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Sample records for hyperpolarization-activated hcn channels

  1. Genetic variation in Hyperpolarization-activated cyclic nucleotide-gated (HCN channels and its relationship with neuroticism, cognition and risk of depression

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    Andrew Mark Mcintosh

    2012-07-01

    Full Text Available Hyperpolarization-activated cyclic nucleotide-gated (HCN channels are encoded by four genes (HCN1-4 and, through activation by cyclic AMP (cAMP, represent a point of convergence for several psychosis risk genes. On the basis of positive preliminary data, we sought to test whether genetic variation in HCN1-4 conferred risk of depression or cognitive impairment in the Generation Scotland: Scottish Family Health Study. HCN1, HCN2, HCN3 and HCN4 were genotyped for 43 haplotype-tagging SNPs and tested for association with DSM-IV depression, neuroticism and a battery of cognitive tests assessing cognitive ability, memory, verbal fluency and psychomotor performance. No association was found between any HCN channel gene SNP and risk of depression, neuroticism or on any cognitive measure. The current study does not support a genetic role for HCN channels in conferring risk of depression or cognitive impairment in human subjects within the Scottish population.

  2. Maturation and processing of the amyloid precursor protein is regulated by the potassium/sodium hyperpolarization-activated cyclic nucleotide-gated ion channel 2 (HCN2).

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    Frykman, Susanne; Inoue, Mitsuhiro; Ikeda, Atsushi; Teranishi, Yasuhiro; Kihara, Takahiro; Lundgren, Jolanta L; Yamamoto, Natsuko G; Bogdanovic, Nenad; Winblad, Bengt; Schedin-Weiss, Sophia; Tjernberg, Lars O

    2017-01-29

    The toxic amyloid β-peptide (Aβ) is a key player in Alzheimer Disease (AD) pathogenesis and selective inhibition of the production of this peptide is sought for. Aβ is produced by the sequential cleavage of the Aβ precursor protein (APP) by β-secretase (to yield APP-C-terminal fragment β (APP-CTFβ) and soluble APPβ (sAPPβ)) and γ-secretase (to yield Aβ). We reasoned that proteins that associate with γ-secretase are likely to regulate Aβ production and to be targets of pharmaceutical interventions and therefore performed a pull-down assay to screen for such proteins in rat brain. Interestingly, one of the purified proteins was potassium/sodium hyperpolarization-activated cyclic nucleotide-gated ion channel 2 (HCN2), which has been shown to be involved in epilepsy. We found that silencing of HCN2 resulted in decreased secreted Aβ levels. To further investigate the mechanism behind this reduction, we also determined the levels of full-length APP, sAPP and APP-CTF species after silencing of HCN2. A marked reduction in sAPP and APP-CTF, as well as glycosylated APP levels was detected. Decreased Aβ, sAPP and APP-CTF levels were also detected after treatment with the HCN2 inhibitor ZD7288. These results indicate that the effect on Aβ levels after HCN2 silencing or inhibition is due to altered APP maturation or processing by β-secretase rather than a direct effect on γ-secretase. However, HCN2 and γ-secretase were found to be in close proximity, as evident by proximity ligation assay and immunoprecipitation. In summary, our results indicate that silencing or inhibition of HCN2 affects APP processing and thereby could serve as a potential treatment strategy. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Effects of ZD7288, a hyperpolarization-activated cyclic nucleotide-gated (HCN) channel blocker, on term-pregnant rat uterine contractility in vitro.

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    Alotaibi, Mohammed; Kahlat, Karima; Nedjadi, Taoufik; Djouhri, Laiche

    2017-03-01

    The uterus is a myogenic organ that is able to produce discrete spontaneous action potentials and contractions without any stimuli. Myometrial excitability is governed by ion channels including Ca+2 and K+ channels, but whether or not other channels such as hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, which play an important role in regulating cellular excitability, are also involved has not been reported in uterine smooth muscles. The aim of the present study was to examine whether blocking HCN channels with a specific blocker ZD7288 would modulate the uterine contractility in a rat model. Using longitudinal uterine strips from term-pregnant rats, the effects of varying concentrations of ZD7288 (50 μM, 100 μM, and 200 μM) were examined on uterine contractions generated spontaneously or by oxytocin (5 nmol/L) and on uterine strips depolarized by high-KCl (60 mM/L), or activated by L-type Ca2+ channels agonist (Bay K8644; 1 μM). Application of ZD7288 at concentrations of 200 μM and 100 μM, but not 50 μM, significantly decreased the amplitude of spontaneous uterine contractions. In addition, 200 μM of ZD7288 significantly reduced the force of contractions induced by oxytocin with a pronounced reduction while the tissues were depolarized by high-KCl solution, or activated by Bay K8644. The present study provides pharmacological evidence suggesting that pregnant uterine contractility is modulated by HCN channels and that these channels might represent a therapeutic target for controlling premature activation of uterine activity associated with preterm labor. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Filamin A promotes dynamin-dependent internalization of hyperpolarization-activated cyclic nucleotide-gated type 1 (HCN1) channels and restricts /h in hippocampal neurons

    NARCIS (Netherlands)

    Noam, Y.; Ehrengruber, M.U.; Koh, A.; Feyen, P.; Manders, E.M.M.; Abbott, G.W.; Wadman, W.J.; Baram, T.Z.

    2014-01-01

    The actin-binding protein filamin A (FLNa) regulates neuronal migration during development, yet its roles in the mature brain remain largely obscure. Here, we probed the effects of FLNa on the regulation of ion channels that influence neuronal properties. We focused on the HCN1 channels that conduct

  5. A leucine zipper motif essential for gating of hyperpolarization-activated channels.

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    Wemhöner, Konstantin; Silbernagel, Nicole; Marzian, Stefanie; Netter, Michael F; Rinné, Susanne; Stansfeld, Phillip J; Decher, Niels

    2012-11-23

    It is poorly understood how hyperpolarization-activated cyclic nucleotide-gated channels (HCNs) function. We have identified a leucine zipper in the S5 segment of HCNs, regulating hyperpolarization-activated and instantaneous current components. The leucine zipper is essential for HCN channel gating. The identification and functional characterization of the leucine zipper is an important step toward the understanding of HCN channel function. Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are pacemakers in cardiac myocytes and neurons. Although their membrane topology closely resembles that of voltage-gated K(+) channels, the mechanism of their unique gating behavior in response to hyperpolarization is still poorly understood. We have identified a highly conserved leucine zipper motif in the S5 segment of HCN family members. In order to study the role of this motif for channel function, the leucine residues of the zipper were individually mutated to alanine, arginine, or glutamine residues. Leucine zipper mutants traffic to the plasma membrane, but the channels lose their sensitivity to open upon hyperpolarization. Thus, our data indicate that the leucine zipper is an important molecular determinant for hyperpolarization-activated channel gating. Residues of the leucine zipper interact with the adjacent S6 segment of the channel. This interaction is essential for voltage-dependent gating of the channel. The lower part of the leucine zipper, at the intracellular mouth of the channel, is important for stabilizing the closed state. Mutations at these sites increase current amplitudes or result in channels with deficient closing and increased min-P(o). Our data are further supported by homology models of the open and closed state of the HCN2 channel pore. Thus, we conclude that the leucine zipper of HCN channels is a major determinant for hyperpolarization-activated channel gating.

  6. A Leucine Zipper Motif Essential for Gating of Hyperpolarization-activated Channels*

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    Wemhöner, Konstantin; Silbernagel, Nicole; Marzian, Stefanie; Netter, Michael F.; Rinné, Susanne; Stansfeld, Phillip J.; Decher, Niels

    2012-01-01

    Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are pacemakers in cardiac myocytes and neurons. Although their membrane topology closely resembles that of voltage-gated K+ channels, the mechanism of their unique gating behavior in response to hyperpolarization is still poorly understood. We have identified a highly conserved leucine zipper motif in the S5 segment of HCN family members. In order to study the role of this motif for channel function, the leucine residues of the zipper were individually mutated to alanine, arginine, or glutamine residues. Leucine zipper mutants traffic to the plasma membrane, but the channels lose their sensitivity to open upon hyperpolarization. Thus, our data indicate that the leucine zipper is an important molecular determinant for hyperpolarization-activated channel gating. Residues of the leucine zipper interact with the adjacent S6 segment of the channel. This interaction is essential for voltage-dependent gating of the channel. The lower part of the leucine zipper, at the intracellular mouth of the channel, is important for stabilizing the closed state. Mutations at these sites increase current amplitudes or result in channels with deficient closing and increased min-Po. Our data are further supported by homology models of the open and closed state of the HCN2 channel pore. Thus, we conclude that the leucine zipper of HCN channels is a major determinant for hyperpolarization-activated channel gating. PMID:23048023

  7. Hyperpolarization-activated cyclic nucleotide-gated channels may contribute to regional anesthetic effects of lidocaine.

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    Zhou, Cheng; Ke, Bowen; Zhao, Yi; Liang, Peng; Liao, Daqing; Li, Tao; Liu, Jin; Chen, Xiangdong

    2015-03-01

    Local anesthetics (e.g., lidocaine) have been found to inhibit hyperpolarization-activated cyclic nucleotide-gated (HCN) channels besides sodium channels. However, the exact role of HCN channels in regional anesthesia in vivo is still elusive. Sciatic nerve block and intrathecal anesthesia were performed using lidocaine in wild-type and HCN1 channel knockout (HCN1) mice. EC50 of lidocaine and durations of 1% lidocaine were determined. In electrophysiologic recordings, effects of lidocaine on HCN channel currents, voltage-gated sodium channel currents, and neural membrane properties were recorded on dorsal root ganglia neurons. In both sciatic nerve block and intrathecal anesthesia, EC50 of lidocaine for tactile sensory blockade (2 g von Frey fiber) was significantly increased in HCN1 mice, whereas EC50 of lidocaine for pinprick blockade was unaffected. Durations of 1% lidocaine were significantly shorter in HCN1 mice for both sciatic nerve block and intrathecal anesthesia (n = 10). ZD7288 (HCN blocker) could significantly prolong durations of 1% lidocaine including pinprick blockade in sciatic nerve block (n = 10). Forskolin (raising cyclic adenosine monophosphate to enhance HCN2) could significantly shorten duration of pinprick blockade of 1% lidocaine in sciatic nerve block (n = 10). In electrophysiologic recordings, lidocaine could nonselectively inhibit HCN channel and sodium channel currents both in large and in small dorsal root ganglia neurons (n = 5 to 6). Meanwhile, lidocaine caused neural membrane hyperpolarization and increased input resistance of dorsal root ganglia neurons but not in large dorsal root ganglia neurons from HCN1 mice (n = 5-7). These data indicate that HCN channels may contribute to regional anesthetic effects of lidocaine. By inhibiting HCN channels, lidocaine could alter membrane properties of neurons.

  8. Dysfunctional Hyperpolarization-Activated Cyclic Nucleotide-gated Ion Channels in Cardiac Diseases

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    Xiaoqi Zhao

    Full Text Available Abstract Hyperpolarization-activated cyclic nucleotide-gated (HCN channels are reverse voltage-dependent, and their activation depends on the hyperpolarization of the membrane and may be directly or indirectly regulated by the cyclic adenosine monophosphate (cAMP or other signal-transduction cascades. The distribution, quantity and activation states of HCN channels differ in tissues throughout the body. Evidence exhibits that HCN channels play critical roles in the generation and conduction of the electrical impulse and the physiopathological process of some cardiac diseases. They may constitute promising drug targets in the treatment of these cardiac diseases. Pharmacological treatment targeting HCN channels is of benefit to these cardiac conditions.

  9. Dysfunctional HCN ion channels in neurological diseases

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    Jacopo C. DiFrancesco

    2015-03-01

    Full Text Available Hyperpolarization-activated cyclic nucleotide-gated (HCN channels are expressed as four different isoforms (HCN1-4 in the heart and in the central and peripheral nervous systems. HCN channels are activated by membrane hyperpolarization at voltages close to resting membrane potentials and carry the hyperpolarization-activated current, dubbed If (funny current in heart and Ih in neurons. HCN channels contribute in several ways to neuronal activity and are responsible for many important cellular functions, including cellular excitability, generation and modulation of rhythmic activity, dendritic integration, transmission of synaptic potentials and plasticity phenomena. Because of their role, defective HCN channels are natural candidates in the search for potential causes of neurological disorders in humans. Several data, including growing evidence that some forms of epilepsy are associated with HCN mutations, support the notion of an involvement of dysfunctional HCN channels in different experimental models of the disease. Additionally, some anti-epileptic drugs are known to modify the activity of the Ih current. HCN channels are widely expressed in the peripheral nervous system and recent evidence has highlighted the importance of the HCN2 isoform in the transmission of pain. HCN channels are also present in the midbrain system, where they finely regulate the activity of dopaminergic neurons, and a potential role of these channels in the pathogenesis of Parkinson’s disease has recently emerged. The function of HCN channels is regulated by specific accessory proteins, which control the correct expression and modulation of the neuronal Ih current. Alteration of these proteins can severely interfere with the physiological channel function, potentially predisposing to pathological conditions. In this review we address the present knowledge of the association between HCN dysfunctions and neurological diseases, including clinical, genetic and

  10. Hyperpolarization-activated cyclic-nucleotide-gated channels potentially modulate axonal excitability at different thresholds.

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    Weerasinghe, Dinushi; Menon, Parvathi; Vucic, Steve

    2017-12-01

    Hyperpolarization-activated cyclic-nucleotide-gated (HCN) channels mediate differences in sensory and motor axonal excitability at different thresholds in animal models. Importantly, HCN channels are responsible for voltage-gated inward rectifying (Ih) currents activated during hyperpolarization. The Ih currents exert a crucial role in determining the resting membrane potential and have been implicated in a variety of neurological disorders, including neuropathic pain. In humans, differences in biophysical properties of motor and sensory axons at different thresholds remain to be elucidated and could provide crucial pathophysiological insights in peripheral neurological diseases. Consequently, the aim of this study was to characterize sensory and motor axonal function at different threshold. Median nerve motor and sensory axonal excitability studies were undertaken in 15 healthy subjects (45 studies in total). Tracking targets were set to 20, 40, and 60% of maximum for sensory and motor axons. Hyperpolarizing threshold electrotonus (TEh) at 90-100 ms was significantly increased in lower threshold sensory axons times (F = 11.195, P sensory axons. In conclusion, variation in the kinetics of HCN isoforms could account for the findings in motor and sensory axons. Importantly, assessing the function of HCN channels in sensory and motor axons of different thresholds may provide insights into the pathophysiological processes underlying peripheral neurological diseases in humans, particularly focusing on the role of HCN channels with the potential of identifying novel treatment targets.NEW & NOTEWORTHY Hyperpolarization-activated cyclic-nucleotide-gated (HCN) channels, which underlie inward rectifying currents (Ih), appear to mediate differences in sensory and motor axonal properties. Inward rectifying currents are increased in lower threshold motor and sensory axons, although different HCN channel isoforms appear to underlie these changes. While faster activating HCN

  11. The Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels: from Biophysics to Pharmacology of a Unique Family of Ion Channels.

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    Sartiani, Laura; Mannaioni, Guido; Masi, Alessio; Novella Romanelli, Maria; Cerbai, Elisabetta

    2017-10-01

    Hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels are important members of the voltage-gated pore loop channels family. They show unique features: they open at hyperpolarizing potential, carry a mixed Na/K current, and are regulated by cyclic nucleotides. Four different isoforms have been cloned (HCN1-4) that can assemble to form homo- or heterotetramers, characterized by different biophysical properties. These proteins are widely distributed throughout the body and involved in different physiologic processes, the most important being the generation of spontaneous electrical activity in the heart and the regulation of synaptic transmission in the brain. Their role in heart rate, neuronal pacemaking, dendritic integration, learning and memory, and visual and pain perceptions has been extensively studied; these channels have been found also in some peripheral tissues, where their functions still need to be fully elucidated. Genetic defects and altered expression of HCN channels are linked to several pathologies, which makes these proteins attractive targets for translational research; at the moment only one drug (ivabradine), which specifically blocks the hyperpolarization-activated current, is clinically available. This review discusses current knowledge about HCN channels, starting from their biophysical properties, origin, and developmental features, to (patho)physiologic role in different tissues and pharmacological modulation, ending with their present and future relevance as drug targets. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

  12. Gabapentin Modulates HCN4 Channel Voltage-Dependence

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    Han-Shen Tae

    2017-08-01

    Full Text Available Gabapentin (GBP is widely used to treat epilepsy and neuropathic pain. There is evidence that GBP can act on hyperpolarization-activated cation (HCN channel-mediated Ih in brain slice experiments. However, evidence showing that GBP directly modulates HCN channels is lacking. The effect of GBP was tested using two-electrode voltage clamp recordings from human HCN1, HCN2, and HCN4 channels expressed in Xenopus oocytes. Whole-cell recordings were also made from mouse spinal cord slices targeting either parvalbumin positive (PV+ or calretinin positive (CR+ inhibitory neurons. The effect of GBP on Ih was measured in each inhibitory neuron population. HCN4 expression was assessed in the spinal cord using immunohistochemistry. When applied to HCN4 channels, GBP (100 μM caused a hyperpolarizing shift in the voltage of half activation (V1/2 thereby reducing the currents. Gabapentin had no impact on the V1/2 of HCN1 or HCN2 channels. There was a robust increase in the time to half activation for HCN4 channels with only a small increase noted for HCN1 channels. Gabapentin also caused a hyperpolarizing shift in the V1/2 of Ih measured from HCN4-expressing PV+ inhibitory neurons in the spinal dorsal horn. Gabapentin had minimal effect on Ih recorded from CR+ neurons. Consistent with this, immunohistochemical analysis revealed that the majority of CR+ inhibitory neurons do not express somatic HCN4 channels. In conclusion, GBP reduces HCN4 channel-mediated currents through a hyperpolarized shift in the V1/2. The HCN channel subtype selectivity of GBP provides a unique tool for investigating HCN4 channel function in the central nervous system. The HCN4 channel is a candidate molecular target for the acute analgesic and anticonvulsant actions of GBP.

  13. Hyperpolarization-activated cyclic nucleotide-gated channels in peripheral diaphragmatic lymphatics.

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    Negrini, Daniela; Marcozzi, Cristiana; Solari, Eleonora; Bossi, Elena; Cinquetti, Raffaella; Reguzzoni, Marcella; Moriondo, Andrea

    2016-10-01

    Diaphragmatic lymphatic function is mainly sustained by pressure changes in the tissue and serosal cavities during cardiorespiratory cycles. The most peripheral diaphragmatic lymphatics are equipped with muscle cells (LMCs), which exhibit spontaneous contraction, whose molecular machinery is still undetermined. Hypothesizing that spontaneous contraction might involve hyperpolarization-activated cyclic nucleotide-gated (HCN) channels in lymphatic LMCs, diaphragmatic specimens, including spontaneously contracting lymphatics, were excised from 33 anesthetized rats, moved to a perfusion chamber containing HEPES-Tyrode's solution, and treated with HCN channels inhibitors cesium chloride (CsCl), ivabradine, and ZD-7288. Compared with control, exposure to 10 mM CsCl reduced (-65%, n = 13, P < 0.01) the contraction frequency (FL) and increased end-diastolic diameter (DL-d, +7.3%, P < 0.01) without changes in end-systolic diameter (DL-s). Ivabradine (300 μM) abolished contraction and increased DL-d (-14%, n = 10, P < 0.01) or caused an incomplete inhibition of FL (n = 3, P < 0.01), leaving DL-d and DL-s unaltered. ZD-7288 (200 μM) completely (n = 12, P < 0.01) abolished FL, while DL-d decreased to 90.9 ± 2.7% of control. HCN gene expression and immunostaining confirmed the presence of HCN1-4 channel isoforms, likely arranged in different configurations, in LMCs. Hence, all together, data suggest that HCN channels might play an important role in affecting contraction frequency of LMCs. Copyright © 2016 the American Physiological Society.

  14. Expression of hyperpolarization-activated cyclic nucleotide-gated channel isoforms in a canine model of atrial fibrillation.

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    He, Wei; Zhang, Jian; Gan, Tianyi; Xu, Guojun; Tang, Baopeng

    2016-07-01

    The aim of the present study was to analyze the mRNA and protein expression levels of atrial hyperpolarization-activated cyclic nucleotide-gated (HCN) channel isoforms in the left atrial muscle of dogs with multiple organ failure. A total of 14 beagle dogs with multiple organ failure, including seven cases with sinus rhythm and seven cases with atrial fibrillation (AF), underwent surgery to remove a sample of left atrial appendage tissue. The expression levels of a number of HCN channel subtypes were subsequently measured using quantitative polymerase chain reaction and western blot analysis. The mRNA and protein expression levels of HCN2 and HCN4 increased significantly in the AF group when compared with the sinus rhythm group. However, expression of the HCN1 isoform was not detected. Therefore, increased expression levels of HCN2 and HCN4 may be important molecular mechanisms in the pathogenesis of AF, which were associated with differences in patients with valvular heart disease.

  15. Hyperpolarization-activated cyclic nucleotide-gated channels in olfactory sensory neurons regulate axon extension and glomerular formation.

