented repeat ably with pure memory channels. In the special case of qubit channels we also show that every unital qubit channel has a repeatable implementation. We also briefly explore the possibilities of stroboscopical simulation of channels and show that all random unitary channels can be stroboscopically simulated. Particularly in qubit case, all indivisible qubit channels are also random unitary, hence for qubit all indivisible channels can be stroboscopically simulated. Memory channels also naturally capture the framework of correlated experiments. We develop methods to gather and interpret data obtained in such setting and in detail examine the two qubit case. We also show that for control unitary interactions the measured data will never contradict a simple unitary evolution. Thus no memory effects can be spotted then. (author)

  8. Eight channel fast scalar

    Energy Technology Data Exchange (ETDEWEB)

    Waddoup, W D; Stubbs, R J [Durham Univ. (UK)

    1977-11-01

    An eight channel 64-bit scaler has been constructed with a static CMOS memory. Scaling frequencies are independently variable, at each channel, as are the number of bits/channel. The scaler, when used in conjunction with a multichannel charge to time converter results in a very flexible, gated multichannel ADC.

  9. KV7 potassium channels

    DEFF Research Database (Denmark)

    Stott, Jennifer B; Jepps, Thomas Andrew; Greenwood, Iain A

    2014-01-01

    Potassium channels are key regulators of smooth muscle tone, with increases in activity resulting in hyperpolarisation of the cell membrane, which acts to oppose vasoconstriction. Several potassium channels exist within smooth muscle, but the KV7 family of voltage-gated potassium channels have been...

  10. A Micromechanical RF Channelizer

    Science.gov (United States)

    Akgul, Mehmet

    The power consumption of a radio generally goes as the number and strength of the RF signals it must process. In particular, a radio receiver would consume much less power if the signal presented to its electronics contained only the desired signal in a tiny percent bandwidth frequency channel, rather than the typical mix of signals containing unwanted energy outside the desired channel. Unfortunately, a lack of filters capable of selecting single channel bandwidths at RF forces the front-ends of contemporary receivers to accept unwanted signals, and thus, to operate with sub-optimal efficiency. This dissertation focuses on the degree to which capacitive-gap transduced micromechanical resonators can achieve the aforementioned RF channel-selecting filters. It aims to first show theoretically that with appropriate scaling capacitive-gap transducers are strong enough to meet the needed coupling requirements; and second, to fully detail an architecture and design procedure needed to realize said filters. Finally, this dissertation provides an actual experimentally demonstrated RF channel-select filter designed using the developed procedures and confirming theoretical predictions. Specifically, this dissertation introduces four methods that make possible the design and fabrication of RF channel-select filters. The first of these introduces a small-signal equivalent circuit for parallel-plate capacitive-gap transduced micromechanical resonators that employs negative capacitance to model the dependence of resonance frequency on electrical stiffness in a way that facilitates the analysis of micromechanical circuits loaded with arbitrary electrical impedances. The new circuit model not only correctly predicts the dependence of electrical stiffness on the impedances loading the input and output electrodes of parallel-plate capacitive-gap transduced micromechanical device, but does so in a visually intuitive way that identifies current drive as most appropriate for

  11. Fine Channel Networks

    Science.gov (United States)

    1997-01-01

    A color image of fine channel networks on Mars; north toward top. The scene shows heavily cratered highlands dissected by dendritic open channel networks that dissect steep slopes of impact crater walls. This image is a composite of Viking high-resolution images in black and white and low-resolution images in color. The image extends from latitude 9 degrees S. to 5 degrees S. and from longitude 312 degrees to 320 degrees; Mercator projection. The dendritic pattern of the fine channels and their location on steep slopes leads to the interpretation that these are runoff channels. The restriction of these types of channels to ancient highland rocks suggests that these channels are old and date from a time on Mars when conditions existed for precipitation to actively erode rocks. After the channels reach a low plain, they appear to end. Termination may have resulted from burial by younger deposits or perhaps the flows percolated into the surface materials and continued underground.

  12. Ca2+-dependent K+ Channels in Exocrine Salivary Glands

    Science.gov (United States)

    Catalán, Marcelo A.; Peña-Munzenmayer, Gaspar; Melvin, James E.

    2014-01-01

    In the last 15 years, remarkable progress has been realized in identifying the genes that encode the ion-transporting proteins involved in exocrine gland function, including salivary glands. Among these proteins, Ca2+-dependent K+ channels take part in key functions including membrane potential regulation, fluid movement and K+ secretion in exocrine glands. Two K+ channels have been identified in exocrine salivary glands: 1) a Ca2+-activated K+ channel of intermediate single channel conductance encoded by the KCNN4 gene; and, 2) a voltage- and Ca2+-dependent K+ channel of large single channel conductance encoded by the KCNMA1 gene. This review focuses on the physiological roles of Ca2+-dependent K+ channels in exocrine salivary glands. We also discuss interesting recent findings on the regulation of Ca2+-dependent K+ channels by protein-protein interactions that may significantly impact exocrine gland physiology. PMID:24559652

  13. Compound Wiretap Channels

    Directory of Open Access Journals (Sweden)

    Shlomo Shamai (Shitz

    2009-01-01

    Full Text Available This paper considers the compound wiretap channel, which generalizes Wyner's wiretap model to allow the channels to the (legitimate receiver and to the eavesdropper to take a number of possible states. No matter which states occur, the transmitter guarantees that the receiver decodes its message and that the eavesdropper is kept in full ignorance about the message. The compound wiretap channel can also be viewed as a multicast channel with multiple eavesdroppers, in which the transmitter sends information to all receivers and keeps the information secret from all eavesdroppers. For the discrete memoryless channel, lower and upper bounds on the secrecy capacity are derived. The secrecy capacity is established for the degraded channel and the semideterministic channel with one receiver. The parallel Gaussian channel is further studied. The secrecy capacity and the secrecy degree of freedom (s.d.o.f. are derived for the degraded case with one receiver. Schemes to achieve the s.d.o.f. for the case with two receivers and two eavesdroppers are constructed to demonstrate the necessity of a prefix channel in encoder design. Finally, the multi-antenna (i.e., MIMO compound wiretap channel is studied. The secrecy capacity is established for the degraded case and an achievable s.d.o.f. is given for the general case.

  14. Compound Wiretap Channels

    Directory of Open Access Journals (Sweden)

    Kramer Gerhard

    2009-01-01

    Full Text Available Abstract This paper considers the compound wiretap channel, which generalizes Wyner's wiretap model to allow the channels to the (legitimate receiver and to the eavesdropper to take a number of possible states. No matter which states occur, the transmitter guarantees that the receiver decodes its message and that the eavesdropper is kept in full ignorance about the message. The compound wiretap channel can also be viewed as a multicast channel with multiple eavesdroppers, in which the transmitter sends information to all receivers and keeps the information secret from all eavesdroppers. For the discrete memoryless channel, lower and upper bounds on the secrecy capacity are derived. The secrecy capacity is established for the degraded channel and the semideterministic channel with one receiver. The parallel Gaussian channel is further studied. The secrecy capacity and the secrecy degree of freedom ( are derived for the degraded case with one receiver. Schemes to achieve the for the case with two receivers and two eavesdroppers are constructed to demonstrate the necessity of a prefix channel in encoder design. Finally, the multi-antenna (i.e., MIMO compound wiretap channel is studied. The secrecy capacity is established for the degraded case and an achievable is given for the general case.

  15. ATP Release Channels

    Directory of Open Access Journals (Sweden)

    Akiyuki Taruno

    2018-03-01

    Full Text Available Adenosine triphosphate (ATP has been well established as an important extracellular ligand of autocrine signaling, intercellular communication, and neurotransmission with numerous physiological and pathophysiological roles. In addition to the classical exocytosis, non-vesicular mechanisms of cellular ATP release have been demonstrated in many cell types. Although large and negatively charged ATP molecules cannot diffuse across the lipid bilayer of the plasma membrane, conductive ATP release from the cytosol into the extracellular space is possible through ATP-permeable channels. Such channels must possess two minimum qualifications for ATP permeation: anion permeability and a large ion-conducting pore. Currently, five groups of channels are acknowledged as ATP-release channels: connexin hemichannels, pannexin 1, calcium homeostasis modulator 1 (CALHM1, volume-regulated anion channels (VRACs, also known as volume-sensitive outwardly rectifying (VSOR anion channels, and maxi-anion channels (MACs. Recently, major breakthroughs have been made in the field by molecular identification of CALHM1 as the action potential-dependent ATP-release channel in taste bud cells, LRRC8s as components of VRACs, and SLCO2A1 as a core subunit of MACs. Here, the function and physiological roles of these five groups of ATP-release channels are summarized, along with a discussion on the future implications of understanding these channels.

  16. Volume Regulated Channels

    DEFF Research Database (Denmark)

    Klausen, Thomas Kjær

    of volume perturbations evolution have developed system of channels and transporters to tightly control volume homeostasis. In the past decades evidence has been mounting, that the importance of these volume regulated channels and transporters are not restricted to the defense of cellular volume...... but are also essential for a number of physiological processes such as proliferation, controlled cell death, migration and endocrinology. The thesis have been focusing on two Channels, namely the swelling activated Cl- channel (ICl, swell) and the transient receptor potential Vanilloid (TRPV4) channel. I: Cl......- serves a multitude of functions in the mammalian cell, regulating the membrane potential (Em), cell volume, protein activity and the driving force for facilitated transporters giving Cl- and Cl- channels a major potential of regulating cellular function. These functions include control of the cell cycle...

  17. HIPPI and Fibre Channel

    International Nuclear Information System (INIS)

    Tolmie, D.E.

    1992-01-01

    The High-Performance Parallel Interface (HIPPI) and Fibre Channel are near-gigabit per second data communications interfaces being developed in ANSI standards Task Group X3T9.3. HIPPI is the current interface of choice in the high-end and supercomputer arena, and Fibre Channel is a follow-on effort. HIPPI came from a local area network background, and Fibre Channel came from a mainframe to peripheral interface background

  18. Nuclear reactor coolant channels

    International Nuclear Information System (INIS)

    Macbeth, R.V.

    1978-01-01

    Reference is made to coolant channels for pressurised water and boiling water reactors and the arrangement described aims to improve heat transfer between the fuel rods and the coolant. Baffle means extending axially within the channel are provided and disposed relative to the fuel rods so as to restrict flow oscillations occurring within the coolant from being propagated transversely to the axis of the channel. (UK)

  19. New Channels, New Possibilities

    DEFF Research Database (Denmark)

    Pieterson, Willem; Ebbers, Wolfgang; Østergaard Madsen, Christian

    2017-01-01

    In this contribution we discuss the characteristics of what we call the fourth generation of public sector service channels: social robots. Based on a review of relevant literature we discuss their characteristics and place into multi-channel models of service delivery. We argue that social robots......-channel models of service delivery. This is especially relevant given the current lack of evaluations of such models, the broad range of channels available, and their different stages of deployment at governments around the world. Nevertheless, social robots offer an potentially very relevant addition...

  20. Calcium Channel Blockers

    Science.gov (United States)

    ... Certain calcium channel blockers interact with grapefruit products. Kaplan NM, et al. Treatment of hypertension: Drug therapy. In: Kaplan's Clinical Hypertension. 11th ed. Philadelphia, Pa.: Wolters Kluwer ...

  1. A channel profile analyser

    International Nuclear Information System (INIS)

    Gobbur, S.G.

    1983-01-01

    It is well understood that due to the wide band noise present in a nuclear analog-to-digital converter, events at the boundaries of adjacent channels are shared. It is a difficult and laborious process to exactly find out the shape of the channels at the boundaries. A simple scheme has been developed for the direct display of channel shape of any type of ADC on a cathode ray oscilliscope display. This has been accomplished by sequentially incrementing the reference voltage of a precision pulse generator by a fraction of a channel and storing ADC data in alternative memory locations of a multichannel pulse height analyser. Alternative channels are needed due to the sharing at the boundaries of channels. In the flat region of the profile alternate memory locations are channels with zero counts and channels with the full scale counts. At the boundaries all memory locations will have counts. The shape of this is a direct display of the channel boundaries. (orig.)

  2. TRPA1 mediates changes in heart rate variability and cardiac mechanical function in mice exposed to acrolein

    Science.gov (United States)

    Short-term exposure to ambient air pollution is linked with adverse cardiovascular effects. While previous research focused primarily on particulate matter-induced responses, gaseous air pollutants also contribute to cause short-term cardiovascular effects. Mechanisms underlying ...

  3. Acrolein Causes TRPA1-Mediated Sensory Irritation and Indirect Potentiation of TRPV1-Mediated Pulmonary Chemoreflex Response

    Science.gov (United States)

    We previously demonstrated that acute exposure to acrolein causes immediate sensory irritation, with rapid decrease in heart rate (HR) and increase in inspiratory time (Ti), and potentiation of pulmonary chemoreflex response 24hrs later; of these effects only the latter is mediat...

  4. Co-exposure to inhaled ambient particulate matter and acrolein alters myocardial synchrony in mice: evidence for TRPA1 involvement

    Science.gov (United States)

    Because air pollution is a complex mixture of constituents, often including particulates and aldehydes, attributing health effects to air pollutants in a given ambient air shed can be difficult when pollutants are studied in isolation. The purpose of this study was to examine the...

  5. Oxaliplatin-Induced Peripheral Neuropathy via TRPA1 Stimulation in Mice Dorsal Root Ganglion Is Correlated with Aluminum Accumulation.

    Directory of Open Access Journals (Sweden)

    Jin-Hee Park

    Full Text Available Oxaliplatin is a platinum-based anticancer drug used to treat metastatic colorectal, breast, and lung cancers. While oxaliplatin kills cancer cells effectively, it exhibits several side effects of varying severity. Neuropathic pain is commonly experienced during treatment with oxaliplatin. Patients describe symptoms of paresthesias or dysesthesias that are triggered by cold (acute neuropathy, or as abnormal sensory or motor function (chronic neuropathy. In particular, we found that aluminum levels were relatively high in some cancer patients suffering from neuropathic pain based on clinical observations. Based on these findings, we hypothesized that aluminum accumulation in the dorsal root ganglion (DRG in the course of oxaliplatin treatment exacerbates neuropathic pain. In mice injected with oxaliplatin (three cycles of 3 mg/kg i.p. daily for 5 days, followed by 5 days of rest, we detected cold allodynia using the acetone test, but not heat hyperalgesia using a hot plate. However, co-treatment with aluminum chloride (AlCl3∙6H2O; 7 mg/kg i.p. for 14 days: equivalent 0.78 mg/kg of elemental Al and oxaliplatin (1 cycle of 3 mg/kg i.p. daily for 5 days, followed by 5 days of rest synergistically induced cold allodynia as well as increased TRPAl mRNA and protein expression. Inductively Coupled Plasma Mass Spectrometry (ICP-MS analysis showed a significant increase in aluminum concentrations in the DRG of mice treated with aluminum chloride and oxaliplatin compared to aluminum chloride alone. Similarly, in a mouse induced-tumor model, aluminum concentrations were increased in DRG tissue and tumor cells after oxaliplatin treatment. Taken together, these findings suggest that aluminum accumulation in the DRG may exacerbate neuropathic pain in oxaliplatin-treated mice.

  6. Channel Planform Dynamics Monitoring and Channel Stability Assessment in Two Sediment-Rich Rivers in Taiwan

    Directory of Open Access Journals (Sweden)

    Cheng-Wei Kuo

    2017-01-01

    Full Text Available Recurrent flood events induced by typhoons are powerful agents to modify channel morphology in Taiwan’s rivers. Frequent channel migrations reflect highly sensitive valley floors and increase the risk to infrastructure and residents along rivers. Therefore, monitoring channel planforms is essential for analyzing channel stability as well as improving river management. This study analyzed annual channel changes along two sediment-rich rivers, the Zhuoshui River and the Gaoping River, from 2008 to 2015 based on satellite images of FORMOSAT-2. Channel areas were digitized from mid-catchment to river mouth (~90 km. Channel stability for reaches was assessed through analyzing the changes of river indices including braid index, active channel width, and channel activity. In general, the valley width plays a key role in braided degree, active channel width, and channel activity. These indices increase as the valley width expands whereas the braid index decreases slightly close to the river mouth due to the change of river types. This downstream pattern in the Zhuoshui River was interrupted by hydraulic construction which resulted in limited changes downstream from the weir, due to the lack of water and sediment supply. A 200-year flood, Typhoon Morakot in 2009, induced significant changes in the two rivers. The highly active landscape in Taiwan results in very sensitive channels compared to other regions. An integrated Sensitivity Index was proposed for identifying unstable reaches, which could be a useful reference for river authorities when making priorities in river regulation strategy. This study shows that satellite image monitoring coupled with river indices analysis could be an effective tool to evaluate spatial and temporal changes in channel stability in highly dynamic river systems.

  7. A linearization of quantum channels

    Science.gov (United States)

    Crowder, Tanner

    2015-06-01

    Because the quantum channels form a compact, convex set, we can express any quantum channel as a convex combination of extremal channels. We give a Euclidean representation for the channels whose inverses are also valid channels; these are a subset of the extreme points. They form a compact, connected Lie group, and we calculate its Lie algebra. Lastly, we calculate a maximal torus for the group and provide a constructive approach to decomposing any invertible channel into a product of elementary channels.

  8. Omni channel fashion shopping

    NARCIS (Netherlands)

    Kemperman, A.D.A.M.; van Delft, L.; Borgers, A.W.J.; Pantano, E.

    2015-01-01

    This chapter gives insight into consumers' online and offline fashion shopping behavior, consumers' omni-channel usage during the shopping process, and consumer fashion shopper segments. Based on a literature review, omni-channel shopping behavior during the shopping process was operationalized.

  9. Major Channels Involved In Neuropsychiatric Disorders And Therapeutic Perspectives

    Directory of Open Access Journals (Sweden)

    Paola eImbrici

    2013-05-01

    Full Text Available Voltage-gated ion channels are important mediators of physiological functions in the central nervous system. The cyclic activation of these channels influences neurotransmitter release, neuron excitability, gene transcription and plasticity, providing distinct brain areas with unique physiological and pharmacological response. A growing body of data has implicated ion channels in the susceptibility or pathogenesis of psychiatric diseases. Indeed, population studies support the association of polymorphisms in calcium and potassium channels with the genetic risk for bipolar disorders or schizophrenia. Moreover, point mutations in calcium, sodium and potassium channel genes have been identified in some childhood developmental disorders. Finally, antibodies against potassium channel complexes occur in a series of autoimmune psychiatric diseases. Here we report recent studies assessing the role of calcium, sodium and potassium channels in bipolar disorder, schizophrenia and autism spectrum disorders, and briefly summarize promising pharmacological strategies targeted on ion channels for the therapy of mental illness and related genetic tests.

  10. Channel electron multipliers

    International Nuclear Information System (INIS)

    Seidman, A.; Avrahami, Z.; Sheinfux, B.; Grinberg, J.

    1976-01-01

    A channel electron multiplier is described having a tubular wall coated with a secondary-electron emitting material and including an electric field for accelerating the electrons, the electric field comprising a plurality of low-resistive conductive rings each alternating with a high-resistive insulating ring. The thickness of the low-resistive rings is many times larger than that of the high-resistive rings, being in the order of tens of microns for the low-resistive rings and at least one order of magnitude lower for the high-resistive rings; and the diameter of the channel tubular walls is also many times larger than the thickness of the high-resistive rings. Both single-channel and multiple-channel electron multipliers are described. A very important advantage, particularly in making multiple-channel multipliers, is the simplicity of the procedure that may be used in constructing such multipliers. Other operational advantages are described

  11. Cardiac potassium channel subtypes

    DEFF Research Database (Denmark)

    Schmitt, Nicole; Grunnet, Morten; Olesen, Søren-Peter

    2014-01-01

    About 10 distinct potassium channels in the heart are involved in shaping the action potential. Some of the K(+) channels are primarily responsible for early repolarization, whereas others drive late repolarization and still others are open throughout the cardiac cycle. Three main K(+) channels...... drive the late repolarization of the ventricle with some redundancy, and in atria this repolarization reserve is supplemented by the fairly atrial-specific KV1.5, Kir3, KCa, and K2P channels. The role of the latter two subtypes in atria is currently being clarified, and several findings indicate...... that they could constitute targets for new pharmacological treatment of atrial fibrillation. The interplay between the different K(+) channel subtypes in both atria and ventricle is dynamic, and a significant up- and downregulation occurs in disease states such as atrial fibrillation or heart failure...

  12. CHANNEL ESTIMATION TECHNIQUE

    DEFF Research Database (Denmark)

    2015-01-01

    A method includes determining a sequence of first coefficient estimates of a communication channel based on a sequence of pilots arranged according to a known pilot pattern and based on a receive signal, wherein the receive signal is based on the sequence of pilots transmitted over the communicat......A method includes determining a sequence of first coefficient estimates of a communication channel based on a sequence of pilots arranged according to a known pilot pattern and based on a receive signal, wherein the receive signal is based on the sequence of pilots transmitted over...... the communication channel. The method further includes determining a sequence of second coefficient estimates of the communication channel based on a decomposition of the first coefficient estimates in a dictionary matrix and a sparse vector of the second coefficient estimates, the dictionary matrix including...... filter characteristics of at least one known transceiver filter arranged in the communication channel....

  13. Coherifying quantum channels

    Science.gov (United States)

    Korzekwa, Kamil; Czachórski, Stanisław; Puchała, Zbigniew; Życzkowski, Karol

    2018-04-01

    Is it always possible to explain random stochastic transitions between states of a finite-dimensional system as arising from the deterministic quantum evolution of the system? If not, then what is the minimal amount of randomness required by quantum theory to explain a given stochastic process? Here, we address this problem by studying possible coherifications of a quantum channel Φ, i.e., we look for channels {{{Φ }}}{ \\mathcal C } that induce the same classical transitions T, but are ‘more coherent’. To quantify the coherence of a channel Φ we measure the coherence of the corresponding Jamiołkowski state J Φ. We show that the classical transition matrix T can be coherified to reversible unitary dynamics if and only if T is unistochastic. Otherwise the Jamiołkowski state {J}{{Φ }}{ \\mathcal C } of the optimally coherified channel is mixed, and the dynamics must necessarily be irreversible. To assess the extent to which an optimal process {{{Φ }}}{ \\mathcal C } is indeterministic we find explicit bounds on the entropy and purity of {J}{{Φ }}{ \\mathcal C }, and relate the latter to the unitarity of {{{Φ }}}{ \\mathcal C }. We also find optimal coherifications for several classes of channels, including all one-qubit channels. Finally, we provide a non-optimal coherification procedure that works for an arbitrary channel Φ and reduces its rank (the minimal number of required Kraus operators) from {d}2 to d.

  14. CANDU channel flow verification

    International Nuclear Information System (INIS)

    Mazalu, N.; Negut, Gh.

    1997-01-01

    The purpose of this evaluation was to obtain accurate information on each channel flow that enables us to assess precisely the level of reactor thermal power and, for reasons of safety, to establish which channel is boiling. In order to assess the channel flow parameters, computer simulations were done with the NUCIRC code and the results were checked by measurements. The complete channel flow measurements were made in the zero power cold condition. In hot conditions there were made flow measurements using the Shut Down System 1 (SDS 1) flow devices from 0.1 % F.P. up to 100 % F.P. The NUCIRC prediction for CANDU channel flows and the measurements by Ultrasonic Flow Meter at zero power cold conditions and SDS 1 flow channel measurements at different reactor power levels showed an acceptable agreement. The 100 % F.P. average errors for channel flow of R, shows that suitable NUCIRC flow assessment can be made. So, it can be done a fair prediction of the reactor power distribution. NUCIRC can predict accurately the onset of boiling and helps to warn at the possible power instabilities at high powers or it can detect the flow blockages. The thermal hydraulic analyst has in NUCIRC a suitable tool to do accurate predictions for the thermal hydraulic parameters for different steady state power levels which subsequently leads to an optimal CANDU reactor operation. (authors)

  15. Reconfigurable virtual electrowetting channels.

    Science.gov (United States)

    Banerjee, Ananda; Kreit, Eric; Liu, Yuguang; Heikenfeld, Jason; Papautsky, Ian

    2012-02-21

    Lab-on-a-chip systems rely on several microfluidic paradigms. The first uses a fixed layout of continuous microfluidic channels. Such lab-on-a-chip systems are almost always application specific and far from a true "laboratory." The second involves electrowetting droplet movement (digital microfluidics), and allows two-dimensional computer control of fluidic transport and mixing. The merging of the two paradigms in the form of programmable electrowetting channels takes advantage of both the "continuous" functionality of rigid channels based on which a large number of applications have been developed to date and the "programmable" functionality of digital microfluidics that permits electrical control of on-chip functions. In this work, we demonstrate for the first time programmable formation of virtual microfluidic channels and their continuous operation with pressure driven flows using an electrowetting platform. Experimental, theoretical, and numerical analyses of virtual channel formation with biologically relevant electrolyte solutions and electrically-programmable reconfiguration are presented. We demonstrate that the "wall-less" virtual channels can be formed reliably and rapidly, with propagation rates of 3.5-3.8 mm s(-1). Pressure driven transport in these virtual channels at flow rates up to 100 μL min(-1) is achievable without distortion of the channel shape. We further demonstrate that these virtual channels can be switched on-demand between multiple inputs and outputs. Ultimately, we envision a platform that would provide rapid prototyping of microfluidic concepts and would be capable of a vast library of functions and benefitting applications from clinical diagnostics in resource-limited environments to rapid system prototyping to high throughput pharmaceutical applications.

  16. Evaluation channel performance in multichannel environments

    NARCIS (Netherlands)

    Gensler, S.; Dekimpe, M.; Skiera, B.

    2007-01-01

    Evaluating channel performance is crucial for actively managing multiple sales channels, and requires understanding the customers' channel preferences. Two key components of channel performance are (i) the existing customers' intrinsic loyalty to a particular channel and (ii) the channel's ability

  17. Channel follower leakage restrictor

    International Nuclear Information System (INIS)

    Williamson, H.E.; Smith, B.A.

    1977-01-01

    An improved means is provided to control coolant leakage between the flow channel and the lower tie plate of a nuclear fuel assembly. The means includes an opening in the lower tie plate and a movable element adjacent thereto. The coolant pressure within the tie plate biases the movable means toward the inner surface of the surrounding flow channel to compensate for any movement of the flow channel away from the lower tie plate to thereby control the leakage of coolant flow from the fuel assemblies to the spaces among the fuel assemblies of the core. 9 figures

  18. Direct channel problems and phenomena

    International Nuclear Information System (INIS)

    Cutkosky, R.E.

    1975-01-01

    Direct channel problems and phenomena are considered covering the need for precision hadron spectroscopy, the data base for precision hadron spectroscopy, some relations between direct-channel and cross-channel effects, and spin rotation phenomena

  19. Plant ion channels: gene families, physiology, and functional genomics analyses.

    Science.gov (United States)

    Ward, John M; Mäser, Pascal; Schroeder, Julian I

    2009-01-01

    Distinct potassium, anion, and calcium channels in the plasma membrane and vacuolar membrane of plant cells have been identified and characterized by patch clamping. Primarily owing to advances in Arabidopsis genetics and genomics, and yeast functional complementation, many of the corresponding genes have been identified. Recent advances in our understanding of ion channel genes that mediate signal transduction and ion transport are discussed here. Some plant ion channels, for example, ALMT and SLAC anion channel subunits, are unique. The majority of plant ion channel families exhibit homology to animal genes; such families include both hyperpolarization- and depolarization-activated Shaker-type potassium channels, CLC chloride transporters/channels, cyclic nucleotide-gated channels, and ionotropic glutamate receptor homologs. These plant ion channels offer unique opportunities to analyze the structural mechanisms and functions of ion channels. Here we review gene families of selected plant ion channel classes and discuss unique structure-function aspects and their physiological roles in plant cell signaling and transport.

  20. Many channel spectrum unfolding

    International Nuclear Information System (INIS)

    Najzer, M.; Glumac, B.; Pauko, M.

    1980-01-01

    The principle of the ITER unfolding code as used for the many channel spectrum unfolding is described. Its unfolding ability is tested on seven typical neutron spectra. The effect of the initial spectrum approximation upon the solution is discussed

  1. Coding for optical channels

    CERN Document Server

    Djordjevic, Ivan; Vasic, Bane

    2010-01-01

    This unique book provides a coherent and comprehensive introduction to the fundamentals of optical communications, signal processing and coding for optical channels. It is the first to integrate the fundamentals of coding theory and optical communication.

  2. Sensing with Ion Channels

    CERN Document Server

    Martinac, Boris

    2008-01-01

    All living cells are able to detect and translate environmental stimuli into biologically meaningful signals. Sensations of touch, hearing, sight, taste, smell or pain are essential to the survival of all living organisms. The importance of sensory input for the existence of life thus justifies the effort made to understand its molecular origins. Sensing with Ion Channels focuses on ion channels as key molecules enabling biological systems to sense and process the physical and chemical stimuli that act upon cells in their living environment. Its aim is to serve as a reference to ion channel specialists and as a source of new information to non specialists who want to learn about the structural and functional diversity of ion channels and their role in sensory physiology.

  3. Calcium channel blocker poisoning

    Directory of Open Access Journals (Sweden)

    Miran Brvar

    2005-04-01

    Full Text Available Background: Calcium channel blockers act at L-type calcium channels in cardiac and vascular smooth muscles by preventing calcium influx into cells with resultant decrease in vascular tone and cardiac inotropy, chronotropy and dromotropy. Poisoning with calcium channel blockers results in reduced cardiac output, bradycardia, atrioventricular block, hypotension and shock. The findings of hypotension and bradycardia should suggest poisoning with calcium channel blockers.Conclusions: Treatment includes immediate gastric lavage and whole-bowel irrigation in case of ingestion of sustainedrelease products. All patients should receive an activated charcoal orally. Specific treatment includes calcium, glucagone and insulin, which proved especially useful in shocked patients. Supportive care including the use of catecholamines is not always effective. In the setting of failure of pharmacological therapy transvenous pacing, balloon pump and cardiopulmonary by-pass may be necessary.

  4. TRP channels: an overview

    DEFF Research Database (Denmark)

    Pedersen, Stine Falsig; Owsianik, Grzegorz; Nilius, Bernd

    2005-01-01

    The TRP ("transient receptor potential") family of ion channels now comprises more than 30 cation channels, most of which are permeable for Ca2+, and some also for Mg2+. On the basis of sequence homology, the TRP family can be divided in seven main subfamilies: the TRPC ('Canonical') family......, the TRPV ('Vanilloid') family, the TRPM ('Melastatin') family, the TRPP ('Polycystin') family, the TRPML ('Mucolipin') family, the TRPA ('Ankyrin') family, and the TRPN ('NOMPC') family. The cloning and characterization of members of this cation channel family has exploded during recent years, leading...... to a plethora of data on the roles of TRPs in a variety of tissues and species, including mammals, insects, and yeast. The present review summarizes the most pertinent recent evidence regarding the structural and functional properties of TRP channels, focusing on the regulation and physiology of mammalian TRPs....

  5. Authentication over Noisy Channels

    OpenAIRE

    Lai, Lifeng; Gamal, Hesham El; Poor, H. Vincent

    2008-01-01

    In this work, message authentication over noisy channels is studied. The model developed in this paper is the authentication theory counterpart of Wyner's wiretap channel model. Two types of opponent attacks, namely impersonation attacks and substitution attacks, are investigated for both single message and multiple message authentication scenarios. For each scenario, information theoretic lower and upper bounds on the opponent's success probability are derived. Remarkably, in both scenarios,...

  6. Channelling versus inversion

    DEFF Research Database (Denmark)

    Gale, A.S.; Surlyk, Finn; Anderskouv, Kresten

    2013-01-01

    Evidence from regional stratigraphical patterns in Santonian−Campanian chalk is used to infer the presence of a very broad channel system (5 km across) with a depth of at least 50 m, running NNW−SSE across the eastern Isle of Wight; only the western part of the channel wall and fill is exposed. W......−Campanian chalks in the eastern Isle of Wight, involving penecontemporaneous tectonic inversion of the underlying basement structure, are rejected....

  7. Stream Channel Stability.

    Science.gov (United States)

    1981-04-01

    Cycles of wetting and drying are also t ,v itiue swelling and shrinkage of the soil. S 11ied blocks or peds of soil fabric ,,ks. id downslope soil creep ...hydrographs of water and sediment at the point in question. By feeding the output from the hydrology-transport model into the finite element model...the banks as undercut banks fail. Channel irregularities such as seepage zones, cattle crossings, overbank drainage, buried channels, organic deposits

  8. Channeling and dynamic chaos

    Energy Technology Data Exchange (ETDEWEB)

    Bolotin, IU L; Gonchar, V IU; Truten, V I; Shulga, N F

    1986-01-01

    It is shown that axial channeling of relativistic electrons can give rise to the effect of dynamic chaos which involves essentially chaotic motion of a particle in the channel. The conditions leading to the effect of dynamic chaos and the manifestations of this effect in physical processes associated with the passage of particles through a crystal are examined using a silicon crystal as an example. 7 references.

  9. Calcium homeostasis modulator (CALHM) ion channels.

    Science.gov (United States)

    Ma, Zhongming; Tanis, Jessica E; Taruno, Akiyuki; Foskett, J Kevin

    2016-03-01

    Calcium homeostasis modulator 1 (CALHM1), formerly known as FAM26C, was recently identified as a physiologically important plasma membrane ion channel. CALHM1 and its Caenorhabditis elegans homolog, CLHM-1, are regulated by membrane voltage and extracellular Ca(2+) concentration ([Ca(2+)]o). In the presence of physiological [Ca(2+)]o (∼1.5 mM), CALHM1 and CLHM-1 are closed at resting membrane potentials but can be opened by strong depolarizations. Reducing [Ca(2+)]o increases channel open probability, enabling channel activation at negative membrane potentials. Together, voltage and Ca(2+) o allosterically regulate CALHM channel gating. Through convergent evolution, CALHM has structural features that are reminiscent of connexins and pannexins/innexins/LRRC8 (volume-regulated anion channel (VRAC)) gene families, including four transmembrane helices with cytoplasmic amino and carboxyl termini. A CALHM1 channel is a hexamer of CALHM1 monomers with a functional pore diameter of ∼14 Å. CALHM channels discriminate poorly among cations and anions, with signaling molecules including Ca(2+) and ATP able to permeate through its pore. CALHM1 is expressed in the brain where it plays an important role in cortical neuron excitability induced by low [Ca(2+)]o and in type II taste bud cells in the tongue that sense sweet, bitter, and umami tastes where it functions as an essential ATP release channel to mediate nonsynaptic neurotransmitter release. CLHM-1 is expressed in C. elegans sensory neurons and body wall muscles, and its genetic deletion causes locomotion defects. Thus, CALHM is a voltage- and Ca(2+) o-gated ion channel, permeable to large cations and anions, that plays important roles in physiology.