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    Mobley, Arie S; Miller, Alexandra M; Araneda, Ricardo C; Maurer, Lydia R; Müller, Frank; Greer, Charles A

    2010-12-08

    Mechanisms influencing the development of olfactory bulb glomeruli are poorly understood. While odor receptors (ORs) play an important role in olfactory sensory neuron (OSN) axon targeting/coalescence (Mombaerts et al., 1996; Wang et al., 1998; Feinstein and Mombaerts, 2004), recent work showed that G protein activation alone is sufficient to induce OSN axon coalescence (Imai et al., 2006; Chesler et al., 2007), suggesting an activity-dependent mechanism in glomerular development. Consistent with these data, OSN axon projections and convergence are perturbed in mice deficient for adenylyl cyclase III, which is downstream from the OR and catalyzes the conversion of ATP to cAMP. However, in cyclic nucleotide-gated (CNG) channel knock-out mice OSN axons are only transiently perturbed (Lin et al., 2000), suggesting that the CNG channel may not be the sole target of cAMP. This prompted us to investigate an alternative channel, the hyperpolarization-activated, cyclic nucleotide-gated cation channel (HCN), as a potential developmental target of cAMP in OSNs. Here, we demonstrate that HCN channels are developmentally precocious in OSNs and therefore are plausible candidates for affecting OSN axon development. Inhibition of HCN channels in dissociated OSNs significantly reduced neurite outgrowth. Moreover, in HCN1 knock-out mice the formation of glomeruli was delayed in parallel with perturbations of axon organization in the olfactory nerve. These data support the hypothesis that the outgrowth and coalescence of OSN axons is, at least in part, subject to activity-dependent mechanisms mediated via HCN channels.

  16. Investigating cyclic nucleotide and cyclic dinucleotide binding to HCN channels by surface plasmon resonance.

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    Sebastien Hayoz

    Full Text Available Hyperpolarization-activated cyclic nucleotide-modulated (HCN channels control cardiac and neuronal rhythmicity. HCN channels contain cyclic nucleotide-binding domain (CNBD in their C-terminal region linked to the pore-forming transmembrane segment with a C-linker. The C-linker couples the conformational changes caused by the direct binding of cyclic nucleotides to the HCN pore opening. Recently, cyclic dinucleotides were shown to antagonize the effect of cyclic nucleotides in HCN4 but not in HCN2 channels. Based on the structural analysis and mutational studies it has been proposed that cyclic dinucleotides affect HCN4 channels by binding to the C-linker pocket (CLP. Here, we first show that surface plasmon resonance (SPR can be used to accurately measure cyclic nucleotide binding affinity to the C-linker/CNBD of HCN2 and HCN4 channels. We then used SPR to investigate cyclic dinucleotide binding in HCN channels. To our surprise, we detected no binding of cyclic dinucleotides to the isolated monomeric C-linker/CNBDs of HCN4 channels with SPR. The binding of cyclic dinucleotides was further examined with isothermal calorimetry (ITC, which indicated no binding of cyclic dinucleotides to both monomeric and tetrameric C-linker/CNBDs of HCN4 channels. Taken together, our results suggest that interaction of the C-linker/CNBD with other parts of the channel is necessary for cyclic-dinucleotide binding in HCN4 channels.

  17. CNG and HCN channels: two peas, one pod.

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    Craven, Kimberley B; Zagotta, William N

    2006-01-01

    Cyclic nucleotide-activated ion channels play a fundamental role in a variety of physiological processes. By opening in response to intracellular cyclic nucleotides, they translate changes in concentrations of signaling molecules to changes in membrane potential. These channels belong to two families: the cyclic nucleotide-gated (CNG) channels and the hyperpolarization-activated cyclic nucleotide-modulated (HCN) channels. The two families exhibit high sequence similarity and belong to the superfamily of voltage-gated potassium channels. Whereas HCN channels are activated by voltage and CNG channels are virtually voltage independent, both channels are activated by cyclic nucleotide binding. Furthermore, the channels are thought to have similar channel structures, leading to similar mechanisms of activation by cyclic nucleotides. However, although these channels are structurally and behaviorally similar, they have evolved to perform distinct physiological functions. This review describes the physiological roles and biophysical behavior of CNG and HCN channels. We focus on how similarities in structure and activation mechanisms result in common biophysical models, allowing CNG and HCN channels to be viewed as a single genre.

  18. TRIP8b independent trafficking and plasticity of adult cortical pre-synaptic HCN1 channels

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    Huang, Zhuo; Lujan, Rafael; Martinez-Hernandez, Jose; Lewis, Alan S.; Chetkovich, Dane M.; Shah, Mala M.

    2014-01-01

    Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are subthreshold activated voltage-gated ion channels. In the cortex, these channels are predominantly expressed in dendrites where they significantly modify dendritic intrinsic excitability as well synaptic potential shapes and integration. HCN channel trafficking to dendrites is regulated by the protein, TRIP8b. Additionally, altered TRIP8b expression may be one mechanism underlying seizure-induced dendritic HCN channel plasticity. HCN channels, though, are also located in certain mature cortical synaptic terminals, where they play a vital role in modulating synaptic transmission. In this study, using electrophysiological recordings as well as electron microscopy we show that pre-synaptic, but not dendritic, cortical HCN channel expression and function is comparable in adult TRIP8b null mice and wildtype littermates. We further investigated if pre-synaptic HCN channels undergo seizure-dependent plasticity. We found that, like dendritic channels, wildtype pre-synaptic HCN channel function was persistently decreased following induction of kainic acid-induced seizures. Since TRIP8b does not affect pre-synaptic HCN subunit trafficking, seizure dependent plasticity of these cortical HCN channels is not conditional upon TRIP8b. Our results, thus, suggest that the molecular mechanisms underlying HCN subunit targeting, expression and plasticity in adult neurons is compartment selective, providing a means by which pre- and post-synaptic processes that are critically dependent upon HCN channel function may be distinctly influenced. PMID:23077068

  19. Impact of Hyperpolarization-activated, Cyclic Nucleotide-gated Cation Channel Type 2 for the Xenon-mediated Anesthetic Effect: Evidence from In Vitro and In Vivo Experiments.

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    Mattusch, Corinna; Kratzer, Stephan; Buerge, Martina; Kreuzer, Matthias; Engel, Tatiana; Kopp, Claudia; Biel, Martin; Hammelmann, Verena; Ying, Shui-Wang; Goldstein, Peter A; Kochs, Eberhard; Haseneder, Rainer; Rammes, Gerhard

    2015-05-01

    The thalamus is thought to be crucially involved in the anesthetic state. Here, we investigated the effect of the inhaled anesthetic xenon on stimulus-evoked thalamocortical network activity and on excitability of thalamocortical neurons. Because hyperpolarization-activated, cyclic nucleotide-gated cation (HCN) channels are key regulators of neuronal excitability in the thalamus, the effect of xenon on HCN channels was examined. The effects of xenon on thalamocortical network activity were investigated in acutely prepared brain slices from adult wild-type and HCN2 knockout mice by means of voltage-sensitive dye imaging. The influence of xenon on single-cell excitability in brain slices was investigated using the whole-cell patch-clamp technique. Effects of xenon on HCN channels were verified in human embryonic kidney cells expressing HCN2 channels. Xenon concentration-dependently diminished thalamocortical signal propagation. In neurons, xenon reduced HCN channel-mediated Ih current amplitude by 33.4 ± 12.2% (at -133 mV; n = 7; P = 0.041) and caused a left-shift in the voltage of half-maximum activation (V1/2) from -98.8 ± 1.6 to -108.0 ± 4.2 mV (n = 8; P = 0.035). Similar effects were seen in human embryonic kidney cells. The impairment of HCN channel function was negligible when intracellular cyclic adenosine monophosphate level was increased. Using HCN2 mice, we could demonstrate that xenon did neither attenuate in vitro thalamocortical signal propagation nor did it show sedating effects in vivo. Here, we clearly showed that xenon impairs HCN2 channel function, and this impairment is dependent on intracellular cyclic adenosine monophosphate levels. We provide evidence that this effect reduces thalamocortical signal propagation and probably contributes to the hypnotic properties of xenon.

  20. HCN channels are not required for mechanotransduction in sensory hair cells of the mouse inner ear.

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    Geoffrey C Horwitz

    Full Text Available The molecular composition of the hair cell transduction channel has not been identified. Here we explore the novel hypothesis that hair cell transduction channels include HCN subunits. The HCN family of ion channels includes four members, HCN1-4. They were originally identified as the molecular correlates of the hyperpolarization-activated, cyclic nucleotide gated ion channels that carry currents known as If, IQ or Ih. However, based on recent evidence it has been suggested that HCN subunits may also be components of the elusive hair cell transduction channel. To investigate this hypothesis we examined expression of mRNA that encodes HCN1-4 in sensory epithelia of the mouse inner ear, immunolocalization of HCN subunits 1, 2 and 4, uptake of the transduction channel permeable dye, FM1-43 and electrophysiological measurement of mechanotransduction current. Dye uptake and transduction current were assayed in cochlear and vestibular hair cells of wildtype mice exposed to HCN channel blockers or a dominant-negative form of HCN2 that contained a pore mutation and in mutant mice that lacked HCN1, HCN2 or both. We found robust expression of HCNs 1, 2 and 4 but little evidence that localized HCN subunits in hair bundles, the site of mechanotransduction. Although high concentrations of the HCN antagonist, ZD7288, blocked 50-70% of the transduction current, we found no reduction of transduction current in either cochlear or vestibular hair cells of HCN1- or HCN2- deficient mice relative to wild-type mice. Furthermore, mice that lacked both HCN1 and HCN2 also had normal transduction currents. Lastly, we found that mice exposed to the dominant-negative mutant form of HCN2 had normal transduction currents as well. Taken together, the evidence suggests that HCN subunits are not required for mechanotransduction in hair cells of the mouse inner ear.

  1. HCN channels in the heart: lessons from mouse mutants.

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    Herrmann, S; Hofmann, F; Stieber, J; Ludwig, A

    2012-05-01

    Hyperpolarization-activated cation channels generate the I(f) current in the heart. In the sino-atrial node (SAN), I(f) is thought to play an essential role in setting the heart rate and mediating its autonomic control. This review focuses on the role of I(f) in pacemaking and non-pacemaking cardiomyocytes and the resulting therapeutic implications. HCN4 represents the principal isoform underlying sino-atrial I(f) , but other isoforms may also be of importance. To examine the functional role of cardiac channels, several mouse mutants, most of them targeting HCN4, have been generated by different groups. Unexpectedly, these lines display greatly different and as yet unexplained phenotypes. We provide an overview about these HCN mutants and suggest an interpretation of the functional significance of I(f) in the SAN in light of these studies. HCN channels are also present in ventricular myocytes, and an up-regulation of I(f) in the hypertrophic and failing heart may contribute to arrhythmogenesis. Inhibition of I(f) by HCN channel blockers is a novel approach in the treatment of cardiac disorders, and ivabradine is approved for treatment of stable angina pectoris. Remarkably, a recent clinical trial assessing this substance in heart failure showed a significantly improved outcome. The mechanism underlying this beneficial effect is not yet clear and might lie beyond heart rate slowing. Thus, the growing knowledge about cardiac HCN channels will undoubtedly promote the development of the promising class of HCN channel blockers. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

  2. Distribution of voltage-gated potassium and hyperpolarization-activated channels in sensory afferent fibers in the rat carotid body.

    Science.gov (United States)

    Buniel, Maria; Glazebrook, Patricia A; Ramirez-Navarro, Angelina; Kunze, Diana L

    2008-10-01

    The chemosensory glomus cells of the carotid body (CB) detect changes in O2 tension. Carotid sinus nerve fibers, which originate from peripheral sensory neurons located within the petrosal ganglion, innervate the CB. Release of transmitter from glomus cells activates the sensory afferent fibers to transmit information to the nucleus of the solitary tract in the brainstem. The ion channels expressed within the sensory nerve terminals play an essential role in the ability of the terminal to initiate action potentials in response to transmitter-evoked depolarization. However, with a few exceptions, the identity of ion channels expressed in these peripheral nerve fibers is unknown. This study addresses the expression of voltage-gated channels in the sensory fibers with a focus on channels that set the resting membrane potential and regulate discharge patterns. By using immunohistochemistry and fluorescence confocal microscopy, potassium channel subunits and HCN (hyperpolarization-activated) family members were localized both in petrosal neurons that expressed tyrosine hydroxylase and in the CSN axons within the carotid body. Channels contributing to resting membrane potential, including HCN2 responsible in part for I(h) current and the KCNQ2 and KCNQ5 subunits thought to underlie the neuronal "M current," were identified in the sensory neurons and their axons innervating the carotid body. In addition, the results presented here demonstrate expression of several potassium channels that shape the action potential and the frequency of discharge, including Kv1.4, Kv1.5, Kv4.3, and K(Ca) (BK). The role of these channels should be considered in interpretation of the fiber discharge in response to perturbation of the carotid body environment.

  3. Prefrontal cortex HCN1 channels enable intrinsic persistent neural firing and executive memory function.

    Science.gov (United States)

    Thuault, Sébastien J; Malleret, Gaël; Constantinople, Christine M; Nicholls, Russell; Chen, Irene; Zhu, Judy; Panteleyev, Andrey; Vronskaya, Svetlana; Nolan, Matthew F; Bruno, Randy; Siegelbaum, Steven A; Kandel, Eric R

    2013-08-21

    In many cortical neurons, HCN1 channels are the major contributors to Ih, the hyperpolarization-activated current, which regulates the intrinsic properties of neurons and shapes their integration of synaptic inputs, paces rhythmic activity, and regulates synaptic plasticity. Here, we examine the physiological role of Ih in deep layer pyramidal neurons in mouse prefrontal cortex (PFC), focusing on persistent activity, a form of sustained firing thought to be important for the behavioral function of the PFC during working memory tasks. We find that HCN1 contributes to the intrinsic persistent firing that is induced by a brief depolarizing current stimulus in the presence of muscarinic agonists. Deletion of HCN1 or acute pharmacological blockade of Ih decreases the fraction of neurons capable of generating persistent firing. The reduction in persistent firing is caused by the membrane hyperpolarization that results from the deletion of HCN1 or Ih blockade, rather than a specific role of the hyperpolarization-activated current in generating persistent activity. In vivo recordings show that deletion of HCN1 has no effect on up states, periods of enhanced synaptic network activity. Parallel behavioral studies demonstrate that HCN1 contributes to the PFC-dependent resolution of proactive interference during working memory. These results thus provide genetic evidence demonstrating the importance of HCN1 to intrinsic persistent firing and the behavioral output of the PFC. The causal role of intrinsic persistent firing in PFC-mediated behavior remains an open question.

  4. A Calcium-Dependent Plasticity Rule for HCN Channels Maintains Activity Homeostasis and Stable Synaptic Learning

    Science.gov (United States)

    Honnuraiah, Suraj; Narayanan, Rishikesh

    2013-01-01

    Theoretical and computational frameworks for synaptic plasticity and learning have a long and cherished history, with few parallels within the well-established literature for plasticity of voltage-gated ion channels. In this study, we derive rules for plasticity in the hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, and assess the synergy between synaptic and HCN channel plasticity in establishing stability during synaptic learning. To do this, we employ a conductance-based model for the hippocampal pyramidal neuron, and incorporate synaptic plasticity through the well-established Bienenstock-Cooper-Munro (BCM)-like rule for synaptic plasticity, wherein the direction and strength of the plasticity is dependent on the concentration of calcium influx. Under this framework, we derive a rule for HCN channel plasticity to establish homeostasis in synaptically-driven firing rate, and incorporate such plasticity into our model. In demonstrating that this rule for HCN channel plasticity helps maintain firing rate homeostasis after bidirectional synaptic plasticity, we observe a linear relationship between synaptic plasticity and HCN channel plasticity for maintaining firing rate homeostasis. Motivated by this linear relationship, we derive a calcium-dependent rule for HCN-channel plasticity, and demonstrate that firing rate homeostasis is maintained in the face of synaptic plasticity when moderate and high levels of cytosolic calcium influx induced depression and potentiation of the HCN-channel conductance, respectively. Additionally, we show that such synergy between synaptic and HCN-channel plasticity enhances the stability of synaptic learning through metaplasticity in the BCM-like synaptic plasticity profile. Finally, we demonstrate that the synergistic interaction between synaptic and HCN-channel plasticity preserves robustness of information transfer across the neuron under a rate-coding schema. Our results establish specific physiological roles

  5. Disturbed Processing of Contextual Information in HCN3 Channel Deficient Mice

    Directory of Open Access Journals (Sweden)

    Marc S. Stieglitz

    2018-01-01

    Full Text Available Hyperpolarization-activated cyclic nucleotide-gated channels (HCNs in the nervous system are implicated in a variety of neuronal functions including learning and memory, regulation of vigilance states and pain. Dysfunctions or genetic loss of these channels have been shown to cause human diseases such as epilepsy, depression, schizophrenia, and Parkinson's disease. The physiological functions of HCN1 and HCN2 channels in the nervous system have been analyzed using genetic knockout mouse models. By contrast, there are no such genetic studies for HCN3 channels so far. Here, we use a HCN3-deficient (HCN3−/− mouse line, which has been previously generated in our group to examine the expression and function of this channel in the CNS. Specifically, we investigate the role of HCN3 channels for the regulation of circadian rhythm and for the determination of behavior. Contrary to previous suggestions we find that HCN3−/− mice show normal visual, photic, and non-photic circadian function. In addition, HCN3−/− mice are impaired in processing contextual information, which is characterized by attenuated long-term extinction of contextual fear and increased fear to a neutral context upon repeated exposure.

  6. Prefrontal Cortex HCN1 Channels Enable Intrinsic Persistent Neural Firing and Executive Memory Function

    OpenAIRE

    Thuault, Sébastien J.; Malleret, Gaël; Constantinople, Christine M.; Nicholls, Russell; Chen, Irene; Zhu, Judy; Panteleyev, Andrey; Vronskaya, Svetlana; Nolan, Matthew F.; Bruno, Randy; Siegelbaum, Steven A.; Kandel, Eric R.

    2013-01-01

    In many cortical neurons, HCN1 channels are the major contributors to I-h, the hyperpolarization-activated current, which regulates the intrinsic properties of neurons and shapes their integration of synaptic inputs, paces rhythmic activity, and regulates synaptic plasticity. Here, we examine the physiological role of I-h in deep layer pyramidal neurons in mouse prefrontal cortex (PFC), focusing on persistent activity, a form of sustained firing thought to be important for the behavioral func...

  7. Regulated expression of HCN channels and cAMP levels shape the properties of the h current in developing rat hippocampus

    Science.gov (United States)

    Surges, Rainer; Brewster, Amy L.; Bender, Roland A.; Beck, Heinz; Feuerstein, Thomas J.; Baram, Tallie Z.

    2010-01-01

    The hyperpolarization-activated current (Ih) contributes to intrinsic properties and network responses of neurons. Its biophysical properties depend on the expression profiles of the underlying hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels and the presence of cyclic AMP (cAMP) that potently and differentially modulates Ih conducted by HCN1, HCN2 and/or HCN4. Here, we studied the properties of Ih in hippocampal CA1 pyramidal cells, the developmental evolution of the HCN-subunit isoforms that contribute to this current, and their interplay with age-dependent free cAMP concentrations, using electrophysiological, molecular and biochemical methods. Ih amplitude increased progressively during the first four postnatal weeks, consistent with the observed overall increased expression of HCN channels. Activation kinetics of the current accelerated during this period, consonant with the quantitative reduction of mRNA and protein expression of the slow-kinetics HCN4 isoform and increased levels of HCN1. The sensitivity of Ih to cAMP, and the contribution of the slow component to the overall Ih, decreased with age. These are likely a result of the developmentally regulated transition of the complement of HCN channel isoforms from cAMP sensitive to relatively cAMP insensitive. Thus, although hippocampal cAMP concentrations increased over twofold during the developmental period studied, the coordinated changes in expression of three HCN channel isoforms resulted in reduced effects of this signalling molecule on neuronal h currents. PMID:16882011

  8. Distribution and function of HCN channels in the apical dendritic tuft of neocortical pyramidal neurons.

    Science.gov (United States)

    Harnett, Mark T; Magee, Jeffrey C; Williams, Stephen R

    2015-01-21

    The apical tuft is the most remote area of the dendritic tree of neocortical pyramidal neurons. Despite its distal location, the apical dendritic tuft of layer 5 pyramidal neurons receives substantial excitatory synaptic drive and actively processes corticocortical input during behavior. The properties of the voltage-activated ion channels that regulate synaptic integration in tuft dendrites have, however, not been thoroughly investigated. Here, we use electrophysiological and optical approaches to examine the subcellular distribution and function of hyperpolarization-activated cyclic nucleotide-gated nonselective cation (HCN) channels in rat layer 5B pyramidal neurons. Outside-out patch recordings demonstrated that the amplitude and properties of ensemble HCN channel activity were uniform in patches excised from distal apical dendritic trunk and tuft sites. Simultaneous apical dendritic tuft and trunk whole-cell current-clamp recordings revealed that the pharmacological blockade of HCN channels decreased voltage compartmentalization and enhanced the generation and spread of apical dendritic tuft and trunk regenerative activity. Furthermore, multisite two-photon glutamate uncaging demonstrated that HCN channels control the amplitude and duration of synaptically evoked regenerative activity in the distal apical dendritic tuft. In contrast, at proximal apical dendritic trunk and somatic recording sites, the blockade of HCN channels decreased excitability. Dynamic-clamp experiments revealed that these compartment-specific actions of HCN channels were heavily influenced by the local and distributed impact of the high density of HCN channels in the distal apical dendritic arbor. The properties and subcellular distribution pattern of HCN channels are therefore tuned to regulate the interaction between integration compartments in layer 5B pyramidal neurons. Copyright © 2015 the authors 0270-6474/15/351024-14$15.00/0.

  9. Contribution of large-sized primary sensory neuronal sensitization to mechanical allodynia by upregulation of hyperpolarization-activated cyclic nucleotide gated channels via cyclooxygenase 1 cascade.

    Science.gov (United States)

    Sun, Wei; Yang, Fei; Wang, Yan; Fu, Han; Yang, Yan; Li, Chun-Li; Wang, Xiao-Liang; Lin, Qing; Chen, Jun

    2017-02-01

    Under physiological state, small- and medium-sized dorsal root ganglia (DRG) neurons are believed to mediate nociceptive behavioral responses to painful stimuli. However, recently it has been found that a number of large-sized neurons are also involved in nociceptive transmission under neuropathic conditions. Nonetheless, the underlying mechanisms that large-sized DRG neurons mediate nociception are poorly understood. In the present study, the role of large-sized neurons in bee venom (BV)-induced mechanical allodynia and the underlying mechanisms were investigated. Behaviorally, it was found that mechanical allodynia was still evoked by BV injection in rats in which the transient receptor potential vanilloid 1-positive DRG neurons were chemically deleted. Electrophysiologically, in vitro patch clamp recordings of large-sized neurons showed hyperexcitability in these neurons. Interestingly, the firing pattern of these neurons was changed from phasic to tonic under BV-inflamed state. It has been suggested that hyperpolarization-activated cyclic nucleotide gated channels (HCN) expressed in large-sized DRG neurons contribute importantly to repeatedly firing. So we examined the roles of HCNs in BV-induced mechanical allodynia. Consistent with the overexpression of HCN1/2 detected by immunofluorescence, HCNs-mediated hyperpolarization activated cation current (Ih) was significantly increased in the BV treated samples. Pharmacological experiments demonstrated that the hyperexcitability and upregulation of Ih in large-sized neurons were mediated by cyclooxygenase-1 (COX-1)-prostaglandin E2 pathway. This is evident by the fact that the COX-1 inhibitor significantly attenuated the BV-induced mechanical allodynia. These results suggest that BV can excite the large-sized DRG neurons at least in part by increasing Ih through activation of COX-1. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. HCN Channel Modulation of Synaptic Integration in GABAergic Interneurons in Malformed Rat Neocortex

    Directory of Open Access Journals (Sweden)

    John J. Hablitz

    2017-04-01

    Full Text Available Cortical malformations are often associated with pharmaco-resistant epilepsy. Alterations in hyperpolarization-activated, cyclic nucleotide-gated, non-specific cation (HCN channels have been shown to contribute to malformation associated hyperexcitability. We have recently demonstrated that expression of HCN channels and Ih current amplitudes are reduced in layer (L 5 pyramidal neurons of rats with freeze lesion induced malformations. These changes were associated with an increased EPSP temporal summation. Here, we examine the effects of HCN channel inhibition on synaptic responses in fast spiking, presumptive basket cells and accommodating, presumptive Martinotti, GABAergic interneurons in slices from freeze lesioned animals. In control animals, fast spiking cells showed small sag responses which were reduced by the HCN channel antagonist ZD7288. Fast spiking cells in lesioned animals showed absent or reduced sag responses. The amplitude of single evoked EPSPs in fast spiking cells in the control group was not affected by HCN channel inhibition with ZD7288. EPSP ratios during short stimulus trains at 25 Hz were not significantly different between control and lesion groups. ZD7288 produced an increase in EPSP ratios in the control but not lesion groups. Under voltage clamp conditions, ZD7288 did not affect EPSC ratios. In the control group, accommodating interneurons showed robust sag responses which were significantly reduced by ZD7288. HCN channel inhibition increased EPSP ratios and area in controls but not the lesioned group. The results indicate that HCN channels differentially modulate EPSPs in different classes of GABAergic interneurons and that this control is reduced in malformed rat neocortex.

  11. Local Anesthetic Inhibits Hyperpolarization-Activated Cationic Currents

    Science.gov (United States)

    Meng, Qing-tao; Xia, Zhong-yuan; Liu, Jin; Bayliss, Douglas A.

    2011-01-01

    Systemic administration of local anesthetics has beneficial perioperative properties and an anesthetic-sparing and antiarrhythmic effect, although the detailed mechanisms of these actions remain unclear. In the present study, we investigated the effects of a local anesthetic, lidocaine, on hyperpolarization-activated and cyclic nucleotide-gated (HCN) channels that contribute to the pacemaker currents in rhythmically oscillating cells of the heart and brain. Voltage-clamp recordings were used to examine the properties of cloned HCN subunit currents expressed in Xenopus laevis oocytes and human embryonic kidney (HEK) 293 cells under control condition and lidocaine administration. Lidocaine inhibited HCN1, HCN2, HCN1-HCN2, and HCN4 channel currents at 100 μM in both oocytes and/or HEK 293 cells; it caused a decrease in both tonic and maximal current (∼30–50% inhibition) and slowed current activation kinetics for all subunits. In addition, lidocaine evoked a hyperpolarizing shift in half-activation voltage (ΔV1/2 of ∼−10 to −14 mV), but only for HCN1 and HCN1-HCN2 channels. By fitting concentration-response data to logistic functions, we estimated half-maximal (EC50) concentrations of lidocaine of ∼30 to 40 μM for the shift in V1/2 observed with HCN1 and HCN1-HCN2; for inhibition of current amplitude, calculated EC50 values were ∼50 to 70 μM for HCN1, HCN2, and HCN1-HCN2 channels. A lidocaine metabolite, monoethylglycinexylidide (100 μM), had similar inhibitory actions on HCN channels. These results indicate that lidocaine potently inhibits HCN channel subunits in dose-dependent manner over a concentration range relevant for systemic application. The ability of local anesthetics to modulate Ih in central neurons may contribute to central nervous system depression, whereas effects on If in cardiac pacemaker cells may contribute to the antiarrhythmic and/or cardiovascular toxic action. PMID:21303986

  12. HCN4 ion channel function is required for early events that regulate anatomical left-right patterning in a nodal and lefty asymmetric gene expression-independent manner

    Directory of Open Access Journals (Sweden)

    Vaibhav P. Pai

    2017-10-01

    Full Text Available Laterality is a basic characteristic of all life forms, from single cell organisms to complex plants and animals. For many metazoans, consistent left-right asymmetric patterning is essential for the correct anatomy of internal organs, such as the heart, gut, and brain; disruption of left-right asymmetry patterning leads to an important class of birth defects in human patients. Laterality functions across multiple scales, where early embryonic, subcellular and chiral cytoskeletal events are coupled with asymmetric amplification mechanisms and gene regulatory networks leading to asymmetric physical forces that ultimately result in distinct left and right anatomical organ patterning. Recent studies have suggested the existence of multiple parallel pathways regulating organ asymmetry. Here, we show that an isoform of the hyperpolarization-activated cyclic nucleotide-gated (HCN family of ion channels (hyperpolarization-activated cyclic nucleotide-gated channel 4, HCN4 is important for correct left-right patterning. HCN4 channels are present very early in Xenopus embryos. Blocking HCN channels (Ih currents with pharmacological inhibitors leads to errors in organ situs. This effect is only seen when HCN4 channels are blocked early (pre-stage 10 and not by a later block (post-stage 10. Injections of HCN4-DN (dominant-negative mRNA induce left-right defects only when injected in both blastomeres no later than the 2-cell stage. Analysis of key asymmetric genes' expression showed that the sidedness of Nodal, Lefty, and Pitx2 expression is largely unchanged by HCN4 blockade, despite the randomization of subsequent organ situs, although the area of Pitx2 expression was significantly reduced. Together these data identify a novel, developmental role for HCN4 channels and reveal a new Nodal-Lefty-Pitx2 asymmetric gene expression-independent mechanism upstream of organ positioning during embryonic left-right patterning.

  13. HCN4 ion channel function is required for early events that regulate anatomical left-right patterning in a nodal and lefty asymmetric gene expression-independent manner.

    Science.gov (United States)

    Pai, Vaibhav P; Willocq, Valerie; Pitcairn, Emily J; Lemire, Joan M; Paré, Jean-François; Shi, Nian-Qing; McLaughlin, Kelly A; Levin, Michael

    2017-10-15

    Laterality is a basic characteristic of all life forms, from single cell organisms to complex plants and animals. For many metazoans, consistent left-right asymmetric patterning is essential for the correct anatomy of internal organs, such as the heart, gut, and brain; disruption of left-right asymmetry patterning leads to an important class of birth defects in human patients. Laterality functions across multiple scales, where early embryonic, subcellular and chiral cytoskeletal events are coupled with asymmetric amplification mechanisms and gene regulatory networks leading to asymmetric physical forces that ultimately result in distinct left and right anatomical organ patterning. Recent studies have suggested the existence of multiple parallel pathways regulating organ asymmetry. Here, we show that an isoform of the hyperpolarization-activated cyclic nucleotide-gated (HCN) family of ion channels (hyperpolarization-activated cyclic nucleotide-gated channel 4, HCN4) is important for correct left-right patterning. HCN4 channels are present very early in Xenopus embryos. Blocking HCN channels (Ih currents) with pharmacological inhibitors leads to errors in organ situs. This effect is only seen when HCN4 channels are blocked early (pre-stage 10) and not by a later block (post-stage 10). Injections of HCN4-DN (dominant-negative) mRNA induce left-right defects only when injected in both blastomeres no later than the 2-cell stage. Analysis of key asymmetric genes' expression showed that the sidedness of Nodal, Lefty, and Pitx2 expression is largely unchanged by HCN4 blockade, despite the randomization of subsequent organ situs, although the area of Pitx2 expression was significantly reduced. Together these data identify a novel, developmental role for HCN4 channels and reveal a new Nodal-Lefty-Pitx2 asymmetric gene expression-independent mechanism upstream of organ positioning during embryonic left-right patterning. © 2017. Published by The Company of Biologists Ltd.

  14. Constellation of HCN channels and cAMP regulating proteins in dendritic spines of the primate prefrontal cortex: potential substrate for working memory deficits in schizophrenia.

    Science.gov (United States)

    Paspalas, Constantinos D; Wang, Min; Arnsten, Amy F T

    2013-07-01

    Schizophrenia associates with impaired prefrontal cortical (PFC) function and alterations in cyclic AMP (cAMP) signaling pathways. These include genetic insults to disrupted-in-schizophrenia (DISC1) and phosphodiesterases (PDE4s) regulating cAMP hydrolysis, and increased dopamine D1 receptor (D1R) expression that elevates cAMP. We used immunoelectron microscopy to localize DISC1, PDE4A, PDE4B, and D1R in monkey PFC and to view spatial interactions with hyperpolarization-activated cyclic nucleotide-gated (HCN) channels that gate network inputs when opened by cAMP. Physiological interactions between PDE4s and HCN channels were tested in recordings of PFC neurons in monkeys performing a spatial working memory task. The study reveals a constellation of cAMP-related proteins (DISC1, PDE4A, and D1R) and HCN channels next to excitatory synapses and the spine neck in thin spines of superficial PFC, where working memory microcircuits interconnect and spine loss is most evident in schizophrenia. In contrast, channels in dendrites were distant from synapses and cAMP-related proteins, and were associated with endosomal trafficking. The data suggest that a cAMP signalplex is selectively positioned in the spines to gate PFC pyramidal cell microcircuits. Single-unit recordings confirmed physiological interactions between cAMP and HCN channels, consistent with gating actions. These data may explain why PFC networks are especially vulnerable to genetic insults that dysregulate cAMP signaling.

  15. Novel insights into the distribution of cardiac HCN channels: an expression study in the mouse heart.

    Science.gov (United States)

    Herrmann, Stefan; Layh, Beate; Ludwig, Andreas

    2011-12-01

    HCN pacemaker channels (I(f) channels) are believed to contribute to important functions in the heart; thus these channels became an attractive target for generating transgenic mouse mutants to elucidate their role in physiological and pathophysiological cardiac conditions. A full understanding of cardiac I(f) and the interpretation of studies using HCN mouse mutants require detailed information about the expression profile of the individual HCN subunits. Here we investigate the cardiac expression pattern of the HCN isoforms at the mRNA as well as at the protein level. The specificity of antibodies used was strictly confirmed by the use of HCN1, HCN2 and HCN4 knockout animals. We find a low, but highly differential HCN expression profile outside the cardiac conduction pathway including left and right atria and ventricles. Additionally HCN distribution was investigated in tissue slices of the sinoatrial node, the atrioventricular node, the bundle of His and the bundle branches. The conduction system was marked by acetylcholine esterase staining. HCN4 was confirmed as the predominant isoform of the primary pacemaker followed by a distinct expression of HCN1. In contrast HCN2 shows only a confined expression to individual pacemaker cells. Immunolabeling of the AV-node reveals also a pronounced specificity for HCN1 and HCN4. Compared to the SN and AVN we found a low but selective expression of HCN4 as the only isoform in the atrioventricular bundle. However in the bundle branches HCN1, HCN4 and also HCN2 show a prominent and selective expression pattern. Our results display a characteristic distribution of individual HCN isoforms in several cardiac compartments and reveal that beside HCN4, HCN1 represents the isoform which is selectively expressed in most parts of the conduction system suggesting a substantial contribution of HCN1 to pacemaking. 2011 Elsevier Ltd. All rights reserved.

  16. Predissociation of methyl cyanoformate: The HCN and HNC channels

    CERN Document Server

    Wilhelm, Michael J; González-Vázquez, Jesús; Vázquez, Saulo A; Smith, Jonathan M; Dai, Hai-Lung

    2016-01-01

    We present a combined experimental and theoretical investigation of the 193 nm photolysis of the cyano-ester, methyl cyanoformate (MCF). Specifically, nanosecond time-resolved infrared emission spectroscopy was used to monitor the ro-vibrationally excited photoproducts generated in the photolysis reaction. The signal-to-noise of all time-resolved spectra were enhanced using the recently developed algorithm, spectral reconstruction analysis, which allowed observation of previously obscured minor resonances, and revealed new dissociation channels producing HCN and HNC. Spectral fit analysis of the nascent HCN and electronically excited CN($A^2\\Pi_1$) resonances yield a lower bound estimate for the HCN quantum yield of ca. 0.42$\\pm$0.24%. Multi-configuration self-consistent field calculations were used to interrogate the ground and four lowest energy singlet excited states of MCF. At 193 nm, dissociation is predicted to occur predominantly on the repulsive S$_2$ state. Nevertheless, minor pathways leading to the...

  17. De novo mutations in HCN1 cause early infantile epileptic encephalopathy

    DEFF Research Database (Denmark)

    Nava, Caroline; Dalle, Carine; Rastetter, Agnès

    2014-01-01

    Hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels contribute to cationic Ih current in neurons and regulate the excitability of neuronal networks. Studies in rat models have shown that the Hcn1 gene has a key role in epilepsy, but clinical evidence implicating HCN1 mutations...... acid substitutions. Patch-clamp recordings of Ih currents in cells expressing wild-type or mutant human HCN1 channels showed that the mutations had striking but divergent effects on homomeric channels. Individuals with mutations had clinical features resembling those of Dravet syndrome with progression...

  18. Niflumic acid alters gating of HCN2 pacemaker channels by interaction with the outer region of S4 voltage sensing domains.

    Science.gov (United States)

    Cheng, Lan; Sanguinetti, Michael C

    2009-05-01

    Niflumic acid, 2-[[3-(trifluoromethyl)phenyl]amino]pyridine-3-carboxylic acid (NFA), is a nonsteroidal anti-inflammatory drug that also blocks or modifies the gating of many ion channels. Here, we investigated the effects of NFA on hyperpolarization-activated cyclic nucleotide-gated cation (HCN) pacemaker channels expressed in X. laevis oocytes using site-directed mutagenesis and the two-electrode voltage-clamp technique. Extracellular NFA acted rapidly and caused a slowing of activation and deactivation and a hyperpolarizing shift in the voltage dependence of HCN2 channel activation (-24.5 +/- 1.2 mV at 1 mM). Slowed channel gating and reduction of current magnitude was marked in oocytes treated with NFA, while clamped at 0 mV but minimal in oocytes clamped at -100 mV, indicating the drug preferentially interacts with channels in the closed state. NFA at 0.1 to 3 mM shifted the half-point for channel activation in a concentration-dependent manner, with an EC(50) of 0.54 +/- 0.068 mM and a predicted maximum shift of -38 mV. NFA at 1 mM also reduced maximum HCN2 conductance by approximately 20%, presumably by direct block of the pore. The rapid onset and state-dependence of NFA-induced changes in channel gating suggests an interaction with the extracellular region of the S4 transmembrane helix, the primary voltage-sensing domain of HCN2. Neutralization (by mutation to Gln) of any three of the outer four basic charged residues in S4, but not single mutations, abrogated the NFA-induced shift in channel activation. We conclude that NFA alters HCN2 gating by interacting with the extracellular end of the S4 voltage sensor domains.

  19. Functional Characterization of Cnidarian HCN Channels Points to an Early Evolution of Ih.

    Directory of Open Access Journals (Sweden)

    Emma C Baker

    Full Text Available HCN channels play a unique role in bilaterian physiology as the only hyperpolarization-gated cation channels. Their voltage-gating is regulated by cyclic nucleotides and phosphatidylinositol 4,5-bisphosphate (PIP2. Activation of HCN channels provides the depolarizing current in response to hyperpolarization that is critical for intrinsic rhythmicity in neurons and the sinoatrial node. Additionally, HCN channels regulate dendritic excitability in a wide variety of neurons. Little is known about the early functional evolution of HCN channels, but the presence of HCN sequences in basal metazoan phyla and choanoflagellates, a protozoan sister group to the metazoans, indicate that the gene family predates metazoan emergence. We functionally characterized two HCN channel orthologs from Nematostella vectensis (Cnidaria, Anthozoa to determine which properties of HCN channels were established prior to the emergence of bilaterians. We find Nematostella HCN channels share all the major functional features of bilaterian HCNs, including reversed voltage-dependence, activation by cAMP and PIP2, and block by extracellular Cs+. Thus bilaterian-like HCN channels were already present in the common parahoxozoan ancestor of bilaterians and cnidarians, at a time when the functional diversity of voltage-gated K+ channels was rapidly expanding. NvHCN1 and NvHCN2 are expressed broadly in planulae and in both the endoderm and ectoderm of juvenile polyps.

  20. cAMP control of HCN2 channel Mg2+ block reveals loose coupling between the cyclic nucleotide-gating ring and the pore.

    Directory of Open Access Journals (Sweden)

    Alex K Lyashchenko

    Full Text Available Hyperpolarization-activated cyclic nucleotide-regulated HCN channels underlie the Na+-K+ permeable IH pacemaker current. As with other voltage-gated members of the 6-transmembrane KV channel superfamily, opening of HCN channels involves dilation of a helical bundle formed by the intracellular ends of S6 albeit this is promoted by inward, not outward, displacement of S4. Direct agonist binding to a ring of cyclic nucleotide-binding sites, one of which lies immediately distal to each S6 helix, imparts cAMP sensitivity to HCN channel opening. At depolarized potentials, HCN channels are further modulated by intracellular Mg2+ which blocks the open channel pore and blunts the inhibitory effect of outward K+ flux. Here, we show that cAMP binding to the gating ring enhances not only channel opening but also the kinetics of Mg2+ block. A combination of experimental and simulation studies demonstrates that agonist acceleration of block is mediated via acceleration of the blocking reaction itself rather than as a secondary consequence of the cAMP enhancement of channel opening. These results suggest that the activation status of the gating ring and the open state of the pore are not coupled in an obligate manner (as required by the often invoked Monod-Wyman-Changeux allosteric model but couple more loosely (as envisioned in a modular model of protein activation. Importantly, the emergence of second messenger sensitivity of open channel rectification suggests that loose coupling may have an unexpected consequence: it may endow these erstwhile "slow" channels with an ability to exert voltage and ligand-modulated control over cellular excitability on the fastest of physiologically relevant time scales.

  1. An essential role for modulation of hyperpolarization-activated current in the development of binaural temporal precision.