  10. Course on Ionic Channels

    CERN Document Server

    1986-01-01

    This book is based on a series of lectures for a course on ionic channels held in Santiago, Chile, on November 17-20, 1984. It is intended as a tutorial guide on the properties, function, modulation, and reconstitution of ionic channels, and it should be accessible to graduate students taking their first steps in this field. In the presentation there has been a deliberate emphasis on the spe­ cific methodologies used toward the understanding of the workings and function of channels. Thus, in the first section, we learn to "read" single­ channel records: how to interpret them in the theoretical frame of kinetic models, which information can be extracted from gating currents in re­ lation to the closing and opening processes, and how ion transport through an open channel can be explained in terms of fluctuating energy barriers. The importance of assessing unequivocally the origin and purity of mem­ brane preparations and the use of membrane vesicles and optical tech­ niques in the stUGY of ionic channels a...

  11. Channel Bottom Morphology in the Deltaic Reach of the Song Hau (mekong) River Channel in Vietnam

    Science.gov (United States)

    Allison, M. A.; Weathers, H. D., III; Meselhe, E. A.

    2016-02-01

    Boat-based, channel bathymetry and bankline elevation studies were conducted in the tidal and estuarine Mekong River channel using multibeam bathymetry and LIDAR corrected for elevation by RTK satellite positioning. Two mapping campaigns, one at high discharge in October 2014 and one at low discharge in March 2015, were conducted in the lower 100 km reach of the Song Hau distributary channel to (1) examine bottom morphology and its relationship to sediment transport, and (2) to provide information to setup the grid for a multi-dimensional and reduced complexity models of channel hydrodynamics and sediment dynamics. Sand fields were identified in multibeam data by the presence of dunes that were as large as 2-4 m high and 40-80 m wavelength and by clean sands in bottom grabs. Extensive areas of sand at the head and toe of mid-channel islands displayed 10-25 m diameter circular pits that could be correlated with bucket dredge, sand mining activities observed at some of the sites. Large areas of the channel floor were relict (containing little or no modern sediment) in the high discharge campaign, identifiable by the presence of along channel erosional furrows and terraced outcrops along the channel floor and margins. Laterally extensive flat areas were also observed in the channel thalweg. Both these and the relict areas were sampled by bottom grab as stiff silty clays. Complex cross-channel combinations of these morphologies were observed in some transects, suggesting strong bottom steering of tidal and riverine currents. Relative to high discharge, transects above and below the salt penetration limit showed evidence of shallowing in the thalweg and adjacent sloping areas at low discharge in March 2015. This shallowing, combined with the reduced extent of sand fields and furrowed areas, and soft muds in grabs, suggests seasonal trapping of fine grained sediment is occurring by estuarine and tidal circulation.

  12. Ion channelling in diamond

    International Nuclear Information System (INIS)

    Derry, T.E.

    1978-06-01

    Diamond is one of the most extreme cases from a channelling point of view, having the smallest thermal vibration amplitude and the lowest atomic number of commonly-encountered crystals. These are the two parameters most important for determining channelling behaviour. It is of consiberable interest therefore to see how well the theories explaining and predicting the channeling properties of other substance, succeed with diamond. Natural diamond, although the best available form for these experiments, is rather variable in its physical properties. Part of the project was devoted to considering and solving the problem of obtaining reproducible results representative of the ideal crystal. Channelling studies were performed on several good crystals, using the Rutherford backscattering method. Critical angles for proton channelling were measured for incident energies from 0.6 to 4.5 MeV, in the three most open axes and three most open planes of the diamond structure, and for α-particle channelling at 0.7 and 1.0 MeV (He + ) in the same axes and planes. For 1.0 MeV protons, the crystal temperature was varied from 20 degrees Celsius to 700 degrees Celsius. The results are presented as curves of backscattered yield versus angle in the region of each axis or plane, and summarised in the form of tables and graphs. Generally the critical angles, axial minimum yields, and temperature dependence are well predicted by the accepted theories. The most valuable overall conclusion is that the mean thermal vibration amplitude of the atoms in a crytical determines the critical approach distance to the channel walls at which an ion can remain channelled, even when this distance is much smaller than the Thomas-Fermi screening distance of the atomic potential, as is the case in diamond. A brief study was made of the radiation damage caused by α-particle bombardment, via its effect on the channelling phenomenon. It was possible to hold damage down to negligible levels during the

  13. Channel Choice: A Literature Review

    DEFF Research Database (Denmark)

    Østergaard Madsen, Christian; Kræmmergaard, Pernille

    2015-01-01

    The channel choice branch of e-government studies citizens’ and businesses’ choice of channels for interacting with government, and how government organizations can integrate channels and migrate users towards the most cost-efficient channels. In spite of the valuable contributions offered...

  14. Applying alpha-channeling to mirror machines

    Energy Technology Data Exchange (ETDEWEB)

    Zhmoginov, A. I.; Fisch, N. J. [Department of Astrophysical Sciences, Princeton University, Princeton, New Jersey 08544 (United States)

    2012-05-15

    The {alpha}-channeling effect entails the use of radio-frequency waves to expel and cool high-energetic {alpha} particles born in a fusion reactor; the device reactivity can then be increased even further by redirecting the extracted energy to fuel ions. Originally proposed for tokamaks, this technique has also been shown to benefit open-ended fusion devices. Here, the fundamental theory and practical aspects of {alpha} channeling in mirror machines are reviewed, including the influence of magnetic field inhomogeneity and the effect of a finite wave region on the {alpha}-channeling mechanism. For practical implementation of the {alpha}-channeling effect in mirror geometry, suitable contained weakly damped modes are identified. In addition, the parameter space of candidate waves for implementing the {alpha}-channeling effect can be significantly extended through the introduction of a suitable minority ion species that has the catalytic effect of moderating the transfer of power from the {alpha}-channeling wave to the fuel ions.

  15. A novel potassium channel in photosynthetic cyanobacteria.

    Directory of Open Access Journals (Sweden)

    Manuela Zanetti

    Full Text Available Elucidation of the structure-function relationship of a small number of prokaryotic ion channels characterized so far greatly contributed to our knowledge on basic mechanisms of ion conduction. We identified a new potassium channel (SynK in the genome of the cyanobacterium Synechocystis sp. PCC6803, a photosynthetic model organism. SynK, when expressed in a K(+-uptake-system deficient E. coli strain, was able to recover growth of these organisms. The protein functions as a potassium selective ion channel when expressed in Chinese hamster ovary cells. The location of SynK in cyanobacteria in both thylakoid and plasmamembranes was revealed by immunogold electron microscopy and Western blotting of isolated membrane fractions. SynK seems to be conserved during evolution, giving rise to a TPK (two-pore K(+ channel family member which is shown here to be located in the thylakoid membrane of Arabidopsis. Our work characterizes a novel cyanobacterial potassium channel and indicates the molecular nature of the first higher plant thylakoid cation channel, opening the way to functional studies.

  16. Cryogenic microwave channelized receiver

    International Nuclear Information System (INIS)

    Rauscher, C.; Pond, J.M.; Tait, G.B.

    1996-01-01

    The channelized receiver being presented demonstrates the use of high temperature superconductor technology in a microwave system setting where superconductor, microwave-monolithic-integrated-circuit, and hybrid-integrated-circuit components are united in one package and cooled to liquid-nitrogen temperatures. The receiver consists of a superconducting X-band four-channel demultiplexer with 100-MHz-wide channels, four commercial monolithically integrated mixers, and four custom-designed hybrid-circuit detectors containing heterostructure ramp diodes. The composite receiver unit has been integrated into the payload of the second-phase NRL high temperature superconductor space experiment (HTSSE-II). Prior to payload assembly, the response characteristics of the receiver were measured as functions of frequency, temperature, and drive levels. The article describes the circuitry, discusses the key issues related to design and implementation, and summarizes the experimental results

  17. Chaos in quantum channels

    Energy Technology Data Exchange (ETDEWEB)

    Hosur, Pavan; Qi, Xiao-Liang [Department of Physics, Stanford University,476 Lomita Mall, Stanford, California 94305 (United States); Roberts, Daniel A. [Center for Theoretical Physics and Department of Physics, Massachusetts Institute of Technology,77 Massachusetts Ave, Cambridge, Massachusetts 02139 (United States); Yoshida, Beni [Perimeter Institute for Theoretical Physics,31 Caroline Street North, Waterloo, Ontario N2L 2Y5 (Canada); Walter Burke Institute for Theoretical Physics, California Institute of Technology,1200 E California Blvd, Pasadena CA 91125 (United States)

    2016-02-01

    We study chaos and scrambling in unitary channels by considering their entanglement properties as states. Using out-of-time-order correlation functions to diagnose chaos, we characterize the ability of a channel to process quantum information. We show that the generic decay of such correlators implies that any input subsystem must have near vanishing mutual information with almost all partitions of the output. Additionally, we propose the negativity of the tripartite information of the channel as a general diagnostic of scrambling. This measures the delocalization of information and is closely related to the decay of out-of-time-order correlators. We back up our results with numerics in two non-integrable models and analytic results in a perfect tensor network model of chaotic time evolution. These results show that the butterfly effect in quantum systems implies the information-theoretic definition of scrambling.

  18. Distribution Channels Conflict and Management

    OpenAIRE

    Kiran, Dr Vasanth; Majumdar, Dr Mousumi; Kishore, Dr Krishna

    2012-01-01

    Relationships in distribution channels tend to be long-term oriented and members of the channel rely on each other to jointly realize their goals by serving buyers. Despite the channels focus on serving buyers, conflicts often arise between channel members because of each members self-interest. When conflicts arise, the perceptions of a channel member based on normative, rational/instrumental, or emotional reasoning will influence relational norms like trust and commitment that characterize t...

  19. Role of TRP Channels in Dinoflagellate Mechanotransduction.

    Science.gov (United States)

    Lindström, J B; Pierce, N T; Latz, M I

    2017-10-01

    Transient receptor potential (TRP) ion channels are common components of mechanosensing pathways, mainly described in mammals and other multicellular organisms. To gain insight into the evolutionary origins of eukaryotic mechanosensory proteins, we investigated the involvement of TRP channels in mechanosensing in a unicellular eukaryotic protist, the dinoflagellate Lingulodinium polyedra. BLASTP analysis of the protein sequences predicted from the L. polyedra transcriptome revealed six sequences with high similarity to human TRPM2, TRPM8, TRPML2, TRPP1, and TRPP2; and characteristic TRP domains were identified in all sequences. In a phylogenetic tree including all mammalian TRP subfamilies and TRP channel sequences from unicellular and multicellular organisms, the L. polyedra sequences grouped with the TRPM, TPPML, and TRPP clades. In pharmacological experiments, we used the intrinsic bioluminescence of L. polyedra as a reporter of mechanoresponsivity. Capsaicin and RN1734, agonists of mammalian TRPV, and arachidonic acid, an agonist of mammalian TRPV, TRPA, TRPM, and Drosophila TRP, all stimulated bioluminescence in L. polyedra. Mechanical stimulation of bioluminescence, but not capsaicin-stimulated bioluminescence, was inhibited by gadolinium (Gd 3+ ), a general inhibitor of mechanosensitive ion channels, and the phospholipase C (PLC) inhibitor U73122. These pharmacological results are consistent with the involvement of TRP-like channels in mechanosensing by L. polyedra. The TRP channels do not appear to be mechanoreceptors but rather are components of the mechanotransduction signaling pathway and may be activated via a PLC-dependent mechanism. The presence and function of TRP channels in a dinoflagellate emphasize the evolutionary conservation of both the channel structures and their functions.

  20. Fuel channel refilling

    International Nuclear Information System (INIS)

    Shoukri, M.; Abdul-Razzak, A.

    1992-11-01

    This report extends the work reported in document INFO-0370 on fuel channel refilling by providing analysis of the refilling tests conducted using the RD-14 and RD-14M test facilities. The analysis focuses on the general thermal-hydraulic characteristics of the facilities following various small and large inlet and outlet header breaks with emergency coolant injection. The two-fluid model thermal-hydraulic computer code CATHENA was tested against results obtained from selected experiments carried out in the two facilities. Conclusions related to the effect of break size, mode of emergency core injection, primary pump operation and parallel channels are presented. (Author) (116 figs., 17 tabs., 53 refs.)

  1. Ion channels in glioblastoma.

    Science.gov (United States)

    Molenaar, Remco J

    2011-01-01

    Glioblastoma is the most common primary brain tumor with the most dismal prognosis. It is characterized by extensive invasion, migration, and angiogenesis. Median survival is only 15 months due to this behavior, rendering focal surgical resection ineffective and adequate radiotherapy impossible. At this moment, several ion channels have been implicated in glioblastoma proliferation, migration, and invasion. This paper summarizes studies on potassium, sodium, chloride, and calcium channels of glioblastoma. It provides an up-to-date overview of the literature that could ultimately lead to new therapeutic targets.

  2. Fuel channel refilling

    International Nuclear Information System (INIS)

    Shoukri, M.; Abdul-Razzak, A.

    1990-04-01

    Analysis of existing data on fuel channel refilling is presented. The analysis focuses on the data obtained using the Stern Laboratories Cold Water Injection Test (CWIT) Facility. The two-fluid model thermal-hydraulics computer code CATHENA is also used to simulate experimental results on fuel channel refilling from both the CWIT and RD-14 facilities. Conclusions related to single and double break tests, including the effect of non-condensible gases, are presented. A set of recommendations is given for further analysis and separate effect experiments. (67 figs., 5 tabs., 24 refs.)

  3. Distinctive fingerprints of erosional regimes in terrestrial channel networks

    Science.gov (United States)

    Grau Galofre, A.; Jellinek, M.

    2017-12-01

    Satellite imagery and digital elevation maps capture the large scale morphology of channel networks attributed to long term erosional processes, such as fluvial, glacial, groundwater sapping and subglacial erosion. Characteristic morphologies associated with each of these styles of erosion have been studied in detail, but there exists a knowledge gap related to their parameterization and quantification. This knowledge gap prevents a rigorous analysis of the dominant processes that shaped a particular landscape, and a comparison across styles of erosion. To address this gap, we use previous morphological descriptions of glaciers, rivers, sapping valleys and tunnel valleys to identify and measure quantitative metrics diagnostic of these distinctive styles of erosion. From digital elevation models, we identify four geometric metrics: The minimum channel width, channel aspect ratio (longest length to channel width at the outlet), presence of undulating longitudinal profiles, and tributary junction angle. We also parameterize channel network complexity in terms of its stream order and fractal dimension. We then perform a statistical classification of the channel networks using a Principal Component Analysis on measurements of these six metrics on a dataset of 70 channelized systems. We show that rivers, glaciers, groundwater seepage and subglacial meltwater erode the landscape in rigorously distinguishable ways. Our methodology can more generally be applied to identify the contributions of different processes involved in carving a channel network. In particular, we are able to identify transitions from fluvial to glaciated landscapes or vice-versa.

  4. Sub-nanometre channels embedded in two-dimensional materials

    KAUST Repository

    Han, Yimo; Li, Ming-yang; Jung, Gang-Seob; Marsalis, Mark A.; Qin, Zhao; Buehler, Markus J.; Li, Lain-Jong; Muller, David A.

    2017-01-01

    with the embedding 2D matrix. Periodic dislocation arrays produce 2D superlattices of coherent MoS2 1D channels in WSe2. Using molecular dynamics simulations, we have identified other combinations of 2D materials where 1D channels can also be formed. The electronic

  5. MITOCHONDRIAL BKCa CHANNEL

    Directory of Open Access Journals (Sweden)

    Enrique eBalderas

    2015-03-01

    Full Text Available Since its discovery in a glioma cell line 15 years ago, mitochondrial BKCa channel (mitoBKCa has been studied in brain cells and cardiomyocytes sharing general biophysical properties such as high K+ conductance (~300 pS, voltage-dependency and Ca2+-sensitivity. Main advances in deciphering the molecular composition of mitoBKCa have included establishing that it is encoded by the Kcnma1 gene, that a C-terminal splice insert confers mitoBKCa ability to be targeted to cardiac mitochondria, and evidence for its potential coassembly with β subunits. Notoriously, β1 subunit directly interacts with cytochrome c oxidase and mitoBKCa can be modulated by substrates of the respiratory chain. mitoBKCa channel has a central role in protecting the heart from ischemia, where pharmacological activation of the channel impacts the generation of reactive oxygen species and mitochondrial Ca2+ preventing cell death likely by impeding uncontrolled opening of the mitochondrial transition pore. Supporting this view, inhibition of mitoBKCa with Iberiotoxin, enhances cytochrome c release from glioma mitochondria. Many tantalizing questions remain. Some of them are: how is mitoBKCa coupled to the respiratory chain? Does mitoBKCa play non-conduction roles in mitochondria physiology? Which are the functional partners of mitoBKCa? What are the roles of mitoBKCa in other cell types? Answers to these questions are essential to define the impact of mitoBKCa channel in mitochondria biology and disease.

  6. Chemistry in Microfluidic Channels

    Science.gov (United States)

    Chia, Matthew C.; Sweeney, Christina M.; Odom, Teri W.

    2011-01-01

    General chemistry introduces principles such as acid-base chemistry, mixing, and precipitation that are usually demonstrated in bulk solutions. In this laboratory experiment, we describe how chemical reactions can be performed in a microfluidic channel to show advanced concepts such as laminar fluid flow and controlled precipitation. Three sets of…

  7. Workshop on Gas Channels

    Science.gov (United States)

    2013-02-07

    Effect of pressure on gas permeability. In Fish … Different channels or splice variants at different depth.  HRE (hypoxia-response elements): which...proteins unexpectedly have HREs . HIF-1.  Shear stress:  expression of NOS  Are different splice variants used under different conditions?  Size

  8. Improving the service life and performance of CANDU fuel channels

    International Nuclear Information System (INIS)

    Causey, A.R.; Cheadle, B.A.; Coleman, C.E.; Price, E.G.

    1997-01-01

    The development objective for CANDU fuel channels is to produce a design that can operate for 40 years at 90% capacity. Steady progress toward this objective is being made. The factors that determine the life of the channel are reviewed and the processes necessary to achieve the objectives identified. Performance of future fuel channels will be enhanced by reduced operating costs, increased safety margins to postulated accident conditions, and reduced retubing costs compared to current channels. The approaches to these issues are discussed briefly in the paper. (author)

  9. Improving the service life and performance of CANDU fuel channels

    International Nuclear Information System (INIS)

    Causey, A.R.; Cheadle, B.A.; Coleman, C.E.; Price, E.G.

    1996-02-01

    The development objective for CANDU fuel channels is to produce a design that can operate for 40 years at 90% capacity. Steady progress toward this objective is being made. The factors that determine the life of a CANDU fuel channel are reviewed and the processes necessary to achieve the objectives identified. Performance of future fuel channels will be enhanced by reduced operating costs, increased safety margins to postulated accident conditions, and reduced retubing costs compared with those for current channels. The approaches to these issues are discussed briefly in this report. (author). 14 refs., 1 tab., 8 figs

  10. Improving the service life and performance of CANDU fuel channels

    International Nuclear Information System (INIS)

    Coleman, C.E.; Cheadle, B.A.; Causey, A.R.; Doubt, G.L.; Fong, R.W.L.; Venkatapathi, S.

    1996-03-01

    The development objective for CANDU fuel channels is to produce a design that can operate for 40 years at 90% capacity. Steady progress toward this objective is being made. The factors that determine the life of a CANDU fuel channel are reviewed and the processes necessary to achieve the objectives are identified. Performance of future fuel channels will be enhanced by reduced operating costs and increased safety margins to postulated accident conditions compared with those for current channels. The approaches to these issues are discussed briefly in this report. (author)

  11. The least channel capacity for chaos synchronization.

    Science.gov (United States)

    Wang, Mogei; Wang, Xingyuan; Liu, Zhenzhen; Zhang, Huaguang

    2011-03-01

    Recently researchers have found that a channel with capacity exceeding the Kolmogorov-Sinai entropy of the drive system (h(KS)) is theoretically necessary and sufficient to sustain the unidirectional synchronization to arbitrarily high precision. In this study, we use symbolic dynamics and the automaton reset sequence to distinguish the information that is required in identifying the current drive word and obtaining the synchronization. Then, we show that the least channel capacity that is sufficient to transmit the distinguished information and attain the synchronization of arbitrarily high precision is h(KS). Numerical simulations provide support for our conclusions.

  12. Deep Learning for Distribution Channels' Management

    Directory of Open Access Journals (Sweden)

    Sabina-Cristiana NECULA

    2017-01-01

    Full Text Available This paper presents an experiment of using deep learning models for distribution channel management. We present an approach that combines self-organizing maps with artificial neural network with multiple hidden layers in order to identify the potential sales that might be addressed for channel distribution change/ management. Our study aims to highlight the evolution of techniques from simple features/learners to more complex learners and feature engineering or sampling techniques. This paper will allow researchers to choose best suited techniques and features to prepare their churn prediction models.

  13. Pathophysiological Role of Transient Receptor Potential Ankyrin 1 in a Mouse Long-Lasting Cystitis Model Induced by an Intravesical Injection of Hydrogen Peroxide

    Directory of Open Access Journals (Sweden)

    Shohei Oyama

    2017-11-01

    Full Text Available Chronic inflammatory bladder disorders, such as interstitial cystitis/bladder pain syndrome, are associated with poor quality of life. The exact pathological processes remain unclear, but accumulating evidence suggests that reactive oxidative species (ROS are involved in urinary bladder disorders. Transient receptor potential ankyrin 1 (TRPA1, the most sensitive TRP channel to ROS, was shown to be responsible for urinary bladder abnormalities and hyperalgesia in an acute cystitis model. However, the roles of TRPA1 in chronic inflammatory bladder are not fully understood. We previously established a novel mouse cystitis model induced by intravesical injection of hydrogen peroxide (H2O2, resulting in long-lasting frequent urination, bladder inflammation, pain-related behavior, and histopathological changes. In the present study, we investigated the pathophysiological role of TRPA1 in the H2O2-induced long-lasting cystitis mouse model. Under anesthesia, 1.5% H2O2 solution was introduced transurethrally into the bladder of female wild-type (WT and TRPA1-knockout mice and maintained for 30 min. This increased the number of voids in WT mice at 1 and 7 days after injection, but reduced the number in TRPA1-knockout mice at 1 day but not 7 days after injection. Spontaneous locomotor activities (increase in freezing time and decrease in distance moved were reduced at 3 h after injection in WT mice, whereas the spontaneous visceral pain-related behaviors were attenuated in TRPA1-knockout mice. Furthermore, upregulation of c-fos mRNA in the spinal cord at 1 day after injection was observed in WT but not TRPA1-knockout mice. However, there was no difference in histopathological changes in the urinary bladder, such as edematous thickening in the submucosa, between WT and TRPA1-knockout mice at 1 or 7 days after injection. Finally, Trpa1 mRNA levels in the L5-S1 dorsal root ganglion were not altered, but levels in the urinary bladder were drastically increased

  14. A methodology for delineating planning-level channel migration zones.

    Science.gov (United States)

    2014-07-01

    The Washington State administrative codes that implement the Shoreline Management Act (SMA) require communities to identify the general location of channel migration zones (CMZs), and regulate development within these areas on shoreline streams. Shor...

  15. Quantum communication under channel uncertainty

    International Nuclear Information System (INIS)

    Noetzel, Janis Christian Gregor

    2012-01-01

    This work contains results concerning transmission of entanglement and subspaces as well as generation of entanglement in the limit of arbitrary many uses of compound- and arbitrarily varying quantum channels (CQC, AVQC). In both cases, the channel is described by a set of memoryless channels. Only forward communication between one sender and one receiver is allowed. A code is said to be ''good'' only, if it is ''good'' for every channel out of the set. Both settings describe a scenario, in which sender and receiver have only limited channel knowledge. For different amounts of information about the channel available to sender or receiver, coding theorems are proven for the CQC. For the AVQC, both deterministic and randomised coding schemes are considered. Coding theorems are proven, as well as a quantum analogue of the Ahlswede-dichotomy. The connection to zero-error capacities of stationary memoryless quantum channels is investigated. The notion of symmetrisability is defined and used for both classes of channels.

  16. Acoustic Imaging of a Turbidity Current Flowing along a Channel

    Science.gov (United States)

    Hughes Clarke, J. E.; Hiroji, A.; Cahill, L.; Fedele, J. J.

    2017-12-01

    As part of a 3 month sequence of repetitive surveys and ADCP monitoring, more than 30 turbidity currents have been identified modifying a lobe channel in 130 to 190m of water on the Squamish prodelta. For a 6 day period, daily surveys at low tide tried to capture the change resulting from a single flow. On the 8thof June three flows occurred within a half hour. Along channel multibeam images of the seabed and water column were obtained from a moving vessel immediately before, during and after the passage of the third flow. In this manner the spatial extent of the in-channel and overbank flow could be constrained. By following the flow, the spatial pattern of scattering from the flow upper surface could be examined over a 2 km length of the channel. Along channel bands of high scattering appear related to enhanced release of gas along the channel flanks. Notably, no signature of the underlying across-channel bedform modulations were evident, suggesting that the upper surface of the flow does not feel the influence of the channel floor. Overbank spillage of the flow could be detected by perturbation of a plankton scattering layer just above the seabed. Additionally, evidence of enhanced overbank deposition due to flow stripping on the outer corner of a bend was identified from backscatter changes. The specific seabed alteration due to this flow could be identified and compared with the cumulative change over three months in the channel and adjacent channel-lobe transition zone. As the flow passed under the ADCP, it had a peak velocity of over 2 m/s, a thickness of 4-5m and duration of 35 minutes. Based on the timing of the flow head when in view of the surface vessel, it was decelerating as it exited the mouth of the channel.

  17. VAX CAMAC channel

    International Nuclear Information System (INIS)

    Nelson, D.J.; Breidenbach, M.; Granieri, C.D.; Grund, J.E.; Patrick, J.F.; Weaver, L.J.

    1980-10-01

    A new generation CAMAC System has been developed for the Mark II Detector at SLAC's PEP storage ring. This flexible system can efficiently transfer data between a host computer and a very large set of CAMAC data acquisition and control modules. A bipolar microprocessor operates as a Channel interface by supervising the CAMAC system and minimizing the host computer's work. This programmable channel couples the host to a set of System Crates; each System Crate houses Branch Drivers that can directly control a set of crates or communicate over differential parallel highways to Branch Receivers for control of distant crates. A coherent software package integrates the high level programs, system driver level programs, and microcode control of the system

  18. Geysering in boiling channels

    Energy Technology Data Exchange (ETDEWEB)

    Aritomi, Masanori; Takemoto, Takatoshi [Tokyo Institute of Technology, Tokyo (Japan); Chiang, Jing-Hsien [Japan NUS Corp. Ltd., Toyko (Japan)] [and others

    1995-09-01

    A concept of natural circulation BWRs such as the SBWR has been proposed and seems to be promising in that the primary cooling system can be simplified. The authors have been investigating thermo-hydraulic instabilities which may appear during the start-up in natural circulation BWRs. In our previous works, geysering was investigated in parallel boiling channels for both natural and forced circulations, and its driving mechanism and the effect of system pressure on geysering occurrence were made clear. In this paper, geysering is investigated in a vertical column and a U-shaped vertical column heated in the lower parts. It is clarified from the results that the occurrence mechanism of geysering and the dependence of system pressure on geysering occurrence coincide between parallel boiling channels in circulation systems and vertical columns in non-circulation systems.

  19. Coolant channel module CCM

    International Nuclear Information System (INIS)

    Hoeld, Alois

    2007-01-01

    A complete and detailed description of the theoretical background of an '(1D) thermal-hydraulic drift-flux based mixture-fluid' coolant channel model and its resulting module CCM will be presented. The objective of this module is to simulate as universally as possible the steady state and transient behaviour of the key characteristic parameters of a single- or two-phase fluid flowing within any type of heated or non-heated coolant channel. Due to the possibility that different flow regimes can appear along any channel, such a 'basic (BC)' 1D channel is assumed to be subdivided into a number of corresponding sub-channels (SC-s). Each SC can belong to only two types of flow regime, an SC with just a single-phase fluid, containing exclusively either sub-cooled water or superheated steam, or an SC with a two-phase mixture flow. After an appropriate nodalisation of such a BC (and therefore also its SC-s) a 'modified finite volume method' has been applied for the spatial discretisation of the partial differential equations (PDE-s) which represent the basic conservation equations of thermal-hydraulics. Special attention had to be given to the possibility of variable SC entrance or outlet positions (which describe boiling boundaries or mixture levels) and thus the fact that an SC can even disappear or be created anew. The procedure yields for each SC type (and thus the entire BC), a set of non-linear ordinary 1st order differential equations (ODE-s). To link the resulting mean nodal with the nodal boundary function values, both of which are present in the discretised differential equations, a special quadratic polygon approximation procedure (PAX) had to be constructed. Together with the very thoroughly tested packages for drift-flux, heat transfer and single- and two-phase friction factors this procedure represents the central part of the here presented 'Separate-Region' approach, a theoretical model which provides the basis to the very effective working code package CCM

  20. Tourism distribution channels

    OpenAIRE

    Camilleri, Mark Anthony

    2017-01-01

    The distribution channels link the customers with the businesses. For many years, the tourism businesses may have distributed their products and services through intermediaries. However, the latest advances in technology have brought significant changes in this regard. More individuals and corporate customers are increasingly benefiting of ubiquitous technologies, including digital media. The development of mobile devices and their applications, are offering a wide range of possibilities to t...

  1. Athermal channeled spectropolarimeter

    Science.gov (United States)

    Jones, Julia Craven

    2015-12-08

    A temperature insensitive (athermal) channeled spectropolarimeter (CSP) is described. The athermal CSP includes a crystal retarder formed of a biaxial crystal. The crystal retarder has three crystal axes, wherein each axis has its own distinct index of refraction. The axes are oriented in a particular manner, causing an amplitude modulating carrier frequency induced by the crystal retarder to be thermally invariant. Accordingly, a calibration beam technique can be used over a relatively wide range of ambient temperatures, with a common calibration data set.

  2. Nuclear reactor coolant channels

    International Nuclear Information System (INIS)

    Macbeth, R.V.

    1978-01-01

    A nuclear reactor coolant channel is described that is suitable for sub-cooled reactors as in pressurised water reactors as well as for bulk boiling, as in boiling water reactors and steam generating nuclear reactors. The arrangement aims to improve heat transfer between the fuel elements and the coolant. Full constructional details are given. See also other similar patents by the author. (U.K.)

  3. The M2 Channel

    DEFF Research Database (Denmark)

    Santner, Paul

    Drug resistance of Influenza A against antivirals is an increasing problem. No effective Influenza A drugs targeting the crucial viral protein, the proton transporter M2 are available anymore due to widespread resistance. Thanks to research efforts elucidating M2 protein structure, function and i...... resistance escape routes from drug inhibition. We thereby were hopefully able to provide a platform for the large-scale evaluation of M2 channel activity, inhibitors and resistance....

  4. Aquaglyceroporins: generalized metalloid channels

    Science.gov (United States)

    Mukhopadhyay, Rita; Bhattacharjee, Hiranmoy; Rosen, Barry P.

    2014-01-01

    Background: Aquaporins (AQPs), members of a superfamily of transmembrane channel proteins, are ubiquitous in all domains of life. They fall into a number of branches that can be functionally categorized into two major sub-groups: i) orthodox aquaporins, which are water-specific channels, and ii) aquaglyceroporins, which allow the transport of water, non-polar solutes, such as urea or glycerol, the reactive oxygen species hydrogen peroxide, and gases such as ammonia, carbon dioxide and nitric oxide and, as described in this review, metalloids. Scope of Review: This review summarizes the key findings that AQP channels conduct bidirectional movement of metalloids into and out of cells. Major Conclusions: As(OH)3 and Sb(OH)3 behave as inorganic molecular mimics of glycerol, a property that allows their passage through AQP channels. Plant AQPs also allow the passage of boron and silicon as their hydroxyacids, boric acid (B(OH)3) and orthosilicic acid (Si(OH)4), respectively. Genetic analysis suggests that germanic acid (GeO2) is also a substrate. While As(III), Sb(III) and Ge(IV) are toxic metalloids, borate (B(III)) and silicate (Si(IV)) are essential elements in higher plants. General Significance: The uptake of environmental metalloids by aquaporins provides an understanding of (i) how toxic elements such as arsenic enter the food chain; (ii) the delivery of arsenic and antimony containing drugs in the treatment of certain forms of leukemia and chemotherapy of diseases caused by pathogenic protozoa; and (iii) the possibility that food plants such as rice could be made safer by genetically modifying them to exclude arsenic while still accumulating boron and silicon. PMID:24291688

  5. Matching Dyadic Distributions to Channels

    OpenAIRE

    Böcherer, Georg; Mathar, Rudolf

    2010-01-01

    Many communication channels with discrete input have non-uniform capacity achieving probability mass functions (PMF). By parsing a stream of independent and equiprobable bits according to a full prefix-free code, a modu-lator can generate dyadic PMFs at the channel input. In this work, we show that for discrete memoryless channels and for memoryless discrete noiseless channels, searching for good dyadic input PMFs is equivalent to minimizing the Kullback-Leibler distance between a dyadic PMF ...

  6. Radar channel balancing with commutation

    Energy Technology Data Exchange (ETDEWEB)

    Doerry, Armin Walter

    2014-02-01

    When multiple channels are employed in a pulse-Doppler radar, achieving and maintaining balance between the channels is problematic. In some circumstances the channels may be commutated to achieve adequate balance. Commutation is the switching, trading, toggling, or multiplexing of the channels between signal paths. Commutation allows modulating the imbalance energy away from the balanced energy in Doppler, where it can be mitigated with filtering.

  7. Microstructural information from channeling measurements

    International Nuclear Information System (INIS)

    Quere, Y.

    1984-09-01

    Channeling is sensitive to nearly all structural changes in solids. One briefly recalls how particles are dechanneled by lattice defects and describes the main applications of channeling to materials science: detection of radiation damage, location of impurity atoms, precipitations in alloys... Channeling being a phenomenon characteristic of perfect crystals, any type of lattice imperfection (phonons, crystal defects, precipitation etc.) is expected to produce dechanneling. Consequently channeling and its opposite, dechanneling, have both been used to study structure and structural changes of materials

  8. Ion channeling revisited

    Energy Technology Data Exchange (ETDEWEB)

    Doyle, Barney Lee [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Corona, Aldo [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Nguyen, Anh [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2014-09-01

    A MS Excel program has been written that calculates accidental, or unintentional, ion channeling in cubic bcc, fcc and diamond lattice crystals or polycrystalline materials. This becomes an important issue when simulating the creation by energetic neutrons of point displacement damage and extended defects using beams of ions. All of the tables and graphs in the three Ion Beam Analysis Handbooks that previously had to be manually looked up and read from were programed into Excel in handy lookup tables, or parameterized, for the case of the graphs, using rather simple exponential functions with different powers of the argument. The program then offers an extremely convenient way to calculate axial and planar half-angles and minimum yield or dechanneling probabilities, effects on half-angles of amorphous overlayers, accidental channeling probabilities for randomly oriented crystals or crystallites, and finally a way to automatically generate stereographic projections of axial and planar channeling half-angles. The program can generate these projections and calculate these probabilities for axes and [hkl] planes up to (555).

  9. The alpha channeling effect

    Science.gov (United States)

    Fisch, N. J.