    Science.gov (United States)

    Khurana, Sukant; Liu, Zhiqiang; Lewis, Alan S; Rosa, Kristen; Chetkovich, Dane; Golding, Nace L

    2012-02-22

    In sensory circuits of the brain, developmental changes in the expression and modulation of voltage-gated ion channels are a common occurrence, but such changes are often difficult to assign to clear functional roles. We have explored this issue in the binaural neurons of the medial superior olive (MSO), whose temporal precision in detecting the coincidence of binaural inputs dictates the resolution of azimuthal sound localization. We show that in MSO principal neurons of gerbils during the first week of hearing, a hyperpolarization-activated current (I(h)) progressively undergoes a 13-fold increase in maximal conductance, a >10-fold acceleration of kinetics, and, most surprisingly, a 30 mV depolarizing shift in the voltage dependence of activation. This period is associated with an upregulation of the hyperpolarization-activated and cyclic nucleotide-gated (HCN) channel subunits HCN1, HCN2, and HCN4 in the MSO, but only HCN1 and HCN4 were expressed strongly in principal neurons. I(h) recorded in nucleated patches from electrophysiologically mature MSO neurons (>P18) exhibited kinetics and an activation range nearly identical to the I(h) found in whole-cell recordings before hearing onset. These results indicate that the developmental changes in I(h) in MSO neurons can be explained predominantly by modulation from diffusible intracellular factors, and not changes in channel subunit composition. The exceptionally large modulatory changes in I(h), together with refinements in synaptic properties transform the coding strategy from one of summation and integration to the submillisecond coincidence detection known to be required for transmission of sound localization cues.

  2. Nitric Oxide Modulates HCN Channels in Magnocellular Neurons of the Supraoptic Nucleus of Rats by an S-Nitrosylation-Dependent Mechanism.

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    Pires da Silva, Melina; de Almeida Moraes, Davi José; Mecawi, André de Souza; Rodrigues, José Antunes; Varanda, Wamberto Antonio

    2016-11-02

    The control of the excitability in magnocellular neurosecretory cells (MNCs) of the supraoptic nucleus has been attributed mainly to synaptic inputs from circunventricular organs. However, nitric oxide (NO), a gaseous messenger produced in this nucleus during isotonic and short-term hypertonic conditions, is an example of a modulator that can act directly on MNCs to modulate their firing rate. NO inhibits the electrical excitability of MNCs, leading to a decrease in the release of vasopressin and oxytocin. Although the effects of NO on MNCs are well established, the mechanism by which this gas produces its effect is, so far, unknown. Because NO acts independently of synaptic inputs, we hypothesized that ion channels present in MNCs are the targets of NO. To investigate this hypothesis, we used the patch-clamp technique in vitro and in situ to measure currents carried by hyperpolarization-activated and nucleotide-gated cation (HCN) channels and establish their role in determining the electrical excitability of MNCs in rats. Our results show that blockade of HCN channels by ZD7288 decreases MNC firing rate with significant consequences on the release of OT and VP, measured by radioimmunoassay. NO induced a significant reduction in HCN currents by binding to cysteine residues and forming S-nitrosothiol complexes. These findings shed new light on the mechanisms that control the electrical excitability of MNCs via the nitrergic system and strengthen the importance of HCN channels in the control of hydroelectrolyte homeostasis. Cells in our organism live in a liquid environment whose composition and osmolality are maintained within tight limits. Magnocellular neurons (MNCs) of the supra optic nucleus can sense osmolality and control the synthesis and secretion of vasopressin (VP) and oxytocin (OT) by the neurohypophysis. OT and VP act on the kidneys controlling the excretion of water and sodium to maintain homeostasis. Here we combined electrophysiology, molecular

  3. Mechanotransduction and hyperpolarization-activated currents contribute to spontaneous activity in mouse vestibular ganglion neurons

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    Horwitz, Geoffrey C.; Risner-Janiczek, Jessica R.

    2014-01-01

    The hyperpolarization-activated, cyclic nucleotide–sensitive current, Ih, is present in vestibular hair cells and vestibular ganglion neurons, and is required for normal balance function. We sought to identify the molecular correlates and functional relevance of Ih in vestibular ganglion neurons. Ih is carried by channels consisting of homo- or heteromeric assemblies of four protein subunits from the Hcn gene family. The relative expression of Hcn1–4 mRNA was examined using a quantitative reverse transcription PCR (RT-PCR) screen. Hcn2 was the most highly expressed subunit in vestibular neuron cell bodies. Immunolocalization of HCN2 revealed robust expression in cell bodies of all vestibular ganglion neurons. To characterize Ih in vestibular neuron cell bodies and at hair cell–afferent synapses, we developed an intact, ex vivo preparation. We found robust physiological expression of Ih in 89% of cell bodies and 100% of calyx terminals. Ih was significantly larger in calyx terminals than in cell bodies; however, other biophysical characteristics were similar. Ih was absent in calyces lacking Hcn1 and Hcn2, but small Ih was still present in cell bodies, which suggests expression of an additional subunit, perhaps Hcn4. To determine the contributions of hair cell mechanotransduction and Ih to the firing patterns of calyx terminals, we recorded action potentials in current-clamp mode. Mechanotransduction currents were modulated by hair bundle defection and application of calcium chelators to disrupt tip links. Ih activity was modulated using ZD7288 and cAMP. We found that both hair cell transduction and Ih contribute to the rate and regularity of spontaneous action potentials in the vestibular afferent neurons. We propose that modulation of Ih in vestibular ganglion neurons may provide a mechanism for modulation of spontaneous activity in the vestibular periphery. PMID:24638995

  4. Reduced Hyperpolarization-Activated Current Contributes to Enhanced Intrinsic Excitability in Cultured Neonatal Hippocampal Neurons from PrP−/− Mice

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    Jing eFan

    2016-03-01

    Full Text Available Genetic ablation of cellular prion protein (PrPC has been linked to increased neuronal excitability and synaptic activity in the hippocampus. We have previously shown that synaptic activity in hippocampi of PrP-null mice is increased due to enhanced N-methyl-D-aspartate receptor (NMDAR function. Here, we focused on the effect of PRNP gene knock-out (KO on intrinsic neuronal excitability, and in particular, the underlying ionic mechanism in hippocampal neurons cultured from P0 mouse pups. We found that the absence of PrPC profoundly affected the firing properties of cultured hippocampal neurons in the presence of synaptic blockers. The membrane impedance was greater in PrP-null neurons, and this difference was abolished by the hyperpolarization-activated cyclic nucleotide-gated (HCN channel blocker ZD7288 (100 µM. HCN channel activity appeared to be functionally regulated by PrPC. The amplitude of voltage sag, a characteristic of activating HCN channel current (Ih, was decreased in null mice. Moreover, Ih peak current was reduced, along with a hyperpolarizing shift in activation gating and slower kinetics. However, neither HCN1 nor HCN2 formed a biochemical complex with PrPC. These results suggest that the absence of PrP downregulates the activity of HCN channels through activation of a cell signaling pathway rather than through direct interactions. This in turn contributes to an increase in membrane impedance to potentiate neuronal excitability.

  5. Hyperpolarization-activated current Ihin mouse trigeminal sensory neurons in a transgenic mouse model of familial hemiplegic migraine type-1.

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    Eroli, Francesca; Vilotti, Sandra; van den Maagdenberg, Arn M J M; Nistri, Andrea

    2017-05-20

    Transgenic knock-in (KI) mice that express Ca V 2.1 channels containing an R192Q gain-of-function mutation in the α 1A subunit known to cause familial hemiplegic migraine type-1 in patients, exhibit key disease characteristics and provide a useful tool to investigate pathophysiological mechanisms of pain transduction. Previously, KI trigeminal sensory neurons were shown to exhibit constitutive hyperexcitability due to up-regulation of ATP-gated P2X3 receptors that trigger spike activity at a more negative threshold. This implies that intrinsic neuronal conductances may shape action potential generation in response to ATP, which could act as a mediator of migraine headache. Here we investigated whether the hyperpolarization-activated conductance I h , mediated by hyperpolarization activated cyclic nucleotide-gated channels (HCN), contributes to sub-threshold behavior and firing in wild-type (WT) and KI trigeminal ganglia (TG) neurons. Whereas most WT and KI trigeminal neurons expressed I h current, blocked by the specific inhibitor ZD7288, it was smaller in KI neurons despite similar activation and deactivation kinetics. HCN1 and HCN2 were the most abundantly expressed subunits in TG, both in situ and in culture. In KI TG neurons, HCN2 subunits were predominantly present in the cytoplasm, not at the plasma membrane, likely accounting for the smaller I h of such cells. ZD7288 hyperpolarized the membrane potential, thereby raising the firing threshold, and prolonging the spike trajectory to generate fewer spikes due to P2X3 receptor activation. The low amplitude of I h in KI TG neurons suggests that down-regulation of I h current in sub-threshold behavior acts as a compensatory mechanism to limit sensory hyperexcitability, manifested under certain stressful stimuli. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  6. Ectopic automaticity induced in ventricular myocytes by transgenic overexpression of HCN2.

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    Oshita, Kensuke; Itoh, Masayuki; Hirashima, Shingo; Kuwabara, Yoshihiro; Ishihara, Keiko; Kuwahara, Koichiro; Nakao, Kazuwa; Kimura, Takeshi; Nakamura, Kei-Ichiro; Ushijima, Kazuo; Takano, Makoto

    2015-03-01

    Hyperpolarization-activated cyclic nucleotide-gated channels (HCNs) are expressed in the ventricles of fetal hearts but are normally down-regulated as development progresses. In the hypertrophied heart, however, these channels are re-expressed and generate a hyperpolarization-activated, nonselective cation current (Ih), which evidence suggests may increase susceptibility to arrhythmia. To test this hypothesis, we generated and analyzed transgenic mice overexpressing HCN2 specifically in their hearts (HCN2-Tg). Under physiological conditions, HCN2-Tg mice exhibited no discernible abnormalities. After the application of isoproterenol (ISO), however, ECG recordings from HCN2-Tg mice showed intermittent atrioventricular dissociation followed by idioventricular rhythm. Consistent with this observation, 0.3 μmol/L ISO-induced spontaneous action potentials (SAPs) in 76% of HCN2-Tg ventricular myocytes. In the remaining 24%, ISO significantly depolarized the resting membrane potential (RMP), and the late repolarization phase of evoked action potentials (APs) was significantly longer than in WT myocytes. Analysis of membrane currents revealed that these differences are attributable to the Ih tail current. These findings suggest HCN2 channel activity reduces the repolarization reserve of the ventricular action potential and increases ectopic automaticity under pathological conditions such as excessive β-adrenergic stimulation. Copyright © 2015. Published by Elsevier Ltd.

  7. Sensory deprivation regulates the development of the hyperpolarization-activated current in auditory brainstem neurons.

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    Hassfurth, Benjamin; Magnusson, Anna K; Grothe, Benedikt; Koch, Ursula

    2009-10-01

    Hyperpolarization-activated and cyclic nucleotide-gated (HCN) channels are highly expressed in the superior olivary complex, the primary locus for binaural information processing. This hyperpolarization-activated current (I(h)) regulates the excitability of neurons and enhances the temporally precise analysis of the binaural acoustic cues. By using the whole-cell patch-clamp technique, we examined the properties of I(h) current in neurons of the lateral superior olive (LSO) and the medial nucleus of the trapezoid body (MNTB) before and after hearing onset. Moreover, we tested the hypothesis that I(h) currents are actively regulated by sensory input activity by performing bilateral and unilateral cochlear ablations before hearing onset, resulting in a chronic auditory deprivation. The results show that after hearing onset, I(h) currents are rapidly upregulated in LSO neurons, but change only marginally in neurons of the MNTB. We also found a striking difference in maximal current density, voltage dependence and activation time constant between the LSO and the MNTB in mature-like animals. Following bilateral cochlear ablations before hearing onset, the I(h) currents were scaled up in the LSO and scaled down in the MNTB. Consequently, in the LSO this resulted in a depolarized resting membrane potential and a lower input resistance of these neurons. This type of activity-dependent homeostatic change could thus result in an augmented response to the remaining inputs.

  8. Tonotopic Organization of the Hyperpolarization-activated Current (Ih in the Mammalian Medial Superior Olive

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    Veronika eBaumann

    2013-07-01

    Full Text Available Abstract Neuronal membrane properties can largely vary even within distinct morphological cell classes. The mechanisms and functional consequences of this diversity, however, are little explored. In the medial superior olive (MSO, a brainstem nucleus that performs binaural coincidence detection, membrane properties at rest are largely governed by the hyperpolarization-activated inward current (Ih which enables the temporally precise integration of excitatory and inhibitory inputs. Here, we report that Ih density varies along the putative tonotopic axis of the MSO with Ih being largest in ventral, high-frequency processing neurons. Also Ih half-maximal activation voltage and time constant are differentially distributed such that Ih of the putative high-frequency processing neurons activate faster and at more depolarized levels. Intracellular application of saturating concentrations of cyclic AMP removed the regional difference in hyperpolarization-activated cyclic nucleotide gated (HCN channel activation, but not Ih density. Experimental data in conjunction with a computational model suggest that increased Ih levels are helpful in counteracting temporal summation of phase-locked inhibitory inputs which is particularly prominent in high-frequency neurons.

  9. hERG potassium channel blockade by the HCN channel inhibitor bradycardic agent ivabradine.

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    Melgari, Dario; Brack, Kieran E; Zhang, Chuan; Zhang, Yihong; El Harchi, Aziza; Mitcheson, John S; Dempsey, Christopher E; Ng, G André; Hancox, Jules C

    2015-04-24

    Ivabradine is a specific bradycardic agent used in coronary artery disease and heart failure, lowering heart rate through inhibition of sinoatrial nodal HCN-channels. This study investigated the propensity of ivabradine to interact with KCNH2-encoded human Ether-à-go-go-Related Gene (hERG) potassium channels, which strongly influence ventricular repolarization and susceptibility to torsades de pointes arrhythmia. Patch clamp recordings of hERG current (IhERG) were made from hERG expressing cells at 37°C. Ih ERG was inhibited with an IC50 of 2.07 μmol/L for the hERG 1a isoform and 3.31 μmol/L for coexpressed hERG 1a/1b. The voltage and time-dependent characteristics of Ih ERG block were consistent with preferential gated-state-dependent channel block. Inhibition was partially attenuated by the N588K inactivation-mutant and the S624A pore-helix mutant and was strongly reduced by the Y652A and F656A S6 helix mutants. In docking simulations to a MthK-based homology model of hERG, the 2 aromatic rings of the drug could form multiple π-π interactions with the aromatic side chains of both Y652 and F656. In monophasic action potential (MAP) recordings from guinea-pig Langendorff-perfused hearts, ivabradine delayed ventricular repolarization and produced a steepening of the MAPD90 restitution curve. Ivabradine prolongs ventricular repolarization and alters electrical restitution properties at concentrations relevant to the upper therapeutic range. In absolute terms ivabradine does not discriminate between hERG and HCN channels: it inhibits Ih ERG with similar potency to that reported for native If and HCN channels, with S6 binding determinants resembling those observed for HCN4. These findings may have important implications both clinically and for future bradycardic drug design. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  10. HCN1 and HCN2 in Rat DRG neurons: levels in nociceptors and non-nociceptors, NT3-dependence and influence of CFA-induced skin inflammation on HCN2 and NT3 expression.

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    Acosta, Cristian; McMullan, Simon; Djouhri, Laiche; Gao, Linlin; Watkins, Roger; Berry, Carol; Dempsey, Katherine; Lawson, Sally N

    2012-01-01

    I(h), which influences neuronal excitability, has recently been measured in vivo in sensory neuron subtypes in dorsal root ganglia (DRGs). However, expression levels of HCN (hyperpolarization-activated cyclic nucleotide-gated) channel proteins that underlie I(h) were unknown. We therefore examined immunostaining of the most abundant isoforms in DRGs, HCN1 and HCN2 in these neuron subtypes. This immunostaining was cytoplasmic and membrane-associated (ring). Ring-staining for both isoforms was in neurofilament-rich A-fiber neurons, but not in small neurofilament-poor C-fiber neurons, although some C-neurons showed cytoplasmic HCN2 staining. We recorded intracellularly from DRG neurons in vivo, determined their sensory properties (nociceptive or low-threshold-mechanoreceptive, LTM) and conduction velocities (CVs). We then injected fluorescent dye enabling subsequent immunostaining. For each dye-injected neuron, ring- and cytoplasmic-immunointensities were determined relative to maximum ring-immunointensity. Both HCN1- and HCN2-ring-immunointensities were positively correlated with CV in both nociceptors and LTMs; they were high in Aβ-nociceptors and Aα/β-LTMs. High HCN1 and HCN2 levels in Aα/β-neurons may, via I(h), influence normal non-painful (e.g. touch and proprioceptive) sensations as well as nociception and pain. HCN2-, not HCN1-, ring-intensities were higher in muscle spindle afferents (MSAs) than in all other neurons. The previously reported very high I(h) in MSAs may relate to their very high HCN2. In normal C-nociceptors, low HCN1 and HCN2 were consistent with their low/undetectable I(h.) In some C-LTMs HCN2-intensities were higher than in C-nociceptors. Together, HCN1 and HCN2 expressions reflect previously reported I(h) magnitudes and properties in neuronal subgroups, suggesting these isoforms underlie I(h) in DRG neurons. Expression of both isoforms was NT3-dependent in cultured DRG neurons. HCN2-immunostaining in small neurons increased 1 day after

  11. Remodeling of hyperpolarization-activated current, Ih, in Ah-type visceral ganglion neurons following ovariectomy in adult rats.

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    Guo-Fen Qiao

    Full Text Available Hyperpolarization-activated currents (Ih mediated by hyperpolarization-activated cyclic nucleotide-gated (HCN channels modulate excitability of myelinated A- and Ah-type visceral ganglion neurons (VGN. Whether alterations in Ih underlie the previously reported reduction of excitability of myelinated Ah-type VGNs following ovariectomy (OVX has remained unclear. Here we used the intact nodose ganglion preparation in conjunction with electrophysiological approaches to examine the role of Ih remodeling in altering Ah-type neuron excitability following ovariectomy in adult rats. Ah-type neurons were identified based on their afferent conduction velocity. Ah-type neurons in nodose ganglia from non-OVX rats exhibited a voltage 'sag' as well as 'rebound' action potentials immediately following hyperpolarizing current injections, which both were suppressed by the Ih blocker ZD7288. Repetitive spike activity induced afterhyperpolarizations lasting several hundreds of milliseconds (termed post-excitatory membrane hyperpolarizations, PEMHs, which were significantly reduced by ZD7288, suggesting that they resulted from transient deactivation of Ih during the preceding spike trains. Ovariectomy reduced whole-cell Ih density, caused a hyperpolarizing shift of the voltage-dependence of Ih activation, and slowed Ih activation. OVX-induced Ih remodeling was accompanied by a flattening of the stimulus frequency/response curve and loss of PEMHs. Also, HCN1 mRNA levels were reduced by ∼30% in nodose ganglia from OVX rats compared with their non-OVX counterparts. Acute exposure of nodose ganglia to 17beta-estradiol partly restored Ih density and accelerated Ih activation in Ah-type cells. In conclusion, Ih plays a significant role in modulating the excitability of myelinated Ah-type VGNs in adult female rats.

  12. Structural Changes and Lack of HCN1 Channels in the Binaural Auditory Brainstem of the Naked Mole-Rat (Heterocephalus glaber).

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    Gessele, Nikodemus; Garcia-Pino, Elisabet; Omerbašić, Damir; Park, Thomas J; Koch, Ursula

    2016-01-01

    Naked mole-rats (Heterocephalus glaber) live in large eu-social, underground colonies in narrow burrows and are exposed to a large repertoire of communication signals but negligible binaural sound localization cues, such as interaural time and intensity differences. We therefore asked whether monaural and binaural auditory brainstem nuclei in the naked mole-rat are differentially adjusted to this acoustic environment. Using antibody stainings against excitatory and inhibitory presynaptic structures, namely the vesicular glutamate transporter VGluT1 and the glycine transporter GlyT2 we identified all major auditory brainstem nuclei except the superior paraolivary nucleus in these animals. Naked mole-rats possess a well structured medial superior olive, with a similar synaptic arrangement to interaural-time-difference encoding animals. The neighboring lateral superior olive, which analyzes interaural intensity differences, is large and elongated, whereas the medial nucleus of the trapezoid body, which provides the contralateral inhibitory input to these binaural nuclei, is reduced in size. In contrast, the cochlear nucleus, the nuclei of the lateral lemniscus and the inferior colliculus are not considerably different when compared to other rodent species. Most interestingly, binaural auditory brainstem nuclei lack the membrane-bound hyperpolarization-activated channel HCN1, a voltage-gated ion channel that greatly contributes to the fast integration times in binaural nuclei of the superior olivary complex in other species. This suggests substantially lengthened membrane time constants and thus prolonged temporal integration of inputs in binaural auditory brainstem neurons and might be linked to the severely degenerated sound localization abilities in these animals.

  13. Structural Changes and Lack of HCN1 Channels in the Binaural Auditory Brainstem of the Naked Mole-Rat (Heterocephalus glaber.

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    Nikodemus Gessele

    Full Text Available Naked mole-rats (Heterocephalus glaber live in large eu-social, underground colonies in narrow burrows and are exposed to a large repertoire of communication signals but negligible binaural sound localization cues, such as interaural time and intensity differences. We therefore asked whether monaural and binaural auditory brainstem nuclei in the naked mole-rat are differentially adjusted to this acoustic environment. Using antibody stainings against excitatory and inhibitory presynaptic structures, namely the vesicular glutamate transporter VGluT1 and the glycine transporter GlyT2 we identified all major auditory brainstem nuclei except the superior paraolivary nucleus in these animals. Naked mole-rats possess a well structured medial superior olive, with a similar synaptic arrangement to interaural-time-difference encoding animals. The neighboring lateral superior olive, which analyzes interaural intensity differences, is large and elongated, whereas the medial nucleus of the trapezoid body, which provides the contralateral inhibitory input to these binaural nuclei, is reduced in size. In contrast, the cochlear nucleus, the nuclei of the lateral lemniscus and the inferior colliculus are not considerably different when compared to other rodent species. Most interestingly, binaural auditory brainstem nuclei lack the membrane-bound hyperpolarization-activated channel HCN1, a voltage-gated ion channel that greatly contributes to the fast integration times in binaural nuclei of the superior olivary complex in other species. This suggests substantially lengthened membrane time constants and thus prolonged temporal integration of inputs in binaural auditory brainstem neurons and might be linked to the severely degenerated sound localization abilities in these animals.

  14. The HCN4 channel mutation D553N associated with bradycardia has a C-linker mediated gating defect.

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    Netter, Michael F; Zuzarte, Marylou; Schlichthörl, Günter; Klöcker, Nikolaj; Decher, Niels

    2012-01-01

    The D553N mutation located in the C-linker of the cardiac pacemaker channel HCN4 is thought to cause sino-atrial dysfunction via a pronounced dominant-negative trafficking defect. Since HCN4 mutations usually have a minor defect in channel gating, it was our aim to further characterize the disease causing mechanism of D553N. Fluorescence microscopy, FACS, TEVC and patch-clamp recordings were performed to characterize D553N. Surprisingly, we found that D553N channels reach the plasma membrane and have no apparent trafficking defect. Co-expression of D553N with HCN4 also revealed no dominant-negative effect on wild-type channels. Consistent with the normal cell surface expression of D553N, it was possible to extensively characterize D553N mutants in Xenopus oocytes and mammalian cells. D553N channels generate currents with reduced amplitude, while the kinetics of activation and deactivation are not altered. While the regulation of D553N by tyrosine kinases is normal, we observed a change in the cAMP regulation which however cannot account for the strong loss-of-function of the mutant. The pronounced current reduction and the regular surface expression indicate a major gating defect of the C-linker gate. We hypothesize that the D553N mutation stabilizes a previously reported salt bridge important for the gating of the channel. Copyright © 2012 S. Karger AG, Basel.

  15. Funny current and cardiac rhythm: insights from HCN knockout mouse models

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    Mirko eBaruscotti

    2012-07-01

    Full Text Available In the adult animal the sinoatrial node (SAN rhythmically generates a depolarizing wave that propagates to the rest of the heart. However, the SAN is more than a simple clock; it is a clock that adjusts its pace according to the metabolic requirements of the organism. The Hyperpolarization-activated Cyclic Nucleotide-gated channels (HCN1-4 are the structural component of the funny (If channels; in the SAN the If current is the main driving electrical force of the diastolic depolarization and the HCN4 is the most abundant isoform. The generation of HCN KO mouse models has advanced the understanding of the role of these channels in cardiac excitability. The HCN4 KO models that were first developed allowed either global or cardiac-specific constitutive ablation of HCN4 channels, and resulted in embryonic lethality. A further progress was made with the development of three separate inducible HCN4 KO models; in one model KO was induced globally in the entire organism, in a second, ablation occurred only in HCN4-expressing cells, and finally in a third model KO was confined to cardiac cells. Unexpectedly, the three models yielded different results; similarities and differences among these models will be presented and discussed. The functional effects of HCN2 and HCN3 knockout models and transgenic HCN4 mouse models will also be discussed.In conclusion, HCN KO/transgenic models have allowed to evaluate the functional role of the If currents in intact animals as well as in single SAN cells isolated from the same animals. This opportunity is therefore unique since it allows to 1 verify the contribution of specific HCN isoforms to cardiac activity in intact animals, and 2 to compare these results to those obtained in single cell experiments. These combined studies were not possible prior to the development of KO models. Finally, these models represent critical tools to improve our understanding of the molecular basis of some inheritable arrhythmic human

  16. A novel 'splice site' HCN4 Gene mutation, c.1737+1 G>T, causes familial bradycardia, reduced heart rate response, impaired chronotropic competence and increased short-term heart rate variability.

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    Hategan, Lidia; Csányi, Beáta; Ördög, Balázs; Kákonyi, Kornél; Tringer, Annamária; Kiss, Orsolya; Orosz, Andrea; Sághy, László; Nagy, István; Hegedűs, Zoltán; Rudas, László; Széll, Márta; Varró, András; Forster, Tamás; Sepp, Róbert

    2017-08-15

    The most important molecular determinant of heart rate regulation in sino-atrial pacemaker cells includes hyperpolarization-activated, cyclic nucleotide-gated ion channels, the major isoform of which is encoded by the HCN4 gene. Mutations affecting the HCN4 gene are associated primarily with sick sinus syndrome. A novel c.1737+1 G>T 'splice-site' HCN4 mutation was identified in a large family with familial bradycardia which co-segregated with the disease providing a two-point LOD score of 4.87. Twelve out of the 22 investigated family members [4 males, 8 females average age 36 (SD 6) years] were considered as clinically affected (heart ratesite' HCN4 gene mutation, c.1737+1 G>T, causes familial bradycardia and leads to reduced heart rate response, impaired chronotropic competence and increased short-term heart rate variability in the mutation carriers. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Lidocaine Inhibits HCN Currents in Rat Spinal Substantia Gelatinosa Neurons

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    Hu, Tao; Liu, Nana; Lv, Minhua; Ma, Longxian; Peng, Huizhen; Peng, Sicong

    2016-01-01

    BACKGROUND: Lidocaine, which blocks voltage-gated sodium channels, is widely used in surgical anesthesia and pain management. Recently, it has been proposed that the hyperpolarization-activated cyclic nucleotide (HCN) channel is one of the other novel targets of lidocaine. Substantia gelatinosa in the spinal dorsal horn, which plays key roles in modulating nociceptive information from primary afferents, comprises heterogeneous interneurons that can be electrophysiologically categorized by firing pattern. Our previous study demonstrated that a substantial proportion of substantia gelatinosa neurons reveal the presence of HCN current (Ih); however, the roles of lidocaine and HCN channel expression in different types of substantia gelatinosa neurons remain unclear. METHODS: By using the whole-cell patch-clamp technique, we investigated the effect of lidocaine on Ih in rat substantia gelatinosa neurons of acute dissociated spinal cord slices. RESULTS: We found that lidocaine rapidly decreased the peak Ih amplitude with an IC50 of 80 μM. The inhibition rate on Ih was not significantly different with a second application of lidocaine in the same neuron. Tetrodotoxin, a sodium channel blocker, did not affect lidocaine’s effect on Ih. In addition, lidocaine shifted the half-activation potential of Ih from −109.7 to −114.9 mV and slowed activation. Moreover, the reversal potential of Ih was shifted by −7.5 mV by lidocaine. In the current clamp, lidocaine decreased the resting membrane potential, increased membrane resistance, delayed rebound depolarization latency, and reduced the rebound spike frequency. We further found that approximately 58% of substantia gelatinosa neurons examined expressed Ih, in which most of them were tonically firing. CONCLUSIONS: Our studies demonstrate that lidocaine strongly inhibits Ih in a reversible and concentration-dependent manner in substantia gelatinosa neurons, independent of tetrodotoxin-sensitive sodium channels. Thus, our

  18. Noise-induced plasticity of KCNQ2/3 and HCN channels underlies vulnerability and resilience to tinnitus

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    Li, Shuang; Kalappa, Bopanna I; Tzounopoulos, Thanos

    2015-01-01

    Vulnerability to noise-induced tinnitus is associated with increased spontaneous firing rate in dorsal cochlear nucleus principal neurons, fusiform cells. This hyperactivity is caused, at least in part, by decreased Kv7.2/3 (KCNQ2/3) potassium currents. However, the biophysical mechanisms underlying resilience to tinnitus, which is observed in noise-exposed mice that do not develop tinnitus (non-tinnitus mice), remain unknown. Our results show that noise exposure induces, on average, a reduction in KCNQ2/3 channel activity in fusiform cells in noise-exposed mice by 4 days after exposure. Tinnitus is developed in mice that do not compensate for this reduction within the next 3 days. Resilience to tinnitus is developed in mice that show a re-emergence of KCNQ2/3 channel activity and a reduction in HCN channel activity. Our results highlight KCNQ2/3 and HCN channels as potential targets for designing novel therapeutics that may promote resilience to tinnitus. DOI: http://dx.doi.org/10.7554/eLife.07242.001 PMID:26312501

  19. Morphology of mouse sinoatrial node and its expression of NF-160 and HCN4

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    Wen, Yu; Li, Bin

    2015-01-01

    Objective: To explore the morphology and cell component of the sinoatrial node in adult mice and to observe the expressions of neurofilament protein (NF-160) and hyperpolarization-activated cyclic nucleotide regulation of cation channel 4 (HCN4) in sinus node cells. Methods: The right and left atria were collected from 10 adult mice. After paraffin embedding and serial section, these sections underwent Masson trichrome staining and NF-160 immunohistochemical staining, respectively, followed by observation under a light microscope. The right and left atria from another 5 mice were used for immunofluorescence staining using NF-160 and HCN4 antibodies, respectively, followed by observation under a confocal microscope. Results: The mouse sinoatrial node was close to the superior vena cava and below the epicardium. The shape of the mouse sinoatrial node was ovoid or irregular in the horizontal sections. We clearly saw a sinus node artery passing through the sinoatrial node, so the artery can be used as a location marker of the sinoatrial node. Immunofluorescence displayed the expression of NF-160 and HCN4 in both pacemaker cells and transitional cells of the sinoatrial node. Finally, sinoatrial node migrated along with Purkinje fibers of the right atrium. Conclusion: The position of mouse sinoatrial node is more stable. The distal end of sinoatrial node extends to the right subendocardial layer and migrates with Purkinje fibers. In mouse sinoatrial node, both pacemaker cells and transitional cells are regularly distributed, and all have HCN4 and NF-160 expression. PMID:26550270

  20. Involvement of the S4-S5 linker and the C-linker domain regions to voltage-gating in plant Shaker channels: comparison with animal HCN and Kv channels.

    Science.gov (United States)

    Nieves-Cordones, Manuel; Gaillard, Isabelle

    2014-01-01

    Among the different transport systems present in plant cells, Shaker channels constitute the major pathway for K(+) in the plasma membrane. Plant Shaker channels are members of the 6 transmembrane-1 pore (6TM-1P) cation channel superfamily as the animal Shaker (Kv) and HCN channels. All these channels are voltage-gated K(+) channels: Kv channels are outward-rectifiers, opened at depolarized voltages and HCN channels are inward-rectifiers, opened by membrane hyperpolarization. Among plant Shaker channels, we can find outward-rectifiers, inward-rectifiers and also weak-rectifiers, with weak voltage dependence. Despite the absence of crystal structures of plant Shaker channels, functional analyses coupled to homology modeling, mostly based on Kv and HCN crystals, have permitted the identification of several regions contributing to plant Shaker channel gating. In the present mini-review, we make an update on the voltage-gating mechanism of plant Shaker channels which seem to be comparable to that proposed for HCN channels.

  1. Ketamine, propofol and the EEG: a neural field analysis of HCN1-mediated interactions

    Directory of Open Access Journals (Sweden)

    Ingo eBojak

    2013-04-01

    Full Text Available Ketamine and propofol are two well-known, powerful anesthetic agents, yet at first sight this appears to be their only commonality. Ketamine is a dissociative anesthetic agent, whose main mechanism of action is considered to be N-methyl-D-aspartate (NMDA antagonism; whereas propofol is a general anesthetic agent, which is assumed to primarily potentiate currents gated by γ-aminobutyric acid type A (GABA A receptors. However, several experimental observations suggest a closer relationship. First, the effect of ketamine on the electroencephalogram (EEG is markedly changed in the presence of propofol: on its own ketamine increases theta (4–8 Hz and decreases alpha (8–13 Hz oscillations, whereas ketamine induces a significant shift to beta band frequencies (13–30 Hz in the presence of propofol. Second, both ketamine and propofol cause inhibition of the inward pacemaker current Ih, by binding to the corresponding hyperpolarization-activated cyclic nucleotide-gated potassium channel 1 (HCN1 subunit. The resulting effect is a hyperpolarization of the neuron’s resting membrane potential. Third, the ability of both ketamine and propofol to induce hypnosis is reduced in HCN1-knockout mice. Here we show that one can theoretically understand the observed spectral changes of the EEG based on HCN1-mediated hyperpolarizations alone, without involving the supposed main mechanisms of action of these drugs through NMDA and GABA A, respectively. On the basis of our successful EEG model we conclude that ketamine and propofol should be antagonistic to each other in their interaction at HCN1 subunits. Such a prediction is in accord with the results of clinical experiment in which it is found that ketamine and propofol interact in an infra-additive manner with respect to the endpoints of hypnosis and immobility.

  2. Relevance of HCN2-expressing human mesenchymal stem cells for the generation of biological pacemakers.

    Science.gov (United States)

    Bruzauskaite, Ieva; Bironaite, Daiva; Bagdonas, Edvardas; Skeberdis, Vytenis Arvydas; Denkovskij, Jaroslav; Tamulevicius, Tomas; Uvarovas, Valentinas; Bernotiene, Eiva

    2016-04-30

    The transfection of human mesenchymal stem cells (hMSCs) with the hyperpolarization-activated cyclic nucleotide-gated ion channel 2 (HCN2) gene has been demonstrated to provide biological pacing in dogs with complete heart block. The mechanism appears to be the generation of the ion current (If) by the HCN2-expressing hMSCs. However, it is not clear how the transfection process and/or the HCN2 gene affect the growth functions of the hMSCs. Therefore, we investigated survival, proliferation, cell cycle, and growth on a Kapton® scaffold of HCN2-expressing hMSCs. hMSCs were isolated from the bone marrow of healthy volunteers applying a selective cell adhesion procedure and were identified by their expression of specific surface markers. Cells from passages 2-3 were transfected by electroporation using commercial transfection kits and a pIRES2-EGFP vector carrying the pacemaker gene, mouse HCN2 (mHCN2). Transfection efficiency was confirmed by enhanced green fluorescent protein (EGFP) fluorescence, quantitative real-time polymerase chain reaction (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA). After hMSCs were transfected, their viability, proliferation, If generation, apoptosis, cell cycle, and expression of transcription factors were measured and compared with non-transfected cells and cells transfected with pIRES2-EGFP vector alone. Intracellular mHCN2 expression after transfection increased from 22.14 to 62.66 ng/mg protein (p cells was 82 ± 5 %; they grew stably for more than 3 weeks and induced If current. mHCN2-transfected cells had low mitotic activity (10.4 ± 1.24 % in G2/M and 83.6 ± 2.5 % in G1 phases) as compared with non-transfected cells (52-53 % in G2/M and 31-35 % in G1 phases). Transfected cells showed increased activation of nine cell cycle-regulating transcription factors: the most prominent upregulation was of AMP-dependent transcription factor ATF3 (7.11-fold, p = 0.00056) which regulates the G1 phase. mHCN2-expressing hMSCs were

  3. An N-terminal deletion variant of HCN1 in the epileptic WAG/Rij strain modulates HCN current densities

    Directory of Open Access Journals (Sweden)

    Konstantin eWemhöner

    2015-11-01

    Full Text Available Rats of the Wistar Albino Glaxo/Rij (WAG/Rij strain show symptoms resembling human absence epilepsy. Thalamocortical neurons of WAG/Rij rats are characterized by an increased HCN1 expression, a negative shift in Ih activation curve, and an altered responsiveness of Ih to cAMP. We cloned HCN1 channels from rat thalamic cDNA libraries of the WAG/Rij strain and found an N-terminal deletion of 37 amino acids. In addition, WAG-HCN1 has a stretch of six amino acids, directly following the deletion, where the wild-type sequence (GNSVCF is changed to a polyserine motif. These alterations were found solely in thalamus mRNA but not in genomic DNA. The truncated WAG-HCN1 was detected late postnatal in WAG/Rij rats and was not passed on to rats obtained from pairing WAG/Rij and non-epileptic August Copenhagen Irish (ACI rats. Heterologous expression in Xenopus oocytes revealed 2.2-fold increased current amplitude of WAG-HCN1 compared to rat HCN1. While WAG-HCN1 channels did not have altered current kinetics or changed regulation by protein kinases, fluorescence imaging revealed a faster and more pronounced surface expression of WAG-HCN1. Using co-expression experiments, we found that WAG-HCN1 channels suppress heteromeric HCN2 and HCN4 currents. Moreover, heteromeric channels of WAG HCN1 with HCN2 have a reduced cAMP sensitivity. Functional studies revealed that the gain-of-function of WAG-HCN1 is not caused by the N-terminal deletion alone, thus requiring a change of the N-terminal GNSVCF motif. Our findings may help to explain previous observations in neurons of the WAG/Rij strain and indicate that WAG HCN1 may contribute to the genesis of absence seizures in WAG/Rij rats.

  4. An N-terminal deletion variant of HCN1 in the epileptic WAG/Rij strain modulates HCN current densities.

    Science.gov (United States)

    Wemhöner, Konstantin; Kanyshkova, Tatyana; Silbernagel, Nicole; Fernandez-Orth, Juncal; Bittner, Stefan; Kiper, Aytug K; Rinné, Susanne; Netter, Michael F; Meuth, Sven G; Budde, Thomas; Decher, Niels

    2015-01-01

    Rats of the Wistar Albino Glaxo/Rij (WAG/Rij) strain show symptoms resembling human absence epilepsy. Thalamocortical neurons of WAG/Rij rats are characterized by an increased HCN1 expression, a negative shift in I h activation curve, and an altered responsiveness of I h to cAMP. We cloned HCN1 channels from rat thalamic cDNA libraries of the WAG/Rij strain and found an N-terminal deletion of 37 amino acids. In addition, WAG-HCN1 has a stretch of six amino acids, directly following the deletion, where the wild-type sequence (GNSVCF) is changed to a polyserine motif. These alterations were found solely in thalamus mRNA but not in genomic DNA. The truncated WAG-HCN1 was detected late postnatal in WAG/Rij rats and was not passed on to rats obtained from pairing WAG/Rij and non-epileptic August Copenhagen Irish rats. Heterologous expression in Xenopus oocytes revealed 2.2-fold increased current amplitude of WAG-HCN1 compared to rat HCN1. While WAG-HCN1 channels did not have altered current kinetics or changed regulation by protein kinases, fluorescence imaging revealed a faster and more pronounced surface expression of WAG-HCN1. Using co-expression experiments, we found that WAG-HCN1 channels suppress heteromeric HCN2 and HCN4 currents. Moreover, heteromeric channels of WAG-HCN1 with HCN2 have a reduced cAMP sensitivity. Functional studies revealed that the gain-of-function of WAG-HCN1 is not caused by the N-terminal deletion alone, thus requiring a change of the N-terminal GNSVCF motif. Our findings may help to explain previous observations in neurons of the WAG/Rij strain and indicate that WAG-HCN1 may contribute to the genesis of absence seizures in WAG/Rij rats.

  5. Minocycline inhibits hyperpolarization-activated currents in rat substantia gelatinosa neurons.

    Science.gov (United States)

    Liu, Nana; Zhang, Daying; Zhu, Mengye; Luo, Shiwen; Liu, Tao

    2015-08-01

    Minocycline is a widely used glial activation inhibitor that could suppress pain-related behaviors in a number of different pain animal models, yet, its analgesic mechanisms are not fully understood. Hyperpolarization-activated cation channel-induced Ih current plays an important role in neuronal excitability and pathological pain. In this study, we investigated the possible effect of minocycline on Ih of substantia gelatinosa neuron in superficial spinal dorsal horn by using whole-cell patch-clamp recording. We found that extracellular minocycline rapidly decreases Ih amplitude in a reversible and concentration-dependent manner (IC50 = 41 μM). By contrast, intracellular minocycline had no effect. Minocycline-induced inhibition of Ih was not affected by Na(+) channel blocker tetrodotoxin, glutamate-receptor antagonists (CNQX and D-APV), GABAA receptor antagonist (bicuculine methiodide), or glycine receptor antagonist (strychnine). Minocycline also caused a negative shift in the activation curve of Ih, but did not alter the reversal potential. Moreover, minocycline slowed down the inter-spike depolarizing slope and produced a robust decrease in the rate of action potential firing. Together, these results illustrate a novel cellular mechanism underlying minocycline's analgesic effect by inhibiting Ih currents of spinal dorsal horn neurons. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  6. Qualification of a Multi-Channel Infrared Laser Absorption Spectrometer for Monitoring CO, HCl, HCN, HF, and CO2 Aboard Manned Spacecraft

    Science.gov (United States)

    Briggs, Ryan M.; Frez, Clifford; Forouhar, Siamak; May, Randy D.; Meyer, Marit E.; Kulis, Michael J.; Berger, Gordon M.