    2015-12-01

    Alpha particles born through fusion reactions in a tokamak reactor tend to slow down on electrons, but that could take up to hundreds of milliseconds. Before that happens, the energy in these alpha particles can destabilize on collisionless timescales toroidal Alfven modes and other waves, in a way deleterious to energy confinement. However, it has been speculated that this energy might be instead be channeled into useful energy, so as to heat fuel ions or to drive current. Such a channeling needs to be catalyzed by waves Waves can produce diffusion in energy of the alpha particles in a way that is strictly coupled to diffusion in space. If these diffusion paths in energy-position space point from high energy in the center to low energy on the periphery, then alpha particles will be cooled while forced to the periphery. The energy from the alpha particles is absorbed by the wave. The amplified wave can then heat ions or drive current. This process or paradigm for extracting alpha particle energy collisionlessly has been called alpha channeling. While the effect is speculative, the upside potential for economical fusion is immense. The paradigm also operates more generally in other contexts of magnetically confined plasma.

  10. TRP channels in kidney disease.

    NARCIS (Netherlands)

    Hsu, Y.J.; Hoenderop, J.G.J.; Bindels, R.J.M.

    2007-01-01

    Mammalian TRP channel proteins form six-transmembrane cation-permeable channels that may be grouped into six subfamilies on the basis of amino acid sequence homology (TRPC, TRPV, TRPM, TRPA, TRPP, and TRPML). Recent studies of TRP channels indicate that they are involved in numerous fundamental cell

  11. Parallel inter channel interaction mechanisms

    International Nuclear Information System (INIS)

    Jovic, V.; Afgan, N.; Jovic, L.

    1995-01-01

    Parallel channels interactions are examined. For experimental researches of nonstationary regimes flow in three parallel vertical channels results of phenomenon analysis and mechanisms of parallel channel interaction for adiabatic condition of one-phase fluid and two-phase mixture flow are shown. (author)

  12. Molecular analysis of a thylakoid K+ channel

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2000-05-01

    The work undertaken during the prior granting period sought to use a novel probe to identify and clone plant ion (K) channels. It was also proposed that in vitro biochemical studies of cation transport across purified preparations of thylakoid membrane be employed to characterize a putative K channel in this membrane system. Over the last several years (including those of the previous grant period), an enormous data base of partially-sequenced mRNAs and numerous genomes (including those of plants) has evolved and provides a powerful alternative to this brute-force approach to identify and clone cDNAs ending physiologically important membrane proteins such as channels. The utility of searching genetic databases for relevant sequences, in addition to the difficulty of working with membrane proteins, led to changes in research focus during the prior granting period, and has resulted in the identification of a new class of plant ion channels, which will be the focus of research during the proposed new granting period.

  13. Voltage-Gated Calcium Channels

    Science.gov (United States)

    Zamponi, Gerald Werner

    Voltage Gated Calcium Channels is the first comprehensive book in the calcium channel field, encompassing over thirty years of progress towards our understanding of calcium channel structure, function, regulation, physiology, pharmacology, and genetics. This book balances contributions from many of the leading authorities in the calcium channel field with fresh perspectives from risings stars in the area, taking into account the most recent literature and concepts. This is the only all-encompassing calcium channel book currently available, and is an essential resource for academic researchers at all levels in the areas neuroscience, biophysics, and cardiovascular sciences, as well as to researchers in the drug discovery area.

  14. Strategies for sustainable channel relations in mobile telecom sector

    Directory of Open Access Journals (Sweden)

    Githa Heggde

    2011-01-01

    Full Text Available The telecom sector in India largely comprises of wireless connections for phones. As of today, there are approximately 21 network providers in the country with about 7 per each circle, each offering competitive pricing to the consumers. The main objective of the study is to provide an accurate role for the company executive in developing channel relations. Further to this, the study explores the strategies which can sustain a good working relationship between the company and its channel members in the mobile telecom sector. The constructs identified for developing sustainable relationships were Setting distribution objectives, Channel design, Logistics, Image Building, Inventory management, Channel management, Payment & credit, Promotional assistance, Setting targets, Coverage frequency , Motivating channel members to perform. The sample selected contained distributors from the Mobile telecom sector and company executives/channel managers of leading telecom companies. Factor analysis and Friedman’s test was applied. The findings revealed a correlation in attitude between distributors and the executives. Motivating distributors was rated as the most important strategy by the company. The distributors felt that all channel partners needed to have positive attitude towards the channel while company executives felt that aggression made channel members perform effectively. Such findings will be of use to mobile telecom companies who are new entrants to the Indian market and to existing companies who plan to expand their coverage.

  15. Evaluation of portable near infrared spectrophotometer to stage maturity in channel catfish

    Science.gov (United States)

    Gonadal maturity of channel catfish varies within the same cohort of fish. Female channel catfish with superior maturity need to be identified and staged for higher success to induce spawn wit ovulating hormones to produce channel x blue hybrid catfish fry in hatcheries. Maturation is not synchron...

  16. Ion Channels in Leukocytes

    Science.gov (United States)

    1991-07-01

    muscle k142), heart muscle (80), bo- are released. In recent years much has been learned vine pulmonar arter endothelial cells (251), and rat about the...b3 Zn or cytes from cystic fibrosis patients lack a Cl current that Ni (1 mM)-added to the cytoplasmic side of the mem- can be acti% ated b3 the...that at37’C hu- to be defectiv.- in cystic fibrosis (55, 277), and Chen et al. man T-cell CiL channels are active at rest, implies that (25) have shown

  17. Ca²⁺-dependent K⁺ channels in exocrine salivary glands.

    Science.gov (United States)

    Catalán, Marcelo A; Peña-Munzenmayer, Gaspar; Melvin, James E

    2014-06-01

    In the last 15 years, remarkable progress has been realized in identifying the genes that encode the ion-transporting proteins involved in exocrine gland function, including salivary glands. Among these proteins, Ca(2+)-dependent K(+) channels take part in key functions including membrane potential regulation, fluid movement and K(+) secretion in exocrine glands. Two K(+) channels have been identified in exocrine salivary glands: (1) a Ca(2+)-activated K(+) channel of intermediate single channel conductance encoded by the KCNN4 gene, and (2) a voltage- and Ca(2+)-dependent K(+) channel of large single channel conductance encoded by the KCNMA1 gene. This review focuses on the physiological roles of Ca(2+)-dependent K(+) channels in exocrine salivary glands. We also discuss interesting recent findings on the regulation of Ca(2+)-dependent K(+) channels by protein-protein interactions that may significantly impact exocrine gland physiology. Published by Elsevier Ltd.

  18. Channel stability of Turkey Creek, Nebraska

    Science.gov (United States)

    Rus, David L.; Soenksen, Philip J.

    1998-01-01

    Channelization on Turkey Creek and its receiving stream, the South Fork Big Nemaha River, has disturbed the equilibrium of Turkey Creek and has led to channel-stability problems, such as degradation and channel widening, which pose a threat to bridges and land adjacent to the stream. As part of a multiagency study, the U.S. Geological Survey assessed channel stability at two bridge sites on upper and middle portions of Turkey Creek by analyzing streambed-elevation data for gradation changes, comparing recent cross-section surveys and historic accounts, identifying bank-failure blocks, and analyzing tree-ring samples. These results were compared to gradation data and trend results for a U.S. Geological Survey streamflow-gaging station near the mouth of Turkey Creek from a previous study. Examination of data on streambed elevations reveals that degradation has occurred. The streambed elevation declined 0.5 m at the upper site from 1967-97. The streambed elevation declined by 3.2 m at the middle site from 1948-97 and exposed 2 m of the pilings of the Nebraska Highway 8 bridge. Channel widening could not be verified at the two sites from 1967-97, but a historic account indicates widening at the middle site to be two to three times that of the 1949 channel width. Small bank failures were evident at the upper site and a 4-m-wide bank failure occurred at the middle site in 1987 according to tree ring analyses. Examination of streambed-elevation data from a previous study at the lower site reveals a statistically significant aggrading trend from 1958-93. Further examination of these data suggests minor degradation occurred until 1975, followed by aggradation.

  19. Assessing the Returns from Organic Marketing Channels

    OpenAIRE

    Park, Timothy A.

    2009-01-01

    Organic farmers face heightened pressure in developing a portfolio of different marketing channels and in bargaining competitively with increasingly sophisticated marketing participants in the supply chain for organic products. This research assists producers by identifying specific farm and demographic factors that enhance earnings given the choice of marketing outlet. The two significant selectivity coefficients confirm that organic earnings when marketing through a single outlet are biased...

  20. Risk Modelling for Passages in Approach Channel

    Directory of Open Access Journals (Sweden)

    Leszek Smolarek

    2013-01-01

    Full Text Available Methods of multivariate statistics, stochastic processes, and simulation methods are used to identify and assess the risk measures. This paper presents the use of generalized linear models and Markov models to study risks to ships along the approach channel. These models combined with simulation testing are used to determine the time required for continuous monitoring of endangered objects or period at which the level of risk should be verified.

  1. Immunolocalization and expression of small-conductance calcium-activated potassium channels in human myometrium

    DEFF Research Database (Denmark)

    Rosenbaum, Sofia T; Svalø, Julie; Nielsen, Karsten

    2012-01-01

    Small-conductance calcium-activated potassium (SK3) channels have been detected in human myometrium and we have previously shown a functional role of SK channels in human myometrium in vitro. The aims of this study were to identify the precise localization of SK3 channels and to quantify SK3 m....... This is the first report to provide evidence for a possible role of SK3 channels in human uterine telocytes....

  2. Ion channels in the central regulation of energy and glucose homeostasis

    OpenAIRE

    Sohn, Jong-Woo

    2013-01-01

    Ion channels are critical regulators of neuronal excitability and synaptic function in the brain. Recent evidence suggests that ion channels expressed by neurons within the brain are responsible for regulating energy and glucose homeostasis. In addition, the central effects of neurotransmitters and hormones are at least in part achieved by modifications of ion channel activity. This review focuses on ion channels and their neuronal functions followed by a discussion of the identified roles fo...

  3. Mimicking multi-channel scattering with single-channel approaches

    OpenAIRE

    Grishkevich, Sergey; Schneider, Philipp-Immanuel; Vanne, Yulian V.; Saenz, Alejandro

    2009-01-01

    The collision of two atoms is an intrinsic multi-channel (MC) problem as becomes especially obvious in the presence of Feshbach resonances. Due to its complexity, however, single-channel (SC) approximations, which reproduce the long-range behavior of the open channel, are often applied in calculations. In this work the complete MC problem is solved numerically for the magnetic Feshbach resonances (MFRs) in collisions between generic ultracold 6Li and 87Rb atoms in the ground state and in the ...

  4. Kv7 channels can function without constitutive calmodulin tethering.

    Directory of Open Access Journals (Sweden)

    Juan Camilo Gómez-Posada

    Full Text Available M-channels are voltage-gated potassium channels composed of Kv7.2-7.5 subunits that serve as important regulators of neuronal excitability. Calmodulin binding is required for Kv7 channel function and mutations in Kv7.2 that disrupt calmodulin binding cause Benign Familial Neonatal Convulsions (BFNC, a dominantly inherited human epilepsy. On the basis that Kv7.2 mutants deficient in calmodulin binding are not functional, calmodulin has been defined as an auxiliary subunit of Kv7 channels. However, we have identified a presumably phosphomimetic mutation S511D that permits calmodulin-independent function. Thus, our data reveal that constitutive tethering of calmodulin is not required for Kv7 channel function.

  5. Identification of Distribution Channels to Create Sustainable Vegetable Prices

    Directory of Open Access Journals (Sweden)

    Aflit Nuryulia Praswati

    2017-12-01

    Full Text Available The price of vegetables has a role as a contributor to the rate of inflation. Currently the number of vegetable production in Boyolali region can no longer meet the needs of local communities. The limited amount of vegetable production and the inhibition of the vegetable distribution channel creates a scarcity of vegetables that result in price increases. This study aims to identify the distribution channel and the formation of vegetable prices derived from Boyolali area. The method used in this research is quantitative and qualitative. Respondents from this study consisted of farmers, wholesalers, small trader and end consumers. The type of distribution channel prevailing in Boyolali area are traditional and modern distribution channels. Intermediate distribution channels play a greater role in determining vegetable prices. If farmers want to improve their economic condition, it needs innovation and creativity in the process of planting, harvesting, packaging and marketing vegetable products.

  6. Water removal characteristics of parallel serpentine channels

    Energy Technology Data Exchange (ETDEWEB)

    Jiao, K.; Zhou, B.; Quan, P. [Windsor Univ., ON (Canada). Dept. of Mechanical, Automotive and Materials Engineering

    2005-07-01

    A study was conducted in which the liquid water behaviours in parallel serpentine channels with manifolds on the cathode side of a proton exchange membrane (PEM) fuel cell stack were examined. A 3-dimensional, unsteady two-phase flow model within the commercial computational fluid dynamics software package FLUENT was used. Membrane electrode assemblies (MEA) were placed on different sides in the numerical analysis. Several water management issues were identified for this type of fuel cell stack by examining the flow behaviours of liquid water and airflow velocity fields. It was shown that water in the outflow manifold could be blocked by air streams from the gas flow channels, with water flowing continuously into the outflow manifold. It was also shown that the pressure drop along all the unit cells can never increase or decrease at the same pace. Water which adheres to the end wall of both the inlet and outlet manifolds is difficult to remove. It was suggested that faster water drainage can be achieved by keeping the MEA side of the gas flow channels close to the outlet of the outflow manifold. It was also suggested that the collecting and separating effect at the serpentine gas flow channels could improve the water drainage. 8 refs., 10 figs.

  7. Multiplicative properties of quantum channels

    Science.gov (United States)

    Rahaman, Mizanur

    2017-08-01

    In this paper, we study the multiplicative behaviour of quantum channels, mathematically described by trace preserving, completely positive maps on matrix algebras. It turns out that the multiplicative domain of a unital quantum channel has a close connection to its spectral properties. A structure theorem (theorem 2.5), which reveals the automorphic property of an arbitrary unital quantum channel on a subalgebra, is presented. Various classes of quantum channels (irreducible, primitive, etc) are then analysed in terms of this stabilising subalgebra. The notion of the multiplicative index of a unital quantum channel is introduced, which measures the number of times a unital channel needs to be composed with itself for the multiplicative algebra to stabilise. We show that the maps that have trivial multiplicative domains are dense in completely bounded norm topology in the set of all unital completely positive maps. Some applications in quantum information theory are discussed.

  8. Voltage-gated calcium channels of Paramecium cilia.

    Science.gov (United States)

    Lodh, Sukanya; Yano, Junji; Valentine, Megan S; Van Houten, Judith L

    2016-10-01

    Paramecium cells swim by beating their cilia, and make turns by transiently reversing their power stroke. Reversal is caused by Ca 2+ entering the cilium through voltage-gated Ca 2+ (Ca V ) channels that are found exclusively in the cilia. As ciliary Ca 2+ levels return to normal, the cell pivots and swims forward in a new direction. Thus, the activation of the Ca V channels causes cells to make a turn in their swimming paths. For 45 years, the physiological characteristics of the Paramecium ciliary Ca V channels have been known, but the proteins were not identified until recently, when the P. tetraurelia ciliary membrane proteome was determined. Three Ca V α1 subunits that were identified among the proteins were cloned and confirmed to be expressed in the cilia. We demonstrate using RNA interference that these channels function as the ciliary Ca V channels that are responsible for the reversal of ciliary beating. Furthermore, we show that Pawn (pw) mutants of Paramecium that cannot swim backward for lack of Ca V channel activity do not express any of the three Ca V 1 channels in their ciliary membrane, until they are rescued from the mutant phenotype by expression of the wild-type PW gene. These results reinforce the correlation of the three Ca V channels with backward swimming through ciliary reversal. The PwB protein, found in endoplasmic reticulum fractions, co-immunoprecipitates with the Ca V 1c channel and perhaps functions in trafficking. The PwA protein does not appear to have an interaction with the channel proteins but affects their appearance in the cilia. © 2016. Published by The Company of Biologists Ltd.

  9. Upgrading a marketing channels role

    Directory of Open Access Journals (Sweden)

    Tišma-Borota Ankica

    2002-01-01

    Full Text Available As one of the marketing mix instruments, marketing channels were usually behind other instruments (product, price and promotion. Many companies regarded marketing channels as something that was 'left' after more important strategies of price, product and promotion were created. In recent past, things have changed and marketing channels became more interesting for research. This change came as a result of change in global market functioning especially in competitive advantage, distributors' strength and increasing technology.

  10. Single-channel kinetics of BK (Slo1 channels

    Directory of Open Access Journals (Sweden)

    Yanyan eGeng

    2015-01-01

    Full Text Available Single-channel kinetics has proven a powerful tool to reveal information about the gating mechanisms that control the opening and closing of ion channels. This introductory review focuses on the gating of large conductance Ca2+- and voltage-activated K+ (BK or Slo1 channels at the single-channel level. It starts with single-channel current records and progresses to presentation and analysis of single-channel data and the development of gating mechanisms in terms of discrete state Markov (DSM models. The DSM models are formulated in terms of the tetrameric modular structure of BK channels, consisting of a central transmembrane pore-gate domain (PGD attached to four surrounding transmembrane voltage sensing domains (VSD and a large intracellular cytosolic domain (CTD, also referred to as the gating ring. The modular structure and data analysis shows that the Ca2+ and voltage dependent gating considered separately can each be approximated by 10-state two-tiered models with 5 closed states on the upper tier and 5 open states on the lower tier. The modular structure and joint Ca2+ and voltage dependent gating are consistent with a 50 state two-tiered model with 25 closed states on the upper tier and 25 open states on the lower tier. Adding an additional tier of brief closed (flicker states to the 10-state or 50-state models improved the description of the gating. For fixed experimental conditions a channel would gate in only a subset of the potential number of states. The detected number of states and the correlations between adjacent interval durations are consistent with the tiered models. The examined models can account for the single-channel kinetics and the bursting behavior of gating. Ca2+ and voltage activate BK channels by predominantly increasing the effective opening rate of the channel with a smaller decrease in the effective closing rate. Ca2+ and depolarization thus activate by mainly destabilizing the closed states.

  11. New Trends in Cancer Therapy: Targeting Ion Channels and Transporters

    Directory of Open Access Journals (Sweden)

    Annarosa Arcangeli

    2010-04-01

    Full Text Available The expression and activity of different channel types mark and regulate specific stages of cancer establishment and progression. Blocking channel activity impairs the growth of some tumors, both in vitro and in vivo, which opens a new field for pharmaceutical research. However, ion channel blockers may produce serious side effects, such as cardiac arrhythmias. For instance, Kv11.1 (hERG1 channels are aberrantly expressed in several human cancers, in which they control different aspects of the neoplastic cell behaviour. hERG1 blockers tend to inhibit cancer growth. However they also retard the cardiac repolarization, thus lengthening the electrocardiographic QT interval, which can lead to life-threatening ventricular arrhythmias. Several possibilities exist to produce less harmful compounds, such as developing specific drugs that bind hERG1 channels in the open state or disassemble the ion channel/integrin complex which appears to be crucial in certain stages of neoplastic progression. The potential approaches to improve the efficacy and safety of ion channel targeting in oncology include: (1 targeting specific conformational channel states; (2 finding ever more specific inhibitors, including peptide toxins, for channel subtypes mainly expressed in well-identified tumors; (3 using specific ligands to convey traceable or cytotoxic compounds; (4 developing channel blocking antibodies; (5 designing new molecular tools to decrease channel expression in selected cancer types. Similar concepts apply to ion transporters such as the Na+/K+ pump and the Na+/H+ exchanger. Pharmacological targeting of these transporters is also currently being considered in anti-neoplastic therapy.

  12. Global versus local mechanisms of temperature sensing in ion channels.

    Science.gov (United States)

    Arrigoni, Cristina; Minor, Daniel L

    2018-05-01

    Ion channels turn diverse types of inputs, ranging from neurotransmitters to physical forces, into electrical signals. Channel responses to ligands generally rely on binding to discrete sensor domains that are coupled to the portion of the channel responsible for ion permeation. By contrast, sensing physical cues such as voltage, pressure, and temperature arises from more varied mechanisms. Voltage is commonly sensed by a local, domain-based strategy, whereas the predominant paradigm for pressure sensing employs a global response in channel structure to membrane tension changes. Temperature sensing has been the most challenging response to understand and whether discrete sensor domains exist for pressure and temperature has been the subject of much investigation and debate. Recent exciting advances have uncovered discrete sensor modules for pressure and temperature in force-sensitive and thermal-sensitive ion channels, respectively. In particular, characterization of bacterial voltage-gated sodium channel (BacNa V ) thermal responses has identified a coiled-coil thermosensor that controls channel function through a temperature-dependent unfolding event. This coiled-coil thermosensor blueprint recurs in other temperature sensitive ion channels and thermosensitive proteins. Together with the identification of ion channel pressure sensing domains, these examples demonstrate that "local" domain-based solutions for sensing force and temperature exist and highlight the diversity of both global and local strategies that channels use to sense physical inputs. The modular nature of these newly discovered physical signal sensors provides opportunities to engineer novel pressure-sensitive and thermosensitive proteins and raises new questions about how such modular sensors may have evolved and empowered ion channel pores with new sensibilities.

  13. UMTS Common Channel Sensitivity Analysis

    DEFF Research Database (Denmark)

    Pratas, Nuno; Rodrigues, António; Santos, Frederico

    2006-01-01

    and as such it is necessary that both channels be available across the cell radius. This requirement makes the choice of the transmission parameters a fundamental one. This paper presents a sensitivity analysis regarding the transmission parameters of two UMTS common channels: RACH and FACH. Optimization of these channels...... is performed and values for the key transmission parameters in both common channels are obtained. On RACH these parameters are the message to preamble offset, the initial SIR target and the preamble power step while on FACH it is the transmission power offset....

  14. Demystifying Mechanosensitive Piezo Ion Channels.

    Science.gov (United States)

    Xu, X Z Shawn

    2016-06-01

    Mechanosensitive channels mediate touch, hearing, proprioception, and blood pressure regulation. Piezo proteins, including Piezo1 and Piezo2, represent a new class of mechanosensitive channels that have been reported to play key roles in most, if not all, of these modalities. The structural architecture and molecular mechanisms by which Piezos act as mechanosensitive channels, however, remain mysterious. Two new studies have now provided critical insights into the atomic structure and molecular basis of the ion permeation and mechano-gating properties of the Piezo1 channel.

  15. Defect Distributions in Channeling Experiments

    DEFF Research Database (Denmark)

    Andersen, Hans Henrik; Sigmund, P.

    1965-01-01

    A simple collision model allows to calculate energy losses of perfectly channeled particles. The maximum energy loss is related in a simple way to the displacement energy of lattice atoms perpendicular to the channel. From that, one obtains rather definite predictions on the possibility...... of radiation damage by channeled particles. As an application, one gets a necessary criterion for the occurence of super tails in channeling experiments. The theory involves some assumptions on the behaviour of Born-Mayer potentials which are verified by comparison to experimental displacement energies....

  16. Mechanically Gated Ion Channels in Mammalian Hair Cells

    Directory of Open Access Journals (Sweden)

    Xufeng Qiu

    2018-04-01

    Full Text Available Hair cells in the inner ear convert mechanical stimuli provided by sound waves and head movements into electrical signal. Several mechanically evoked ionic currents with different properties have been recorded in hair cells. The search for the proteins that form the underlying ion channels is still in progress. The mechanoelectrical transduction (MET channel near the tips of stereociliary in hair cells, which is responsible for sensory transduction, has been studied most extensively. Several components of the sensory mechanotransduction machinery in stereocilia have been identified, including the multi-transmembrane proteins tetraspan membrane protein in hair cell stereocilia (TMHS/LHFPL5, transmembrane inner ear (TMIE and transmembrane channel-like proteins 1 and 2 (TMC1/2. However, there remains considerable uncertainty regarding the molecules that form the channel pore. In addition to the sensory MET channel, hair cells express the mechanically gated ion channel PIEZO2, which is localized near the base of stereocilia and not essential for sensory transduction. The function of PIEZO2 in hair cells is not entirely clear but it might have a role in damage sensing and repair processes. Additional stretch-activated channels of unknown molecular identity and function have been found to localize at the basolateral membrane of hair cells. Here, we review current knowledge regarding the different mechanically gated ion channels in hair cells and discuss open questions concerning their molecular composition and function.

  17. Preservation of meandering river channels in uniformly aggrading channel belts

    NARCIS (Netherlands)

    Lageweg, W.I. van de; Schuurman, F.; Cohen, K.M.; Dijk, W.M. van; Shimizu, Y.; Kleinhans, M.G.

    2016-01-01

    Channel belt deposits from meandering river systems commonly display an internal architecture of stacked depositional features with scoured basal contacts due to channel and bedform migration across a range of scales. Recognition and correct interpretation of these bounding surfaces is essential to

  18. MONETARY TRANSMISSION CHANNELS IN ROMANIA – THE CREDIT CHANNEL

    Directory of Open Access Journals (Sweden)

    Magdalena RĂDULESCU

    2009-12-01

    Full Text Available The theoretical – intuitive analysis applied to the segment of monetary transmission evidences the fact that forming the traditional monetary impulses transmission channels are in a starting phase due to the long financial non – intermediary process which Romanian economy had known. In these conditions, the exchange rate channel, and also NBR currency purchases was, for a long time, an important way through which monetary authorities actions influenced macro economical behaviors. But starting with 2000, it is observed a credit channel reactivation and, especially, interest rate channel. Anyhow, the credit channel continues to be undermined by the existence of liquidity surplus within the system, by the phenomena of substitution of national currency credit with currency credits, and also moral hazardous displays. Albeit some of these phenomena also affect the interest rate channel, its role in sending monetary policy impulses is in a continuous progress. Apparently, it acts by way of nominal interest rates, their real level seeming less relevant. Once with remaking the two traditional channels, the companies and households balance is configured and consolidated, which shall potentate in the future the efficiency of the monetary policy. This paper analyses the credit channel in Romania, through an unrestricted VAR analysis.. It shows the responses of exchange rate, inflation rate, GDP, interest rate, imports and exports to a shock on non-governmental credit

  19. Peripheral Receptor Mechanisms Underlying Orofacial Muscle Pain and Hyperalgesia

    Science.gov (United States)

    Saloman, Jami L.

    Musculoskeletal pain conditions, particularly those associated with temporomandibular joint and muscle disorders (TMD) are severely debilitating and affect approximately 12% of the population. Identifying peripheral nociceptive mechanisms underlying mechanical hyperalgesia, a prominent feature of persistent muscle pain, could contribute to the development of new treatment strategies for the management of TMD and other muscle pain conditions. This study provides evidence of functional interactions between ligand-gated channels, P2X3 and TRPV1/TRPA1, in trigeminal sensory neurons, and proposes that these interactions underlie the development of mechanical hyperalgesia. In the masseter muscle, direct P2X3 activation, via the selective agonist αβmeATP, induced a dose- and time-dependent hyperalgesia. Importantly, the αβmeATP-induced hyperalgesia was prevented by pretreatment of the muscle with a TRPV1 antagonist, AMG9810, or the TRPA1 antagonist, AP18. P2X3 was co-expressed with both TRPV1 and TRPA1 in masseter muscle afferents confirming the possibility for intracellular interactions. Moreover, in a subpopulation of P2X3 /TRPV1 positive neurons, capsaicin-induced Ca2+ transients were significantly potentiated following P2X3 activation. Inhibition of Ca2+-dependent kinases, PKC and CaMKII, prevented P2X3-mechanical hyperalgesia whereas blockade of Ca2+-independent PKA did not. Finally, activation of P2X3 induced phosphorylation of serine, but not threonine, residues in TRPV1 in trigeminal sensory neurons. Significant phosphorylation was observed at 15 minutes, the time point at which behavioral hyperalgesia was prominent. Similar data were obtained regarding another nonselective cation channel, the NMDA receptor (NMDAR). Our data propose P2X3 and NMDARs interact with TRPV1 in a facilitatory manner, which could contribute to the peripheral sensitization underlying masseter hyperalgesia. This study offers novel mechanisms by which individual pro-nociceptive ligand

  20. Computational Investigations in Rectangular Convergent and Divergent Ribbed Channels

    Science.gov (United States)

    Sivakumar, Karthikeyan; Kulasekharan, N.; Natarajan, E.

    2018-05-01

    Computational investigations on the rib turbulated flow inside a convergent and divergent rectangular channel with square ribs of different rib heights and different Reynolds numbers (Re=20,000, 40,000 and 60,000). The ribs were arranged in a staggered fashion between the upper and lower surfaces of the test section. Computational investigations are carried out using computational fluid dynamic software ANSYS Fluent 14.0. Suitable solver settings like turbulence models were identified from the literature and the boundary conditions for the simulations on a solution of independent grid. Computations were carried out for both convergent and divergent channels with 0 (smooth duct), 1.5, 3, 6, 9 and 12 mm rib heights, to identify the ribbed channel with optimal performance, assessed using a thermo hydraulic performance parameter. The convergent and divergent rectangular channels show higher Nu values than the standard correlation values.

  1. Three-dimensional (3-D) video systems: bi-channel or single-channel optics?

    Science.gov (United States)

    van Bergen, P; Kunert, W; Buess, G F

    1999-11-01

    This paper presents the results of a comparison between two different three-dimensional (3-D) video systems, one with single-channel optics, the other with bi-channel optics. The latter integrates two lens systems, each transferring one half of the stereoscopic image; the former uses only one lens system, similar to a two-dimensional (2-D) endoscope, which transfers the complete stereoscopic picture. In our training centre for minimally invasive surgery, surgeons were involved in basic and advanced laparoscopic courses using both a 2-D system and the two 3-D video systems. They completed analog scale questionnaires in order to record a subjective impression of the relative convenience of operating in 2-D and 3-D vision, and to identify perceived deficiencies in the 3-D system. As an objective test, different experimental tasks were developed, in order to measure performance times and to count pre-defined errors made while using the two 3-D video systems and the 2-D system. Using the bi-channel optical system, the surgeon has a heightened spatial perception, and can work faster and more safely than with a single-channel system. However, single-channel optics allow the use of an angulated endoscope, and the free rotation of the optics relative to the camera, which is necessary for some operative applications.

  2. ZnO-channel thin-film transistors: Channel mobility

    International Nuclear Information System (INIS)

    Hoffman, R.L.

    2004-01-01

    ZnO-channel thin-film transistor (TFT) test structures are fabricated using a bottom-gate structure on thermally oxidized Si; ZnO is deposited via RF sputtering from an oxide target, with an unheated substrate. Electrical characteristics are evaluated, with particular attention given to the extraction and interpretation of transistor channel mobility. ZnO-channel TFT mobility exhibits severe deviation from that assumed by ideal TFT models; mobility extraction methodology must accordingly be recast so as to provide useful insight into device operation. Two mobility metrics, μ avg and μ inc , are developed and proposed as relevant tools in the characterization of nonideal TFTs. These mobility metrics are employed to characterize the ZnO-channel TFTs reported herein; values for μ inc as high as 25 cm2/V s are measured, comprising a substantial increase in ZnO-channel TFT mobility as compared to previously reported performance for such devices

  3. Bupivacaine-induced cellular entry of QX-314 and its contribution to differential nerve block

    Science.gov (United States)

    Brenneis, C; Kistner, K; Puopolo, M; Jo, S; Roberson, DP; Sisignano, M; Segal, D; Cobos, EJ; Wainger, BJ; Labocha, S; Ferreirós, N; Hehn, C; Tran, J; Geisslinger, G; Reeh, PW; Bean, BP; Woolf, C J

    2014-01-01

    Background and Purpose: Selective nociceptor fibre block is achieved by introducing the cell membrane impermeant sodium channel blocker lidocaine N-ethyl bromide (QX-314) through transient receptor potential V1 (TRPV1) channels into nociceptors. We screened local anaesthetics for their capacity to activate TRP channels, and characterized the nerve block obtained by combination with QX-314. Experimental Approach: We investigated TRP channel activation in dorsal root ganglion (DRG) neurons by calcium imaging and patch-clamp recordings, and cellular QX-314 uptake by MS. To characterize nerve block, compound action potential (CAP) recordings from isolated nerves and behavioural responses were analysed. Key Results: Of the 12 compounds tested, bupivacaine was the most potent activator of ruthenium red-sensitive calcium entry in DRG neurons and activated heterologously expressed TRPA1 channels. QX-314 permeated through TRPA1 channels and accumulated intracellularly after activation of these channels. Upon sciatic injections, QX-314 markedly prolonged bupivacaine's nociceptive block and also extended (to a lesser degree) its motor block. Bupivacaine's blockade of C-, but not A-fibre, CAPs in sciatic nerves was extended by co-application of QX-314. Surprisingly, however, this action was the same in wild-type, TRPA1-knockout and TRPV1/TRPA1-double knockout mice, suggesting a TRP-channel independent entry pathway. Consistent with this, high doses of bupivacaine promoted a non-selective, cellular uptake of QX-314. Conclusions and Implications: Bupivacaine, combined with QX-314, produced a long-lasting sensory nerve block. This did not require QX-314 permeation through TRPA1, although bupivacaine activated these channels. Regardless of entry pathway, the greatly extended duration of block produced by QX-314 and bupivacaine may be clinically useful. PMID:24117225

  4. Planar Superconducting Millimeter-Wave/Terahertz Channelizing Filter

    Science.gov (United States)

    Ehsan, Negar; U-yen, Kongpop; Brown, Ari; Hsieh, Wen-Ting; Wollack, Edward; Moseley, Samuel

    2013-01-01

    This innovation is a compact, superconducting, channelizing bandpass filter on a single-crystal (0.45 m thick) silicon substrate, which operates from 300 to 600 GHz. This device consists of four channels with center frequencies of 310, 380, 460, and 550 GHz, with approximately 50-GHz bandwidth per channel. The filter concept is inspired by the mammalian cochlea, which is a channelizing filter that covers three decades of bandwidth and 3,000 channels in a very small physical space. By using a simplified physical cochlear model, and its electrical analog of a channelizing filter covering multiple octaves bandwidth, a large number of output channels with high inter-channel isolation and high-order upper stopband response can be designed. A channelizing filter is a critical component used in spectrometer instruments that measure the intensity of light at various frequencies. This embodiment was designed for MicroSpec in order to increase the resolution of the instrument (with four channels, the resolution will be increased by a factor of four). MicroSpec is a revolutionary wafer-scale spectrometer that is intended for the SPICA (Space Infrared Telescope for Cosmology and Astrophysics) Mission. In addition to being a vital component of MicroSpec, the channelizing filter itself is a low-resolution spectrometer when integrated with only an antenna at its input, and a detector at each channel s output. During the design process for this filter, the available characteristic impedances, possible lumped element ranges, and fabrication tolerances were identified for design on a very thin silicon substrate. Iterations between full-wave and lumped-element circuit simulations were performed. Each channel s circuit was designed based on the availability of characteristic impedances and lumped element ranges. This design was based on a tabular type bandpass filter with no spurious harmonic response. Extensive electromagnetic modeling for each channel was performed. Four channels

  5. ZAP: a distributed channel assignment algorithm for cognitive radio networks

    OpenAIRE

    Junior , Paulo Roberto ,; Fonseca , Mauro; Munaretto , Anelise; Viana , Aline ,; Ziviani , Artur

    2011-01-01

    Abstract We propose ZAP, an algorithm for the distributed channel assignment in cognitive radio (CR) networks. CRs are capable of identifying underutilized licensed bands of the spectrum, allowing their reuse by secondary users without interfering with primary users. In this context, efficient channel assignment is challenging as ideally it must be simple, incur acceptable communication overhead, provide timely response, and be adaptive to accommodate frequent changes in the network. Another ...