    2015-01-01

    Monitoring of specific combustion products can provide early-warning detection of accidental fires aboard manned spacecraft and also identify the source and severity of combustion events. Furthermore, quantitative in situ measurements are important for gauging levels of exposure to hazardous gases, particularly on long-duration missions where analysis of returned samples becomes impractical. Absorption spectroscopy using tunable laser sources in the 2 to 5 micrometer wavelength range enables accurate, unambiguous detection of CO, HCl, HCN, HF, and CO2, which are produced in varying amounts through the heating of electrical components and packaging materials commonly used aboard spacecraft. Here, we report on calibration and testing of a five-channel laser absorption spectrometer designed to accurately monitor ambient gas-phase concentrations of these five compounds, with low-level detection limits based on the Spacecraft Maximum Allowable Concentrations. The instrument employs a two-pass absorption cell with a total optical pathlength of 50 cm and a dedicated infrared semiconductor laser source for each target gas. We present results from testing the five-channel sensor in the presence of trace concentrations of the target compounds that were introduced using both gas sources and oxidative pyrolysis (non-flaming combustion) of solid material mixtures.

  7. Hyperpolarization-activated current, Ih, in inspiratory brainstem neurons and its inhibition by hypoxia.

    Science.gov (United States)

    Mironov, S L; Langohr, K; Richter, D W

    2000-02-01

    A hyperpolarization-activated current, Ih, is often implied in pacemaker-like depolarizations during rhythmic oscillatory activity. We describe Ih in the isolated respiratory centre of immature mice (P6-P11). Ih was recorded in 15% (22/146) of all inspiratory neurons examined. The mean half-maximal Ih activation occurred at -78 mV and the reversal potential was -40 mV. Ih was inhibited by Cs+ (1-5 mM) and by organic blockers N-ethyl-1,6-dihydro-1, 2-dimethyl-6-(methylimino)-N-phenyl-4-pyrimidinamine (ZD 7288; 0.3-3 microM) and N,N'-bis-(3,4-dimethylphenylethyl)-N-methylamine (YS 035, 3-30 microM), but not by Ba2+ (0.5 mM). The organic Ih blockers did not change the inspiratory bursts recorded from the XIIth nerve and synaptic drives in inspiratory neurons. Hypoxia reversibly inhibited Ih but, in the presence of organic blockers, the hypoxic reaction remained unchanged. We conclude that although Ih channels are functional in a minority of inspiratory neurons, Ih does not contribute to respiratory rhythm generation or its modulation by hypoxia.

  8. Fluoxetine ameliorates cognitive impairments induced by chronic cerebral hypoperfusion via down-regulation of HCN2 surface expression in the hippocampal CA1 area in rats.

    Science.gov (United States)

    Luo, Pan; Zhang, Xiaoxue; Lu, Yun; Chen, Cheng; Li, Changjun; Zhou, Mei; Lu, Qing; Xu, Xulin; Shen, Guanxin; Guo, Lianjun

    2016-01-01

    Chronic cerebral hypoperfusion (CCH) causes cognitive impairments and increases the risk of Alzheimer's disease (AD) and vascular dementia (VD) through several biologically plausible pathways, yet the underlying neurobiological mechanisms are still poorly understood. In this study, we investigated whether fluoxetine, a selective serotonin reuptake inhibitor (SSRI), could play a neuroprotective role against chronic cerebral hypoperfusion injury and to clarify underlying mechanisms of its efficacy. Rats were subjected to permanent bilateral occlusion of the common carotid arteries (two-vessel occlusion, 2VO). Two weeks later, rats were treated with 30 mg/kg fluoxetine (intragastric injection, i.g.) for 6 weeks. Cognitive function was evaluated by Morris water maze (MWM) and novel objects recognition (NOR) test. Long-term potentiation (LTP) was used to address the underlying synaptic mechanisms. Western blotting was used to quantify the protein levels. Our results showed that fluoxetine treatment significantly improved the cognitive impairments caused by 2VO, accompanied with a reversion of 2VO-induced inhibitory of LTP. Furthermore, 2VO caused an up-regulation of hyperpolarization-activated cyclic nucleotide-gated channel 2 (HCN2) surface expressions in the hippocampal CA1 area and fluoxetine also effectively recovered the disorder of HCN2 surface expressions, which may be a possible mechanism that fluoxetine treatment ameliorates cognitive impairments in rats with CCH. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. SwissProt search result: AK100739 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK100739 J023118D04 (Q9TV66) Potassium/sodium hyperpolarization-activated cyclic nu...cleotide-gated channel 4 (Hyperpolarization-activated cation channel 4) (HAC-4) HCN4_RABIT 7e-29 ...

  10. SwissProt search result: AK100808 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK100808 J023121M17 (Q9TV66) Potassium/sodium hyperpolarization-activated cyclic nu...cleotide-gated channel 4 (Hyperpolarization-activated cation channel 4) (HAC-4) HCN4_RABIT 4e-36 ...

  11. SwissProt search result: AK099993 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK099993 J013132D09 (O88705) Potassium/sodium hyperpolarization-activated cyclic nu...cleotide-gated channel 3 (Hyperpolarization-activated cation channel 3) (HAC-3) HCN3_MOUSE 8e-18 ...

  12. SwissProt search result: AK060339 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK060339 001-008-C12 (O88705) Potassium/sodium hyperpolarization-activated cyclic n...ucleotide-gated channel 3 (Hyperpolarization-activated cation channel 3) (HAC-3) HCN3_MOUSE 9e-11 ...

  13. SwissProt search result: AK100312 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK100312 J023078M02 (O88705) Potassium/sodium hyperpolarization-activated cyclic nu...cleotide-gated channel 3 (Hyperpolarization-activated cation channel 3) (HAC-3) HCN3_MOUSE 2e-13 ...

  14. SwissProt search result: AK243602 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK243602 J100084P18 (Q9TV66) Potassium/sodium hyperpolarization-activated cyclic nu...cleotide-gated channel 4 (Hyperpolarization-activated cation channel 4) (HAC-4) HCN4_RABIT 3e-20 ...

  15. SwissProt search result: AK100739 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK100739 J023118D04 (O88705) Potassium/sodium hyperpolarization-activated cyclic nu...cleotide-gated channel 3 (Hyperpolarization-activated cation channel 3) (HAC-3) HCN3_MOUSE 5e-23 ...

  16. SwissProt search result: AK242807 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK242807 J090060H17 (O88705) Potassium/sodium hyperpolarization-activated cyclic nu...cleotide-gated channel 3 (Hyperpolarization-activated cation channel 3) (HAC-3) HCN3_MOUSE 4e-26 ...

  17. SwissProt search result: AK105506 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK105506 001-127-D12 (O88705) Potassium/sodium hyperpolarization-activated cyclic n...ucleotide-gated channel 3 (Hyperpolarization-activated cation channel 3) (HAC-3) HCN3_MOUSE 2e-11 ...

  18. SwissProt search result: AK069229 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK069229 J023012H21 (Q9TV66) Potassium/sodium hyperpolarization-activated cyclic nu...cleotide-gated channel 4 (Hyperpolarization-activated cation channel 4) (HAC-4) HCN4_RABIT 9e-16 ...

  19. SwissProt search result: AK067626 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK067626 J013112I06 (Q9TV66) Potassium/sodium hyperpolarization-activated cyclic nu...cleotide-gated channel 4 (Hyperpolarization-activated cation channel 4) (HAC-4) HCN4_RABIT 4e-11 ...

  20. SwissProt search result: AK100808 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK100808 J023121M17 (O88705) Potassium/sodium hyperpolarization-activated cyclic nu...cleotide-gated channel 3 (Hyperpolarization-activated cation channel 3) (HAC-3) HCN3_MOUSE 7e-27 ...

  1. SwissProt search result: AK112041 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK112041 001-044-H11 (O88705) Potassium/sodium hyperpolarization-activated cyclic n...ucleotide-gated channel 3 (Hyperpolarization-activated cation channel 3) (HAC-3) HCN3_MOUSE 2e-13 ...

  2. SwissProt search result: AK120308 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK120308 J013054N15 (Q9TV66) Potassium/sodium hyperpolarization-activated cyclic nu...cleotide-gated channel 4 (Hyperpolarization-activated cation channel 4) (HAC-4) HCN4_RABIT 2e-20 ...

  3. SwissProt search result: AK100312 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK100312 J023078M02 (Q9TV66) Potassium/sodium hyperpolarization-activated cyclic nu...cleotide-gated channel 4 (Hyperpolarization-activated cation channel 4) (HAC-4) HCN4_RABIT 6e-14 ...

  4. SwissProt search result: AK242807 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK242807 J090060H17 (Q9TV66) Potassium/sodium hyperpolarization-activated cyclic nu...cleotide-gated channel 4 (Hyperpolarization-activated cation channel 4) (HAC-4) HCN4_RABIT 3e-28 ...

  5. SwissProt search result: AK243602 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK243602 J100084P18 (O88705) Potassium/sodium hyperpolarization-activated cyclic nu...cleotide-gated channel 3 (Hyperpolarization-activated cation channel 3) (HAC-3) HCN3_MOUSE 3e-18 ...

  6. SwissProt search result: AK069229 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK069229 J023012H21 (O88705) Potassium/sodium hyperpolarization-activated cyclic nu...cleotide-gated channel 3 (Hyperpolarization-activated cation channel 3) (HAC-3) HCN3_MOUSE 4e-16 ...

  7. SwissProt search result: AK099993 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK099993 J013132D09 (Q9TV66) Potassium/sodium hyperpolarization-activated cyclic nu...cleotide-gated channel 4 (Hyperpolarization-activated cation channel 4) (HAC-4) HCN4_RABIT 5e-17 ...

  8. Rates and equilibrium constants of the ligand-induced conformational transition of an HCN ion channel protein domain determined by DEER spectroscopy.

    Science.gov (United States)

    Collauto, Alberto; DeBerg, Hannah A; Kaufmann, Royi; Zagotta, William N; Stoll, Stefan; Goldfarb, Daniella

    2017-06-14

    Ligand binding can induce significant conformational changes in proteins. The mechanism of this process couples equilibria associated with the ligand binding event and the conformational change. Here we show that by combining the application of W-band double electron-electron resonance (DEER) spectroscopy with microfluidic rapid freeze quench (μRFQ) it is possible to resolve these processes and obtain both equilibrium constants and reaction rates. We studied the conformational transition of the nitroxide labeled, isolated carboxy-terminal cyclic-nucleotide binding domain (CNBD) of the HCN2 ion channel upon binding of the ligand 3',5'-cyclic adenosine monophosphate (cAMP). Using model-based global analysis, the time-resolved data of the μRFQ DEER experiments directly provide fractional populations of the open and closed conformations as a function of time. We modeled the ligand-induced conformational change in the protein using a four-state model: apo/open (AO), apo/closed (AC), bound/open (BO), bound/closed (BC). These species interconvert according to AC + L ⇌ AO + L ⇌ BO ⇌ BC. By analyzing the concentration dependence of the relative contributions of the closed and open conformations at equilibrium, we estimated the equilibrium constants for the two conformational equilibria and the open-state ligand dissociation constant. Analysis of the time-resolved μRFQ DEER data gave estimates for the intrinsic rates of ligand binding and unbinding as well as the rates of the conformational change. This demonstrates that DEER can quantitatively resolve both the thermodynamics and the kinetics of ligand binding and the associated conformational change.

  9. Hyperpolarization-Activated Currents and Subthreshold Resonance in Granule Cells of the Olfactory Bulb

    NARCIS (Netherlands)

    Hu, Ruilong; Ferguson, Katie A; Whiteus, Christina B; Meijer, Dimphna H; Araneda, Ricardo C

    2016-01-01

    An important contribution to neural circuit oscillatory dynamics is the ongoing activation and inactivation of hyperpolarization-activated currents (Ih). Network synchrony dynamics play an important role in the initial processing of odor signals by the main olfactory bulb (MOB) and accessory

  10. Structure of the SthK carboxy-terminal region reveals a gating mechanism for cyclic nucleotide-modulated ion channels.

    Directory of Open Access Journals (Sweden)

    Divya Kesters

    Full Text Available Cyclic nucleotide-sensitive ion channels are molecular pores that open in response to cAMP or cGMP, which are universal second messengers. Binding of a cyclic nucleotide to the carboxyterminal cyclic nucleotide binding domain (CNBD of these channels is thought to cause a conformational change that promotes channel opening. The C-linker domain, which connects the channel pore to this CNBD, plays an important role in coupling ligand binding to channel opening. Current structural insight into this mechanism mainly derives from X-ray crystal structures of the C-linker/CNBD from hyperpolarization-activated cyclic nucleotide-modulated (HCN channels. However, these structures reveal little to no conformational changes upon comparison of the ligand-bound and unbound form. In this study, we take advantage of a recently identified prokaryote ion channel, SthK, which has functional properties that strongly resemble cyclic nucleotide-gated (CNG channels and is activated by cAMP, but not by cGMP. We determined X-ray crystal structures of the C-linker/CNBD of SthK in the presence of cAMP or cGMP. We observe that the structure in complex with cGMP, which is an antagonist, is similar to previously determined HCN channel structures. In contrast, the structure in complex with cAMP, which is an agonist, is in a more open conformation. We observe that the CNBD makes an outward swinging movement, which is accompanied by an opening of the C-linker. This conformation mirrors the open gate structures of the Kv1.2 channel or MthK channel, which suggests that the cAMP-bound C-linker/CNBD from SthK represents an activated conformation. These results provide a structural framework for better understanding cyclic nucleotide modulation of ion channels, including HCN and CNG channels.

  11. Dual Regulation of Voltage-Sensitive Ion Channels by PIP2

    Directory of Open Access Journals (Sweden)

    Aldo A Rodríguez Menchaca

    2012-09-01

    Full Text Available Over the past 16 years, there has been an impressive number of ion channels shown to be sensitive to the major phosphoinositide in the plasma membrane, phosphatidilinositol 4,5-bisphosphate (PIP2. Among them are voltage-gated channels, which are crucial for both neuronal and cardiac excitability. Voltage-gated calcium (Cav channels were shown to be regulated bidirectionally by PIP2. On one hand, PIP2 stabilized their activity by reducing current rundown but on the other hand it produced a voltage-dependent inhibition by shifting the activation curve to more positive voltages. For voltage-gated potassium (Kv channels PIP2 was first shown to prevent N-type inactivation. Careful examination of the effects of PIP2 on the activation mechanism of Kv1.2 has shown a similar bidirectional regulation as in the Cav channels. The two effects could be distinguished kinetically, in terms of their sensitivities to PIP2 and by distinct molecular determinants. The rightward shift of the Kv1.2 voltage dependence implicated basic residues in the S4-S5 linker and was consistent with stabilization of the inactive state of the voltage sensor. A third type of a voltage-gated ion channel modulated by PIP2 is the hyperpolarization-activated cyclic nucleotide-gated (HCN channel. PIP2 has been shown to enhance the opening of HCN channels by shifting their voltage-dependent activation toward depolarized potentials. The sea urchin HCN channel, SpIH, showed again a PIP2-mediated bidirectional effect but in reverse order than the depolarization-activated Cav and Kv channels: a voltage-dependent potentiation, like the mammalian HCN channels, but also an inhibition of the cGMP-induced current activation. Just like the Kv1.2 channels, distinct molecular determinants underlied the PIP2 dual effects on SpIH channels. The dual regulation of these very different ion channels, all of which are voltage dependent, points to conserved mechanisms of regulation of these channels by PIP2.

  12. Structural studies on HCN oligomers.

    Science.gov (United States)

    Ferris, J P; Edelson, E H; Auyeung, J M; Joshi, P C

    1981-01-01

    NMR spectral studies on the HCN oligomers suggest the presence of carboxamide and urea groupings. The release of CO2, H2O, HCN, CH3CN, HCONH2 and pyridine on pyrolysis is consistent with the presence of these groupings as well as carboxylic acid groups. No basic primary amine groupings could be detected with fluorescamine. Hydrazinolysis of the HCN oligomers releases 10% of the amino acids normally released by acid hydrolysis. The oligomers give a positive biuret test but this is not due to the presence of peptide bonds. There is no conclusive evidence for the presence of peptide bonds in the HCN oligomers. No diglycine was detected on partial hydrolysis of the HCN oligomers at pH 8.5 suggesting that HCN oligomers were not a source of prebiotic peptides.

  13. NCBI nr-aa BLAST: CBRC-PHAM-01-1625 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-PHAM-01-1625 emb|CAB42602.1| hyperpolarization-activated cation channel HCN2 [...Homo sapiens] emb|CAB42630.1| hyperpolarization-activated cyclic nucleotide-gated channel hHCN2 [Homo sapiens] CAB42602.1 8e-05 34% ...

  14. NCBI nr-aa BLAST: CBRC-RMAC-14-0006 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-RMAC-14-0006 emb|CAB42602.1| hyperpolarization-activated cation channel HCN2 [...Homo sapiens] emb|CAB42630.1| hyperpolarization-activated cyclic nucleotide-gated channel hHCN2 [Homo sapiens] CAB42602.1 6e-05 34% ...

  15. NCBI nr-aa BLAST: CBRC-HSAP-15-0018 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-HSAP-15-0018 emb|CAB42602.1| hyperpolarization-activated cation channel HCN2 [...Homo sapiens] emb|CAB42630.1| hyperpolarization-activated cyclic nucleotide-gated channel hHCN2 [Homo sapiens] CAB42602.1 0.0 94% ...

  16. NCBI nr-aa BLAST: CBRC-PTRO-16-0005 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-PTRO-16-0005 emb|CAB42602.1| hyperpolarization-activated cation channel HCN2 [...Homo sapiens] emb|CAB42630.1| hyperpolarization-activated cyclic nucleotide-gated channel hHCN2 [Homo sapiens] CAB42602.1 0.0 94% ...

  17. Signal processing by T-type calcium channel interactions in the cerebellum.

    Science.gov (United States)

    Engbers, Jordan D T; Anderson, Dustin; Zamponi, Gerald W; Turner, Ray W

    2013-11-27

    T-type calcium channels of the Cav3 family are unique among voltage-gated calcium channels due to their low activation voltage, rapid inactivation, and small single channel conductance. These special properties allow Cav3 calcium channels to regulate neuronal processing in the subthreshold voltage range. Here, we review two different subthreshold ion channel interactions involving Cav3 channels and explore the ability of these interactions to expand the functional roles of Cav3 channels. In cerebellar Purkinje cells, Cav3 and intermediate conductance calcium-activated potassium (IKCa) channels form a novel complex which creates a low voltage-activated, transient outward current capable of suppressing temporal summation of excitatory postsynaptic potentials (EPSPs). In large diameter neurons of the deep cerebellar nuclei, Cav3-mediated calcium current (I T) and hyperpolarization-activated cation current (I H) are activated during trains of inhibitory postsynaptic potentials. These currents have distinct, and yet synergistic, roles in the subthreshold domain with I T generating a rebound burst and I H controlling first spike latency and rebound spike precision. However, by shortening the membrane time constant the membrane returns towards resting value at a faster rate, allowing I H to increase the efficacy of I T and increase the range of burst frequencies that can be generated. The net effect of Cav3 channels thus depends on the channels with which they are paired. When expressed in a complex with a KCa channel, Cav3 channels reduce excitability when processing excitatory inputs. If functionally coupled with an HCN channel, the depolarizing effect of Cav3 channels is accentuated, allowing for efficient inversion of inhibitory inputs to generate a rebound burst output. Therefore, signal processing relies not only on the activity of individual subtypes of channels but also on complex interactions between ion channels whether based on a physical complex or by indirect

  18. Signal processing by T-type calcium channel interactions in the cerebellum

    Directory of Open Access Journals (Sweden)

    Jordan D.T. Engbers

    2013-11-01

    Full Text Available T-type calcium channels of the Cav3 family are unique among voltage-gated calcium channels due to their low activation voltage, rapid inactivation, and small single channel conductance. These special properties allow Cav3 calcium channels to regulate neuronal processing in the subthreshold voltage range. Here, we review two different subthreshold ion channel interactions involving Cav3 channels and explore the ability of these interactions to expand the functional roles of Cav3 channels. In cerebellar Purkinje cells, Cav3 and intermediate conductance calcium-activated potassium (IKCa channels form a novel complex which creates a low voltage-activated, transient outward current capable of suppressing temporal summation of excitatory postsynaptic potentials (EPSPs. In large diameter neurons of the deep cerebellar nuclei, Cav3-mediated calcium current (IT and hyperpolarization-activated cation current (IH are activated during trains of IPSPs. These currents have distinct, and yet synergistic, roles in the subthreshold domain with IT generating a rebound burst and IH controlling first spike latency and rebound spike precision. However, by shortening the membrane time constant the membrane returns towards resting value at a faster rate, allowing IH to increase the efficacy of IT, and increase the range of burst frequencies that can be generated. The net effect of Cav3 channels thus depends on the channels with which they are paired. When expressed in a complex with a KCa channel, Cav3 channels reduce excitability when processing excitatory inputs. If functionally coupled with an HCN channel, the depolarizing effect of Cav3 channels is accentuated, allowing for efficient inversion of inhibitory inputs to generate a rebound burst output. Therefore, signal processing relies not only on the activity of individual subtypes of channels but also on complex interactions between ion channels whether based on a physical complex or by indirect effects on

  19. NCBI nr-aa BLAST: CBRC-XTRO-01-2190 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-XTRO-01-2190 ref|NP_005468.1| hyperpolarization activated cyclic nucleotide-ga...ted potassium channel 4 [Homo sapiens] sp|Q9Y3Q4|HCN4_HUMAN Potassium/sodium hyperpolarization-activated cyc...lic nucleotide-gated channel 4 emb|CAB42604.1| hyperpolarization-activated cyclic nucleotide gated cation ch...annel hHCN4 [Homo sapiens] gb|EAW77925.1| hyperpolarization activated cyclic nucleotide-gated potassium channel 4 [Homo sapiens] NP_005468.1 5e-71 75% ...

  20. NCBI nr-aa BLAST: CBRC-PTRO-16-0005 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-PTRO-16-0005 ref|NP_032252.1| hyperpolarization-activated, cyclic nucleotide-g...ated K+ 2 [Mus musculus] sp|O88703|HCN2_MOUSE Potassium/sodium hyperpolarization-activated cyclic nucleotide...-gated channel 2 (Brain cyclic nucleotide-gated channel 2) (BCNG-2) (Hyperpolarization-activated cation chan...nel 1) (HAC-1) emb|CAA12406.1| hyperpolarization-activated cation channel, HAC1 [...Mus musculus] gb|EDL31671.1| hyperpolarization-activated, cyclic nucleotide-gated K+ 2 [Mus musculus] NP_032252.1 0.0 93% ...

  1. NCBI nr-aa BLAST: CBRC-HSAP-15-0018 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-HSAP-15-0018 ref|NP_032252.1| hyperpolarization-activated, cyclic nucleotide-g...ated K+ 2 [Mus musculus] sp|O88703|HCN2_MOUSE Potassium/sodium hyperpolarization-activated cyclic nucleotide...-gated channel 2 (Brain cyclic nucleotide-gated channel 2) (BCNG-2) (Hyperpolarization-activated cation chan...nel 1) (HAC-1) emb|CAA12406.1| hyperpolarization-activated cation channel, HAC1 [...Mus musculus] gb|EDL31671.1| hyperpolarization-activated, cyclic nucleotide-gated K+ 2 [Mus musculus] NP_032252.1 0.0 94% ...

  2. NCBI nr-aa BLAST: CBRC-XTRO-01-2190 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-XTRO-01-2190 ref|NP_001076176.1| hyperpolarization activated cation channel [O...ryctolagus cuniculus] sp|Q9TV66|HCN4_RABIT Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4 (Hyperpolar...ization-activated cation channel 4) (HAC-4) dbj|BAA77511.2| hyperpolarization activated cation channel [Oryctolagus cuniculus] NP_001076176.1 3e-70 75% ...

  3. SwissProt search result: AK105506 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK105506 001-127-D12 (Q9TV66) Potassium/sodium hyperpolarization-activated cyclic n...ucleotide-gated channel 4 (Hyperpolarization-activated cation channel 4) (HAC-4) HCN4_RABIT 8e-12 ...

  4. SwissProt search result: AK060339 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK060339 001-008-C12 (Q9TV66) Potassium/sodium hyperpolarization-activated cyclic n...ucleotide-gated channel 4 (Hyperpolarization-activated cation channel 4) (HAC-4) HCN4_RABIT 4e-11 ...

  5. SwissProt search result: AK112041 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK112041 001-044-H11 (Q9TV66) Potassium/sodium hyperpolarization-activated cyclic n...ucleotide-gated channel 4 (Hyperpolarization-activated cation channel 4) (HAC-4) HCN4_RABIT 4e-14 ...

  6. Activity-dependent Regulation of h Channel Distribution in Hippocampal CA1 Pyramidal Neurons

    National Research Council Canada - National Science Library

    Minyoung Shin; Dane M. Chetkovich

    2007-01-01

    ...) channel subunits, HCN1 and HCN2. Pyramidal neuron h channels within hippocampal area CA1 are remarkably enriched in distal apical dendrites, and this unique distribution pattern is critical for regulating dendritic excitability...

  7. Health Code Number (HCN) Development Procedure

    Energy Technology Data Exchange (ETDEWEB)

    Petrocchi, Rocky; Craig, Douglas K.; Bond, Jayne-Anne; Trott, Donna M.; Yu, Xiao-Ying

    2013-09-01

    This report provides the detailed description of health code numbers (HCNs) and the procedure of how each HCN is assigned. It contains many guidelines and rationales of HCNs. HCNs are used in the chemical mixture methodology (CMM), a method recommended by the department of energy (DOE) for assessing health effects as a result of exposures to airborne aerosols in an emergency. The procedure is a useful tool for proficient HCN code developers. Intense training and quality assurance with qualified HCN developers are required before an individual comprehends the procedure to develop HCNs for DOE.

  8. CO and HCN observations of carbon stars

    NARCIS (Netherlands)

    Baas, F; deJong, T; Loup, C

    We present CO and HCN observations of carbon stars. They consist of partly new detections in the (CO)-C-12 J = (1-0), (2-1) and HCN(1-0) lines obtained with the SEST and the IRAM telescope, and of (CO)-C-12 and (CO)-C-13 J = (1-0), (2-1) and (3-2) observations with IRAM and the JCMT of some of the

  9. NCBI nr-aa BLAST: CBRC-TGUT-12-0017 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-TGUT-12-0017 ref|NP_067690.1| hyperpolarization-activated, cyclic nucleotide-g...ated K+ 4 [Rattus norvegicus] sp|Q9JKA7|HCN4_RAT Potassium/sodium hyperpolarization-activated cyclic nucleot...ide-gated channel 4 gb|AAF62176.1|AF247453_1 hyperpolarization-activated, cyclic nucleotide-gated potassium ...channel 4 [Rattus norvegicus] gb|EDL95687.1| hyperpolarization-activated, cyclic nucleotide-gated K+ 4 [Rattus norvegicus] NP_067690.1 0.002 26% ...

  10. Single Ih channels in pyramidal neuron dendrites: properties, distribution, and impact on action potential output

    NARCIS (Netherlands)

    Kole, Maarten H. P.; Hallermann, Stefan; Stuart, Greg J.

    2006-01-01

    The hyperpolarization-activated cation current (Ih) plays an important role in regulating neuronal excitability, yet its native single-channel properties in the brain are essentially unknown. Here we use variance-mean analysis to study the properties of single Ih channels in the apical dendrites of

  11. On the HCN – HNC Energy Difference

    Energy Technology Data Exchange (ETDEWEB)

    Nguyen, Thanh L.; Baraban, Joshua H.; Ruscic, Branko; Stanton, John F.

    2015-11-05

    The value for the HCN → HNC 0 K isomerization energy has been investigated by combining state-of-the-art electronic structure methods with the Active Thermochemical Tables (ATcT) approach. The directly computed energy difference between HCN and HNC at the HEAT-456QP level of theory is 5236 ± 50 cm–1. This is substantially lower (by ~470 cm–1 or ~1.3 kcal/mol) than the recently proposed high-level multireference configuration interaction value of 5705 ± 20 cm–1 of Barber et al. (Mon. Not. R. Astron. Soc.2014, 437, 1828–1835). The discrepancy was analyzed by the ATcT approach, using several distinct steps, which (a) independently corroborated the current single-reference HEAT-456QP result, (b) independently found that the recent multireference-based value is highly unlikely to be correct within its originally stated uncertainty, and (c) produced a recommended value of 5212 ± 30 cm–1 for the HCN → HNC isomerization energy at 0 K, based on all currently available knowledge. The ATcT standard enthalpies of formation at 0 and 298 K for HCN, HNC, and their cations and anions are also presented.

  12. HNC, HCN and CN in seyfert galaxies

    NARCIS (Netherlands)

    Perez-Beaupuits, J. P.; Aalto, S.; Gerebro, H.

    2007-01-01

    Aims. Bright HNC 1-0 emission, rivalling that of HCN 1-0, has been found towards several Seyfert galaxies. This is unexpected since traditionally HNC is a tracer of cold (10 K) gas, and the molecular gas of luminous galaxies like Seyferts is thought to have bulk kinetic temperatures surpassing 50 K.

  13. Collision-induced dissociation of HS-(HCN): unsymmetrical hydrogen bonding in a proton-bound dimer anion.

    Science.gov (United States)

    Akin, F Ahu; Ervin, Kent M

    2006-02-02

    The energy-resolved competitive collision-induced dissociation of the proton-bound complex [HS.H.CN](-) is studied in a guided ion beam tandem mass spectrometer. H(2)S and HCN have nearly identical gas-phase acidities, and therefore, the HS(-) + HCN and the CN(-) + H(2)S product channels exhibit nearly the same threshold energies, as expected. However, the HS(-) + HCN channel has a cross section up to a factor of 50 larger than CN(-) + H(2)S at higher energies. The cross sections are modeled using RRKM theory and phase space theory. The complex dissociates to HS(-)+ HCN via a loose transition state, and it dissociates to CN(-) + H(2)S via a tight transition state. Theoretical calculations show that the proton-transfer potential energy surface has a single minimum and that the hydrogen bonding in the complex is strongly unsymmetrical, with an ion-molecule complex of the form HS(-)..HCN rather than CN(-)..H(2)S or an intermediate structure. The requirement for proton transfer before dissociation and curvature along the reaction path impedes the CN(-) + H(2)S product channel.

  14. A Submillimeter HCN Laser in IRC +10216.

    Science.gov (United States)

    Schilke; Mehringer; Menten

    2000-01-01

    We report the detection of a strong submillimeter-wavelength HCN laser line at a frequency near 805 GHz toward the carbon star IRC +10216. This line, the J=9-8 rotational transition within the (0400) vibrationally excited state, is one of a series of HCN laser lines that were first detected in the laboratory in the early days of laser spectroscopy. Since its lower energy level is 4200 K above the ground state, the laser emission must arise from the innermost part of IRC +10216's circumstellar envelope. To better characterize this environment, we observed other, thermally emitting, vibrationally excited HCN lines and found that they, like the laser line, arise in a region of temperature approximately 1000 K that is located within the dust formation radius; this conclusion is supported by the line width of the laser. The (0400), J=9-8 laser might be chemically pumped and may be the only known laser (or maser) that is excited both in the laboratory and in space by a similar mechanism.

  15. THE NITROGEN ISOTOPIC COMPOSITION OF METEORITIC HCN

    Energy Technology Data Exchange (ETDEWEB)

    Pizzarello, Sandra, E-mail: pizzar@asu.edu [Department of Chemistry and Biochemistry, Arizona State University, Tempe, AZ 85018-1604 (United States)

    2014-12-01

    HCN is ubiquitous in extraterrestrial environments and is central to current theories on the origin of early solar system organic compounds such as amino acids. These compounds, observed in carbonaceous meteorites, were likely important in the origin and/or evolution of early life. As part of our attempts to understand the origin(s) of meteoritic CN{sup –}, we have analyzed the {sup 15}N/{sup 14}N isotopic composition of HCN gas released from water extracts of the Murchison meteorite and found its value to be near those of the terrestrial atmosphere. The findings, when evaluated viz-a-viz molecular abundances and isotopic data of meteoritic organic compounds, suggest that HCN formation could have occurred during the protracted water alteration processes known to have affected the mineralogy of many asteroidal bodies during their solar residence. This was an active synthetic stage, which likely involved simple gasses, organic molecules, their presolar precursors, as well as mineral catalysts and would have lead to the formation of molecules of differing isotopic composition, including some with solar values.

  16. Pacemaker current inhibition in experimental human cardiac sympathetic activation: a double-blind, randomized, crossover study

    NARCIS (Netherlands)

    Schroeder, C.; Heusser, K.; Zoerner, A.A.; Grosshennig, A.; Wenzel, D.; May, M.; Sweep, F.C.; Mehling, H.; Luft, F.C.; Tank, J.; Jordan, J.

    2014-01-01

    Hyperpolarization-activated, cyclic nucleotide-gated 4 (HCN4) channels comprise the final pathway for autonomic heart rate (HR) regulation. We hypothesized that HCN4 inhibition could reverse autonomic imbalance in a human model of cardiac sympathetic activation. Nineteen healthy men ingested oral

  17. Structural studies on HCN oligomers. [catalysts for prebiotic processes

    Science.gov (United States)

    Ferris, J. P.; Edelson, E. H.; Auyeung, J. M.; Joshi, P. C.

    1981-01-01

    NMR spectral studies on the HCN oligomers suggest the presence of carboxamide and urea groupings. The release of CO2, H2O, HCN, CH3CN, HCONH2 and pyridine on pyrolysis is consistent with the presence of these groupings as well as carboxylic acid groups. No basic primary amine groupings could be detected with fluorescamine. Hydrazinolysis of the HCN oligomers releases 10% of the amino acids normally released by acid hydrolysis. The oligomers give a positive biuret test but this is not due to the presence of peptide bonds. There is no conclusive evidence for the presence of peptide bonds in the HCN oligomers. No diglycine was detected on partial hydrolysis of the HCN oligomers at pH 8.5 suggesting that HCN oligomers were not a source of prebiotic peptides.

  18. Catalytic and Gas-Solid Reactions Involving HCN over Limestone

    DEFF Research Database (Denmark)

    Jensen, Anker; Johnsson, Jan Erik; Dam-Johansen, Kim

    1997-01-01

    In coal-fired combustion systems solid calcium species may be present as ash components or limestone added to the combustion chamber. In this study heterogeneous reactions involving HCN over seven different limestones were investigated in a laboratory fixed-bed quartz reactor at 873-1,173 K....... Calcined limestone is an effective catalyst for oxidation of HCN. Under conditions with complete conversion of HCN at O-2 concentrations above about 5,000 ppmv the selectivity for formation of NO and N2O is 50-70% and below 5%, respectively. Nitric oxide can be reduced by HCN to N-2 in the absence of O-2...

  19. Genetically engineered cardiac pacemaker: Stem cells transfected with HCN2 gene and myocytes-A model

    Energy Technology Data Exchange (ETDEWEB)

    Kanani, S. [Institut Genomique Fonctionelle, 141 Rue de la Cardonille, 34396 Montpellier (France); Institut Non Lineaire de Nice, CNRS and Universite de Nice, 1361 route des Lucioles, 06560 Valbonne (France); Pumir, A. [Institut Non Lineaire de Nice, CNRS and Universite de Nice, 1361 route des Lucioles, 06560 Valbonne (France); Laboratoire J.A. Dieudonne, CNRS and Universite de Nice, Parc Valrose, 06108 Nice (France)], E-mail: alain.pumir@unice.fr; Krinsky, V. [Institut Non Lineaire de Nice, CNRS and Universite de Nice, 1361 route des Lucioles, 06560 Valbonne (France)

    2008-01-07

    One of the successfully tested methods to design genetically engineered cardiac pacemaker cells consists in transfecting a human mesenchymal stem cell (hMSC) with a HCN2 gene and connecting it to a myocyte. We develop and study a mathematical model, describing a myocyte connected to a hMSC transfected with a HCN2 gene. The cardiac action potential is described both with the simple Beeler-Reuter model, as well as with the elaborate dynamic Luo-Rudy model. The HCN2 channel is described by fitting electrophysiological records, in the spirit of Hodgkin-Huxley. The model shows that oscillations can occur in a pair myocyte-stem cell, that was not observed in the experiments yet. The model predicted that: (1) HCN pacemaker channels can induce oscillations only if the number of expressed I{sub K1} channels is low enough. At too high an expression level of I{sub K1} channels, oscillations cannot be induced, no matter how many pacemaker channels are expressed. (2) At low expression levels of I{sub K1} channels, a large domain of values in the parameter space (n, N) exists, where oscillations should be observed. We denote N the number of expressed pacemaker channels in the stem cell, and n the number of gap junction channels coupling the stem cell and the myocyte. (3) The expression levels of I{sub K1} channels observed in ventricular myocytes, both in the Beeler-Reuter and in the dynamic Luo-Rudy models are too high to allow to observe oscillations. With expression levels below {approx}1/4 of the original value, oscillations can be observed. The main consequence of this work is that in order to obtain oscillations in an experiment with a myocyte-stem cell pair, increasing the values of n, N is unlikely to be helpful, unless the expression level of I{sub K1} has been reduced enough. The model also allows us to explore levels of gene expression not yet achieved in experiments, and could be useful to plan new experiments, aimed at improving the robustness of the oscillations.

  20. A new Nav1.7 sodium channel mutation I234T in a child with severe pain.

    NARCIS (Netherlands)

    Ahn, H.S.; Dib-Hajj, S.D.; Cox, J.J.; Tyrrell, L.; Elmslie, F.V.; Clarke, A.A.; Drenth, J.P.H.; Woods, C.G.; Waxman, S.G.

    2010-01-01

    Dominant gain-of-function mutations that hyperpolarize activation of the Na(v)1.7 sodium channel have been linked to inherited erythromelalgia (IEM), a disorder characterized by severe pain and redness in the feet and hands in response to mild warmth. Pharmacotherapy remains largely ineffective for

  1. Simple Organics and Biomonomers Identified in HCN Polymers: An Overview

    Directory of Open Access Journals (Sweden)

    Susana Osuna-Esteban

    2013-07-01

    Full Text Available Hydrogen cyanide (HCN is a ubiquitous molecule in the Universe. It is a compound that is easily produced in significant yields in prebiotic simulation experiments using a reducing atmosphere. HCN can spontaneously polymerise under a wide set of experimental conditions. It has even been proposed that HCN polymers could be present in objects such as asteroids, moons, planets and, in particular, comets. Moreover, it has been suggested that these polymers could play an important role in the origin of life. In this review, the simple organics and biomonomers that have been detected in HCN polymers, the analytical techniques and procedures that have been used to detect and characterise these molecules and an exhaustive classification of the experimental/environmental conditions that favour the formation of HCN polymers are summarised. Nucleobases, amino acids, carboxylic acids, cofactor derivatives and other compounds have been identified in HCN polymers. The great molecular diversity found in HCN polymers encourages their placement at the central core of a plausible protobiological system.

  2. Optical properties of poly-HCN and their astronomical applications.

    Science.gov (United States)

    Khare, B N; Sagan, C; Thompson, W R; Arakawa, E T; Meisse, C; Tuminello, P S

    1994-01-01

    Matthews (1992) has proposed that HCN "polymer" is ubiquitous in the solar system. We apply vacuum deposition and spectroscopic techniques previously used on synthetic organic heteropolymers (tholins), kerogens, and meteoritic organic residues to the measurement of the optical constants of poly-HCN in the wavelength range 0.05-40 micrometers. These measurements allow quantitative comparison with spectrophotometry of organic-rich bodies in the outer solar system. In a specific test of Matthews' hypothesis, poly-HCN fails to match the optical constants of the haze of the Saturnian moon, Titan, in the visible and near-infrared derived from astronomical observations and standard models of the Titan atmosphere. In contrast, a tholin produced from a simulated Titan atmosphere matches within the probable errors. Poly-HCN is much more N-rich than Titan tholin.

  3. Vibrationally Hot HCN in the Laboratory and IRC+10216

    Science.gov (United States)

    Pearson, John C.; Yu, Shanshan; Gupta, Harshal; Drouin, Brian J.

    2011-06-01

    HCN has historically been used as a tracer of the dense gas in the in interstellar medium. The envelopes of carbon rich asymptotic giant branch stars are generally rich in HCN; however, the large and generally variable infrared flux emitted by the star enormously complicates the interpretation. HCN in IRC+10216 shows an enormous number of masers and lasers pumped by the central star and often enhanced by line overlaps with other abundant molecules such as acetylene in the infrared. A total of seven laser transitions including two previously unreported transitions associated with the 040-011 interacting bands have been observed. To understand the astronomical observations a study of the radio frequency discharge plasma of CH_4 and N_2 was performed. Rotational transitions of HCN in vibrational states up to 15,000 Cm-1 have been observed including inverted levels and a number of previously undetected states. The spectra from IRC+10216 and the laboratory are presented.

  4. Testosterone enhances cardiomyogenesis in stem cells and recruits the androgen receptor to the MEF2C and HCN4 genes.

    Science.gov (United States)

    Al Madhoun, Ashraf Said; Voronova, Anastassia; Ryan, Tammy; Zakariyah, Abeer; McIntire, Christian; Gibson, Laura; Shelton, Michael; Ruel, Marc; Skerjanc, Ilona S

    2013-07-01

    Since a previous study (Goldman-Johnson et al., 2008 [4]) has shown that androgens can stimulate increased differentiation of mouse embryonic stem (mES) cells into cardiomyocytes using a genomic pathway, the aim of our study is to elucidate the molecular mechanisms regulating testosterone-enhanced cardiomyogenesis. Testosterone upregulated cardiomyogenic transcription factors, including GATA4, MEF2C, and Nkx2.5, muscle structural proteins, and the pacemaker ion channel HCN4 in a dose-dependent manner, in mES cells and P19 embryonal carcinoma cells. Knock-down of the androgen receptor (AR) or treatment with anti-androgenic compounds inhibited cardiomyogenesis, supporting the requirement of the genomic pathway. Chromatin immunoprecipitation (ChIP) studies showed that testosterone enhanced recruitment of AR to the regulatory regions of MEF2C and HCN4 genes, which was associated with increased histone acetylation. In summary, testosterone upregulated cardiomyogenic transcription factor and HCN4 expression in stem cells. Further, testosterone induced cardiomyogenesis, at least in part, by recruiting the AR receptor to the regulatory regions of the MEF2C and HCN4 genes. These results provide a detailed molecular analysis of the function of testosterone in stem cells and may offer molecular insight into the role of steroids in the heart. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. MLS/Aura Level 2 Hydrogen Cyanide (HCN) Mixing Ratio V003 (ML2HCN) at GES DISC

    Data.gov (United States)

    National Aeronautics and Space Administration — ML2HCN is the EOS Aura Microwave Limb Sounder (MLS) standard product for hydrogen cyanide derived from radiances measured primarily by the 190 GHz radiometer. The...