  6. A protein interaction mechanism for suppressing the mechanosensitive Piezo channels

    OpenAIRE

    Zhang, Tingxin; Chi, Shaopeng; Jiang, Fan; Zhao, Qiancheng; Xiao, Bailong

    2017-01-01

    Piezo proteins are bona fide mammalian mechanotransduction channels for various cell types including endothelial cells. The mouse Piezo1 of 2547 residues forms a three-bladed, propeller-like homo-trimer comprising a central pore-module and three propeller-structures that might serve as mechanotransduction-modules. However, the mechanogating and regulation of Piezo channels remain unclear. Here we identify the sarcoplasmic /endoplasmic-reticulum Ca2+ ATPase (SERCA), including the widely expres...

  7. A Gate Hinge Controls the Epithelial Calcium Channel TRPV5

    OpenAIRE

    van der Wijst, Jenny; Leunissen, Elizabeth H.; Blanchard, Maxime G.; Venselaar, Hanka; Verkaart, Sjoerd; Paulsen, Candice E.; Bindels, Ren? J.; Hoenderop, Joost G.

    2017-01-01

    TRPV5 is unique within the large TRP channel family for displaying a high Ca2+ selectivity together with Ca2+-dependent inactivation. Our study aims to uncover novel insights into channel gating through in-depth structure-function analysis. We identify an exceptional tryptophan (W583) at the terminus of the intracellular pore that is unique for TRPV5 (and TRPV6). A combination of site-directed mutagenesis, biochemical and electrophysiological analysis, together with homology modeling, demonst...

  8. Waves for Alpha-Channeling in Mirror Machines

    International Nuclear Information System (INIS)

    Zhmoginov, A.I.; Fisch, N.J.

    2009-01-01

    Alpha-channeling can, in principle, be implemented in mirror machines via exciting weaklydamped modes in the ion cyclotron frequency range with perpendicular wavelengths smaller than the alpha particle gyroradius. Assuming quasi-longitudinal or quasi-transverse wave propagation, we search systematically for suitable modes in mirror plasmas. Considering two device designs, a proof-of-principle facility and a fusion rector prototype, we in fact identify candidate modes suitable for alpha-channeling.

  9. An improved channel assessment scheme

    KAUST Repository

    Bader, Ahmed

    2014-01-01

    A source node in a multihop network determines whether to transmit in a channel based on whether the channel is occupied by a packet transmission with a large number of relays; whether the source node is in the data tones back-off zone; and the source node is in the busy tone back-off zone.

  10. Quantum communication under channel uncertainty

    Energy Technology Data Exchange (ETDEWEB)

    Noetzel, Janis Christian Gregor

    2012-09-06

    This work contains results concerning transmission of entanglement and subspaces as well as generation of entanglement in the limit of arbitrary many uses of compound- and arbitrarily varying quantum channels (CQC, AVQC). In both cases, the channel is described by a set of memoryless channels. Only forward communication between one sender and one receiver is allowed. A code is said to be ''good'' only, if it is ''good'' for every channel out of the set. Both settings describe a scenario, in which sender and receiver have only limited channel knowledge. For different amounts of information about the channel available to sender or receiver, coding theorems are proven for the CQC. For the AVQC, both deterministic and randomised coding schemes are considered. Coding theorems are proven, as well as a quantum analogue of the Ahlswede-dichotomy. The connection to zero-error capacities of stationary memoryless quantum channels is investigated. The notion of symmetrisability is defined and used for both classes of channels.

  11. Perceived quality of channel zapping

    NARCIS (Netherlands)

    Kooij, R.E.; Ahmed, K.; Brunnström, K.

    2006-01-01

    The end user experience of service quality is critical to the success of a service provider's IPTV deployment program. A key element involved in validating IPTV quality of experience (QoE) is how quickly and reliably users can change TV channels, often referred to as channel zapping. Currently there

  12. Channel's Concurrence and Quantum Teleportation

    Institute of Scientific and Technical Information of China (English)

    LING Yin-Sheng

    2005-01-01

    Concurrence can measure the entanglement property of a system. If the channel is a pure state, positive concurrence state can afford the good performance in the teleportation process. If the channel ia a mixed state, positive concurrence state cannot assure the good performance in the teleportation. The conditions of the positive concurrence and the quantum teleportation in the Heisenberg spin ring is derived.

  13. An improved channel assessment scheme

    KAUST Repository

    Bader, Ahmed

    2014-05-01

    A source node in a multihop network determines whether to transmit in a channel based on whether the channel is occupied by a packet transmission with a large number of relays; whether the source node is in the data tones back-off zone; and the source node is in the busy tone back-off zone.

  14. Tourism and information technologies distribution channels: a panorama of the brazilian reality

    Directory of Open Access Journals (Sweden)

    Elisete Santos da Silva Zagheni

    2011-05-01

    Full Text Available Technological evolution has made it possible that the same service may be delivered by means of multiple channels, including in the tourism sector.  The present study proposes to present a bibliographic summary of the distribution channels in tourism and the impact of information technologies (IT in these channels.  Based on exploratory research, 24 scientific papers were analyzed with the intention of identifying a research structure concerning the channels of Brazilian tourism and IT.  We observed that in Brazil, there is a lack of work concerning distribution channels in tourism, highlighting the management of these channels under the view of supply chains.  Beyond this, these papers concentrate on two elements of the channels: means of lodging and hospitality, and travel agencies.  These elements have used direct channels based on IT in order to support service activities and the commercialization of the tourist product.

  15. An aberrant vascular channel in the petrous bone: persistent lateral capital vein?

    International Nuclear Information System (INIS)

    Hermans, Robert; Rensburg, Leon J. van

    2009-01-01

    An aberrant channel was identified on CT in the petrous bone in four patients presenting with unrelated otological symptoms. These channels occurred unilaterally in each case. In two patients, the channel was seen to run between the sigmoid sinus sulcus and the superior petrosal sinus sulcus; in one of these patients, a vascular structure was identified within this channel on MRI, connecting the sigmoid sinus and the superior petrosal sinus. In the two other patients, an aberrant channel was seen between the superior petrosal sinus sulcus and the posterior genu of the facial nerve canal. There were no symptoms that could be attributed to the presence of these channels. We postulate that these aberrant vascular channels correspond to a persistent embryological vein, the lateral capital vein. (orig.)

  16. Downregulation of Kv7.4 channel activity in primary and secondary hypertension

    DEFF Research Database (Denmark)

    Jepps, Thomas Andrew; Chadha, Preet S; Davis, Alison J

    2011-01-01

    Voltage-gated potassium (K(+)) channels encoded by KCNQ genes (Kv7 channels) have been identified in various rodent and human blood vessels as key regulators of vascular tone; however, nothing is known about the functional impact of these channels in vascular disease. We ascertained the effect of...... structurally different activators of Kv7.2 through Kv7.5 channels (BMS-204352, S-1, and retigabine) on blood vessels from normotensive and hypertensive animals.......Voltage-gated potassium (K(+)) channels encoded by KCNQ genes (Kv7 channels) have been identified in various rodent and human blood vessels as key regulators of vascular tone; however, nothing is known about the functional impact of these channels in vascular disease. We ascertained the effect of 3...

  17. An aberrant vascular channel in the petrous bone: persistent lateral capital vein?

    Energy Technology Data Exchange (ETDEWEB)

    Hermans, Robert [University Hospitals Leuven, Department of Radiology, Leuven (Belgium); Rensburg, Leon J. van [University of the Western Cape, Department of Radiology and Diagnostics, Tygerberg (South Africa)

    2009-12-15

    An aberrant channel was identified on CT in the petrous bone in four patients presenting with unrelated otological symptoms. These channels occurred unilaterally in each case. In two patients, the channel was seen to run between the sigmoid sinus sulcus and the superior petrosal sinus sulcus; in one of these patients, a vascular structure was identified within this channel on MRI, connecting the sigmoid sinus and the superior petrosal sinus. In the two other patients, an aberrant channel was seen between the superior petrosal sinus sulcus and the posterior genu of the facial nerve canal. There were no symptoms that could be attributed to the presence of these channels. We postulate that these aberrant vascular channels correspond to a persistent embryological vein, the lateral capital vein. (orig.)

  18. Decreasing vortex flux in channels

    International Nuclear Information System (INIS)

    Migaj, V.K.; Nosova, I.S.

    1979-01-01

    A new method for reducing vortex flow losses in power plant channels is suggested. The method is based on vortex splitting in vortex flow areas with transverse barriers placed on the channel walls. The upper barrier ends are at the level of the upper boundary of the vortex area and don't protrude to the active flow beyond this boundary. The effectiveness of the method suggested is illustrated taking as an example the investigation of square and flat channels with abrupt widening in one plane, diffusers with widening in one plane, or a rectangualr bend. It is shown that splitting the vortex areas with transverse barriers in the channels results in reduction of hydraulic losses by 10-25%. The above method is characteristic of an extreme simplicity, its application doesn't require changes in the channel shape nor installation of any devices in the flow

  19. Channel box dimension measuring method

    International Nuclear Information System (INIS)

    Oshima, Hirotake; Jo, Hiroto.

    1994-01-01

    The present invention provides a method for measuring the entire length of a channel box of a fuel assembly of a BWR type reactor. Namely, four sensors are used as one set that generate ultrasonic waves from oblique upper portion, oblique lower portion, upper portion and lower portion of the channel box respectively. The distances between the four sensors and each of the portions of the channel box are measured respectively for both of a reference member and a member to be measured. The entire length of the channel box is measured by calculating the measured values and the angles of the obliquely disposed sensors according to a predetermined formula. According to the method of the present invention, the inclination of the channel box to be measured can be corrected. In addition, accuracy of the measurement is improved and the measuring time is saved as well as the measuring device and operation can be simplified. (I.S.)

  20. Marketing channels and competitive advantage

    Directory of Open Access Journals (Sweden)

    Jovičić Dragoljub

    2005-01-01

    Full Text Available Issue that can already be seen and will be very clear in the future is that the central problem in the market of tube caps will not be the product or the price or promotion, but marketing channels. Therefore, the competitive advantage will most probably be built on marketing channels and not the production - as it has been so far, so, the questions of choice functioning and modification of marketing channels, as well as selection of the most appropriate members of channels will become more and more important. Accordingly, it may freely be said that the choice, i.e. the movement of marketing channels represents one of the strategic decisions which has to be made by a company management and which will subsequently very significantly influence the functioning and efficacy of not only the system of distribution, but also the entire business transactions.

  1. Methods of channeling simulation

    International Nuclear Information System (INIS)

    Barrett, J.H.

    1989-06-01

    Many computer simulation programs have been used to interpret experiments almost since the first channeling measurements were made. Certain aspects of these programs are important in how accurately they simulate ions in crystals; among these are the manner in which the structure of the crystal is incorporated, how any quantity of interest is computed, what ion-atom potential is used, how deflections are computed from the potential, incorporation of thermal vibrations of the lattice atoms, correlations of thermal vibrations, and form of stopping power. Other aspects of the programs are included to improve the speed; among these are table lookup, importance sampling, and the multiparameter method. It is desirable for programs to facilitate incorporation of special features of interest in special situations; examples are relaxations and enhanced vibrations of surface atoms, easy substitution of an alternate potential for comparison, change of row directions from layer to layer in strained-layer lattices, and different vibration amplitudes for substitutional solute or impurity atoms. Ways of implementing all of these aspects and features and the consequences of them will be discussed. 30 refs., 3 figs

  2. Based on Channel Characteristics

    Directory of Open Access Journals (Sweden)

    Zhuo Hao

    2013-01-01

    Full Text Available A number of key agreement schemes based on wireless channel characteristics have been proposed recently. However, previous key agreement schemes require that two nodes which need to agree on a key are within the communication range of each other. Hence, they are not suitable for multihop wireless networks, in which nodes do not always have direct connections with each other. In this paper, we first propose a basic multihop key agreement scheme for wireless ad hoc networks. The proposed basic scheme is resistant to external eavesdroppers. Nevertheless, this basic scheme is not secure when there exist internal eavesdroppers or Man-in-the-Middle (MITM adversaries. In order to cope with these adversaries, we propose an improved multihop key agreement scheme. We show that the improved scheme is secure against internal eavesdroppers and MITM adversaries in a single path. Both performance analysis and simulation results demonstrate that the improved scheme is efficient. Consequently, the improved key agreement scheme is suitable for multihop wireless ad hoc networks.

  3. A computational design approach for virtual screening of peptide interactions across K+ channel families

    Directory of Open Access Journals (Sweden)

    Craig A. Doupnik

    2015-01-01

    Full Text Available Ion channels represent a large family of membrane proteins with many being well established targets in pharmacotherapy. The ‘druggability’ of heteromeric channels comprised of different subunits remains obscure, due largely to a lack of channel-specific probes necessary to delineate their therapeutic potential in vivo. Our initial studies reported here, investigated the family of inwardly rectifying potassium (Kir channels given the availability of high resolution crystal structures for the eukaryotic constitutively active Kir2.2 channel. We describe a ‘limited’ homology modeling approach that can yield chimeric Kir channels having an outer vestibule structure representing nearly any known vertebrate or invertebrate channel. These computationally-derived channel structures were tested in silico for ‘docking’ to NMR structures of tertiapin (TPN, a 21 amino acid peptide found in bee venom. TPN is a highly selective and potent blocker for the epithelial rat Kir1.1 channel, but does not block human or zebrafish Kir1.1 channel isoforms. Our Kir1.1 channel-TPN docking experiments recapitulated published in vitro findings for TPN-sensitive and TPN-insensitive channels. Additionally, in silico site-directed mutagenesis identified ‘hot spots’ within the channel outer vestibule that mediate energetically favorable docking scores and correlate with sites previously identified with in vitro thermodynamic mutant-cycle analysis. These ‘proof-of-principle’ results establish a framework for virtual screening of re-engineered peptide toxins for interactions with computationally derived Kir channels that currently lack channel-specific blockers. When coupled with electrophysiological validation, this virtual screening approach may accelerate the drug discovery process, and can be readily applied to other ion channels families where high resolution structures are available.

  4. Multi-channel imaging cytometry with a single detector

    Science.gov (United States)

    Locknar, Sarah; Barton, John; Entwistle, Mark; Carver, Gary; Johnson, Robert

    2018-02-01

    Multi-channel microscopy and multi-channel flow cytometry generate high bit data streams. Multiple channels (both spectral and spatial) are important in diagnosing diseased tissue and identifying individual cells. Omega Optical has developed techniques for mapping multiple channels into the time domain for detection by a single high gain, high bandwidth detector. This approach is based on pulsed laser excitation and a serial array of optical fibers coated with spectral reflectors such that up to 15 wavelength bins are sequentially detected by a single-element detector within 2.5 μs. Our multichannel microscopy system uses firmware running on dedicated DSP and FPGA chips to synchronize the laser, scanning mirrors, and sampling clock. The signals are digitized by an NI board into 14 bits at 60MHz - allowing for 232 by 174 pixel fields in up to 15 channels with 10x over sampling. Our multi-channel imaging cytometry design adds channels for forward scattering and back scattering to the fluorescence spectral channels. All channels are detected within the 2.5 μs - which is compatible with fast cytometry. Going forward, we plan to digitize at 16 bits with an A-toD chip attached to a custom board. Processing these digital signals in custom firmware would allow an on-board graphics processing unit to display imaging flow cytometry data over configurable scanning line lengths. The scatter channels can be used to trigger data buffering when a cell is present in the beam. This approach enables a low cost mechanically robust imaging cytometer.

  5. The Breakdown: Hillslope Sources of Channel Blocks in Bedrock Landscapes

    Science.gov (United States)

    Selander, B.; Anderson, S. P.; Rossi, M.

    2017-12-01

    Block delivery from hillslopes is a poorly understood process that influences bedrock channel incision rates and shapes steep terrain. Previous studies demonstrate that hillslope sediment delivery rate and grain size increases with channel downcutting rate or fracture density (Attal et al., 2015, ESurf). However, blocks that exceed the competence of the channel can inhibit incision. In Boulder Creek, a bedrock channel in the Colorado Front Range, large boulders (>1 m diameter) are most numerous in the steepest channel reaches; their distribution seems to reflect autogenic channel-hillslope feedback between incision rate and block delivery (Shobe et al., 2016, GRL). It is clear that the processes, rates of production, and delivery of large blocks from hillslopes into channels are critical to our understanding of steep terrain evolution. Fundamental questions are 1) whether block production or block delivery is rate limiting, 2) what mechanisms release blocks, and 3) how block production and transport affect slope morphology. As a first step, we map rock outcrops on the granodiorite hillslopes lining Boulder Creek within Boulder Canyon using a high resolution DEM. Our algorithm uses high ranges of curvature values in conjunction with slopes steeper than the angle of repose to quickly identify rock outcrops. We field verified mapped outcrop and sediment-mantled locations on hillslopes above and below the channel knickzone. We find a greater abundance of exposed rock outcrops on steeper hillslopes in Boulder Canyon. Additionally, we find that channel reaches with large in-channel blocks are located at the base of hillslopes with large areas of exposed bedrock, while reaches lacking large in-channel blocks tend to be at the base of predominately soil mantled and forested hillslopes. These observations support the model of block delivery and channel incision of Shobe et al. (2016, GRL). Moreover, these results highlight the conundrum of how rapid channel incision is

  6. Channel Formation in Physical Experiments: Examples from Deep and Shallow Water Clastic Sedimentary Systems

    Science.gov (United States)

    Hoyal, D. C.; Sheets, B. A.

    2005-12-01

    The degree to which experimental sedimentary systems form channels has an important bearing on their applicability as analogs of large-scale natural systems, where channels and their associated landforms are ubiquitous. The internal geometry and properties (e.g., grain size, vertical succession and stacking) of many depositional landforms can be directly linked to the processes of channel initiation and evolution. Unfortunately, strong self-channelization, a prerequisite for certain natural phenomena (e.g. mouth lobe development, meandering, etc.), has been difficult to reproduce at laboratory scales. In shallow-water experiments (sub-aerial), although weak channelization develops relatively easily, as is commonly observed in gutters after a rain storm, strong channelization with well-developed banks has proved difficult to model. In deep water experiments the challenge is even greater. Despite considerable research effort experimental conditions for deep water channel initiation have only recently been identified. Experiments on the requisite conditions for channelization in shallow and deep water have been ongoing at the ExxonMobil Upstream Research Company (EMURC) for several years. By primarily manipulating the cohesiveness of the sediment supply we have developed models of distributive systems with well-defined channels in shallow water, reminiscent of fine grained river-dominated deltas like the Mississippi. In deep water we have developed models that demonstrate strong channelization and associated lobe behavior in a distributive setting, by scaling up an approach developed by another group using salt-water flows and low-density plastic sediment. The experiments highlight a number of important controls on experimental channel formation, including: (1) bed strength or cohesiveness; (2) bedform development; and (3) Reynolds number. Among these controls bed forms disrupt the channel forming instability, reducing the energy available for channelization. The

  7. Identifying Error in AUV Communication

    National Research Council Canada - National Science Library

    Coleman, Joseph; Merrill, Kaylani; O'Rourke, Michael; Rajala, Andrew G; Edwards, Dean B

    2006-01-01

    Mine Countermeasures (MCM) involving Autonomous Underwater Vehicles (AUVs) are especially susceptible to error, given the constraints on underwater acoustic communication and the inconstancy of the underwater communication channel...

  8. Ion channels in the central regulation of energy and glucose homeostasis

    Directory of Open Access Journals (Sweden)

    Jong-Woo eSohn

    2013-05-01

    Full Text Available Ion channels are critical regulators of neuronal excitability and synaptic function in the brain. Recent evidence suggests that ion channels expressed by neurons within the brain are responsible for regulating energy and glucose homeostasis. In addition, the central effects of neurotransmitters and hormones are at least in part achieved by modifications of ion channel activity. This review focuses on ion channels and their neuronal functions followed by a discussion of the identified roles for specific ion channels in the central pathways regulating food intake, energy expenditure, and glucose balance.

  9. Information geometry of Gaussian channels

    International Nuclear Information System (INIS)

    Monras, Alex; Illuminati, Fabrizio

    2010-01-01

    We define a local Riemannian metric tensor in the manifold of Gaussian channels and the distance that it induces. We adopt an information-geometric approach and define a metric derived from the Bures-Fisher metric for quantum states. The resulting metric inherits several desirable properties from the Bures-Fisher metric and is operationally motivated by distinguishability considerations: It serves as an upper bound to the attainable quantum Fisher information for the channel parameters using Gaussian states, under generic constraints on the physically available resources. Our approach naturally includes the use of entangled Gaussian probe states. We prove that the metric enjoys some desirable properties like stability and covariance. As a by-product, we also obtain some general results in Gaussian channel estimation that are the continuous-variable analogs of previously known results in finite dimensions. We prove that optimal probe states are always pure and bounded in the number of ancillary modes, even in the presence of constraints on the reduced state input in the channel. This has experimental and computational implications. It limits the complexity of optimal experimental setups for channel estimation and reduces the computational requirements for the evaluation of the metric: Indeed, we construct a converging algorithm for its computation. We provide explicit formulas for computing the multiparametric quantum Fisher information for dissipative channels probed with arbitrary Gaussian states and provide the optimal observables for the estimation of the channel parameters (e.g., bath couplings, squeezing, and temperature).

  10. Channel Simulation in Quantum Metrology

    Directory of Open Access Journals (Sweden)

    Laurenza Riccardo

    2018-04-01

    Full Text Available In this review we discuss how channel simulation can be used to simplify the most general protocols of quantum parameter estimation, where unlimited entanglement and adaptive joint operations may be employed. Whenever the unknown parameter encoded in a quantum channel is completely transferred in an environmental program state simulating the channel, the optimal adaptive estimation cannot beat the standard quantum limit. In this setting, we elucidate the crucial role of quantum teleportation as a primitive operation which allows one to completely reduce adaptive protocols over suitable teleportation-covariant channels and derive matching upper and lower bounds for parameter estimation. For these channels,wemay express the quantum Cramér Rao bound directly in terms of their Choi matrices. Our review considers both discrete- and continuous-variable systems, also presenting some new results for bosonic Gaussian channels using an alternative sub-optimal simulation. It is an open problem to design simulations for quantum channels that achieve the Heisenberg limit.

  11. Thoughts on identifiers

    CERN Multimedia

    CERN. Geneva

    2005-01-01

    As business processes and information transactions have become an inextricably intertwined with the Web, the importance of assignment, registration, discovery, and maintenance of identifiers has increased. In spite of this, integrated frameworks for managing identifiers have been slow to emerge. Instead, identification systems arise (quite naturally) from immediate business needs without consideration for how they fit into larger information architectures. In addition, many legacy identifier systems further complicate the landscape, making it difficult for content managers to select and deploy identifier systems that meet both the business case and long term information management objectives. This presentation will outline a model for evaluating identifier applications and the functional requirements of the systems necessary to support them. The model is based on a layered analysis of the characteristics of identifier systems, including: * Functional characteristics * Technology * Policy * Business * Social T...

  12. Identifiability in stochastic models

    CERN Document Server

    1992-01-01

    The problem of identifiability is basic to all statistical methods and data analysis, occurring in such diverse areas as Reliability Theory, Survival Analysis, and Econometrics, where stochastic modeling is widely used. Mathematics dealing with identifiability per se is closely related to the so-called branch of ""characterization problems"" in Probability Theory. This book brings together relevant material on identifiability as it occurs in these diverse fields.

  13. A MHD channel study for the ETF conceptual design

    Science.gov (United States)

    Wang, S. Y.; Staiger, P. J.; Smith, J. M.

    1981-01-01

    The procedures and computations used to identify an MHD channel for a 540 mW(I) EFT-scale plant are presented. Under the assumed constraints of maximum E(x), E(y), J(y) and Beta; results show the best plant performance is obtained for active length, L is approximately 12 M, whereas in the initial ETF studies, L is approximately 16 M. As MHD channel length is reduced from 16 M, the channel enthalpy extraction falls off, slowly. This tends to reduce the MHD power output; however, the shorter channels result in lower heat losses to the MHD channel cooling water which allows for the incorporation of more low pressure boiler feedwater heaters into the system and an increase in steam plant efficiency. The net result of these changes is a net increase in the over all MHD/steam plant efficiency. In addition to the sensitivity of various channel parameters, the trade-offs between the level of oxygen enrichment and the electrical stress on the channel are also discussed.

  14. Skeletal Muscle Na+ Channel Disorders

    Directory of Open Access Journals (Sweden)

    Dina eSimkin

    2011-10-01

    Full Text Available Five inherited human disorders affecting skeletal muscle contraction have been traced to mutations in the gene encoding the voltage-gated sodium channel Nav1.4. The main symptoms of these disorders are myotonia or periodic paralysis caused by changes in skeletal muscle fiber excitability. Symptoms of these disorders vary from mild or latent disease to incapacitating or even death in severe cases. As new human sodium channel mutations corresponding to disease states become discovered, the importance of understanding the role of the sodium channel in skeletal muscle function and disease state grows.

  15. Ciguatoxins activate specific cold pain pathways to elicit burning pain from cooling

    OpenAIRE

    Vetter, Irina; Touska, Filip; Hess, Andreas; Hinsbey, Rachel; Sattler, Simon; Lampert, Angelika; Sergejeva, Marina; Sharov, Anastasia; Collins, Lindon S; Eberhardt, Mirjam; Engel, Matthias; Cabot, Peter J; Wood, John N; Vlachová, Viktorie; Reeh, Peter W

    2012-01-01

    Ciguatoxins derived from fish lead to cold allodynia in humans, the perception of intense burning pain in response to mild cooling. A novel mouse model of ciguatoxin-induced cold allodynia reveals that ciguatoxin activates the TRPA1 thermosensitive ion channel to mediate pain perception.

  16. Dopamine negatively modulates the NCA ion channels in C. elegans.

    Science.gov (United States)

    Topalidou, Irini; Cooper, Kirsten; Pereira, Laura; Ailion, Michael

    2017-10-01

    The NALCN/NCA ion channel is a cation channel related to voltage-gated sodium and calcium channels. NALCN has been reported to be a sodium leak channel with a conserved role in establishing neuronal resting membrane potential, but its precise cellular role and regulation are unclear. The Caenorhabditis elegans orthologs of NALCN, NCA-1 and NCA-2, act in premotor interneurons to regulate motor circuit activity that sustains locomotion. Recently we found that NCA-1 and NCA-2 are activated by a signal transduction pathway acting downstream of the heterotrimeric G protein Gq and the small GTPase Rho. Through a forward genetic screen, here we identify the GPCR kinase GRK-2 as a new player affecting signaling through the Gq-Rho-NCA pathway. Using structure-function analysis, we find that the GPCR phosphorylation and membrane association domains of GRK-2 are required for its function. Genetic epistasis experiments suggest that GRK-2 acts on the D2-like dopamine receptor DOP-3 to inhibit Go signaling and positively modulate NCA-1 and NCA-2 activity. Through cell-specific rescuing experiments, we find that GRK-2 and DOP-3 act in premotor interneurons to modulate NCA channel function. Finally, we demonstrate that dopamine, through DOP-3, negatively regulates NCA activity. Thus, this study identifies a pathway by which dopamine modulates the activity of the NCA channels.

  17. Zirconium ignition in exposed fuel channel

    Energy Technology Data Exchange (ETDEWEB)

    Elias, E., E-mail: merezra@technion.ac.il; Hasan, D.; Nekhamkin, Y.

    2015-05-15

    Highlights: • We demonstrate the idea of runaway zirconium–steam reactions in severe accidents in today's LWRs. • We predict the thermal-hydraulics conditions relevant to cladding oxidation in an exposed fuel channel of a partially uncovered core. • The Semenov theory of metal combustion is extended to define a criterion for runaway oxidation reaction in fuel cladding. - Abstract: A theoretical model based on simultaneous solution of the heat and mass transfer equations is developed for predicting the rate of thermo-chemical reaction between zirconium cladding and a hot steam environment. Ignition conditions relevant to cladding oxidation in an exposed fuel channel of a partially uncovered core are predicted based on the theory of metal combustion. A range of decay power, convective heat transfer coefficients, and initial temperatures leading to uncontrolled runaway cladding oxidation is identified. The model could be readily integrated as part of a fuel channel analysis code for predicting possible outcomes of different accident mitigation procedures in light water nuclear reactors under LOCA conditions.

  18. Functional characterization of a prokaryotic Kir channel.

    Science.gov (United States)

    Enkvetchakul, Decha; Bhattacharyya, Jaya; Jeliazkova, Iana; Groesbeck, Darcy K; Cukras, Catherine A; Nichols, Colin G

    2004-11-05

    The Kir gene family encodes inward rectifying K+ (Kir) channels that are widespread and critical regulators of excitability in eukaryotic cells. A related gene family (KirBac) has recently been identified in prokaryotes. While a crystal structure of one member, Kir-Bac1.1, has been solved, there has been no functional characterization of any KirBac gene products. Here we present functional characterization of KirBac1.1 reconstituted in liposomes. Utilizing a 86Rb+ uptake assay, we demonstrate that KirBac1.1 generates a K+ -selective permeation path that is inhibited by extraliposomal Ba2+ and Ca2+ ions. In contrast to KcsA (an acid-activated bacterial potassium channel), KirBac1.1 is inhibited by extraliposomal acid (pKa approximately 6). This characterization of KirBac1.1 activity now paves the way for further correlation of structure and function in this model Kir channel.

  19. Note: Optical receiver system for 152-channel magnetoencephalography

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jin-Mok; Kwon, Hyukchan; Yu, Kwon-kyu; Lee, Yong-Ho; Kim, Kiwoong [Center for Biosignals, Korea Research Institute of Standards and Science, Daejeon 305-600 (Korea, Republic of)

    2014-11-15

    An optical receiver system composing 13 serial data restore/synchronizer modules and a single module combiner converted optical 32-bit serial data into 32-bit synchronous parallel data for a computer to acquire 152-channel magnetoencephalography (MEG) signals. A serial data restore/synchronizer module identified 32-bit channel-voltage bits from 48-bit streaming serial data, and then consecutively reproduced 13 times of 32-bit serial data, acting in a synchronous clock. After selecting a single among 13 reproduced data in each module, a module combiner converted it into 32-bit parallel data, which were carried to 32-port digital input board in a computer. When the receiver system together with optical transmitters were applied to 152-channel superconducting quantum interference device sensors, this MEG system maintained a field noise level of 3 fT/√Hz @ 100 Hz at a sample rate of 1 kSample/s per channel.

  20. Hydraulic jumps in a channel

    DEFF Research Database (Denmark)

    Bonn, D.; Andersen, Anders Peter; Bohr, Tomas

    2009-01-01

    We present a study of hydraulic jumps with flow predominantly in one direction, created either by confining the flow to a narrow channel with parallel walls or by providing an inflow in the form of a narrow sheet. In the channel flow, we find a linear height profile upstream of the jump as expected......'s mixing-length theory with a mixing length that is proportional to the height of the fluid layer. Using averaged boundary-layer equations, taking into account the friction with the channel walls and the eddy viscosity, the flow both upstream and downstream of the jump can be understood. For the downstream...... subcritical flow, we assume that the critical height is attained close to the channel outlet. We use mass and momentum conservation to determine the position of the jump and obtain an estimate which is in rough agreement with our experiment. We show that the averaging method with a varying velocity profile...

  1. Green channel cargo inspection system

    International Nuclear Information System (INIS)

    Shi Yuanping; Yu Jingsheng; Sun Hongqiang; Hao Pu; Cai Wenxia

    2011-01-01

    A radiation detection device was installed in the lanes of a highway toll station, radioactive rays which was collimated emitted through the measured, and arrived the detector. The average density of the fresh agricultural products belonged to Green channel and other prohibited items vary greatly, the absorption of radiation are different between the Green Channel Cargo and other substances. Prior to the experimental group, different standard samples which represent different models and goods were measured, the different standard samples were stored in a computer database. When the trucks get through the Green Channel, the detector will detect the radiation signal and bring to the computer, the computer will process the measured data, and make a conclusion whether the goods are Green Channel cargo. (authors)

  2. Flooding correlations in narrow channel

    International Nuclear Information System (INIS)

    Kim, S. H.; Baek, W. P.; Chang, S. H.

    1999-01-01

    Heat transfer in narrow gap is considered as important phenomena in severe accidents in nuclear power plants. Also in heat removal of electric chip. Critical heat flux(CHF) in narrow gap limits the maximum heat transfer rate in narrow channel. In case of closed bottom channel, flooding limited CHF occurrence is observed. Flooding correlations will be helpful to predict the CHF in closed bottom channel. In present study, flooding data for narrow channel geometry were collected and the work to recognize the effect of the span, w and gap size, s were performed. And new flooding correlations were suggested for high-aspect-ratio geometry. Also, flooding correlation was applied to flooding limited CHF data

  3. Multi-channel Kondo necklace

    International Nuclear Information System (INIS)

    Fazekas, P.; Kee Haeyoung.

    1993-06-01

    A multi-channel generalization of Doniach's Kondo necklace model is formulated, and its phase diagram studied in the mean-field approximation. Our intention is to introduce the possible simplest model which displays some of the features expected from the overscreened Kondo lattice. The N conduction electron channels are represented by N sets of pseudospins τ J , j = 1 1,..., N which are all antiferromagnetically coupled to a periodic array of modul S = 1/2 spins. Exploiting permutation symmetry in the channel index j allows us to write down the self-consistency equation for general N. For N > 2, we find that the critical temperature is rising with increasing Kondo interaction; we interpret this effect by pointing out that the Kondo coupling creates the composite pseudospin objects which undergo an ordering transition. The relevance of our findings to the underlying fermionic multi-channel problem is discussed. (author). 33 refs, 1 fig

  4. Experimentation with PEC channel prototype

    International Nuclear Information System (INIS)

    Caponetti, R.; Iacovelli, M.

    1984-01-01

    Experimentation on prototypes of PEC components is presently being carried out at Casaccia CRE. This report shows the results of the first cycle of experimentation of the central channel, concerning the aspects of sodium removal after experimentation

  5. Multi-channel Kondo necklace

    Energy Technology Data Exchange (ETDEWEB)

    Fazekas, P; Haeyoung, Kee

    1993-06-01

    A multi-channel generalization of Doniach`s Kondo necklace model is formulated, and its phase diagram studied in the mean-field approximation. Our intention is to introduce the possible simplest model which displays some of the features expected from the overscreened Kondo lattice. The N conduction electron channels are represented by N sets of pseudospins {tau}{sub J}, j = 1 1,..., N which are all antiferromagnetically coupled to a periodic array of modul S = 1/2 spins. Exploiting permutation symmetry in the channel index j allows us to write down the self-consistency equation for general N. For N > 2, we find that the critical temperature is rising with increasing Kondo interaction; we interpret this effect by pointing out that the Kondo coupling creates the composite pseudospin objects which undergo an ordering transition. The relevance of our findings to the underlying fermionic multi-channel problem is discussed. (author). 33 refs, 1 fig.

  6. FMCG companies specific distribution channels

    Directory of Open Access Journals (Sweden)

    Ioana Barin

    2009-12-01

    Full Text Available Distribution includes all activities undertaken by the producer, alone or in cooperation, since the end of the final finished products or services until they are in possession of consumers. The distribution consists of the following major components: distribution channels or marketing channels, which together form a distribution network; logistics o rphysical distribution. In order to effective achieve, distribution of goods requires an amount of activities and operational processes related to transit of goods from producer to consumer, the best conditions, using existing distribution channels and logistics system. One of the essential functions of a distribution is performing acts of sale, through which, with the actual movement of goods, their change of ownership takes place, that the successive transfer of ownership from producer to consumer. This is an itinerary in the economic cycle of goods, called the distribution channel.

  7. Marketing channel behaviour and performance

    OpenAIRE

    Duarte, Margarida

    2000-01-01

    Thesis submitted to University of Manchester for the degree of Doctor of Philosophy in the Faculty of Business Administration. A major aim of this study is to offer a relatively comprehensive picture of marketing channel behaviour and performance. Given the statistical difficulties in testing a very large, comprehensive model to achieve this aim, two separate but overlapping models are proposed. One model specifically addresses behaviour in marketing channels, while the other integrates k...

  8. Channel coincidence counter: version 1

    International Nuclear Information System (INIS)

    Krick, M.S.; Menlove, H.O.

    1980-06-01

    A thermal neutron coincidence counter has been designed for the assay of fast critical assembly fuel drawers and plutonium-bearing fuel rods. The principal feature of the detector is a 7-cm by 7-cm by 97-cm detector channel, which provides a uniform neutron detection efficiency of 16% along the central 40 cm of the channel. The electronics system is identical to that used for the High-Level Neutron Coincidence Counter

  9. TRP Channels in Human Prostate

    Directory of Open Access Journals (Sweden)

    Carl Van Haute

    2010-01-01

    Full Text Available This review gives an overview of morphological and functional characteristics in the human prostate. It will focus on the current knowledge about transient receptor potential (TRP channels expressed in the human prostate, and their putative role in normal physiology and prostate carcinogenesis. Controversial data regarding the expression pattern and the potential impact of TRP channels in prostate function, and their involvement in prostate cancer and other prostate diseases, will be discussed.

  10. Slopes To Prevent Trapping of Bubbles in Microfluidic Channels

    Science.gov (United States)

    Greer, Harold E.; Lee, Michael C.; Smith, J. Anthony; Willis, Peter A.

    2010-01-01

    The idea of designing a microfluidic channel to slope upward along the direction of flow of the liquid in the channel has been conceived to help prevent trapping of gas bubbles in the channel. In the original application that gave rise to this idea, the microfluidic channels are parts of micro-capillary electrophoresis (microCE) devices undergoing development for use on Mars in detecting compounds indicative of life. It is necessary to prevent trapping of gas bubbles in these devices because uninterrupted liquid pathways are essential for sustaining the electrical conduction and flows that are essential for CE. The idea is also applicable to microfluidic devices that may be developed for similar terrestrial microCE biotechnological applications or other terrestrial applications in which trapping of bubbles in microfluidic channels cannot be tolerated. A typical microCE device in the original application includes, among other things, multiple layers of borosilicate float glass wafers. Microfluidic channels are formed in the wafers, typically by use of wet chemical etching. The figure presents a simplified cross section of part of such a device in which the CE channel is formed in the lowermost wafer (denoted the channel wafer) and, according to the present innovation, slopes upward into a via hole in another wafer (denoted the manifold wafer) lying immediately above the channel wafer. Another feature of the present innovation is that the via hole in the manifold wafer is made to taper to a wider opening at the top to further reduce the tendency to trap bubbles. At the time of reporting the information for this article, an effort to identify an optimum technique for forming the slope and the taper was in progress. Of the techniques considered thus far, the one considered to be most promising is precision milling by use of femtosecond laser pulses. Other similar techniques that may work equally well are precision milling using a focused ion beam, or a small diamond

  11. Identifying Strategic Scientific Opportunities

    Science.gov (United States)

    As NCI's central scientific strategy office, CRS collaborates with the institute's divisions, offices, and centers to identify research opportunities to advance NCI's vision for the future of cancer research.

  12. Identifying Breast Cancer Oncogenes

    Science.gov (United States)

    2011-10-01

    cells we observed that it promoted transformation of HMLE cells, suggesting a tumor suppressive role of Merlin in breast cancer (Figure 4B). A...08-1-0767 TITLE: Identifying Breast Cancer Oncogenes PRINCIPAL INVESTIGATOR: Yashaswi Shrestha...Standard Form 298 (Rev. 8-98) Prescribed by ANSI Std. Z39.18 W81XWH-08-1-0767 Identifying Breast Cancer Oncogenes Yashaswi Shrestha Dana-Farber

  13. Joint Channel Assignment and Routing in Multiradio Multichannel Wireless Mesh Networks: Design Considerations and Approaches

    Directory of Open Access Journals (Sweden)

    Omar M. Zakaria

    2016-01-01

    Full Text Available Multiradio wireless mesh network is a promising architecture that improves the network capacity by exploiting multiple radio channels concurrently. Channel assignment and routing are underlying challenges in multiradio architectures since both determine the traffic distribution over links and channels. The interdependency between channel assignments and routing promotes toward the joint solutions for efficient configurations. This paper presents an in-depth review of the joint approaches of channel assignment and routing in multiradio wireless mesh networks. First, the key design issues, modeling, and approaches are identified and discussed. Second, existing algorithms for joint channel assignment and routing are presented and classified based on the channel assignment types. Furthermore, the set of reconfiguration algorithms to adapt the network traffic dynamics is also discussed. Finally, the paper presents some multiradio practical implementations and test-beds and points out the future research directions.

  14. Verification of otolith identity used by fisheries scientists for aging channel catfish

    Science.gov (United States)

    Long, James M.; Stewart, David R.

    2010-01-01

    Previously published studies of the age estimation of channel catfish Ictalurus punctatus based on otoliths have reported using the sagittae, whereas it is likely they were actually using the lapilli. This confusion may have resulted because in catfishes (ostariophyseans) the lapilli are the largest of the three otoliths, whereas in nonostariophysean fish the sagittae are the largest. Based on (1) scanning electron microscope microphotographs of channel catfish otoliths, (2) X-ray computed tomography scans of a channel catfish head, (3) descriptions of techniques used to removed otoliths from channel catfish reported in the literature, and (4) a sample of channel catfish otoliths received from fisheries biologists from around the country, it is clear that lapilli are most often used for channel catfish aging studies, not sagittae, as has been previously reported. Fisheries scientists who obtain otoliths from channel catfish can use the information in this paper to correctly identify otolith age.

  15. Uncertainty analysis for hot channel

    International Nuclear Information System (INIS)

    Panka, I.; Kereszturi, A.

    2006-01-01

    The fulfillment of the safety analysis acceptance criteria is usually evaluated by separate hot channel calculations using the results of neutronic or/and thermo hydraulic system calculations. In case of an ATWS event (inadvertent withdrawal of control assembly), according to the analysis, a number of fuel rods are experiencing DNB for a longer time and must be regarded as failed. Their number must be determined for a further evaluation of the radiological consequences. In the deterministic approach, the global power history must be multiplied by different hot channel factors (kx) taking into account the radial power peaking factors for each fuel pin. If DNB occurs it is necessary to perform a few number of hot channel calculations to determine the limiting kx leading just to DNB and fuel failure (the conservative DNBR limit is 1.33). Knowing the pin power distribution from the core design calculation, the number of failed fuel pins can be calculated. The above procedure can be performed by conservative assumptions (e.g. conservative input parameters in the hot channel calculations), as well. In case of hot channel uncertainty analysis, the relevant input parameters (k x, mass flow, inlet temperature of the coolant, pin average burnup, initial gap size, selection of power history influencing the gap conductance value) of hot channel calculations and the DNBR limit are varied considering the respective uncertainties. An uncertainty analysis methodology was elaborated combining the response surface method with the one sided tolerance limit method of Wilks. The results of deterministic and uncertainty hot channel calculations are compared regarding to the number of failed fuel rods, max. temperature of the clad surface and max. temperature of the fuel (Authors)

  16. Planar channeling in superlattices: Theory

    International Nuclear Information System (INIS)

    Ellison, J.A.; Picraux, S.T.; Allen, W.R.; Chu, W.K.

    1988-01-01

    The well-known continuum model theory for planar channeled energetic particles in perfect crystals is extended to layered crystalline structures and applied to superlattices. In a strained-layer structure, the planar channels with normals which are not perpendicular to the growth direction change their direction at each interface, and this dramatically influences the channeling behavior. The governing equation of motion for a planar channeled ion in a strained-layer superlattice with equal layer thicknesses is a one degree of freedom nonlinear oscillator which is periodically forced with a sequence of δ functions. These δ functions, which are of equal spacing and amplitude with alternating sign, represent the tilts at each of the interfaces. Thus upon matching an effective channeled particle wavelength, corresponding to a natural period of the nonlinear oscillator, to the period of the strained-layer superlattice, corresponding to the periodic forcing, strong resonance effects are expected. The condition of one effective wavelength per period corresponds to a rapid dechanneling at a well-defined depth (catastrophic dechanneling), whereas two wavelengths per period corresponds to no enhanced dechanneling after the first one or two layers (resonance channeling). A phase plane analysis is used to characterize the channeled particle motion. Detailed calculations using the Moliere continuum potential are compared with our previously described modified harmonic model, and new results are presented for the phase plane evolution, as well as the dechanneling as a function of depth, incident angle, energy, and layer thickness. General scaling laws are developed and nearly universal curves are obtained for the dechanneling versus depth under catastrophic dechanneling

  17. Identifying Knowledge and Communication

    Directory of Open Access Journals (Sweden)

    Eduardo Coutinho Lourenço de Lima

    2006-12-01

    Full Text Available In this paper, I discuss how the principle of identifying knowledge which Strawson advances in ‘Singular Terms and Predication’ (1961, and in ‘Identifying Reference and Truth-Values’ (1964 turns out to constrain communication. The principle states that a speaker’s use of a referring expression should invoke identifying knowledge on the part of the hearer, if the hearer is to understand what the speaker is saying, and also that, in so referring, speakers are attentive to hearers’ epistemic states. In contrasting it with Russell’s Principle (Evans 1982, as well as with the principle of identifying descriptions (Donnellan 1970, I try to show that the principle of identifying knowledge, ultimately a condition for understanding, makes sense only in a situation of conversation. This allows me to conclude that the cooperative feature of communication (Grice 1975 and reference (Clark andWilkes-Gibbs 1986 holds also at the understanding level. Finally, I discuss where Strawson’s views seem to be unsatisfactory, and suggest how they might be improved.

  18. A negative charge in transmembrane segment 1 of domain II of the cockroach sodium channel is critical for channel gating and action of pyrethroid insecticides

    International Nuclear Information System (INIS)

    Du Yuzhe; Song Weizhong; Groome, James R.; Nomura, Yoshiko; Luo Ningguang; Dong Ke

    2010-01-01

    Voltage-gated sodium channels are the primary target of pyrethroids, an important class of synthetic insecticides. Pyrethroids bind to a distinct receptor site on sodium channels and prolong the open state by inhibiting channel deactivation and inactivation. Recent studies have begun to reveal sodium channel residues important for pyrethroid binding. However, how pyrethroid binding leads to inhibition of sodium channel deactivation and inactivation remains elusive. In this study, we show that a negatively charged aspartic acid residue at position 802 (D802) located in the extracellular end of transmembrane segment 1 of domain II (IIS1) is critical for both the action of pyrethroids and the voltage dependence of channel activation. Charge-reversing or -neutralizing substitutions (K, G, or A) of D802 shifted the voltage dependence of activation in the depolarizing direction and reduced channel sensitivity to deltamethrin, a pyrethroid insecticide. The charge-reversing mutation D802K also accelerated open-state deactivation, which may have counteracted the inhibition of sodium channel deactivation by deltamethrin. In contrast, the D802G substitution slowed open-state deactivation, suggesting an additional mechanism for neutralizing the action of deltamethrin. Importantly, Schild analysis showed that D802 is not involved in pyrethroid binding. Thus, we have identified a sodium channel residue that is critical for regulating the action of pyrethroids on the sodium channel without affecting the receptor site of pyrethroids.

  19. Volume of the space of qubit-qubit channels and state transformations under random quantum channels

    OpenAIRE

    Lovas, Attila; Andai, Attila

    2017-01-01

    The simplest building blocks for quantum computations are the qubit-qubit quantum channels. In this paper, we analyze the structure of these channels via their Choi representation. The restriction of a quantum channel to the space of classical states (i.e. probability distributions) is called the underlying classical channel. The structure of quantum channels over a fixed classical channel is studied, the volume of general and unital qubit channels with respect to the Lebesgue measure is comp...

  20. Identification of cyclic nucleotide gated channels using regular expressions

    KAUST Repository

    Zelman, Alice K.

    2013-09-03

    Cyclic nucleotide-gated channels (CNGCs) are nonselective cation channels found in plants, animals, and some bacteria. They have a six-transmembrane/one- pore structure, a cytosolic cyclic nucleotide-binding domain, and a cytosolic calmodulin-binding domain. Despite their functional similarities, the plant CNGC family members appear to have different conserved amino acid motifs within corresponding functional domains than animal and bacterial CNGCs do. Here we describe the development and application of methods employing plant CNGC-specific sequence motifs as diagnostic tools to identify novel candidate channels in different plants. These methods are used to evaluate the validity of annotations of putative orthologs of CNGCs from plant genomes. The methods detail how to employ regular expressions of conserved amino acids in functional domains of annotated CNGCs and together with Web tools such as PHI-BLAST and ScanProsite to identify novel candidate CNGCs in species including Physcomitrella patens. © Springer Science+Business Media New York 2013.

  1. Information transfer through quantum channels

    International Nuclear Information System (INIS)

    Kretschmann, D.

    2007-01-01

    This PhD thesis represents work done between Aug. 2003 and Dec. 2006 in Reinhard F. Werner's quantum information theory group at Technische Universitaet Braunschweig, and Artur Ekert's Centre for Quantum Computation at the University of Cambridge. My thesis falls into the field of abstract quantum information theory. This work investigates both fundamental properties of quantum channels and their asymptotic capacities for classical as well as quantum information transfer. Stinespring's theorem is the basic structure theorem for quantum channels. It implies that every quantum channel can be represented as a unitary evolution on an enlarged system. In Ch. 3 we present a continuity theorem for Stinespring's representation: two quantum channels are similar if and only if it is possible to find unitary implementations that are likewise similar, with dimension-independent norm bounds. The continuity theorem allows to derive a formulation of the information-disturbance tradeoff in terms of quantum channels, and a continuity estimate for the no-broadcasting principle. In Ch. 4 we then apply the continuity theorem to give a strengthened no-go proof for quantum bit commitment, an important cryptographic primitive. This result also provides a natural characterization of those protocols that fall outside the standard setting of unconditional security, and thus may allow secure bit commitment. We present a new such protocol whose security relies on decoherence in the receiver's lab. Ch. 5 reviews the capacities of quantum channels for the transfer of both classical and quantum information, and investigates several variations in the notion of channel capacity. Memory effects are then investigated in detail in Ch. 6. We advertise a model which is sufficiently general to encompass all causal automata: every quantum process in which the outputs up to any given time t do not depend on the inputs at times t'>t can be represented as a concatenated memory channel. We then explain how

  2. Information transfer through quantum channels

    Energy Technology Data Exchange (ETDEWEB)

    Kretschmann, D.

    2007-03-12

    This PhD thesis represents work done between Aug. 2003 and Dec. 2006 in Reinhard F. Werner's quantum information theory group at Technische Universitaet Braunschweig, and Artur Ekert's Centre for Quantum Computation at the University of Cambridge. My thesis falls into the field of abstract quantum information theory. This work investigates both fundamental properties of quantum channels and their asymptotic capacities for classical as well as quantum information transfer. Stinespring's theorem is the basic structure theorem for quantum channels. It implies that every quantum channel can be represented as a unitary evolution on an enlarged system. In Ch. 3 we present a continuity theorem for Stinespring's representation: two quantum channels are similar if and only if it is possible to find unitary implementations that are likewise similar, with dimension-independent norm bounds. The continuity theorem allows to derive a formulation of the information-disturbance tradeoff in terms of quantum channels, and a continuity estimate for the no-broadcasting principle. In Ch. 4 we then apply the continuity theorem to give a strengthened no-go proof for quantum bit commitment, an important cryptographic primitive. This result also provides a natural characterization of those protocols that fall outside the standard setting of unconditional security, and thus may allow secure bit commitment. We present a new such protocol whose security relies on decoherence in the receiver's lab. Ch. 5 reviews the capacities of quantum channels for the transfer of both classical and quantum information, and investigates several variations in the notion of channel capacity. Memory effects are then investigated in detail in Ch. 6. We advertise a model which is sufficiently general to encompass all causal automata: every quantum process in which the outputs up to any given time t do not depend on the inputs at times t'>t can be represented as a concatenated memory

  3. A Crash Course in Calcium Channels.

    Science.gov (United States)

    Zamponi, Gerald W

    2017-12-20

    Much progress has been made in understanding the molecular physiology and pharmacology of calcium channels. Recently, there have been tremendous advances in learning about calcium channel structure and function through crystallography and cryo-electron microscopy studies. Here, I will give an overview of our knowledge about calcium channels, and highlight two recent studies that give important insights into calcium channel structure.

  4. Transient receptor potential channels in essential hypertension

    DEFF Research Database (Denmark)

    Liu, Daoyan; Scholze, Alexandra; Zhu, Zhiming

    2006-01-01

    The role of nonselective cation channels of the transient receptor potential channel (TRPC) family in essential hypertension has not yet been investigated.......The role of nonselective cation channels of the transient receptor potential channel (TRPC) family in essential hypertension has not yet been investigated....

  5. The minimum yield in channeling

    International Nuclear Information System (INIS)

    Uguzzoni, A.; Gaertner, K.; Lulli, G.; Andersen, J.U.

    2000-01-01

    A first estimate of the minimum yield was obtained from Lindhard's theory, with the assumption of a statistical equilibrium in the transverse phase-space of channeled particles guided by a continuum axial potential. However, computer simulations have shown that this estimate should be corrected by a fairly large factor, C (approximately equal to 2.5), called the Barrett factor. We have shown earlier that the concept of a statistical equilibrium can be applied to understand this result, with the introduction of a constraint in phase-space due to planar channeling of axially channeled particles. Here we present an extended test of these ideas on the basis of computer simulation of the trajectories of 2 MeV α particles in Si. In particular, the gradual trend towards a full statistical equilibrium is studied. We also discuss the introduction of this modification of standard channeling theory into descriptions of the multiple scattering of channeled particles (dechanneling) by a master equation and show that the calculated minimum yields are in very good agreement with the results of a full computer simulation

  6. Generic theory for channel sinuosity.

    Science.gov (United States)

    Lazarus, Eli D; Constantine, José Antonio

    2013-05-21

    Sinuous patterns traced by fluid flows are a ubiquitous feature of physical landscapes on Earth, Mars, the volcanic floodplains of the Moon and Venus, and other planetary bodies. Typically discussed as a consequence of migration processes in meandering rivers, sinuosity is also expressed in channel types that show little or no indication of meandering. Sinuosity is sometimes described as "inherited" from a preexisting morphology, which still does not explain where the inherited sinuosity came from. For a phenomenon so universal as sinuosity, existing models of channelized flows do not explain the occurrence of sinuosity in the full variety of settings in which it manifests, or how sinuosity may originate. Here we present a generic theory for sinuous flow patterns in landscapes. Using observations from nature and a numerical model of flow routing, we propose that flow resistance (representing landscape roughness attributable to topography or vegetation density) relative to surface slope exerts a fundamental control on channel sinuosity that is effectively independent of internal flow dynamics. Resistance-dominated surfaces produce channels with higher sinuosity than those of slope-dominated surfaces because increased resistance impedes downslope flow. Not limited to rivers, the hypothesis we explore pertains to sinuosity as a geomorphic pattern. The explanation we propose is inclusive enough to account for a wide variety of sinuous channel types in nature, and can serve as an analytical tool for determining the sinuosity a landscape might support.

  7. Charged and Neutral Particles Channeling Phenomena Channeling 2008

    Science.gov (United States)

    Dabagov, Sultan B.; Palumbo, Luigi

    2010-04-01

    On the discovery of coherent Bremsstrahlung in a single crystal at the Frascati National Laboratories / C. Barbiellini, G. P. Murtas and S. B. Dabagov -- Advances in coherent Bremsstrahlung and LPM-effect studies (to the lOOth anniversary from the birth of L. D. Landau) / N. F. Shul'ga -- Spectra of radiation and created particles at intermediate energy in oriented crystal taking into account energy loss / V. N. Baier and V. M. Katkov -- The coherent Bremsstrahlung beam at MAX-lab facility / K. Fissum ... [et al.] -- Radiation from thin, structured targets (CERN NA63) / A. Dizdar -- Hard incoherent radiation in thick crystals / N. F. Shul'ga, V. V. Syshchenko and A. I. Tarnovsky -- Coherent Bremsstrahlung in periodically deformed crystals with a complex base / A. R. Mkrtchyan, A. A. Saharian and V. V. Parazian -- Induction of coherent x-ray Bremsstrahlung in crystals under the influence of acoustic waves / A. R. Mkrtchyan and V. V. Parazian -- Coherent processes in bent single crystals / V. A. Maisheev -- Experimental and theoretical investigation of complete transfer phenomenon for media with various heat exchange coefficients / A. R. Mkrtchyan, A. E. Movsisyan and V. R. Kocharyan -- Coherent pair production in crystals / A. R. Mkrtchyan, A. A. Saharian and V. V. Parazian -- Negative particle planar and axial channeling and channeling collimation / R. A. Carrigan, Jr. -- CERN crystal-based collimation in modern hadron colliders / W. Scandale -- Studies and application of bent crystals for beam steering at 70 GeV IHEP accelerator / A. G. Afonin ... [et al.] -- Crystal collimation studies at the Tevatron (T-980) / N. V. Mokhov ... [et al.] -- Fabrication of crystals for channeling of particles in accellerators / A. Mazzolari ... [et al.] -- New possibilities to facilitate collimation of both positively and negatively charged particle beams by crystals / V. Guidi, A. Mazzolari and V. V. Tikhomirov -- Increase of probability of particle capture into the channeling

  8. Identifying and Managing Risk.

    Science.gov (United States)

    Abraham, Janice M.

    1999-01-01

    The role of the college or university chief financial officer in institutional risk management is (1) to identify risk (physical, casualty, fiscal, business, reputational, workplace safety, legal liability, employment practices, general liability), (2) to develop a campus plan to reduce and control risk, (3) to transfer risk, and (4) to track and…

  9. Tuning the ion selectivity of two-pore channels

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Jiangtao; Zeng, Weizhong; Jiang, Youxing (UTSMC)

    2017-01-17

    Organellar two-pore channels (TPCs) contain two copies of a Shaker-like six-transmembrane (6-TM) domain in each subunit and are ubiquitously expressed in plants and animals. Interestingly, plant and animal TPCs share high sequence similarity in the filter region, yet exhibit drastically different ion selectivity. Plant TPC1 functions as a nonselective cation channel on the vacuole membrane, whereas mammalian TPC channels have been shown to be endo/lysosomal Na+-selective or Ca2+-release channels. In this study, we performed systematic characterization of the ion selectivity of TPC1 from Arabidopsis thaliana (AtTPC1) and compared its selectivity with the selectivity of human TPC2 (HsTPC2). We demonstrate that AtTPC1 is selective for Ca2+ over Na+, but nonselective among monovalent cations (Li+, Na+, and K+). Our results also confirm that HsTPC2 is a Na+-selective channel activated by phosphatidylinositol 3,5-bisphosphate. Guided by our recent structure of AtTPC1, we converted AtTPC1 to a Na+-selective channel by mimicking the selectivity filter of HsTPC2 and identified key residues in the TPC filters that differentiate the selectivity between AtTPC1 and HsTPC2. Furthermore, the structure of the Na+-selective AtTPC1 mutant elucidates the structural basis for Na+ selectivity in mammalian TPCs.

  10. Landuse Types within Channel Corridor and River Channel Morphology of River Ona, Ibadan, Nigeria

    Directory of Open Access Journals (Sweden)

    Olutoyin Fashae

    2017-12-01

    Full Text Available The importance of river a corridor warrants a well thought out and balanced management approach because it helps in improving or maintaining water quality, protecting wetlands, etc. Hence, this study seeks to identify major landuse types within the River Ona Corridor; examine the impact of these landuse types within the River Ona corridor on its channel morphology and understand the risk being posed by these landuse types. The study is designed by selecting two reaches of six times the average width from each of the four major landuse types that exist along the river corridor. This study revealed that along the downstream section of Eleyele Dam of River Ona, natural forest stabilizes river channel banks, thereby presenting a narrow and shallow width and depth respectively but the widest of all is found at the agricultural zones.

  11. Pannexin-1 channels in epilepsy.

    Science.gov (United States)

    Aquilino, Mark S; Whyte-Fagundes, Paige; Zoidl, Georg; Carlen, Peter L

    2017-09-05

    Pannexin-1 (Panx1) expression is raised in several animal seizure models and in resected human epileptic brain tissue, suggesting relevance to epilepsy. Multiple factors that are characteristic of seizures are thought to regulate Panx1 channel opening, including elevated levels of extracellular K + . Panx1, when open, 1) releases ATP, glutamate, and other metabolites into the extracellular medium, and 2) may depolarize the membrane due to a channel reversal potential around 0mV. Resultant ATP release from stimulated Panx1 can activate purinergic receptors, including P2X7 receptors. Glutamate and other signaling molecules released by Panx1 opening may have both excitatory and inhibitory actions on seizure generation. This review examines the critical and complex roles of Panx1 channels in epilepsy, which could provide a basis for future therapeutics. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Axial channeling of uttrarelativistic electrons

    Energy Technology Data Exchange (ETDEWEB)

    Telegin, V.I.; Khokonov, M.Kh. (Moskovskij Gosudarstvennyj Univ. (USSR). Nauchno-Issledovatel' skij Inst. Yadernoj Fiziki)

    1982-07-01

    The dynamics of motion of ultrarelativistic electrons under axial channeling conditions is investigated. The analysis is based on the solution of the kinetic equation obtained recently by Beloshitsky and Kumakhov. The particle dechanneling function is investigated as depending on the type of a crystal, particle energy and angle of entrance into the single crystal. It is found that for most of the beam the major diffusion mechanism is scattering by electrons. It is shown that an optimal depth range exists for which the fraction of channeled particles sharply increases at the expense of the quasi-channeled particles. In a number of cases the dechanneling length for crystals with high atomic numbers may be greater than that of light elements.

  13. Axial channeling of uttrarelativistic electrons

    International Nuclear Information System (INIS)

    Telegin, V.I.; Khokonov, M.Kh.

    1982-01-01

    The dynamics of motion of ultrarelativistic electrons under axial channeling conditions is investigated. The analysis is based on the solution of the kinetic equation obtained recently by Beloshitsky and Kumakhov. The particle dechanneling function is investigated as depending on the type of a crystal, particle energy and angle of entrance into the single crystal. It is found that for most of the beam the major diffusion mechanism is scattering by electrons. It is shown that an optimal depth range exists for which the fraction of channeled particles sharply increases at the expense of the quasi-channeled particles. In a number of cases the dechanneling length for crystals with high atomic numbers may be greater than that of light elements

  14. Local quantum channels preserving classical correlations

    International Nuclear Information System (INIS)

    Guo Zhihua; Cao Huaixin

    2013-01-01

    The aim of this paper is to discuss local quantum channels that preserve classical correlations. First, we give two equivalent characterizations of classical correlated states. Then we obtain the relationships among classical correlation-preserving local quantum channels, commutativity-preserving local quantum channels and commutativity-preserving quantum channels on each subsystem. Furthermore, for a two-qubit system, we show the general form of classical correlation-preserving local quantum channels. (paper)

  15. Streambed adjustment and channel widening in eastern Nebraska

    Science.gov (United States)

    Rus, David L.; Dietsch, Benjamin J.; Simon, Andrew

    2003-01-01

    In eastern Nebraska, stream straightening and dredging efforts since the 1890s have disturbed the natural equilibrium of stream channels and have led to streambed adjustment by degradation and subsequent channel widening. This report describes a study to evaluate the effect these disturbances have had on stream channels in eastern Nebraska. Two sets of survey data were collected approximately 2 years apart during 1996-99 at 151 primary sites. Additionally, historical streambed-elevation data (dating back to the 1890s) were compiled from several sources for the primary sites and 45 supplemental sites, and relevant disturbances were identified for each of eight basin groupings. Streambed-elevation data sets were used to estimate the amount of change to the streambed at the sites over the time period of the data. Recent channel widening was documented for 73 of the primary sites by comparing the two survey sets. The majority of observed streambed-gradation responses appear to be related to the various straightening efforts and to the effects of grade-control structures in the study area. Channel responses were complicated by the presence of multiple disturbances. However, in many cases, the streambed-elevation data sets provide a reliable representation of the past streambed gradation, with some sites showing 6 to 7 meters of degradation since they were straightened. Many sites that had been straightened showed considerable degradation following the disturbance. This indicates that eastern Nebraska stream channels can regain equilibrium mainly through the slope adjustment process of head-ward-progressing degradation. Bank failures were documented at sites in all eight of the basin groupings analyzed, and widening rates were computed at 64 of 73 sites. Observed bank widening in the Big Blue River Basin, a relatively unstraightened basin, indicates that other disturbances besides stream-channel straightening may be causing channel responses in the basin and possibly in

  16. Promotion through Marketing Channels : The Case of Kosovo

    Directory of Open Access Journals (Sweden)

    MSc. Hidajet Karaxha

    2016-01-01

    Full Text Available In order for a product to be put in the hands of the customer, requires a mechanism which is called distribution channel and which enables the connection between the consumer and producer. One of the many strategies applied by Kosovar companies for the involvement of the members of the channel is also the promotion through distribution channels. Therefore, the strategies which involve the members of the channel have a higher probability to be positively accepted by the members of the channel, when they are part of a general program of supporting the needs of the producers. The process of realizing a marketing strategy of a company does not concise only of achieving specific goals of production during the realization of the promotion phase, but it also requires identifying the target market and achieving it. The purpose of this paper is to review the promotion strategy of distribution channels, which emphasize the support by the members of the channel, initiated by the producers through cooperative advertisements, promotional salaries, slotting taxes, incentives, promotions in markets and also special promotional agreements. The theoretical and practical side of the study are very important, especially regarding to new theoretical and practical views in the study context. Besides the theoretical contribution that will be offered by this paper, there will also be interesting findings in the practical aspect where through this paper, the owners, managers, firms will be able to understand the role and importance of promotion through distribution channels. Knowing that there are only few studies offered in this field, this paper offers help for everyone interested in this field. This paper contains empirical data collected by questionnaires and interviews.

  17. Multi-channel service concept design and prototyping

    NARCIS (Netherlands)

    Sperling, C.P.; Simons, L.P.A.; Bouwman, W.A.G.A.

    2007-01-01

    Designing e-services which have to function in a multi-channel context has proved to be challenging for organizations. Previous research has shown that structured design methods are useful to structure the design process. In this paper we proceed from an existing method (which identifies

  18. The ion-channel laser

    International Nuclear Information System (INIS)

    Whittum, D.H.; Sessler, A.M.; Dawson, J.M.

    1990-01-01

    A relativistic electron beam propagating through a plasma in the ion-focused regime exhibits an electromagnetic instability at a resonant frequency ω ∼ 2γ 2 ω β . Growth is enhanced by optical guiding in the ion channel, which acts as dielectric waveguide, with fiber parameter V ∼ 2 (I/I A ) 1/2 . A 1-D theory for such an ''ion-channel laser'' is formulated, scaling laws are derived and numerical examples are given. Possible experimental evidence is noted. 23 refs., 1 fig., 1 tab

  19. Electron angular distribution axial channeling

    International Nuclear Information System (INIS)

    Khokonov, A.Kh.; Khokonov, M.Kh.

    1989-01-01

    Angular distributions of ultra-relativistic electrons are calculated in the assumption about presence of statistical equilibrium. Analysis is based on numerical solution of Fokker-Planck type kinetic equation. It is shown that in contrast to case of amorphous medium, the multiple scattering at axial channeling of negative particles results in self-focusing of the initial beam particles and due to it number of electrons moving at an angles to the chain, which are smaller, than critical angle of channeling, may increase by several times as compared to the initial one

  20. Antenna for Ultrawideband Channel Sounding

    DEFF Research Database (Denmark)

    Zhekov, Stanislav Stefanov; Tatomirescu, Alexandru; Pedersen, Gert F.

    2016-01-01

    A novel compact antenna for ultrawideband channel sounding is presented. The antenna is composed of a symmetrical biconical antenna modified by adding a cylinder and a ring to each cone. A feeding coaxial cable is employed during the simulations in order to evaluate and reduce its impact on the a......A novel compact antenna for ultrawideband channel sounding is presented. The antenna is composed of a symmetrical biconical antenna modified by adding a cylinder and a ring to each cone. A feeding coaxial cable is employed during the simulations in order to evaluate and reduce its impact...

  1. Molecular analysis of a thylakoid K+channel

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1999-09-10

    The work undertaken sought to use a novel probe to identify and clone plant ion (K) channels. It was also proposed that in vitro biochemical studies of cation transport across purified preparations of thylakoid membrane be employed to characterize a putative K channel in this membrane system. Over the last several years, an enormous data base of partially-sequenced mRNAs and numerous genomes (including those of plants) has evolved and provides a powerful alternative to this brute-force approach to identify and clone cDNAs encoding physiologically important membrane proteins such as channels. The utility of searching genetic databases for relevant sequences, in addition to the difficulty of working with membrane proteins, led to changes in research focus during the granting period. During the course of the funding period, work was finished up which documented the presence of a K channel in the thylakoid membrane and demonstrated that K fluxes through this channel were required for optimal photosynthetic activity, likely due to the requirement for charge balancing of proton flux.

  2. Molecular analysis of a thylakoid K+channel

    International Nuclear Information System (INIS)

    1999-01-01

    The work undertaken sought to use a novel probe to identify and clone plant ion (K) channels. It was also proposed that in vitro biochemical studies of cation transport across purified preparations of thylakoid membrane be employed to characterize a putative K channel in this membrane system. Over the last several years, an enormous data base of partially-sequenced mRNAs and numerous genomes (including those of plants) has evolved and provides a powerful alternative to this brute-force approach to identify and clone cDNAs encoding physiologically important membrane proteins such as channels. The utility of searching genetic databases for relevant sequences, in addition to the difficulty of working with membrane proteins, led to changes in research focus during the granting period. During the course of the funding period, work was finished up which documented the presence of a K channel in the thylakoid membrane and demonstrated that K fluxes through this channel were required for optimal photosynthetic activity, likely due to the requirement for charge balancing of proton flux

  3. Internally readable identifying tag

    International Nuclear Information System (INIS)

    Jefferts, K.B.; Jefferts, E.R.

    1980-01-01

    A method of identifying non-metallic objects by means of X-ray equipment is described in detail. A small metal pin with a number of grooves cut in a pre-determined equi-spaced pattern is implanted into the non-metallic object and by decoding the groove patterns using X-ray equipment, the object is uniquely identified. A specific example of such an application is in studying the migratory habits of fish. The pin inserted into the snout of the fish is 0.010 inch in diameter, 0.040 inch in length with 8 possible positions for grooves if spaced 0.005 inch apart. With 6 of the groove positions available for data, the capacity is 2 6 or 64 combinations; clearly longer pins would increase the data capacity. This method of identification is a major advance over previous techniques which necessitated destruction of the fish in order to recover the identification tag. (UK)

  4. Identifying Breast Cancer Oncogenes

    Science.gov (United States)

    2010-10-01

    tyrosine kinases with an SH3, SH2 and catalytic domain, it lacks a native myristylation signal shared by most members of this class [14], [38]. The...therapeutics and consequently, improve clinical outcomes. We aim to identify novel drivers of breast oncogenesis. We hypothesize that a kinase gain-of...human mammary epithelial cells. A pBabe-Puro-Myr-Flag kinase open reading frame (ORF) library was screened in immortalized human mammary epithelial

  5. Rock disposal problems identified

    Energy Technology Data Exchange (ETDEWEB)

    Knox, R

    1978-06-01

    Mathematical models are the only way of examining the return of radioactivity from nuclear waste to the environment over long periods of time. Work in Britain has helped identify areas where more basic data is required, but initial results look very promising for final disposal of high level waste in hard rock repositories. A report by the National Radiological Protection Board of a recent study, is examined.

  6. Multimodal distribution of human cold pain thresholds.

    Science.gov (United States)

    Lötsch, Jörn; Dimova, Violeta; Lieb, Isabel; Zimmermann, Michael; Oertel, Bruno G; Ultsch, Alfred

    2015-01-01

    It is assumed that different pain phenotypes are based on varying molecular pathomechanisms. Distinct ion channels seem to be associated with the perception of cold pain, in particular TRPM8 and TRPA1 have been highlighted previously. The present study analyzed the distribution of cold pain thresholds with focus at describing the multimodality based on the hypothesis that it reflects a contribution of distinct ion channels. Cold pain thresholds (CPT) were available from 329 healthy volunteers (aged 18 - 37 years; 159 men) enrolled in previous studies. The distribution of the pooled and log-transformed threshold data was described using a kernel density estimation (Pareto Density Estimation (PDE)) and subsequently, the log data was modeled as a mixture of Gaussian distributions using the expectation maximization (EM) algorithm to optimize the fit. CPTs were clearly multi-modally distributed. Fitting a Gaussian Mixture Model (GMM) to the log-transformed threshold data revealed that the best fit is obtained when applying a three-model distribution pattern. The modes of the identified three Gaussian distributions, retransformed from the log domain to the mean stimulation temperatures at which the subjects had indicated pain thresholds, were obtained at 23.7 °C, 13.2 °C and 1.5 °C for Gaussian #1, #2 and #3, respectively. The localization of the first and second Gaussians was interpreted as reflecting the contribution of two different cold sensors. From the calculated localization of the modes of the first two Gaussians, the hypothesis of an involvement of TRPM8, sensing temperatures from 25 - 24 °C, and TRPA1, sensing cold from 17 °C can be derived. In that case, subjects belonging to either Gaussian would possess a dominance of the one or the other receptor at the skin area where the cold stimuli had been applied. The findings therefore support a suitability of complex analytical approaches to detect mechanistically determined patterns from pain phenotype data.

  7. Molecular Basis of Paraltyic Neurotoxin Action on Voltage-Sensitive Sodium Channels

    Science.gov (United States)

    1985-10-14

    of 9,700 daltons isolated from the coral Goni2oora gy. (1). The toxin enhances neurally mediated contraction of blood vessels and taenia coli of the...sites on the solium channel and to identify the site of GPT action within the structure of the sodium channel protein. 2. Site of Action of Brvyetoxin

  8. IT IN COMMERCE: E-COMMERCE AND OMNI-CHANNEL SALES IN RUSSIA

    OpenAIRE

    PHILIPP A. ANTIPIN

    2017-01-01

    The article discusses the use of information technologies and possibilities provided by the Internet in commerce. The global and European experience of omni-channel sales is discussed. The prospects and conditions of the development of e-commerce and omni-channel sales are identified.

  9. SK2 channels regulate mitochondrial respiration and mitochondrial Ca2+ uptake

    NARCIS (Netherlands)

    Honrath, Birgit; Matschke, Lina; Meyer, Tammo; Magerhans, Lena; Perocchi, Fabiana; Ganjam, Goutham K; Zischka, Hans; Krasel, Cornelius; Gerding, Albert; Bakker, Barbara M; Bünemann, Moritz; Strack, Stefan; Decher, Niels; Culmsee, Carsten; Dolga, Amalia M

    Mitochondrial calcium ([Ca(2+)]m) overload and changes in mitochondrial metabolism are key players in neuronal death. Small conductance calcium-activated potassium (SK) channels provide protection in different paradigms of neuronal cell death. Recently, SK channels were identified at the inner

  10. Use of color-coded sleeve shutters accelerates oscillograph channel selection

    Science.gov (United States)

    Bouchlas, T.; Bowden, F. W.

    1967-01-01

    Sleeve-type shutters mechanically adjust individual galvanometer light beams onto or away from selected channels on oscillograph papers. In complex test setups, the sleeve-type shutters are color coded to separately identify each oscillograph channel. This technique could be used on any equipment using tubular galvanometer light sources.

  11. Identifying phenomenal consciousness.

    Science.gov (United States)

    Schier, Elizabeth

    2009-03-01

    This paper examines the possibility of finding evidence that phenomenal consciousness is independent of access. The suggestion reviewed is that we should look for isomorphisms between phenomenal and neural activation spaces. It is argued that the fact that phenomenal spaces are mapped via verbal report is no problem for this methodology. The fact that activation and phenomenal space are mapped via different means does not mean that they cannot be identified. The paper finishes by examining how data addressing this theoretical question could be obtained.

  12. EPICS: Channel Access security design

    International Nuclear Information System (INIS)

    Kraimer, M.; Hill, J.

    1994-05-01

    This document presents the design for implementing the requirements specified in: EPICS -- Channel Access Security -- functional requirements, Ned. D. Arnold, 03/09/92. Use of the access security system is described along with a summary of the functional requirements. The programmer's interface is given. Security protocol is described and finally aids for reading the access security code are provided

  13. Improved Ion-Channel Biosensors

    Science.gov (United States)

    Nadeau, Jay; White, Victor; Dougherty, Dennis; Maurer, Joshua

    2004-01-01

    An effort is underway to develop improved biosensors of a type based on ion channels in biomimetic membranes. These sensors are microfabricated from silicon and other materials compatible with silicon. As described, these sensors offer a number of advantages over prior sensors of this type.

  14. Single top t-channel

    CERN Document Server

    Faltermann, Nils

    2017-01-01

    The production of single top quarks allows to study the interplay of top quark physics and the electroweak sector of the standard model. Deviations from predictions can be a hint for physics beyond the standard model. The t-channel is the dominant production mode for single top quarks at the LHC. This talk presents the latest measurements from the ATLAS and CMS collaborations.

  15. Visualizing multi-channel networks

    DEFF Research Database (Denmark)

    Antemijczuk, Paweł; Magiera, Marta; Jørgensen, Sune Lehmann

    2014-01-01

    In this paper, we propose a visualization to illustrate social interactions, built from multiple distinct channels of communication. The visualization displays a summary of dense personal information in a compact graphical notation. The starting point is an abstract drawing of a spider’s web. Below...

  16. CHANNELING IN QUASI-CRYSTALS

    NARCIS (Netherlands)

    VANVOORTHUYSEN, EHD; SMULDERS, PJM; WERKMAN, RD; DEBOER, JL; VANSMAALEN, S

    Ion-beam channeling has been observed in quasicrystals. For 1 MeV He-4+ ions in icosahedral AlCuFe the maximum effect found is 36%. The full width at half maximum of the observed dips is 1.3-degrees. The effect persists up to great depths (> 200 nm), thus showing a high degree of ordering in this

  17. Sorting out river channel patterns

    NARCIS (Netherlands)

    Kleinhans, M.G.

    2010-01-01

    Rivers self-organize their pattern/planform through feedbacks between bars, channels, floodplain and vegetation, which emerge as a result of the basic spatial sorting process of wash load sediment and bed sediment. The balance between floodplain formation and destruction determines the width and

  18. Aquaglyceroporins: ancient channels for metalloids

    Science.gov (United States)

    Bhattacharjee, Hiranmoy; Mukhopadhyay, Rita; Thiyagarajan, Saravanamuthu; Rosen, Barry P

    2008-01-01

    The identification of aquaglyceroporins as uptake channels for arsenic and antimony shows how these toxic elements can enter the food chain, and suggests that food plants could be genetically modified to exclude arsenic while still accumulating boron and silicon. PMID:19014407

  19. Sales promotions and channel coordination

    NARCIS (Netherlands)

    B. Wierenga (Berend); H. Soethoudt (Han)

    2009-01-01

    textabstractConsumer sales promotions are usually the result of the decisions of two marketing channel parties, the manufacturer and the retailer. In making these decisions, each party normally follows its own interest: i.e. maximizes its own profit. Unfortunately, this results in a suboptimal

  20. Sales promotion and channel coordination

    NARCIS (Netherlands)

    Wierenga, B.; Soethoudt, J.M.

    2010-01-01

    Consumer sales promotions are usually the result of the decisions of two marketing channel parties, the manufacturer and the retailer. In making these decisions, each party normally follows its own interest: i.e. maximizes its own profit. Unfortunately, this results in a suboptimal outcome for the

  1. Large conductance Ca2+-activated K+ (BK channel: Activation by Ca2+ and voltage

    Directory of Open Access Journals (Sweden)

    RAMÓN LATORRE

    2006-01-01

    Full Text Available Large conductance Ca2+-activated K+ (BK channels belong to the S4 superfamily of K+ channels that include voltage-dependent K+ (Kv channels characterized by having six (S1-S6 transmembrane domains and a positively charged S4 domain. As Kv channels, BK channels contain a S4 domain, but they have an extra (S0 transmembrane domain that leads to an external NH2-terminus. The BK channel is activated by internal Ca2+, and using chimeric channels and mutagenesis, three distinct Ca2+-dependent regulatory mechanisms with different divalent cation selectivity have been identified in its large COOH-terminus. Two of these putative Ca2+-binding domains activate the BK channel when cytoplasmic Ca2+ reaches micromolar concentrations, and a low Ca2+ affinity mechanism may be involved in the physiological regulation by Mg2+. The presence in the BK channel of multiple Ca2+-binding sites explains the huge Ca2+ concentration range (0.1 μM-100 μM in which the divalent cation influences channel gating. BK channels are also voltage-dependent, and all the experimental evidence points toward the S4 domain as the domain in charge of sensing the voltage. Calcium can open BK channels when all the voltage sensors are in their resting configuration, and voltage is able to activate channels in the complete absence of Ca2+. Therefore, Ca2+ and voltage act independently to enhance channel opening, and this behavior can be explained using a two-tiered allosteric gating mechanism.

  2. Mechanisms of Gain Control by Voltage-Gated Channels in Intrinsically-Firing Neurons

    Science.gov (United States)

    Patel, Ameera X.; Burdakov, Denis

    2015-01-01

    Gain modulation is a key feature of neural information processing, but underlying mechanisms remain unclear. In single neurons, gain can be measured as the slope of the current-frequency (input-output) relationship over any given range of inputs. While much work has focused on the control of basal firing rates and spike rate adaptation, gain control has been relatively unstudied. Of the limited studies on gain control, some have examined the roles of synaptic noise and passive somatic currents, but the roles of voltage-gated channels present ubiquitously in neurons have been less explored. Here, we systematically examined the relationship between gain and voltage-gated ion channels in a conductance-based, tonically-active, model neuron. Changes in expression (conductance density) of voltage-gated channels increased (Ca2+ channel), reduced (K+ channels), or produced little effect (h-type channel) on gain. We found that the gain-controlling ability of channels increased exponentially with the steepness of their activation within the dynamic voltage window (voltage range associated with firing). For depolarization-activated channels, this produced a greater channel current per action potential at higher firing rates. This allowed these channels to modulate gain by contributing to firing preferentially at states of higher excitation. A finer analysis of the current-voltage relationship during tonic firing identified narrow voltage windows at which the gain-modulating channels exerted their effects. As a proof of concept, we show that h-type channels can be tuned to modulate gain by changing the steepness of their activation within the dynamic voltage window. These results show how the impact of an ion channel on gain can be predicted from the relationship between channel kinetics and the membrane potential during firing. This is potentially relevant to understanding input-output scaling in a wide class of neurons found throughout the brain and other nervous systems

  3. CONDUCTIVE CHANNEL FOR ENERGY TRANSMISSION

    Directory of Open Access Journals (Sweden)

    V. V. Apollonov

    2014-01-01

    Full Text Available Laser spark obtained by using a conical optics is much more appropriate to form conducting channels in atmosphere. Only two types of lasers are actively considered to be used in forming high-conductivity channels in atmosphere, controlled by laser spark: pulsed sub-microsecond gas and chemical lasers (CO2, DF and short pulse solid-state and UV lasers. Main advantage of short pulse lasers is their ability in forming of super long ionized channels with a characteristic diameter of ~100  µ  in atmosphere along the  beam propagation direction. At estimated electron densities below  10 ⋅ 16 cm–3 in these filaments and laser wavelengths in the range of 0,5–1,0 mm, the plasma barely absorbs laser radiation.  In this case, the length of the track composed of many filaments is determined by the laser intensity and may reach many kilometers at a femtosecond pulse energy of ~100 mJ. However, these lasers could not be used to form high-conductivity long channels in atmosphere. The ohmic resistance of this type a conducting channels turned out to be very high, and the gas in the channels could not be strongly heated (< 1 J. An electric breakdown controlled by radiation of femtosecond solid-state laser was implemented in only at a length of 3 m with a voltage of 2 MV across the discharge gap (670 kV/m.Not so long ago scientific group from P. N. Lebedev has improved that result, the discharge gap – 1 m had been broken under KrF laser irradiation when switching high-voltage (up to 390 kV/m electric discharge by 100-ns UV pulses. Our previous result  –  16 m long conducting channel controlled by a  laser spark at the voltage  –  3 MV  – was obtained more than 20 years ago in Russia and Japan by using pulsed CO2  laser with energy  –  0,5 kJ. An average electric field strength  was < 190 kV/m. It is still too much for efficient applications.

  4. Ca2+ Channel Re-localization to Plasma-Membrane Microdomains Strengthens Activation of Ca2+-Dependent Nuclear Gene Expression

    Directory of Open Access Journals (Sweden)

    Krishna Samanta

    2015-07-01

    Full Text Available In polarized cells or cells with complex geometry, clustering of plasma-membrane (PM ion channels is an effective mechanism for eliciting spatially restricted signals. However, channel clustering is also seen in cells with relatively simple topology, suggesting it fulfills a more fundamental role in cell biology than simply orchestrating compartmentalized responses. Here, we have compared the ability of store-operated Ca2+ release-activated Ca2+ (CRAC channels confined to PM microdomains with a similar number of dispersed CRAC channels to activate transcription factors, which subsequently increase nuclear gene expression. For similar levels of channel activity, we find that channel confinement is considerably more effective in stimulating gene expression. Our results identify a long-range signaling advantage to the tight evolutionary conservation of channel clustering and reveal that CRAC channel aggregation increases the strength, fidelity, and reliability of the general process of excitation-transcription coupling.

  5. Interior point decoding for linear vector channels

    International Nuclear Information System (INIS)

    Wadayama, T

    2008-01-01

    In this paper, a novel decoding algorithm for low-density parity-check (LDPC) codes based on convex optimization is presented. The decoding algorithm, called interior point decoding, is designed for linear vector channels. The linear vector channels include many practically important channels such as inter-symbol interference channels and partial response channels. It is shown that the maximum likelihood decoding (MLD) rule for a linear vector channel can be relaxed to a convex optimization problem, which is called a relaxed MLD problem

  6. Interior point decoding for linear vector channels

    Energy Technology Data Exchange (ETDEWEB)

    Wadayama, T [Nagoya Institute of Technology, Gokiso, Showa-ku, Nagoya, Aichi, 466-8555 (Japan)], E-mail: wadayama@nitech.ac.jp

    2008-01-15

    In this paper, a novel decoding algorithm for low-density parity-check (LDPC) codes based on convex optimization is presented. The decoding algorithm, called interior point decoding, is designed for linear vector channels. The linear vector channels include many practically important channels such as inter-symbol interference channels and partial response channels. It is shown that the maximum likelihood decoding (MLD) rule for a linear vector channel can be relaxed to a convex optimization problem, which is called a relaxed MLD problem.

  7. List identifies threatened ecosystems

    Science.gov (United States)

    Showstack, Randy

    2012-09-01

    The International Union for Conservation of Nature (IUCN) announced on 9 September that it will develop a new Red List of Ecosystems that will identify which ecosystems are vulnerable or endangered. The list, which is modeled on the group's Red List of Threatened Species™, could help to guide conservation activities and influence policy processes such as the Convention on Biological Diversity, according to the group. “We will assess the status of marine, terrestrial, freshwater, and subterranean ecosystems at local, regional, and global levels,” stated Jon Paul Rodriguez, leader of IUCN's Ecosystems Red List Thematic Group. “The assessment can then form the basis for concerted implementation action so that we can manage them sustainably if their risk of collapse is low or restore them if they are threatened and then monitor their recovery.”

  8. Global Microbial Identifier

    DEFF Research Database (Denmark)

    Wielinga, Peter; Hendriksen, Rene S.; Aarestrup, Frank Møller

    2017-01-01

    ) will likely also enable a much better understanding of the pathogenesis of the infection and the molecular basis of the host response to infection. But the full potential of these advances will only transpire if the data in this area become transferable and thereby comparable, preferably in open-source...... of microorganisms, for the identification of relevant genes and for the comparison of genomes to detect outbreaks and emerging pathogens. To harness the full potential of WGS, a shared global database of genomes linked to relevant metadata and the necessary software tools needs to be generated, hence the global...... microbial identifier (GMI) initiative. This tool will ideally be used in amongst others in the diagnosis of infectious diseases in humans and animals, in the identification of microorganisms in food and environment, and to track and trace microbial agents in all arenas globally. This will require...

  9. Microprobe channeling analysis of pyrite crystals

    International Nuclear Information System (INIS)

    Jamieson, D.N.; Ryan, C.G.

    1992-01-01

    Nuclear microprobe analysis has provided much useful information about the composition of microscopic inclusions in minerals, mainly through the use of Particle Induced X-ray Emission (PIXE). However this technique, while powerful, does not provide any direct information about the chemical state, in particular the lattice location, of the elements in the mineral. This information is often of crucial importance in understanding the ore genesis. The technique of ion channeling may be used to identify lattice location, but many minerals occur as microscopic crystals. Therefore it is necessary to utilize a nuclear microprobe with the technique of Channeling Contrast Microscopy (CCM). As many minerals contain interesting trace elements, it is necessary to measure both the yield of backscattered particles and the induced x-rays to get a clear picture of the lattice location of the elements in the crystal. CCM with PIXE was used to analyse natural pyrite crystals containing a variety of substitutional and non-substitutional elements and natural pyrite crystals from a gold bearing ore. In the latter case, evidence was obtained for two habits for Au in the 400 μm crystals: one as inclusions of Au rich minerals, the other substituted on the pyrite lattice sites. 31 refs., 3 tabs., 6 figs

  10. Micro channels in macro thermal management solutions

    Directory of Open Access Journals (Sweden)

    Kosoy Boris V.

    2006-01-01

    Full Text Available Modern progress in electronics is associated with increase in computing ability and processing speed, as well as decrease in size. Future applications of electronic devices in aviation, aero space and high performance consumer products’ industry demand on very stringent specifications concerning miniaturization, component density, power density and reliability. Excess heat produces stresses on internal components inside the electronic device, thus creating reliability problems. Thus, a problem of heat generation and its efficient removal arises and it has led to the development of advanced thermal control systems. Present research analyses a thermodynamic feasibility of micro capillary heat pumped net works in thermal management of electronic systems, considers basic technological constrains and de sign availability, and identifies perspective directions for the further studies. Computer Fluid Dynamics studies have been per formed on the laminar convective heat transfer and pressure drop of working fluid in silicon micro channels. Surface roughness is simulated via regular constructal, and stochastic models. Three-dimensional numerical solution shows significant effects of surface roughness in terms of the rough element geometry such as height, size, spacing and the channel height on the velocity and pressure fields.

  11. The MISO wiretap channel with channel uncertainty: Asymptotic perspectives

    KAUST Repository

    Chaaban, Anas; Rezki, Zouheir; Alomair, Basel; Alouini, Mohamed-Slim

    2017-01-01

    The N-antenna MISO Gaussian wiretap channel with imperfect channel-state information at the transmitter (CSIT) is studied in terms of secrecy rate scaling versus the signal-to-noise ratio (SNR) and N. Two schemes are considered, beamforming (BF) and artificial noise injection (AN). It is shown that if the CSIT error is independent of SNR, then both schemes do not achieve scaling versus SNR. However, if this error vanishes as SNR increases, then AN achieves the optimal scaling versus SNR, contrary to BF. Scaling can be achieved in BF by increasing N. In fact, BF achieves the optimal scaling versus N. In the AN scheme however, injecting noise in multiple direction deteriorates its scaling versus N. Nevertheless, AN can achieve the optimal scaling if noise is sent in only one direction. This leads to better performance than BF if the CSIT error is smaller than a threshold which is also derived.

  12. The MISO wiretap channel with channel uncertainty: Asymptotic perspectives

    KAUST Repository

    Chaaban, Anas

    2017-05-12

    The N-antenna MISO Gaussian wiretap channel with imperfect channel-state information at the transmitter (CSIT) is studied in terms of secrecy rate scaling versus the signal-to-noise ratio (SNR) and N. Two schemes are considered, beamforming (BF) and artificial noise injection (AN). It is shown that if the CSIT error is independent of SNR, then both schemes do not achieve scaling versus SNR. However, if this error vanishes as SNR increases, then AN achieves the optimal scaling versus SNR, contrary to BF. Scaling can be achieved in BF by increasing N. In fact, BF achieves the optimal scaling versus N. In the AN scheme however, injecting noise in multiple direction deteriorates its scaling versus N. Nevertheless, AN can achieve the optimal scaling if noise is sent in only one direction. This leads to better performance than BF if the CSIT error is smaller than a threshold which is also derived.

  13. An Effective Channel Allocation Scheme to Reduce Co-Channel and Adjacent Channel Interference for WMN Backhaul

    International Nuclear Information System (INIS)

    Abbasi, S.; Ismaili, I.A.; Khuhawar, F.Y.

    2016-01-01

    Two folded work presents channel allocation scheme sustaining channel orthogonality and channel spacing to reduce CCI (Co-Channel Interference) and ACI (Adjacent Channel Interference) for inter flow of an intra-flow link. Proposed scheme as a part of radio resource allocation is applied on infrastructure based backhaul of wireless mesh network using directional antennas. The proposed approach is applied separately on 2.4 and 5GHz bands. Interference of connectivity graph is modelled by strongly connected directed graph and greedy algorithms are used for channel allocation. We have used OPNET Modeller suite to simulate network models for this research. The proposed arrangement reduces the channel interference and increases system throughput. In this research, the influence of channel is computed in terms of network throughput and delay. (author)

  14. Nonverbal channel use in communication of emotion: how may depend on why.

    Science.gov (United States)

    App, Betsy; McIntosh, Daniel N; Reed, Catherine L; Hertenstein, Matthew J

    2011-06-01

    This study investigated the hypothesis that different emotions are most effectively conveyed through specific, nonverbal channels of communication: body, face, and touch. Experiment 1 assessed the production of emotion displays. Participants generated nonverbal displays of 11 emotions, with and without channel restrictions. For both actual production and stated preferences, participants favored the body for embarrassment, guilt, pride, and shame; the face for anger, disgust, fear, happiness, and sadness; and touch for love and sympathy. When restricted to a single channel, participants were most confident about their communication when production was limited to the emotion's preferred channel. Experiment 2 examined the reception or identification of emotion displays. Participants viewed videos of emotions communicated in unrestricted and restricted conditions and identified the communicated emotions. Emotion identification in restricted conditions was most accurate when participants viewed emotions displayed via the emotion's preferred channel. This study provides converging evidence that some emotions are communicated predominantly through different nonverbal channels. Further analysis of these channel-emotion correspondences suggests that the social function of an emotion predicts its primary channel: The body channel promotes social-status emotions, the face channel supports survival emotions, and touch supports intimate emotions.

  15. Expression and distribution of voltage-gated ion channels in ferret sinoatrial node.

    Science.gov (United States)

    Brahmajothi, Mulugu V; Morales, Michael J; Campbell, Donald L; Steenbergen, Charles; Strauss, Harold C

    2010-10-01

    Spontaneous diastolic depolarization in the sinoatrial (SA) node enables it to serve as pacemaker of the heart. The variable cell morphology within the SA node predicts that ion channel expression would be heterogeneous and different from that in the atrium. To evaluate ion channel heterogeneity within the SA node, we used fluorescent in situ hybridization to examine ion channel expression in the ferret SA node region and atrial appendage. SA nodal cells were distinguished from surrounding cardiac myocytes by expression of the slow (SA node) and cardiac (surrounding tissue) forms of troponin I. Nerve cells in the sections were identified by detection of GAP-43 and cytoskeletal middle neurofilament. Transcript expression was characterized for the 4 hyperpolarization-activated cation channels, 6 voltage-gated Na(+) channels, 3 voltage-gated Ca(2+) channels, 24 voltage-gated K(+) channel α-subunits, and 3 ancillary subunits. To ensure that transcript expression was representative of protein expression, immunofluorescence was used to verify localization patterns of voltage-dependent K(+) channels. Colocalizations were performed to observe any preferential patterns. Some overlapping and nonoverlapping binding patterns were observed. Measurement of different cation channel transcripts showed heterogeneous expression with many different patterns of expression, attesting to the complexity of electrical activity in the SA node. This study provides insight into the possible role ion channel heterogeneity plays in SA node pacemaker activity.

  16. Low-Complexity Interference-Free Downlink Channel Assignment with Improved Performance in Coordinated Small Cells

    KAUST Repository

    Radaydeh, Redha M.

    2015-05-01

    This paper proposes a low-complexity interference-free channel assignment scheme with improved desired downlink performance in coordinated multi-antenna small-coverage access points (APs) that employ the open-access control strategy. The adopted system treats the case when each user can be granted an access to one of the available channels at a time. Moreover, each receive terminal can suppress a limited number of resolvable interfering sources via its highly-correlated receive array. On the other hand, the operation of the deployed APs can be coordinated to serve active users, and the availability of multiple physical channels and the use of uncorrelated transmit antennas at each AP are exploited to improve the performance of supported users. The analysis provides new approaches to use the transmit antenna array at each AP, the multiple physical channels, the receive antenna array at each user in order to identify interference-free channels per each user, and then to select a downlink channel that provides the best possible improved performance. The event of concurrent interference-free channel identification by different users is also treated to further improve the desired link associated with the scheduled user. The analysis considers the practical scenario of imperfect identification of interference-free channel by an active user and/or the imperfectness in scheduling concurrent users requests on the same channel. The developed formulations can be used to study any performance metric and they are applicable for any statistical and geometric channel models. © 2015 IEEE.

  17. Clofilium inhibits Slick and Slack potassium channels.

    Science.gov (United States)

    de Los Angeles Tejada, Maria; Stolpe, Kathleen; Meinild, Anne-Kristine; Klaerke, Dan A

    2012-01-01

    Slick and Slack high-conductance potassium channels have been recently discovered, and are found in the central nervous system and in the heart. Both channels are activated by Na(+) and Cl(-), and Slick channels are also inhibited by adenosine triphospate (ATP). An important role of setting the resting membrane potential and controlling the basal excitability of neurons has been suggested for these channels. In addition, no specific blockers for these channels are known up to the present. With the purpose of studying the pharmacological characteristics of Slick and Slack channels, the effects of exposure to the antiarrhythmic compound clofilium were evaluated. Clofilium was able to modulate the activity of Slick and Slack channels effectively, with a stronger effect on Slack than Slick channels. In order to evaluate the pharmacological behavior of Slick and Slack channels further, 38 commonly used potassium channel blockers were tested. Screening of these compounds did not reveal any modulators of Slick and Slack channels, except for clofilium. The present study provides a first approach towards elucidating the pharmacological characteristics of Slick and Slack channels and could be the basis for future studies aimed at developing potent and specific blockers and activators for these channels.

  18. LRRK2 regulates voltage-gated calcium channel function.

    Directory of Open Access Journals (Sweden)

    Cade eBedford

    2016-05-01

    Full Text Available Voltage-gated Ca2+ (CaV channels enable Ca2+ influx in response to membrane depolarization. CaV2.1 channels are localized to the presynaptic membrane of many types of neurons where they are involved in triggering neurotransmitter release. Several signaling proteins have been identified as important CaV2.1 regulators including protein kinases, G-proteins and Ca2+ binding proteins. Recently, we discovered that leucine rich repeat kinase 2 (LRRK2, a protein associated with inherited Parkinson’s disease, interacts with specific synaptic proteins and influences synaptic transmission. Since synaptic proteins functionally interact with CaV2.1 channels and synaptic transmission is triggered by Ca2+ entry via CaV2.1, we investigated whether LRRK2 could impact CaV2.1 channel function. CaV2.1 channel properties were measured using whole cell patch clamp electrophysiology in HEK293 cells transfected with CaV2.1 subunits and various LRRK2 constructs. Our results demonstrate that both wild type LRRK2 and the G2019S LRRK2 mutant caused a significant increase in whole cell Ca2+ current density compared to cells expressing only the CaV2.1 channel complex. In addition, LRRK2 expression caused a significant hyperpolarizing shift in voltage-dependent activation while having no significant effect on inactivation properties. These functional changes in CaV2.1 activity are likely due to a direct action of LRRK2 as we detected a physical interaction between LRRK2 and the β3 CaV channel subunit via coimmunoprecipitation. Furthermore, effects on CaV2.1 channel function are dependent on LRRK2 kinase activity as these could be reversed via treatment with a LRRK2 inhibitor. Interestingly, LRRK2 also augmented endogenous voltage-gated Ca2+ channel function in PC12 cells suggesting other CaV channels could also be regulated by LRRK2. Overall, our findings support a novel physiological role for LRRK2 in regulating CaV2.1 function that could have implications for how

  19. Side-gated ultrathin-channel nanopore FET sensors

    International Nuclear Information System (INIS)

    Yanagi, Itaru; Haga, Takanobu; Ando, Masahiko; Yamamoto, Jiro; Mine, Toshiyuki; Ishida, Takeshi; Hatano, Toshiyuki; Akahori, Rena; Yokoi, Takahide; Anazawa, Takashi; Oura, Takeshi

    2016-01-01

    A side-gated, ultrathin-channel nanopore FET (SGNAFET) is proposed for fast and label-free DNA sequencing. The concept of the SGNAFET comprises the detection of changes in the channel current during DNA translocation through a nanopore and identifying the four types of nucleotides as a result of these changes. To achieve this goal, both p- and n-type SGNAFETs with a channel thicknesses of 2 or 4 nm were fabricated, and the stable transistor operation of both SGNAFETs in air, water, and a KCl buffer solution were confirmed. In addition, synchronized current changes were observed between the ionic current through the nanopore and the SGNAFET’s drain current during DNA translocation through the nanopore. (paper)

  20. ZAP: a distributed channel assignment algorithm for cognitive radio networks

    Directory of Open Access Journals (Sweden)

    Munaretto Anelise

    2011-01-01

    Full Text Available Abstract We propose ZAP, an algorithm for the distributed channel assignment in cognitive radio (CR networks. CRs are capable of identifying underutilized licensed bands of the spectrum, allowing their reuse by secondary users without interfering with primary users. In this context, efficient channel assignment is challenging as ideally it must be simple, incur acceptable communication overhead, provide timely response, and be adaptive to accommodate frequent changes in the network. Another challenge is the optimization of network capacity through interference minimization. In contrast to related work, ZAP addresses these challenges with a fully distributed approach based only on local (neighborhood knowledge, while significantly reducing computational costs and the number of messages required for channel assignment. Simulations confirm the efficiency of ZAP in terms of (i the performance tradeoff between different metrics and (ii the fast achievement of a suitable assignment solution regardless of network size and density.

  1. Sub-micrometer fluidic channel for measuring photon emitting entities

    Science.gov (United States)

    Stavis, Samuel M; Edel, Joshua B; Samiee, Kevan T; Craighead, Harold G

    2014-11-18

    A nanofluidic channel fabricated in fused silica with an approximately 500 nm square cross section was used to isolate, detect and identify individual quantum dot conjugates. The channel enables the rapid detection of every fluorescent entity in solution. A laser of selected wavelength was used to excite multiple species of quantum dots and organic molecules, and the emission spectra were resolved without significant signal rejection. Quantum dots were then conjugated with organic molecules and detected to demonstrate efficient multicolor detection. PCH was used to analyze coincident detection and to characterize the degree of binding. The use of a small fluidic channel to detect quantum dots as fluorescent labels was shown to be an efficient technique for multiplexed single molecule studies. Detection of single molecule binding events has a variety of applications including high throughput immunoassays.

  2. Quantum dot conjugates in a sub-micrometer fluidic channel

    Science.gov (United States)

    Stavis, Samuel M.; Edel, Joshua B.; Samiee, Kevan T.; Craighead, Harold G.

    2010-04-13

    A nanofluidic channel fabricated in fused silica with an approximately 500 nm square cross section was used to isolate, detect and identify individual quantum dot conjugates. The channel enables the rapid detection of every fluorescent entity in solution. A laser of selected wavelength was used to excite multiple species of quantum dots and organic molecules, and the emission spectra were resolved without significant signal rejection. Quantum dots were then conjugated with organic molecules and detected to demonstrate efficient multicolor detection. PCH was used to analyze coincident detection and to characterize the degree of binding. The use of a small fluidic channel to detect quantum dots as fluorescent labels was shown to be an efficient technique for multiplexed single molecule studies. Detection of single molecule binding events has a variety of applications including high throughput immunoassays.

  3. Quantum dot conjugates in a sub-micrometer fluidic channel

    Science.gov (United States)

    Stavis, Samuel M [Ithaca, NY; Edel, Joshua B [Brookline, MA; Samiee, Kevan T [Ithaca, NY; Craighead, Harold G [Ithaca, NY

    2008-07-29

    A nanofluidic channel fabricated in fused silica with an approximately 500 nm square cross section was used to isolate, detect and identify individual quantum dot conjugates. The channel enables the rapid detection of every fluorescent entity in solution. A laser of selected wavelength was used to excite multiple species of quantum dots and organic molecules, and the emission spectra were resolved without significant signal rejection. Quantum dots were then conjugated with organic molecules and detected to demonstrate efficient multicolor detection. PCH was used to analyze coincident detection and to characterize the degree of binding. The use of a small fluidic channel to detect quantum dots as fluorescent labels was shown to be an efficient technique for multiplexed single molecule studies. Detection of single molecule binding events has a variety of applications including high throughput immunoassays.

  4. Ionic channels underlying the ventricular action potential in zebrafish embryo.

    Science.gov (United States)

    Alday, Aintzane; Alonso, Hiart; Gallego, Monica; Urrutia, Janire; Letamendia, Ainhoa; Callol, Carles; Casis, Oscar

    2014-06-01

    Over the last years zebrafish has become a popular model in the study of cardiac physiology, pathology and pharmacology. Recently, the application of the 3Rs regulation and the characteristics of the embryo have reduced the use of adult zebrafish use in many studies. However, the zebrafish embryo cardiac physiology is poorly characterized since most works have used indirect techniques and direct recordings of cardiac action potential and ionic currents are scarce. In order to optimize the zebrafish embryo model, we used electrophysiological, pharmacological and immunofluorescence tools to identify the characteristics and the ionic channels involved in the ventricular action potentials of zebrafish embryos. The application of Na(+) or T-type Ca(+2) channel blockers eliminated the cardiac electrical activity, indicating that the action potential upstroke depends on Na(+) and T-type Ca(+2) currents. The plateau phase depends on L-type Ca(+2) channels since it is abolished by specific blockade. The direct channel blockade indicates that the action potential repolarization and diastolic potential depends on ERG K(+) channels. The presence in the embryonic heart of the Nav1.5, Cav1.2, Cav3.2 and ERG channels was also confirmed by immunofluorescence, while the absence of effect of specific blockers and immunostaining indicate that two K(+) repolarizing currents present in human heart, Ito and IKs, are absent in the embryonic zebrafish heart. Our results describe the ionic channels present and its role in the zebrafish embryo heart and support the use of zebrafish embryos to study human diseases and their use for drug testing. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. Discovery and Development of Calcium Channel Blockers

    Directory of Open Access Journals (Sweden)

    Théophile Godfraind

    2017-05-01

    Full Text Available In the mid 1960s, experimental work on molecules under screening as coronary dilators allowed the discovery of the mechanism of calcium entry blockade by drugs later named calcium channel blockers. This paper summarizes scientific research on these small molecules interacting directly with L-type voltage-operated calcium channels. It also reports on experimental approaches translated into understanding of their therapeutic actions. The importance of calcium in muscle contraction was discovered by Sidney Ringer who reported this fact in 1883. Interest in the intracellular role of calcium arose 60 years later out of Kamada (Japan and Heibrunn (USA experiments in the early 1940s. Studies on pharmacology of calcium function were initiated in the mid 1960s and their therapeutic applications globally occurred in the the 1980s. The first part of this report deals with basic pharmacology in the cardiovascular system particularly in isolated arteries. In the section entitled from calcium antagonists to calcium channel blockers, it is recalled that drugs of a series of diphenylpiperazines screened in vivo on coronary bed precontracted by angiotensin were initially named calcium antagonists on the basis of their effect in depolarized arteries contracted by calcium. Studies on arteries contracted by catecholamines showed that the vasorelaxation resulted from blockade of calcium entry. Radiochemical and electrophysiological studies performed with dihydropyridines allowed their cellular targets to be identified with L-type voltage-operated calcium channels. The modulated receptor theory helped the understanding of their variation in affinity dependent on arterial cell membrane potential and promoted the terminology calcium channel blocker (CCB of which the various chemical families are introduced in the paper. In the section entitled tissue selectivity of CCBs, it is shown that characteristics of the drug, properties of the tissue, and of the stimuli are

  6. Feasibility Studies of Alpha-Channeling in Mirror Machines

    International Nuclear Information System (INIS)

    Zhmoginov, A.I.; Fisch, N.J.

    2010-01-01

    The linear magnetic trap is an attractive concept both for fusion reactors and for other plasma applications due to its relative engineering simplicity and high-beta operation. Applying the α-channeling technique to linear traps, such as mirror machines, can benefit this concept by efficiently redirecting α particle energy to fuel ion heating or by otherwise sustaining plasma confinement, thus increasing the effective fusion reactivity. To identify waves suitable for α-channeling a rough optimization of the energy extraction rate with respect to the wave parameters is performed. After the optimal regime is identified, a systematic search for modes with similar parameters in mirror plasmas is performed, assuming quasi-longitudinal or quasi-transverse wave propagation. Several modes suitable for α particle energy extraction are identified for both reactor designs and for proof- of-principle experiments.

  7. Radiograph identifying means

    International Nuclear Information System (INIS)

    Sheldon, A.D.

    1983-01-01

    A flexible character-indentable plastics embossing tape is backed by and bonded to a lead strip, not more than 0.025 inches thick, to form a tape suitable for identifying radiographs. The lead strip is itself backed by a relatively thin and flimsy plastics or fabric strip which, when removed, allows the lead plastic tape to be pressure-bonded to the surface to be radiographed. A conventional tape-embossing gun is used to indent the desired characters in succession into the lead-backed tape, without necessarily severing the lead; and then the backing strip is peeled away to expose the layer of adhesive which pressure-bonds the indented tape to the object to be radiographed. X-rays incident on the embossed tape will cause the raised characters to show up dark on the subsequently-developed film, whilst the raised side areas will show up white. Each character will thus stand out on the developed film. (author)

  8. Decreased expression of Kv7 channels in Hirchsprung's disease.

    Science.gov (United States)

    O'Donnell, Anne-Marie; Coyle, David; Puri, Prem

    2017-07-01

    Voltage-dependent K + channels (Kv channels) participate in electrical rhythmicity and smooth muscle responses and are regulated by excitatory and inhibitory neurotransmitters. Kv channels also participate in the interstitial cell of Cajal (ICC) and smooth muscle cell (SMC) responses to neural inputs. The Kv family consists of 12 subfamilies, Kv1-Kv12, with five members of the Kv7 family identified to date: Kv7.1-Kv7.5. A recent study identified the potassium channel Kv7.5 as having a role in the excitability of ICC-IM in the mouse colon. We therefore designed this study to test the hypothesis that Kv7 channels are present in the normal human colon and are reduced in Hirschprung's disease (HSCR). HSCR tissue specimens were collected at the time of pull-through surgery (n=10), while normal control tissue specimens were obtained at the time of colostomy closure in patients with imperforate anus (n=10). Kv7.3-Kv7.5 immunohistochemistry was performed and visualized using confocal microscopy to assess their distribution. Western blot analysis was undertaken to determine Kv7.3-Kv7.5 protein quantification. Kv7.3 and Kv7.4-immunoreactivity was co-localized with neuron and ICC markers, while Kv7.5 was found to be expressed on both ICCs and SMCs. Western blot analysis revealed similar levels of Kv7.3 and Kv7.5 expression in the normal colon and HSCR colon, while Kv7.4 proteins were found to be markedly decreased in ganglionic specimens and decreased further in aganglionic specimens. A deficiency of Kv7.4 channels in the ganglionic and aganglionic bowel may place a role in colonic dysmotility in HSCR. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Marine Toxins That Target Voltage-gated Sodium Channels

    Directory of Open Access Journals (Sweden)

    Robert J. French

    2006-04-01

    Full Text Available Abstract: Eukaryotic, voltage-gated sodium (NaV channels are large membrane proteins which underlie generation and propagation of rapid electrical signals in nerve, muscle and heart. Nine different NaV receptor sites, for natural ligands and/or drugs, have been identified, based on functional analyses and site-directed mutagenesis. In the marine ecosystem, numerous toxins have evolved to disrupt NaV channel function, either by inhibition of current flow through the channels, or by modifying the activation and inactivation gating processes by which the channels open and close. These toxins function in their native environment as offensive or defensive weapons in prey capture or deterrence of predators. In composition, they range from organic molecules of varying size and complexity to peptides consisting of ~10-70 amino acids. We review the variety of known NaV-targeted marine toxins, outlining, where known, their sites of interaction with the channel protein and their functional effects. In a number of cases, these natural ligands have the potential applications as drugs in clinical settings, or as models for drug development.

  10. Voltage-gated proton channel is expressed on phagosomes

    International Nuclear Information System (INIS)

    Okochi, Yoshifumi; Sasaki, Mari; Iwasaki, Hirohide; Okamura, Yasushi

    2009-01-01

    Voltage-gated proton channel has been suggested to help NADPH oxidase activity during respiratory burst of phagocytes through its activities of compensating charge imbalance and regulation of pH. In phagocytes, robust production of reactive oxygen species occurs in closed membrane compartments, which are called phagosomes. However, direct evidence for the presence of voltage-gated proton channels in phagosome has been lacking. In this study, the expression of voltage-gated proton channels was studied by Western blot with the antibody specific to the voltage-sensor domain protein, VSOP/Hv1, that has recently been identified as the molecular correlate for the voltage-gated proton channel. Phagosomal membranes of neutrophils contain VSOP/Hv1 in accordance with subunits of NADPH oxidases, gp91, p22, p47 and p67. Superoxide anion production upon PMA activation was significantly reduced in neutrophils from VSOP/Hv1 knockout mice. These are consistent with the idea that voltage-gated proton channels help NADPH oxidase in phagocytes to produce reactive oxygen species.

  11. Sub-nanometre channels embedded in two-dimensional materials

    KAUST Repository

    Han, Yimo

    2017-12-04

    Two-dimensional (2D) materials are among the most promising candidates for next-generation electronics due to their atomic thinness, allowing for flexible transparent electronics and ultimate length scaling1. Thus far, atomically thin p–n junctions2,3,4,5,6,7,8, metal–semiconductor contacts9,10,11, and metal–insulator barriers12,13,14 have been demonstrated. Although 2D materials achieve the thinnest possible devices, precise nanoscale control over the lateral dimensions is also necessary. Here, we report the direct synthesis of sub-nanometre-wide one-dimensional (1D) MoS2 channels embedded within WSe2 monolayers, using a dislocation-catalysed approach. The 1D channels have edges free of misfit dislocations and dangling bonds, forming a coherent interface with the embedding 2D matrix. Periodic dislocation arrays produce 2D superlattices of coherent MoS2 1D channels in WSe2. Using molecular dynamics simulations, we have identified other combinations of 2D materials where 1D channels can also be formed. The electronic band structure of these 1D channels offers the promise of carrier confinement in a direct-gap material and the charge separation needed to access the ultimate length scales necessary for future electronic applications.

  12. Adaptive evolution of the vertebrate skeletal muscle sodium channel

    Directory of Open Access Journals (Sweden)

    Jian Lu

    2011-01-01

    Full Text Available Tetrodotoxin (TTX is a highly potent neurotoxin that blocks the action potential by selectively binding to voltage-gated sodium channels (Na v. The skeletal muscle Na v (Na v1.4 channels in most pufferfish species and certain North American garter snakes are resistant to TTX, whereas in most mammals they are TTX-sensitive. It still remains unclear as to whether the difference in this sensitivity among the various vertebrate species can be associated with adaptive evolution. In this study, we investigated the adaptive evolution of the vertebrate Na v1.4 channels. By means of the CODEML program of the PAML 4.3 package, the lineages of both garter snakes and pufferfishes were denoted to be under positive selection. The positively selected sites identified in the p-loop regions indicated their involvement in Na v1.4 channel sensitivity to TTX. Most of these sites were located in the intracellular regions of the Na v1.4 channel, thereby implying the possible association of these regions with the regulation of voltage-sensor movement.

  13. Calibration through on-line monitoring of instruments channels

    International Nuclear Information System (INIS)

    James, R.W.

    1996-01-01

    Plant technical specifications require periodic calibration of instrument channels, and this has traditionally meant calibration at fixed time intervals for nearly all instruments. Experience has shown that unnecessarily frequent calibrations reduce channel availability and reliability, impact outage durations, and increase maintenance costs. An alternative approach to satisfying existing requirements for periodic calibration consists of on-line monitoring and quantitative comparison of instrument channels during operation to identify instrument degradation and failure. A Utility Working Group has been formed by EPRI to support the technical activities necessary to achieve generic NRC acceptance of on-line monitoring of redundant instrument channels as a basis for determining when to perform calibrations. A topical report proposing NRC acceptance of this approach was submitted in August 1995, and the Working Group is currently resolving NRC technical questions. This paper describes the proposed approach and the current status of the topical report with regard to NRC review. While these activities will not preclude utilities from continuing to use existing calibration approaches, successful acceptance of this performance-based approach will allow utilities to substantially reduce the number of calibrations which are performed. Concurrent benefits will include reduced I ampersand C impact on outage durations and improved sensitivity to instrument channel performance

  14. Biased and flow driven Brownian motion in periodic channels

    Science.gov (United States)

    Martens, S.; Straube, A.; Schmid, G.; Schimansky-Geier, L.; Hänggi, P.

    2012-02-01

    In this talk we will present an expansion of the common Fick-Jacobs approximation to hydrodynamically as well as by external forces driven Brownian transport in two-dimensional channels exhibiting smoothly varying periodic cross-section. We employ an asymptotic analysis to the components of the flow field and to stationary probability density for finding the particles within the channel in a geometric parameter. We demonstrate that the problem of biased Brownian dynamics in a confined 2D geometry can be replaced by Brownian motion in an effective periodic one-dimensional potential ψ(x) which takes the external bias, the change of the local channel width, and the flow velocity component in longitudinal direction into account. In addition, we study the influence of the external force magnitude, respectively, the pressure drop of the fluid on the particle transport quantities like the averaged velocity and the effective diffusion coefficient. The critical ratio between the external force and pressure drop where the average velocity equals zero is identified and the dependence of the latter on the channel geometry is derived. Analytic findings are confirmed by numerical simulations of the particle dynamics in a reflection symmetric sinusoidal channel.

  15. Ion Permeation and Mechanotransduction Mechanisms of Mechanosensitive Piezo Channels.

    Science.gov (United States)

    Zhao, Qiancheng; Wu, Kun; Geng, Jie; Chi, Shaopeng; Wang, Yanfeng; Zhi, Peng; Zhang, Mingmin; Xiao, Bailong

    2016-03-16

    Piezo proteins have been proposed as the long-sought-after mechanosensitive cation channels in mammals that play critical roles in various mechanotransduction processes. However, the molecular bases that underlie their ion permeation and mechanotransduction have remained functionally undefined. Here we report our finding of the miniature pore-forming module of Piezo1 that resembles the pore architecture of other trimeric channels and encodes the essential pore properties. We further identified specific residues within the pore module that determine unitary conductance, pore blockage and ion selectivity for divalent and monovalent cations and anions. The non-pore-containing region of Piezo1 confers mechanosensitivity to mechano-insensitive trimeric acid-sensing ion channels, demonstrating that Piezo1 channels possess intrinsic mechanotransduction modules separate from their pore modules. In conclusion, this is the first report on the bona fide pore module and mechanotransduction components of Piezo channels, which define their ion-conducting properties and gating by mechanical stimuli, respectively. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Sub-Nanometer Channels Embedded in Two-Dimensional Materials

    KAUST Repository

    Han, Yimo

    2017-07-31

    Two-dimensional (2D) materials are among the most promising candidates for next-generation electronics due to their atomic thinness, allowing for flexible transparent electronics and ultimate length scaling1. Thus far, atomically-thin p-n junctions2-7, metal-semiconductor contacts8-10, and metal-insulator barriers11-13 have been demonstrated. While 2D materials achieve the thinnest possible devices, precise nanoscale control over the lateral dimensions are also necessary. Although external one-dimensional (1D) carbon nanotubes14 can be used to locally gate 2D materials, this adds a non-trivial third dimension, complicating device integration and flexibility. Here, we report the direct synthesis of sub-nanometer 1D MoS2 channels embedded within WSe2 monolayers, using a dislocation-catalyzed approach. The 1D channels have edges free of misfit dislocations and dangling bonds, forming a coherent interface with the embedding 2D matrix. Periodic dislocation arrays produce 2D superlattices of coherent MoS2 1D channels in WSe2. Molecular dynamics (MD) simulations have identified other combinations of 2D materials that could form 1D channels. Density function theory (DFT) calculation predicts these 1D channels display type II band alignment needed for carrier confinement and charge separation to access the ultimate length scales necessary for future electronic applications.

  17. Targeting sodium channels in cardiac arrhythmia

    NARCIS (Netherlands)

    Remme, Carol Ann; Wilde, Arthur A. M.

    2014-01-01

    Cardiac voltage-gated sodium channels are responsible for proper electrical conduction in the heart. During acquired pathological conditions and inherited sodium channelopathies, altered sodium channel function causes conduction disturbances and ventricular arrhythmias. Although the clinical,

  18. Matagorda Ship Channel, Texas: Jetty Stability Study

    National Research Council Canada - National Science Library

    Kraus, Nicholas C; Lin, Lihwa; Batten, Brian K; Brown, Gary L

    2006-01-01

    .... The current has produced a large area of scour on the bay side of the inlet adjacent to the west jetty, and vessels encountering a strong along-channel and cross-channel current at the entrance...

  19. Quantum Correlations Evolution Asymmetry in Quantum Channels

    International Nuclear Information System (INIS)

    Li Meng; Huang Yun-Feng; Guo Guang-Can

    2017-01-01

    It was demonstrated that the entanglement evolution of a specially designed quantum state in the bistochastic channel is asymmetric. In this work, we generalize the study of the quantum correlations, including entanglement and quantum discord, evolution asymmetry to various quantum channels. We found that the asymmetry of entanglement and quantum discord only occurs in some special quantum channels, and the behavior of the entanglement evolution may be quite different from the behavior of the quantum discord evolution. To quantum entanglement, in some channels it decreases monotonously with the increase of the quantum channel intensity. In some other channels, when we increase the intensity of the quantum channel, it decreases at first, then keeps zero for some time, and then rises up. To quantum discord, the evolution becomes more complex and you may find that it evolutes unsmoothly at some points. These results illustrate the strong dependence of the quantum correlations evolution on the property of the quantum channels. (paper)

  20. Coastal Maintained Channels in US waters

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This layer shows coastal channels and waterways that are maintained and surveyed by the U.S. Army Corps of Engineers (USACE). These channels are necessary...

  1. Channel Estimation in DCT-Based OFDM

    Science.gov (United States)

    Wang, Yulin; Zhang, Gengxin; Xie, Zhidong; Hu, Jing

    2014-01-01

    This paper derives the channel estimation of a discrete cosine transform- (DCT-) based orthogonal frequency-division multiplexing (OFDM) system over a frequency-selective multipath fading channel. Channel estimation has been proved to improve system throughput and performance by allowing for coherent demodulation. Pilot-aided methods are traditionally used to learn the channel response. Least square (LS) and mean square error estimators (MMSE) are investigated. We also study a compressed sensing (CS) based channel estimation, which takes the sparse property of wireless channel into account. Simulation results have shown that the CS based channel estimation is expected to have better performance than LS. However MMSE can achieve optimal performance because of prior knowledge of the channel statistic. PMID:24757439

  2. Channel CAT: A Tactical Link Analysis Tool

    National Research Council Canada - National Science Library

    Coleman, Michael

    1997-01-01

    .... This thesis produced an analysis tool, the Channel Capacity Analysis Tool (Channel CAT), designed to provide an automated tool for the analysis of design decisions in developing client-server software...

  3. Investigation Of Information Sources And Communication Channels ...

    African Journals Online (AJOL)

    Investigation Of Information Sources And Communication Channels In Ipm Rice ... the information accessibility of farmer groups seems as empowerment strategy. ... information sources and communication channels, in order of importance, ...

  4. The KATP channel in migraine pathophysiology

    DEFF Research Database (Denmark)

    Al-Karagholi, Mohammad Al-Mahdi; Hansen, Jakob Møller; Severinsen, Johanne

    2017-01-01

    BACKGROUND: To review the distribution and function of KATP channels, describe the use of KATP channels openers in clinical trials and make the case that these channels may play a role in headache and migraine. DISCUSSION: KATP channels are widely present in the trigeminovascular system and play...... an important role in the regulation of tone in cerebral and meningeal arteries. Clinical trials using synthetic KATP channel openers report headache as a prevalent-side effect in non-migraine sufferers, indicating that KATP channel opening may cause headache, possibly due to vascular mechanisms. Whether KATP...... channel openers can provoke migraine in migraine sufferers is not known. CONCLUSION: We suggest that KATP channels may play an important role in migraine pathogenesis and could be a potential novel therapeutic anti-migraine target....

  5. Optimization of Communication in Noisy Quantum Channels

    National Research Council Canada - National Science Library

    Ruskai, Mary

    2002-01-01

    .... This project has been concerned with the analysis of mathematical models of noise for qubit channels, with the capacity of qubit channels used to transmit classical information, and with exchange...

  6. Four-channel delay generator model 5740

    International Nuclear Information System (INIS)

    Baumatz, D.; Milner, M.

    1978-01-01

    The 4-channel delay generator model 5740 generates 4-pulse groups in independent channels. The device offers the possibility of controlling both the time intervals between the pulses of a group and the rate of generation of groups

  7. Channelling of flow through fractures in rock

    International Nuclear Information System (INIS)

    Bourke, P.J.

    1987-05-01

    A method of mapping the channelling of flow in rock fractures formed by contacts between rock faces and of measuring the effective apertures of channels has been developed. Some typical results are given. (author)

  8. Consolidation equipment for irradiated nuclear fuel channels

    International Nuclear Information System (INIS)

    Taguchi, M.; Komatsu, Y.; Ose, T.

    1989-01-01

    The authors have developed and put into use a new type of mechanical consolidation equipment for irradiated nuclear fuel channels. This includes round-slice cutting of the top 100mm of the fuel channel with a guillotine cutter, and press cutting of the two corners of the remaining length of the fuel channel. Four guillotine blades work in combination with receiving blades arranged inside the fuel channel to cut the top 100mm, including the clips and spacers, of the fuel channel into a round slice. A press assembled in the consolidation equipment then presses the slice to achieve volume reduction. The press cutting operation uses two press cutting blades arranged inside the fuel channel and the receiving blades outside the fuel channel. The remaining length of fuel channel is cut off into L-shaped pieces by press cutting. This consolidation equipment is highly efficient because the round-slice cutting, pressing, and press cutting are all achieved by one unit

  9. A cement channel-detection technique using the pulsed-neutron log

    International Nuclear Information System (INIS)

    Myers, G.D.

    1991-01-01

    A channel-detection technique has been developed using boron solutions and pulsed-neutron logging (PNL) tools. This technique relies on the extremely high-neutron-absorption cross section that boron exhibits relative to other common elements, including chlorine. The PNL tool is used to detect movement of a boron solution in a log-inject-log procedure. The technique has identified channels in such difficult applications as logging through two strings of pipe and in highly deviated wellbores. Logging procedures are simple and cement channels can be readily identified. The boron solutions are relatively inexpensive, safe to handle, and nonradioactive. Additional PNL information for reservoir performance evaluation is collected simultaneously during channel-detection logging. This paper describes the theory, development, field application, and limitations of this channel-detection logging technique

  10. Channeling experiments at IPNE Cyclotron

    Energy Technology Data Exchange (ETDEWEB)

    Constantin, F; Dumitru, M; Ivan, A [Cyclotron Laboratory, Institute of Atomic Physics, Institute of Physics and Nuclear Engineering, R-76900 Bucharest, P.O.Box MG-6, (Romania)

    1992-01-01

    Channeling experiments have been performed at the I.P.N.E Cyclotron using a 3 MeV alpha beam. A slide system cut the beam up to 5 minutes spatial resolution with a maximum 60 nA beam current on the target. The two-axis goniometer, fully computer-controlled, moves the target, a silicon wafer, with 2.5 minute resolution, while an alpha particle sensitive solid state detector, monitors the backscattered particle fluence. In the first stage, channeling appears to be a simple, fast and reliable method for precise monocrystal orientation. A reduction of the host yield by a factor of two allowed impurities and defects to be studied. (Author).

  11. Thermoelectricity in Heterogeneous Nanofluidic Channels.

    Science.gov (United States)

    Li, Long; Wang, Qinggong

    2018-05-01

    Ionic fluids are essential to energy conversion, water desalination, drug delivery, and lab-on-a-chip devices. Ionic transport in nanoscale confinements and complex physical fields still remain elusive. Here, a nanofluidic system is developed using nanochannels of heterogeneous surface properties to investigate transport properties of ions under different temperatures. Steady ionic currents are observed under symmetric temperature gradients, which is equivalent to generating electricity using waste heat (e.g., electronic chips and solar panels). The currents increase linearly with temperature gradient and nonlinearly with channel size. Contributions to ion motion from temperatures and channel properties are evaluated for this phenomenon. The findings provide insights into the study of confined ionic fluids in multiphysical fields, and suggest applications in thermal energy conversion, temperature sensors, and chip-level thermal management. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Assessment of long-term channel changes in the Mekong River using remote sensing and a channel-evolution model

    Science.gov (United States)

    Miyazawa, N.

    2011-12-01

    River-channel changes are a key factor affecting physical, ecological and management issues in the fluvial environment. In this study, long-term channel changes in the Mekong River were assessed using remote sensing and a channel-evolution model. A channel-evolution model for calculating long-term channel changes of a measndering river was developed using a previous fluid-dynamic model [Zolezzi and Seminara, 2001], and was applied in order to quantify channel changes of two meandering reaches in the Mekong River. Quite few attempts have been made so far to combine remote sensing observation of meandering planform change with the application of channel evolution models within relatively small-scale gravel-bed systems in humid temperate regions. The novel point of the present work is to link state-of-art meandering planform evolution model with observed morphological changes within large-scale sand-bed rivers with higher bank height in tropical monsoonal climate regions, which are the highly dynamic system, and assess the performance. Unstable extents of the reaches could be historically identified using remote-sensing technique. The instability caused i) bank erosion and accretion of meander bends and ii) movement or development of bars and changes in the flow around the bars. The remote sensing measurements indicate that maximum erosion occurred downstream of the maximum curvature of the river-center line in both reaches. The model simulations indicates that under the mean annual peak discharge the maximum of excess longitudinal velocity near the banks occurs downstream of the maximum curvature in both reaches. The channel migration coefficients of the reaches were calibrated by comparing remote-sensing measurements and model simulations. The diffrence in the migration coefficients between both reaches depends on the diffrence in bank height rather than the geotechnical properties of floodplain sediments. Possible eroded floodplain areas and accreted floodplain

  13. Improving Channel Coordination Through Franchising

    OpenAIRE

    Rajiv Lal

    1990-01-01

    In this paper, we explore the role of franchising arrangements in improving coordination between channel members. In particular we focus on two elements of the franchising contract, namely, the royalty structure and the monitoring technology. We begin with a simple analysis where a manufacturer distributes its product through a retailer and the retail demand is affected by the retail price and the service provided by the retailer. In this context we show that neither royalty payments nor moni...

  14. Digital Multi Channel Analyzer Enhancement

    International Nuclear Information System (INIS)

    Gonen, E.; Marcus, E.; Wengrowicz, U.; Beck, A.; Nir, J.; Sheinfeld, M.; Broide, A.; Tirosh, D.

    2002-01-01

    A cement analyzing system based on radiation spectroscopy had been developed [1], using novel digital approach for real-time, high-throughput and low-cost Multi Channel Analyzer. The performance of the developed system had a severe problem: the resulted spectrum suffered from lack of smoothness, it was very noisy and full of spikes and surges, therefore it was impossible to use this spectrum for analyzing the cement substance. This paper describes the work carried out to improve the system performance

  15. Trafficking of neuronal calcium channels

    Czech Academy of Sciences Publication Activity Database

    Weiss, Norbert; Zamponi, G. W.

    2017-01-01

    Roč. 1, č. 1 (2017), č. článku NS20160003. ISSN 2059-6553 R&D Projects: GA ČR GA15-13556S; GA MŠk 7AMB15FR015 Institutional support: RVO:61388963 Keywords : calcium channel * neuron * trafficing Subject RIV: ED - Physiology OBOR OECD: Physiology (including cytology) http://www.neuronalsignaling.org/content/1/1/NS20160003

  16. Spark channel propagation in a microbubble liquid

    Energy Technology Data Exchange (ETDEWEB)

    Panov, V. A.; Vasilyak, L. M., E-mail: vasilyak@ihed.ras.ru; Vetchinin, S. P.; Pecherkin, V. Ya.; Son, E. E. [Russian Academy of Sciences, Joint Institute for High Temperatures (Russian Federation)

    2016-11-15

    Experimental study on the development of the spark channel from the anode needle under pulsed electrical breakdown of isopropyl alcohol solution in water with air microbubbles has been performed. The presence of the microbubbles increases the velocity of the spark channel propagation and increases the current in the discharge gap circuit. The observed rate of spark channel propagation in microbubble liquid ranges from 4 to 12 m/s, indicating the thermal mechanism of the spark channel development in a microbubble liquid.

  17. Assessing the Consequences of a Channel Switch

    OpenAIRE

    Xinlei (Jack) Chen; George John; Om Narasimhan

    2008-01-01

    Switching marketing channels is an expensive and sticky decision. While a number of theories suggest efficiency and strategic differences between channels, there is virtually no work on combining these ideas into an empirically workable methodology to assess the impact of a channel switch. In this study, we undertake to close this gap with an empirical study of the sports drink market, featuring competing producers and heterogeneous channels. We estimate demand and cost parameters for a numbe...

  18. Degenerate RFID Channel Modeling for Positioning Applications

    Directory of Open Access Journals (Sweden)

    A. Povalac

    2012-12-01

    Full Text Available This paper introduces the theory of channel modeling for positioning applications in UHF RFID. It explains basic parameters for channel characterization from both the narrowband and wideband point of view. More details are given about ranging and direction finding. Finally, several positioning scenarios are analyzed with developed channel models. All the described models use a degenerate channel, i.e. combined signal propagation from the transmitter to the tag and from the tag to the receiver.

  19. Channel CAT: A Tactical Link Analysis Tool

    Science.gov (United States)

    1997-09-01

    NAVAL POSTGRADUATE SCHOOL Monterey, California THESIS CHANNEL CAT : A TACTICAL LINK ANALYSIS TOOL by Michael Glenn Coleman September 1997 Thesis...REPORT TYPE AND DATES COVERED September 1997 Master’s Thesis 4. TITLE AND SUBTITLE CHANNEL CAT : A TACTICAL LINK ANALYSIS TOOL 5. FUNDING NUMBERS 6...tool, the Channel Capacity Analysis Tool (Channel CAT ), designed to provide an automated tool for the anlysis of design decisions in developing client

  20. Optimal super dense coding over memory channels

    OpenAIRE

    Shadman, Zahra; Kampermann, Hermann; Macchiavello, Chiara; Bruß, Dagmar

    2011-01-01

    We study the super dense coding capacity in the presence of quantum channels with correlated noise. We investigate both the cases of unitary and non-unitary encoding. Pauli channels for arbitrary dimensions are treated explicitly. The super dense coding capacity for some special channels and resource states is derived for unitary encoding. We also provide an example of a memory channel where non-unitary encoding leads to an improvement in the super dense coding capacity.

  1. Radio propagation measurement and channel modelling

    CERN Document Server

    Salous, Sana

    2013-01-01

    While there are numerous books describing modern wireless communication systems that contain overviews of radio propagation and radio channel modelling, there are none that contain detailed information on the design, implementation and calibration of radio channel measurement equipment, the planning of experiments and the in depth analysis of measured data. The book would begin with an explanation of the fundamentals of radio wave propagation and progress through a series of topics, including the measurement of radio channel characteristics, radio channel sounders, measurement strategies

  2. Spin chain model for correlated quantum channels

    Energy Technology Data Exchange (ETDEWEB)

    Rossini, Davide [International School for Advanced Studies SISSA/ISAS, via Beirut 2-4, I-34014 Trieste (Italy); Giovannetti, Vittorio; Montangero, Simone [NEST-CNR-INFM and Scuola Normale Superiore, Piazza dei Cavalieri 7, I-56126 Pisa (Italy)], E-mail: monta@sns.it

    2008-11-15

    We analyze the quality of the quantum information transmission along a correlated quantum channel by studying the average fidelity between input and output states and the average output purity, giving bounds for the entropy of the channel. Noise correlations in the channel are modeled by the coupling of each channel use with an element of a one-dimensional interacting quantum spin chain. Criticality of the environment chain is seen to emerge in the changes of the fidelity and of the purity.

  3. Subunit Stoichiometry of Human Muscle Chloride Channels

    OpenAIRE

    Fahlke, Christoph; Knittle, Timothy; Gurnett, Christina A.; Campbell, Kevin P.; George, Alfred L.

    1997-01-01

    Voltage-gated Cl? channels belonging to the ClC family appear to function as homomultimers, but the number of subunits needed to form a functional channel is controversial. To determine subunit stoichiometry, we constructed dimeric human skeletal muscle Cl? channels in which one subunit was tagged by a mutation (D136G) that causes profound changes in voltage-dependent gating. Sucrose-density gradient centrifugation experiments indicate that both monomeric and dimeric hClC-1 channels in their ...

  4. Hollow core plasma channel generation

    International Nuclear Information System (INIS)

    Quast, Heinrich Martin

    2018-03-01

    The use of a hollow plasma channel in plasma-based acceleration has beneficial properties for the acceleration of electron and positron bunches. In the scope of the FLASHForward facility at DESY, the generation of such a plasma structure is examined. Therefore, the generation of a ring-shaped laser intensity profile with different techniques is analyzed. From the obtained intensity profiles the electron density of a hollow plasma channel is simulated in the focal region. Different parameters are scanned to understand their influence on the electron density distribution - an important parameter being, for example, the radius of the central region of the channel. In addition to the simulations, experiments are presented, during which a laser pulse is transformed into a hollow beam with a spiral phase plate. Subsequently, it forms a plasma during the interaction with hydrogen, where the plasma is imaged with interferometry. For energies above 0.9 mJ a hollow plasma structure can be observed at the location of first plasma formation.

  5. Local Transfer Coefficient, Smooth Channel

    Directory of Open Access Journals (Sweden)

    R. T. Kukreja

    1998-01-01

    Full Text Available Naphthalene sublimation technique and the heat/mass transfer analogy are used to determine the detailed local heat/mass transfer distributions on the leading and trailing walls of a twopass square channel with smooth walls that rotates about a perpendicular axis. Since the variation of density is small in the flow through the channel, buoyancy effect is negligible. Results show that, in both the stationary and rotating channel cases, very large spanwise variations of the mass transfer exist in he turn and in the region immediately downstream of the turn in the second straight pass. In the first straight pass, the rotation-induced Coriolis forces reduce the mass transfer on the leading wall and increase the mass transfer on the trailing wall. In the turn, rotation significantly increases the mass transfer on the leading wall, especially in the upstream half of the turn. Rotation also increases the mass transfer on the trailing wall, more in the downstream half of the turn than in the upstream half of the turn. Immediately downstream of the turn, rotation causes the mass transfer to be much higher on the trailing wall near the downstream corner of the tip of the inner wall than on the opposite leading wall. The mass transfer in the second pass is higher on the leading wall than on the trailing wall. A slower flow causes higher mass transfer enhancement in the turn on both the leading and trailing walls.

  6. Study of material properties using channeling radiation

    International Nuclear Information System (INIS)

    Pantell, R.H.; Kephart, J.O.; Klein, R.K.; Park, H.; Berman, B.L.; Datz, S.

    1986-01-01

    A possible application for channeling radiation is for investigating the properties of crystals in which the channeling occurs. In this paper we present some general considerations concerning channeling radiation as a measurement technique, and then we proceed to describe several specific examples

  7. Square root approximation to the poisson channel

    NARCIS (Netherlands)

    Tsiatmas, A.; Willems, F.M.J.; Baggen, C.P.M.J.

    2013-01-01

    Starting from the Poisson model we present a channel model for optical communications, called the Square Root (SR) Channel, in which the noise is additive Gaussian with constant variance. Initially, we prove that for large peak or average power, the transmission rate of a Poisson Channel when coding

  8. The Marketing Channels of China Auto Industry

    Institute of Scientific and Technical Information of China (English)

    our reporter

    2001-01-01

    <正> After the 1990’s, the multi-channel structure of sales has still existed although the market mechanism is playing a main role in Chinese auto marketing circulation. Now, the channels of automobile marketing in China are as follows: 1. Manufacturer-established marketing channels

  9. Molecular determinants in TRPV5 channel assembly.

    NARCIS (Netherlands)

    Chang, Q.; Gyftogianni, E.; Graaf, K.F.J. van de; Hoefs, S.J.G.; Weidema, A.F.; Bindels, R.J.M.; Hoenderop, J.G.J.

    2004-01-01

    The epithelial Ca(2+) channels TRPV5 and TRPV6 mediate the Ca(2+) influx in 1,25-dihydroxyvitamin D(3)-responsive epithelia and are therefore essential in the maintenance of the body Ca(2+) balance. These Ca(2+) channels assemble in (hetero)tetrameric channel complexes with different functional

  10. Molecular determinants in TRPV5 channel assembly

    NARCIS (Netherlands)

    Chang, Qing; Gyftogianni, Emmanouela; van de Graaf, Stan F. J.; Hoefs, Susan; Weidema, Freek A.; Bindels, René J. M.; Hoenderop, Joost G. J.

    2004-01-01

    The epithelial Ca(2+) channels TRPV5 and TRPV6 mediate the Ca(2+) influx in 1,25-dihydroxyvitamin D(3)-responsive epithelia and are therefore essential in the maintenance of the body Ca(2+) balance. These Ca(2+) channels assemble in (hetero)tetrameric channel complexes with different functional

  11. Electronic Commerce and Retail Channel Substitution

    NARCIS (Netherlands)

    M.C.W. Janssen (Maarten); R. van der Noll

    2002-01-01

    textabstractWe analyze a market where firms compete in a conventional and an electronic retail channel. Consumers easily compare prices online, but some incur purchase uncertainties on the online channel. We investigate the market shares of the two retail channels and the prices that are charged. We

  12. 47 CFR 95.29 - Channels available.

    Science.gov (United States)

    2010-10-01

    ... with no more than 5 watts ERP. (g) Fixed stations in GMRS systems authorized before March 18, 1968... transmission of another GMRS station on a different channel or channels), the licensee of the GMRS system must... GMRS system from the following 462 MHz channels: 462.5500, 462.5750, 462.6000, 462.6250, 462.6500, 462...

  13. Language Planning, Channel Management, and ESP.

    Science.gov (United States)

    Kennedy, Chris

    Channel management, a concept developed in marketing to refer to the process by which a product is moved from production to consumption, uses a channel of distribution operating at several levels, each responsible for one or more of the activities of moving the product forward to the consumer. The function of channel management is to select the…

  14. Control channels in the brain and their influence on brain executive functions

    Science.gov (United States)

    Meng, Qinglei; Choa, Fow-Sen; Hong, Elliot; Wang, Zhiguang; Islam, Mohammad

    2014-05-01

    In a computer network there are distinct data channels and control channels where massive amount of visual information are transported through data channels but the information streams are routed and controlled by intelligent algorithm through "control channels". Recent studies on cognition and consciousness have shown that the brain control channels are closely related to the brainwave beta (14-40 Hz) and alpha (7-13 Hz) oscillations. The high-beta wave is used by brain to synchronize local neural activities and the alpha oscillation is for desynchronization. When two sensory inputs are simultaneously presented to a person, the high-beta is used to select one of the inputs and the alpha is used to deselect the other so that only one input will get the attention. In this work we demonstrated that we can scan a person's brain using binaural beats technique and identify the individual's preferred control channels. The identified control channels can then be used to influence the subject's brain executive functions. In the experiment, an EEG measurement system was used to record and identify a subject's control channels. After these channels were identified, the subject was asked to do Stroop tests. Binaural beats was again used to produce these control-channel frequencies on the subject's brain when we recorded the completion time of each test. We found that the high-beta signal indeed speeded up the subject's executive function performance and reduced the time to complete incongruent tests, while the alpha signal didn't seem to be able to slow down the executive function performance.

  15. FMRFamide-gated sodium channel and ASIC channels: a new class of ionotropic receptors for FMRFamide and related peptides.

    Science.gov (United States)

    Lingueglia, Eric; Deval, Emmanuel; Lazdunski, Michel

    2006-05-01

    FMRFamide and related peptides typically exert their action through G-protein coupled receptors. However, two ionotropic receptors for these peptides have recently been identified. They are both members of the epithelial amiloride-sensitive Na+ channel and degenerin (ENaC/DEG) family of ion channels. The invertebrate FMRFamide-gated Na+ channel (FaNaC) is a neuronal Na+-selective channel which is directly gated by micromolar concentrations of FMRFamide and related tetrapeptides. Its response is fast and partially desensitizing, and FaNaC has been proposed to participate in peptidergic neurotransmission. On the other hand, mammalian acid-sensing ion channels (ASICs) are not gated but are directly modulated by FMRFamide and related mammalian peptides like NPFF and NPSF. ASICs are activated by external protons and are therefore extracellular pH sensors. They are expressed both in the central and peripheral nervous system and appear to be involved in many physiological and pathophysiological processes such as hippocampal long-term potentiation and defects in learning and memory, acquired fear-related behavior, retinal function, brain ischemia, pain sensation in ischemia and inflammation, taste perception, hearing functions, and mechanoperception. The potentiation of ASIC activity by endogenous RFamide neuropeptides probably participates in the response to noxious acidosis in sensory and central neurons. Available data also raises the possibility of the existence of still unknown FMRFamide related endogenous peptides acting as direct agonists for ASICs.

  16. Search after new agents for hyperpolarization-activated and cyclic nucleotide-gated ion channels; Suche nach neuen Wirkstoffen fuer Hyperpolarisationsaktivierte und zyklisch Nukleotid-gesteuerte Ionenkanaele

    Energy Technology Data Exchange (ETDEWEB)

    Struenker, T.

    2005-12-01

    Rhythmic activity of single cells or cellular networks is a common feature of most organisms. Cellular rhythms govern the beating of the heart, cycles of sleep and wakefulness, breathing, and the release of hormones. The endogenous rhythmic activity of many neurons and cardiac relies on a complex interplay between several distinct ion channels. In particular, one type of ion channel plays a prominent role in the control of rhythmic electrical activity because it determines the frequency of the oscillations. The activity of the channels is thus setting the ''pace'' of the activity; therefore, these channels are often referred to as ''pacemaker'' channels. Despite their obvious physiological importance it hasn't been until a few years ago that the genes encoding pacemaker channels have been identified. Because both hyperpolarization and cyclic nucleotides are key elements that control their activity, pacemaker channels have now been designated hyperpolarization-activated and cyclic nucleotide-gated (HCN) channels. From a scientific as well as medical point of view, HCN channels are interesting drug targets. Only a few substances are known that specifically affect HCN channels. In the present study, a microtiter plate-based high throughput screening assay for HCN1 and HCN4 channels was developed. With this assay, known drugs for HCN channels were characterized. Subsequently, venoms of snails, spiders, scorpions, and snakes were screened for toxins affecting HCN channel activity. A few venoms were identified that possibly contain drugs that act on HCN channels. (orig.)

  17. TASK Channels on Basal Forebrain Cholinergic Neurons Modulate Electrocortical Signatures of Arousal by Histamine.

    Science.gov (United States)

    Vu, Michael T; Du, Guizhi; Bayliss, Douglas A; Horner, Richard L

    2015-10-07

    Basal forebrain cholinergic neurons are the main source of cortical acetylcholine, and their activation by histamine elicits cortical arousal. TWIK-like acid-sensitive K(+) (TASK) channels modulate neuronal excitability and are expressed on basal forebrain cholinergic neurons, but the role of TASK channels in the histamine-basal forebrain cholinergic arousal circuit is unknown. We first expressed TASK channel subunits and histamine Type 1 receptors in HEK cells. Application of histamine in vitro inhibited the acid-sensitive K(+) current, indicating a functionally coupled signaling mechanism. We then studied the role of TASK channels in modulating electrocortical activity in vivo using freely behaving wild-type (n = 12) and ChAT-Cre:TASK(f/f) mice (n = 12), the latter lacking TASK-1/3 channels on cholinergic neurons. TASK channel deletion on cholinergic neurons significantly altered endogenous electroencephalogram oscillations in multiple frequency bands. We then identified the effect of TASK channel deletion during microperfusion of histamine into the basal forebrain. In non-rapid eye movement sleep, TASK channel deletion on cholinergic neurons significantly attenuated the histamine-induced increase in 30-50 Hz activity, consistent with TASK channels contributing to histamine action on basal forebrain cholinergic neurons. In contrast, during active wakefulness, histamine significantly increased 30-50 Hz activity in ChAT-Cre:TASK(f/f) mice but not wild-type mice, showing that the histamine response depended upon the prevailing cortical arousal state. In summary, we identify TASK channel modulation in response to histamine receptor activation in vitro, as well as a role of TASK channels on cholinergic neurons in modulating endogenous oscillations in the electroencephalogram and the electrocortical response to histamine at the basal forebrain in vivo. Attentive states and cognitive function are associated with the generation of γ EEG activity. Basal forebrain

  18. JADSPE, Multi-Channel Gamma Spectra Unfolding Program

    International Nuclear Information System (INIS)

    Rikovska, J.; Stejskalova, E.

    2005-01-01

    1 - Description of program or function: JADSPE is a package of eight programs to process multi-channel gamma-ray spectra. The programs can be used to: - locate automatically spectral peaks and calculate their positions, areas, and full widths at half maximum (FWHM); - plot the spectra on a CALCOMP plotter, TEKTRONIX terminal or a line printer; - add or subtract several spectra with the possibility of adjusting either their start and end channels or the maxima of the chosen corresponding peaks. The JADSPE package comprises the following programs: - SPECTF: automatic location of peaks and calculation of their positions, areas and FWHMS. The standard deviations of peak parameters are also determined, and each evaluated region is plotted on the line printer. - SPECT1: The areas and FWHMs are calculated for peaks whose positions are known beforehand. The standard deviations of calculated parameters are also determined, and each evaluated region is plotted on the line printer. - PLOCHA: The peak net area is calculated by summing the channel contents in specified regions and by subtracting a linear background. - GRAPH: Spectrum plotting on the line printer. - PLTNEW: Spectrum plotting on CALCOMP plotter or on TEKTRONIX terminal. - SUMDIF: The channel contents of several gamma-ray spectra are added or subtracted. - SSPFP: The channel contents of several gamma-ray spectra are added with adjustment of the maxima of specified peaks. - SOUCET: The channel contents of several gamma-ray spectra are added with the adjustment of start and end channels of the spectra. 2 - Method of solution: Non-linear least-square fit. 3 - Restrictions on the complexity of the problem: The full energy peaks are approximated by a symmetrical Gaussian function and the underlying background is approximated by a first-order polynomial. A fixed spectrum length of 4096 channels is assumed. Maxima of: - number of peaks in one multiplet: 9; - number of peaks identified by the automatic search procedure

  19. Separation of Particles in Channels Rotary Engine

    Directory of Open Access Journals (Sweden)

    Zyatikov Pavel

    2015-01-01

    Full Text Available The article considers the separation of particles in channels with different relative length. It is shown that the intensity of turbulence at the inlet section of the channel varies considerably in its length. The dependence of the turbulence damping along the channel expressing by fraction of the distance is shown. The ratio of the particle separation efficiency out the gas flow in the rotor channel is defined. The values of particle separation efficiency in the channel for the angle α=π/4 in turbulent aerosol flow is shows, including without mixing the particles.

  20. CHANNEL EVOLUTION IN MODIFIED ALLUVIAL STREAMS.

    Science.gov (United States)

    Simon, Andrew; Hupp, Cliff R.

    1987-01-01

    This study (a) assesses the channel changes and network trends of bed level response after modifications between 1959 and 1972 of alluvial channels in western Tennessee and (b) develops a conceptual model of bank slope development to qualitatively assess bank stability and potential channel widening. A six-step, semiquantitative model of channel evolution in disturbed channels was developed by quantifying bed level trends and recognizing qualitative stages of bank slope development. Development of the bank profile is defined in terms of three dynamic and observable surfaces: (a) vertical face (70 to 90 degrees), (b) upper bank (25 to 50 degrees), and (c) slough line (20 to 25 degrees).

  1. Regional bankfull-channel dimensions of non-urban wadeable streams in Indiana

    Science.gov (United States)

    Robinson, Bret A.

    2013-01-01

    During floods, damage to properties and community infrastructure may result from inundation and the processes of erosion. The damages imparted by erosion are collectively termed the fluvial erosion hazard (FEH), and the Indiana Silver Jackets Multi-agency Hazard Mitigation Taskforce is supporting a program to build tools that will assist Indiana property owners and communities with FEH-mitigation efforts. As part of that program, regional channel-dimension relations are identified for non-urban wadeable streams in Indiana. With a site-selection process that targeted the three largest physiographic regions of the state, field work was completed to measure channel-dimension and channel-geometry characteristics across Indiana. In total, 82 sites were identified for data collection; 25 in the Northern Moraine and Lake region, 31 in the Central Till Plain region, and 26 in the Southern Hills and Lowlands region. Following well established methods, for each data-collection site, effort was applied to identify bankfull stage, determine bankfull-channel dimensions, and document channel-geometry characteristics that allowed for determinations of channel classification. In this report, regional bankfull-channel dimension results are presented as a combination of plots and regression equations that identify the relations between drainage area and the bankfull-channel dimensions of width, mean depth, and cross-sectional area. This investigation found that the channel-dimension data support independent relations for each of the three physiographic regions noted above. Furthermore, these relations show that, for any given drainage area, northern Indiana channels have the smallest predicted dimensions, southern Indiana channels have the largest predicted dimensions, and central Indiana channels are intermediate in their predicted dimensions. When considering the suite of variables that influence bankfull-channel dimensions, it appears that contrasting runoff characteristics

  2. Identifying Medicinal Plant Leaves using Textures and Optimal Colour Spaces Channel

    Directory of Open Access Journals (Sweden)

    C H Arun

    2017-02-01

    Full Text Available This paper presents an automated medicinal plant leaf identification system. The Colour Texture analysis of the leaves is done using the statistical, the Grey Tone Spatial Dependency Matrix(GTSDM and the Local Binary Pattern(LBP based features with 20 different  colour spaces(RGB, XYZ, CMY, YIQ, YUV, $YC_{b}C_{r}$, YES, $U^{*}V^{*}W^{*}$, $L^{*}a^{*}b^{*}$, $L^{*}u^{*}v^{*}$, lms, $l\\alpha\\beta$, $I_{1} I_{2} I_{3}$, HSV, HSI, IHLS, IHS, TSL, LSLM and KLT.  Classification of the medicinal plant is carried out with 70\\% of the dataset in training set and 30\\% in the test set. The classification performance is analysed with Stochastic Gradient Descent(SGD, kNearest Neighbour(kNN, Support Vector Machines based on Radial basis function kernel(SVM-RBF, Linear Discriminant Analysis(LDA and Quadratic Discriminant Analysis(QDA classifiers. Results of classification on a dataset of 250 leaf images belonging to five different species of plants show the identification rate of 98.7 \\%. The results certainly show better identification due to the use of YUV, $L^{*}a^{*}b^{*}$ and HSV colour spaces.

  3. Credit supply and monetary policy : Identifying the bank balance-sheet channel with loan applications

    NARCIS (Netherlands)

    Jimenez Porras, G.; Ongena, S.; Peydro, J.L.; Saurina, J.

    2012-01-01

    We analyze the impact of monetary policy on the supply of bank credit. Monetary policy affects both loan supply and demand, thus making identification a steep challenge. We therefore analyze a novel, supervisory dataset with loan applications from Spain. Accounting for time-varying firm

  4. IDENTIFYING BANK LENDING CHANNEL IN INDONESIA: A VECTOR ERROR CORRECTION APPROACH WITH STRUCTURAL BREAK

    Directory of Open Access Journals (Sweden)

    Akhsyim Afandi

    2017-03-01

    Full Text Available There was a question whether monetary policy works through bank lending channelrequired a monetary-induced change in bank loans originates from the supply side. Mostempirical studies that employed vector autoregressive (VAR models failed to fulfill thisrequirement. Aiming to offer a solution to this identification problem, this paper developed afive-variable vector error correction (VEC model of two separate bank credit markets inIndonesia. Departing from previous studies, the model of each market took account of onestructural break endogenously determined by implementing a unit root test. A cointegrationtest that took account of one structural break suggested two cointegrating vectors identifiedas bank lending supply and demand relations. The estimated VEC system for both marketssuggested that bank loans adjusted more strongly in the direction of the supply equation.

  5. Modulation of ERG channels by XE991

    DEFF Research Database (Denmark)

    Elmedyb, Pernille; Calloe, Kirstine; Schmitt, Nicole

    2007-01-01

    In neuronal tissue, KCNQ2-5 channels conduct the physiologically important M-current. In some neurones, the M-current may in addition be conducted partly by ERG potassium channels, which have widely overlapping expression with the KCNQ channel subunits. XE991 and linopiridine are known to be stan......In neuronal tissue, KCNQ2-5 channels conduct the physiologically important M-current. In some neurones, the M-current may in addition be conducted partly by ERG potassium channels, which have widely overlapping expression with the KCNQ channel subunits. XE991 and linopiridine are known...... to be standard KCNQ potassium channel blockers. These compounds have been used in many different tissues as specific pharmacological tools to discern native currents conducted by KCNQ channels from other potassium currents. In this article, we demonstrate that ERG1-2 channels are also reversibly inhibited by XE......991 in the micromolar range (EC(50) 107 microM for ERG1). The effect has been characterized in Xenopus laevis oocytes expressing ERG1-2 and in the mammalian HEK293 cell line stably expressing ERG1 channels. The IC(50) values for block of KCNQ channels by XE991 range 1-65 microM. In conclusion, great...

  6. Plasma channels for electron beam transport

    International Nuclear Information System (INIS)

    Schneider, R.F.; Smith, J.R.; Moffatt, M.E.; Nguyen, K.T.; Uhm, H.S.

    1988-01-01

    In recent years, there has been much interest in transport of intense relativistic electron beams using plasma channels. These channels are formed by either: ionization of an organic gas by UV photoionization or electron impact ionization of a low pressure gas utilizing a low energy (typically several hundred volts) electron gun. The second method is discussed here. As their electron gun, the authors used a 12 volt lightbulb filament which is biased to -400 volts with respect to the grounded 15 cm diameter drift tube. The electrons emitted from the filament are confined by an axial magnetic field of --100 Gauss to create a plasma channel which is less than 1 cm in radius. The channel density has been determined with Langmuir probes and the resulting line densities were found to be 10 11 to 10 12 per cm. When a multi-kiloamp electron beam is injected onto this channel, the beam space charge will eject the plasma electrons leaving the ions behind to charge neutralize the electron beam, hence allowing the beam to propagate. In this work, the authors performed experimental studies on the dynamics of the plasma channel. These include Langmuir probe measurements of a steady state (DC) channel, as well as time-resolved Langmuir probe studies of pulsed channels. In addition they performed experimental studies of beam propagation in these plasma channels. Specifically, they observed the behavior of current transport in these channels. Detailed results of beam transport and channel studies are presented

  7. Outward Rectification of Voltage-Gated K+ Channels Evolved at Least Twice in Life History.

    Directory of Open Access Journals (Sweden)

    Janin Riedelsberger

    Full Text Available Voltage-gated potassium (K+ channels are present in all living systems. Despite high structural similarities in the transmembrane domains (TMD, this K+ channel type segregates into at least two main functional categories-hyperpolarization-activated, inward-rectifying (Kin and depolarization-activated, outward-rectifying (Kout channels. Voltage-gated K+ channels sense the membrane voltage via a voltage-sensing domain that is connected to the conduction pathway of the channel. It has been shown that the voltage-sensing mechanism is the same in Kin and Kout channels, but its performance results in opposite pore conformations. It is not known how the different coupling of voltage-sensor and pore is implemented. Here, we studied sequence and structural data of voltage-gated K+ channels from animals and plants with emphasis on the property of opposite rectification. We identified structural hotspots that alone allow already the distinction between Kin and Kout channels. Among them is a loop between TMD S5 and the pore that is very short in animal Kout, longer in plant and animal Kin and the longest in plant Kout channels. In combination with further structural and phylogenetic analyses this finding suggests that outward-rectification evolved twice and independently in the animal and plant kingdom.

  8. Ion channel expression patterns in glioblastoma stem cells with functional and therapeutic implications for malignancy.

    Directory of Open Access Journals (Sweden)

    Julia Pollak

    Full Text Available Ion channels and transporters have increasingly recognized roles in cancer progression through the regulation of cell proliferation, migration, and death. Glioblastoma stem-like cells (GSCs are a source of tumor formation and recurrence in glioblastoma multiforme, a highly aggressive brain cancer, suggesting that ion channel expression may be perturbed in this population. However, little is known about the expression and functional relevance of ion channels that may contribute to GSC malignancy. Using RNA sequencing, we assessed the enrichment of ion channels in GSC isolates and non-tumor neural cell types. We identified a unique set of GSC-enriched ion channels using differential expression analysis that is also associated with distinct gene mutation signatures. In support of potential clinical relevance, expression of selected GSC-enriched ion channels evaluated in human glioblastoma databases of The Cancer Genome Atlas and Ivy Glioblastoma Atlas Project correlated with patient survival times. Finally, genetic knockdown as well as pharmacological inhibition of individual or classes of GSC-enriched ion channels constrained growth of GSCs compared to normal neural stem cells. This first-in-kind global examination characterizes ion channels enriched in GSCs and explores their potential clinical relevance to glioblastoma molecular subtypes, gene mutations, survival outcomes, regional tumor expression, and experimental responses to loss-of-function. Together, the data support the potential biological and therapeutic impact of ion channels on GSC malignancy and provide strong rationale for further examination of their mechanistic and therapeutic importance.

  9. Ion channel expression patterns in glioblastoma stem cells with functional and therapeutic implications for malignancy.

    Science.gov (United States)

    Pollak, Julia; Rai, Karan G; Funk, Cory C; Arora, Sonali; Lee, Eunjee; Zhu, Jun; Price, Nathan D; Paddison, Patrick J; Ramirez, Jan-Marino; Rostomily, Robert C

    2017-01-01

    Ion channels and transporters have increasingly recognized roles in cancer progression through the regulation of cell proliferation, migration, and death. Glioblastoma stem-like cells (GSCs) are a source of tumor formation and recurrence in glioblastoma multiforme, a highly aggressive brain cancer, suggesting that ion channel expression may be perturbed in this population. However, little is known about the expression and functional relevance of ion channels that may contribute to GSC malignancy. Using RNA sequencing, we assessed the enrichment of ion channels in GSC isolates and non-tumor neural cell types. We identified a unique set of GSC-enriched ion channels using differential expression analysis that is also associated with distinct gene mutation signatures. In support of potential clinical relevance, expression of selected GSC-enriched ion channels evaluated in human glioblastoma databases of The Cancer Genome Atlas and Ivy Glioblastoma Atlas Project correlated with patient survival times. Finally, genetic knockdown as well as pharmacological inhibition of individual or classes of GSC-enriched ion channels constrained growth of GSCs compared to normal neural stem cells. This first-in-kind global examination characterizes ion channels enriched in GSCs and explores their potential clinical relevance to glioblastoma molecular subtypes, gene mutations, survival outcomes, regional tumor expression, and experimental responses to loss-of-function. Together, the data support the potential biological and therapeutic impact of ion channels on GSC malignancy and provide strong rationale for further examination of their mechanistic and therapeutic importance.

  10. Structure-based assessment of disease-related mutations in human voltage-gated sodium channels

    Directory of Open Access Journals (Sweden)

    Weiyun Huang

    2017-02-01

    Full Text Available ABSTRACT Voltage-gated sodium (Nav channels are essential for the rapid upstroke of action potentials and the propagation of electrical signals in nerves and muscles. Defects of Nav channels are associated with a variety of channelopathies. More than 1000 disease-related mutations have been identified in Nav channels, with Nav1.1 and Nav1.5 each harboring more than 400 mutations. Nav channels represent major targets for a wide array of neurotoxins and drugs. Atomic structures of Nav channels are required to understand their function and disease mechanisms. The recently determined atomic structure of the rabbit voltage-gated calcium (Cav channel Cav1.1 provides a template for homology-based structural modeling of the evolutionarily related Nav channels. In this Resource article, we summarized all the reported disease-related mutations in human Nav channels, generated a homologous model of human Nav1.7, and structurally mapped disease-associated mutations. Before the determination of structures of human Nav channels, the analysis presented here serves as the base framework for mechanistic investigation of Nav channelopathies and for potential structure-based drug discovery.

  11. Femtosecond laser direct generation of 3D-microfluidic channels inside bulk PMMA.

    Science.gov (United States)

    Roth, Gian-Luca; Esen, Cemal; Hellmann, Ralf

    2017-07-24

    We report on laser direct generation of 3D-microchannels for microfluidic applications inside PMMA bulk material by focused femtosecond pulses. Inner lying channels with cross sectional areas from 100 µm 2 to 4400 µm 2 are directly created in the volume of a PMMA substrate. Using the presented process, the channel length is fundamentally unlimited. Here we demonstrate a channel length of 6 meters inside a substrate with dimensions of 20 × 20 × 1.1 mm. The formation of the micro channels is based on nonlinear absorption around the focal volume that triggers a material modification. The modified volume can be selectively opened to form the channel by a subsequent annealing process. The cross section of the channel is strongly influenced by the energy distribution and illumination around the focal volume determined by the optical setup and process design. The 3D channel layout can easily be realized by moving the specimen using 3D motorized stage, allowing freely chosen complex shaped channel architectures. Within a comprehensive parameter study, varying laser power, number of multi-passes, writing speed and writing depths, we identify an optimized process in terms of attainable channel height, width and aspect ratio, as well as process stability and reproducibility. The proof of concept for an application in three dimensional microfluidic systems is provided by florescence microscopy using a dye rhodamine B solution in isopropanol.

  12. Structure-based assessment of disease-related mutations in human voltage-gated sodium channels.

    Science.gov (United States)

    Huang, Weiyun; Liu, Minhao; Yan, S Frank; Yan, Nieng

    2017-06-01

    Voltage-gated sodium (Na v ) channels are essential for the rapid upstroke of action potentials and the propagation of electrical signals in nerves and muscles. Defects of Na v channels are associated with a variety of channelopathies. More than 1000 disease-related mutations have been identified in Na v channels, with Na v 1.1 and Na v 1.5 each harboring more than 400 mutations. Na v channels represent major targets for a wide array of neurotoxins and drugs. Atomic structures of Na v channels are required to understand their function and disease mechanisms. The recently determined atomic structure of the rabbit voltage-gated calcium (Ca v ) channel Ca v 1.1 provides a template for homology-based structural modeling of the evolutionarily related Na v channels. In this Resource article, we summarized all the reported disease-related mutations in human Na v channels, generated a homologous model of human Na v 1.7, and structurally mapped disease-associated mutations. Before the determination of structures of human Na v channels, the analysis presented here serves as the base framework for mechanistic investigation of Na v channelopathies and for potential structure-based drug discovery.

  13. Quantum capacity of Pauli channels with memory

    International Nuclear Information System (INIS)

    Huang Peng; He Guangqiang; Lu Yuan; Zeng Guihua

    2011-01-01

    The amount of coherent quantum information that can be reliably transmitted down the memory Pauli channels with Markovian correlated noise is investigated. Two methods for evaluating the quantum capacity of the memory Pauli channels are proposed to try to trace the memory effect on the transmissions of quantum information. We show that the evaluation of quantum capacity can be reduced to the calculation of the initial memory state of each successive transmission. Furthermore, we derive quantum capacities of the memory phase flip channel, bit flip channel and bit-phase flip channel. Also, a lower bound of the quantum capacity of the memory depolarizing channel is obtained. An increase of the degree of memory of the channels has a positive effect on the increase of their quantum capacities.

  14. Effects of dislocations on electron channeling

    International Nuclear Information System (INIS)

    George, Juby; Pathak, A P

    2009-01-01

    The phenomenon of electron channeling in a crystal affected by dislocations is considered. Earlier we had considered the quantum aspects of the positron channeling in a crystal bent by dislocations where the effects of longitudinal motion of the particle were also considered along with the transverse motion. In this paper, the effective potential for the electron case is found for the two regions of dislocation-affected channel. There is considerable shift in the potential minima due to dislocations. The frequency and the corresponding spectrum of the channeling radiation due to electrons channeling through the perfect channel and the two regions of dislocation-affected channels are calculated. The spectral distribution of radiation intensity changes with the parameters of dislocation. The continuity of wavefunctions and their derivatives is used at the three boundaries and the reflection and transmission coefficients are found using these boundary conditions in the same way as in the positron case.

  15. Channel selection for automatic seizure detection

    DEFF Research Database (Denmark)

    Duun-Henriksen, Jonas; Kjaer, Troels Wesenberg; Madsen, Rasmus Elsborg

    2012-01-01

    Objective: To investigate the performance of epileptic seizure detection using only a few of the recorded EEG channels and the ability of software to select these channels compared with a neurophysiologist. Methods: Fifty-nine seizures and 1419 h of interictal EEG are used for training and testing...... of an automatic channel selection method. The characteristics of the seizures are extracted by the use of a wavelet analysis and classified by a support vector machine. The best channel selection method is based upon maximum variance during the seizure. Results: Using only three channels, a seizure detection...... sensitivity of 96% and a false detection rate of 0.14/h were obtained. This corresponds to the performance obtained when channels are selected through visual inspection by a clinical neurophysiologist, and constitutes a 4% improvement in sensitivity compared to seizure detection using channels recorded...

  16. On luminescence bleaching of tidal channel sediments

    DEFF Research Database (Denmark)

    Fruergaard, Mikkel; Pejrup, Morten; Murray, Andrew S.

    2015-01-01

    We investigate the processes responsible for bleaching of the quartz OSL signal from tidal channel sediment. Tidal dynamics are expected to play an important role for complete bleaching of tidal sediments. However, no studies have examined the amount of reworking occurring in tidal channels...... and on tidal flats due to the mixing caused by currents and waves. We apply bed level data to evaluate the amount of vertical sediment reworking in modern tidal channels and at a tidal flat. Cycles of deposition and erosion are measured with a bed level sensor, and the results show that gross sedimentation...... was several times higher than net sedimentation. We propose that tidal channel sediment is bleached either on the tidal flat before it is transported to the tidal channels and incorporated in channel-fill successions or, alternatively, on the shallow intertidal part of the channel banks. Based...

  17. Quantum channels with a finite memory

    International Nuclear Information System (INIS)

    Bowen, Garry; Mancini, Stefano

    2004-01-01

    In this paper we study quantum communication channels with correlated noise effects, i.e., quantum channels with memory. We derive a model for correlated noise channels that includes a channel memory state. We examine the case where the memory is finite, and derive bounds on the classical and quantum capacities. For the entanglement-assisted and unassisted classical capacities it is shown that these bounds are attainable for certain classes of channel. Also, we show that the structure of any finite-memory state is unimportant in the asymptotic limit, and specifically, for a perfect finite-memory channel where no information is lost to the environment, achieving the upper bound implies that the channel is asymptotically noiseless

  18. Activation of human IK and SK Ca2+ -activated K+ channels by NS309 (6,7-dichloro-1H-indole-2,3-dione 3-oxime)

    DEFF Research Database (Denmark)

    Strøbaek, Dorte; Teuber, Lene; Jørgensen, Tino D

    2004-01-01

    We have identified and characterized the compound NS309 (6,7-dichloro-1H-indole-2,3-dione 3-oxime) as a potent activator of human Ca2+ -activated K+ channels of SK and IK types, whereas it is devoid of effect on BK type channels. IK- and SK-channels have previously been reported to be activated...

  19. Multicarrier chaotic communications in multipath fading channels without channel estimation

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Shilian, E-mail: wangsl@nudt.edu.cn; Zhang, Zhili [College of Electrical Science and Engineering, National University of Defense Technology, Changsha, 410073, P R China (China)

    2015-01-15

    A multi-carrier chaotic shift keying(MC-CSK) communication scheme with low probability of interception(LPI) is proposed in this article. We apply chaotic spreading sequences in the frequency domain, mapping a different chip of a chaotic sequence to an individual orthogonal frequency division multiplexing(OFDM) subcarrier. In each block size of $M$ OFDM symbols, we use one pilot OFDM symbol inserted time-spaced in all-frequency to transmit the reference chaotic signal and use the other M-1 OFDM symbols to transmit the information-bearing signals each spreaded by the reference chaotic signal. At the receiver, we construct a differential detector after DFT and recover the information bits from the correlations between the pilot OFDM symbol and the other M-1 OFDM symbols in each block size of M. Performance analysis and computer simulations show that the MC-CSK outperforms differential chaos shift keying(DCSK) in AWGN channels with high bandwidth efficiency for the block size of M=2 and that the MC-CSK exploits effectively the frequent diversity of the multipath channel.

  20. Multicarrier chaotic communications in multipath fading channels without channel estimation

    Directory of Open Access Journals (Sweden)

    Shilian Wang

    2015-01-01

    Full Text Available A multi-carrier chaotic shift keying(MC-CSK communication scheme with low probability of interception(LPI is proposed in this article. We apply chaotic spreading sequences in the frequency domain, mapping a different chip of a chaotic sequence to an individual orthogonal frequency division multiplexing(OFDM subcarrier. In each block size of $M$ OFDM symbols, we use one pilot OFDM symbol inserted time-spaced in all-frequency to transmit the reference chaotic signal and use the other M-1 OFDM symbols to transmit the information-bearing signals each spreaded by the reference chaotic signal. At the receiver, we construct a differential detector after DFT and recover the information bits from the correlations between the pilot OFDM symbol and the other M-1 OFDM symbols in each block size of M. Performance analysis and computer simulations show that the MC-CSK outperforms differential chaos shift keying(DCSK in AWGN channels with high bandwidth efficiency for the block size of M=2 and that the MC-CSK exploits effectively the frequent diversity of the multipath channel.