  6. MLS/Aura Level 2 Hydrogen Cyanide (HCN) Mixing Ratio V004 (ML2HCN) at GES DISC

    Data.gov (United States)

    National Aeronautics and Space Administration — ML2HCN is the EOS Aura Microwave Limb Sounder (MLS) standard product for hydrogen cyanide derived from radiances measured primarily by the 190 GHz radiometer. The...

  7. The Photodissociation of HCN and HNC: Effects on the HNC/HCN Abundance Ratio in the Interstellar Medium

    Energy Technology Data Exchange (ETDEWEB)

    Aguado, Alfredo [Departamento de Química Física Aplicada (UAM), Unidad Asociada a IFF-CSIC, Facultad de Ciencias Módulo 14, Universidad Autónoma de Madrid, E-28049, Madrid (Spain); Roncero, Octavio; Zanchet, Alexandre [Instituto de Física Fundamental (IFF-CSIC), C.S.I.C., Serrano 123, E-28006 Madrid (Spain); Agúndez, Marcelino; Cernicharo, José, E-mail: octavio.roncero@csic.es [Instituto de Ciencia de Materiales de Madrid, CSIC, C/ Sor Juana Inés de la Cruz 3, Cantoblanco E-28049 (Spain)

    2017-03-20

    The impact of the photodissociation of HCN and HNC isomers is analyzed in different astrophysical environments. For this purpose, the individual photodissociation cross sections of HCN and HNC isomers have been calculated in the 7–13.6 eV photon energy range for a temperature of 10 K. These calculations are based on the ab initio calculation of three-dimensional adiabatic potential energy surfaces of the 21 lower electronic states. The cross sections are then obtained using a quantum wave packet calculation of the rotational transitions needed to simulate a rotational temperature of 10 K. The cross section calculated for HCN shows significant differences with respect to the experimental one, and this is attributed to the need to consider non-adiabatic transitions. Ratios between the photodissociation rates of HCN and HNC under different ultraviolet radiation fields have been computed by renormalizing the rates to the experimental value. It is found that HNC is photodissociated faster than HCN by a factor of 2.2 for the local interstellar radiation field and 9.2 for the solar radiation field, at 1 au. We conclude that to properly describe the HNC/HCN abundance ratio in astronomical environments illuminated by an intense ultraviolet radiation field, it is necessary to use different photodissociation rates for each of the two isomers, which are obtained by integrating the product of the photodissociation cross sections and ultraviolet radiation field over the relevant wavelength range.

  8. The Photodissociation of HCN and HNC: Effects on the HNC/HCN Abundance Ratio in the Interstellar Medium.

    Science.gov (United States)

    Aguado, Alfredo; Roncero, Octavio; Zanchet, Alexandre; Agúndez, Marcelino; Cernicharo, José

    2017-03-20

    The impact of the photodissociation of HCN and HNC isomers is analyzed in different astrophysical environments. For this purpose, the individual photodissociation cross section of HCN and HNC isomers have been calculated in the 7-13.6 eV photon energy range for a temperature of 10 K. These calculations are based on the ab initio calculation of three-dimensional adiabatic potential energy surfaces of the 21 lower electronic states. The cross sections are then obtained using a quantum wave packet calculation of the rotational transitions needed to simulate a rotational temperature of 10 K. The cross section calculated for HCN shows significant differences with respect to the experimental one, and this is attributed to the need of considering non-adiabatic transitions. Ratios between the photodissociation rates of HCN and HNC under different ultraviolet radiation fields have been computed by renormalizing the rates to the experimental one. It is found that HNC is photodissociated faster than HCN by a factor of 2.2, for the local interstellar radiation field, and 9.2, for the solar radiation field at 1 au. We conclude that to properly describe the HNC/HCN abundance ratio in astronomical environments illuminated by an intense ultraviolet radiation field it is necessary to use different photodissociation rates for each of the two isomers, obtained by integrating the product of the photodissociation cross sections and ultraviolet radiation field over the relevant wavelength range.

  9. ALMA Observations of HCN and Its Isotopologues on Titan

    Science.gov (United States)

    Molter, Edward M.; Nixon, C. A.; Cordiner, M. A.; Serigano, J.; Irwin, P. G. J.; Teanby, N. A.; Charnley, S. B.; Lindberg, J. E.

    2016-08-01

    We present sub-millimeter spectra of HCN isotopologues on Titan, derived from publicly available ALMA flux calibration observations of Titan taken in early 2014. We report the detection of a new HCN isotopologue on Titan, H13C15N, and confirm an earlier report of detection of DCN. We model high signal-to-noise observations of HCN, H13CN, HC15N, DCN, and H13C15N to derive abundances and infer the following isotopic ratios: 12C/13C = 89.8 ± 2.8, 14N/15N = 72.3 ± 2.2, D/H = (2.5 ± 0.2) × 10-4, and HCN/H13C15N = 5800 ± 270 (1σ errors). The carbon and nitrogen ratios are consistent with and improve on the precision of previous results, confirming a factor of ˜2.3 elevation in 14N/15N in HCN compared to N2 and a lack of fractionation in 12C/13C from the protosolar value. This is the first published measurement of D/H in a nitrile species on Titan, and we find evidence for a factor of ˜2 deuterium enrichment in hydrogen cyanide compared to methane. The isotopic ratios we derive may be used as constraints for future models to better understand the fractionation processes occurring in Titan’s atmosphere.

  10. Differential distribution of voltage-gated channels in myelinated and unmyelinated baroreceptor afferents.

    Science.gov (United States)

    Schild, John H; Kunze, Diana L

    2012-12-24

    Voltage gated ion channels (VGC) make possible the frequency coding of arterial pressure and the neurotransmission of this information along myelinated and unmyelinated fiber pathways. Although many of the same VGC isoforms are expressed in both fiber types, it is the relative expression of each that defines the unique discharge properties of myelinated A-type and unmyelinated C-type baroreceptors. For example, the fast inward Na⁺ current is a major determinant of the action potential threshold and the regenerative transmembrane current needed to sustain repetitive discharge. In A-type baroreceptors the TTX-sensitive Na(v)1.7 VGC contributes to the whole cell Na⁺ current. Na(v)1.7 is expressed at a lower density in C-type neurons and in conjunction with TTX-insensitive Na(v)1.8 and Na(v)1.9 VGC. As a result, action potentials of A-type neurons have firing thresholds that are 15-20 mV more negative and upstroke velocities that are 5-10 times faster than unmyelinated C-type neurons. A more depolarized threshold in conjunction with a broader complement of non-inactivating K(V) VGC subtypes produces C-type action potentials that are 3-4 times longer in duration than A-type neurons and at markedly lower levels of cell excitability. Unmyelinated baroreceptors also express KCa1.1 which provides approximately 25% of the total outward K⁺ current. KCa1.1 plays a critically important role in shaping the action potential profile of C-type neurons and strongly impacts neuronal excitability. A-type neurons do not functionally express the KCa1.1 channel despite having a whole cell Ca(V) current quite similar to that of C-type neurons. As a result, A-type neurons do not have the frequency-dependent braking forces of KCa1.1. Lack of a KCa current and only a limited complement of non-inactivating K(V) VGC in addition to a hyperpolarization activated HCN1 current that is nearly 10 times larger than in C-type neurons leads to elevated levels of discharge in A-type neurons, a

  11. Tonic 5nM DA stabilizes neuronal output by enabling bidirectional activity-dependent regulation of the hyperpolarization activated current via PKA and calcineurin.

    Directory of Open Access Journals (Sweden)

    Wulf-Dieter C Krenz

    Full Text Available Volume transmission results in phasic and tonic modulatory signals. The actions of tonic dopamine (DA at type 1 DA receptors (D1Rs are largely undefined. Here we show that tonic 5nM DA acts at D1Rs to stabilize neuronal output over minutes by enabling activity-dependent regulation of the hyperpolarization activated current (I h. In the presence but not absence of 5nM DA, I h maximal conductance (G max was adjusted according to changes in slow wave activity in order to maintain spike timing. Our study on the lateral pyloric neuron (LP, which undergoes rhythmic oscillations in membrane potential with depolarized plateaus, demonstrated that incremental, bi-directional changes in plateau duration produced corresponding alterations in LP I hG max when preparations were superfused with saline containing 5nM DA. However, when preparations were superfused with saline alone there was no linear correlation between LP I hGmax and duty cycle. Thus, tonic nM DA modulated the capacity for activity to modulate LP I h G max; this exemplifies metamodulation (modulation of modulation. Pretreatment with the Ca2+-chelator, BAPTA, or the specific PKA inhibitor, PKI, prevented all changes in LP I h in 5nM DA. Calcineurin inhibitors blocked activity-dependent changes enabled by DA and revealed a PKA-mediated, activity-independent enhancement of LP I hG max. These data suggested that tonic 5nM DA produced two simultaneous, PKA-dependent effects: a direct increase in LP I h G max and a priming event that permitted calcineurin regulation of LP I h. The latter produced graded reductions in LP I hG max with increasing duty cycles. We also demonstrated that this metamodulation preserved the timing of LP's first spike when network output was perturbed with bath-applied 4AP. In sum, 5nM DA permits slow wave activity to provide feedback that maintains spike timing, suggesting that one function of low-level, tonic modulation is to stabilize specific features of a dynamic output.

  12. HCN and HCO+ images of the Orion Bar photodissociation region

    NARCIS (Netherlands)

    Owl, RCY; Meixner, MM; Wolfire, M; Tielens, AGGM; Tauber, J

    2000-01-01

    The Orion Bar is an ideal astrophysical laboratory for studying photodissociation regions because of its nearly edge-on orientation in the observer's line of sight. High angular resolution (similar to 9") maps of the Orion Bar in the J = 1-0 emission lines of HCO+ and HCN have been made by combining

  13. Photochemistry on Pluto: part II HCN and nitrogen isotope fractionation

    Science.gov (United States)

    Mandt, Kathleen; Luspay-Kuti, Adrienn; Hamel, Mark; Jessup, Kandis-Lea; Hue, Vincent; Kammer, Josh; Filwett, Rachael

    2017-11-01

    We have converted our Titan one-dimensional photochemical model to simulate the photochemistry of Pluto's atmosphere and include condensation and aerosol trapping in the model. We find that condensation and aerosol trapping are important processes in producing the HCN altitude profile observed by the Atacama Large Millimeter Array (ALMA). The nitrogen isotope chemistry in Pluto's atmosphere does not appear to significantly fractionate the isotope ratio between N2 and HCN as occurs at Titan. However, our simulations only cover a brief period of time in a Pluto year, and thus only a brief portion of the solar forcing conditions that Pluto's atmosphere experiences. More work is needed to evaluate photochemical fractionation over a Pluto year. Condensation and aerosol trapping appear to have a major impact on the altitude profile of the isotope ratio in HCN. Since ALMA did not detect HC15N in Pluto's atmosphere, we conclude that condensation and aerosol trapping must be much more efficient for HC15N compared to HC14N. The large uncertainty in photochemical fractionation makes it difficult to use any potential current measurement of 14N/15N in N2 to determine the origin of Pluto's nitrogen. More work is needed to understand photochemical fractionation and to evaluate how condensation, sublimation and aerosol trapping will fractionate N2 and HCN.

  14. Is Photolytic Production a Viable Source of HCN and HNC in Astrophysical Environments? A Laboratory-based Feasibility Study of Methyl Cyanoformate

    Science.gov (United States)

    Wilhelm, Michael J.; Martínez-Núñez, Emilio; González-Vázquez, Jesús; Vázquez, Saulo A.; Smith, Jonathan M.; Dai, Hai-Lung

    2017-11-01

    Motivated by the possibility that cyano-containing hydrocarbons may act as photolytic sources for HCN and HNC in astrophysical environments, we conducted a combined experimental and theoretical investigation of the 193 nm photolysis of the cyano-ester, methyl cyanoformate (MCF). Experimentally, nanosecond time-resolved infrared emission spectroscopy was used to detect the emission from nascent products generated in the photolysis reaction. The time-resolved spectra were analyzed using a recently developed spectral reconstruction analysis, which revealed spectral bands assignable to HCN and HNC. Fitting of the emission band shape and intensity allowed determination of the photolysis quantum yields of HCN, HNC, and {CN}({A}2{{{\\Pi }}}1) and an HNC/HCN ratio of ∼0.076 ± 0.059. Additionally, multiconfiguration self-consistent field calculations were used to characterize photoexcitation-induced reactions in the ground and four lowest singlet excited states of MCF. At 193 nm excitation, dissociation is predicted to occur predominantly on the repulsive S 2 state, with minor pathways via internal conversion from S 2 to highly excited ground state. An automated transition-state search algorithm was employed to identify the corresponding ground-state dissociation channels, and Rice–Ramsperger–Kassel–Marcus and Kinetic Monte Carlo simulations were used to calculate the associated branching ratios. The proposed mechanisms were validated using the experimentally measured and quasi-classical trajectory-deduced nascent internal energy distributions of HCN and HNC. This work, along with previous studies, illustrates the propensity for cyano-containing hydrocarbons to act as photolytic sources for astrophysical HCN and HNC and may help explain the observed overabundance of HNC in astrophysical environments.

  15. Disease: H00729 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available und heterozygous mutation in the SCN5A gene, and autosomal dominant type (SSS2) can be caused by heterozygou...it of hyperpolarization-activated cation channel. Cardiovascular disease (SSS1) SCN5A [HSA:6331] [KO:K04838]...s mutation in the HCN4. SCN5A encodes an alpha-subunit of the cardiac sodium chan

  16. Response of Si- and Al-doped graphenes toward HCN: A computational study

    Energy Technology Data Exchange (ETDEWEB)

    Rastegar, Somayeh F.; Peyghan, Ali Ahmadi [Department of Chemistry, Tarbiat Modares University, P.O. Box 14115-175, Tehran (Iran, Islamic Republic of); Hadipour, Nasser L., E-mail: hadipour_n@yahoo.com [Department of Chemistry, Tarbiat Modares University, P.O. Box 14115-175, Tehran (Iran, Islamic Republic of)

    2013-01-15

    Highlights: Black-Right-Pointing-Pointer Sensitivity of Si- and Al-doped graphene (SiG and AlG) toward HCN is investigated. Black-Right-Pointing-Pointer The electronic properties of AlG are significantly changed in the presence of HCN. Black-Right-Pointing-Pointer It is established that AlG can be a good sensor for HCN molecule. - Abstract: Sensitivity of Si- and Al-doped graphenes (SiG and AlG) toward toxic HCN has been investigated using density functional theory (DFT) in terms of energetic, geometric and electronic properties. Optimized configurations corresponding to physisorption and, subsequently, chemisorption of HCN on each surface have been identified. It is found that HCN molecule can be adsorbed on impurity atoms with adsorption energies about -27.20 and -38.75 kcal/mol on the SiG and the AlG, respectively. By comparing to HCN adsorption on SiG, it can be inferred that molecular HCN adsorbed on AlG can induce significant change in AlG conductivity. On the basis of calculated changes in the HOMO/LUMO energy gap it is found that electronic properties of AlG are sensitive toward adsorption of HCN and the reverse is correct for SiG, suggesting that the AlG may be a promising sensor for HCN.

  17. Mutationer i hjertets pacemakerkanaler--ny arsag til syg sinus-syndrom og langt QT-syndrom

    DEFF Research Database (Denmark)

    Vitved, T.; Lianee, H.T.; Stovring, B.

    2008-01-01

    The sinus node hyperpolarization-activated If current generated by the cardiac pacemaker channels HCN2 and HCN4 determines the autonomous beating of the heart. Cardiac arrhythmias, like long-QT syndrome, are often caused by irregularities of the heart action potential generated by mutations...... in cardiac ion channel genes. Mutations in the HCN4 gene have been associated with sick sinus syndrome and long-QT syndrome. The identification of cardiac arrhythmia disease-associated genes makes possible new therapeutic strategies based on gene-specific drug treatment and gene therapy Udgivelsesdato: 2008/3/10...

  18. Quantifying the emissions of HCN from on-road vehicles in urban areas

    Science.gov (United States)

    Moussa, S. G.; Leithead, A.; Wentzell, J. J.; Lu, G.; Li, S.; Brook, J.; Liggio, J.

    2013-12-01

    Hydrogen Cyanide (HCN), has been considered a marker for biomass burning emissions. Despite its adverse health impacts, estimate of its global sources and sinks are highly uncertain due to a limited number of field and laboratory studies. In particular, HCN emissions from automobile exhaust are not well constrained for modern vehicles, and thought to be relatively small compared to emissions from biomass burning. In the current study, HCN emissions from individual diesel and gasoline vehicles were quantified as a function of engine driving mode, and fuel type. Proton transfer Reaction-Time of Flight-Mass spectrometry (PTR-ToF-MS) was used to measure HCN emissions from diesel engines operating on ultra-low sulfur diesel (ULSD) and various bio-diesel blends including Soy, Tallow, and Canola. Significant emissions of HCN were observed from all vehicles, and enhanced with the use of biodiesel. In addition, ambient measurements of HCN in a traffic dominated urban area in Toronto, Canada demonstrated that a correlation between HCN, and traditional vehicle emissions markers such as benzene and xylenes exists and indicating that HCN has the potential to be a marker of fuel combustion. The ambient data and the calculated emission factors further suggest that vehicular emissions are a major source of HCN even in the presence of biomass burning, and that near roadway conditions may represent the dominant exposure pathway to HCN in urban areas. Results of this study have important implications on HCN global budget, health impacts in urban areas and the effect of alternate fuels on the emissions of this toxic species.

  19. An Ab Initio MP2 Study of HCN-HX Hydrogen Bonded Complexes

    Directory of Open Access Journals (Sweden)

    Araújo Regiane C.M.U.

    1998-01-01

    Full Text Available An ab initio MP2/6-311++G** study has been performed to obtain geometries, binding energies and vibrational properties of HCN-HX H-bonded complexes with X = F, Cl, NC, CN and CCH. These MP2/6-311++G** results have revealed that: (i the calculated H-bond lengths are in very good agreement with the experimental ones; (ii the H-bond strength is associated with the intermolecular charge transfer and follows the order: HCN-HNC ~ HCN-HF > HCN-HCl ~ HCN-HCN > HCN-HCCH; (iii BSSE correction introduces an average reduction of 2.4 kJ/mol on the MP2/6-311++G** binding energies, i.e. 11% of the uncorrected binding energy; (iv the calculated zero-point energies reduce the stability of these complexes and show a good agreement with the available experimental values; (v the H-X stretching frequency is shifted downward upon H-bond formation. This displacement is associated with the H-bond length; (vi The more pronounced effect on the infrared intensities occurs with the H-X stretching intensity. It is much enhanced after complexation due to the charge-flux term; (vii the calculated intermolecular stretching frequencies are in very good agreement with the experimental ones; and, finally, (viii the results obtained for the HCN-HX complexes follow the same profile as those found for the acetylene-HX series but, in the latter case, the effects on the properties of the free molecules due to complexation are less pronounced than those in HCN-HX.

  20. MLS/Aura L2 Hydrogen Cyanide (HCN) Mixing Ratio V003

    Data.gov (United States)

    National Aeronautics and Space Administration — ML2HCN is the EOS Aura Microwave Limb Sounder (MLS) standard product for hydrogen cyanide derived from radiances measured primarily by the 190 GHz radiometer. The...

  1. MLS/Aura L2 Hydrogen Cyanide (HCN) Mixing Ratio V002

    Data.gov (United States)

    National Aeronautics and Space Administration — ML2HCN is the EOS Aura Microwave Limb Sounder (MLS) standard product for hydrogen cyanide derived from radiances measured primarily by the 190 GHz radiometer. The...

  2. A 1D coordination polymer of UF{sub 5} with HCN as a ligand

    Energy Technology Data Exchange (ETDEWEB)

    Scheibe, Benjamin; Rudel, Stefan S.; Buchner, Magnus R.; Kraus, Florian [Fachbereich Chemie, Philipps-Universitaet Marburg (Germany); Karttunen, Antti J. [Department of Chemistry, Aalto University (Finland)

    2017-01-05

    β-Uranium(V) fluoride was reacted with liquid anhydrous hydrogen cyanide to obtain a 1D coordination polymer with the composition {sup 1}{sub ∞}[UF{sub 5}(HCN){sub 2}], {sup 1}{sub ∞}[UF{sub 4/1}F{sub 2/2}-(HCN){sub 2/1}], revealed by single-crystal X-ray structure determination. The reaction system was furthermore studied by means of vibrational and NMR spectroscopy, as well as by quantum chemical calculations. The compound presents the first described polymeric HCN Lewis adduct and the first HCN adduct of a uranium fluoride. (copyright 2017 Wiley-VCH Verlag GmbH and Co. KGaA, Weinheim)

  3. MLS/Aura Level 2 Hydrogen Cyanide (HCN) Mixing Ratio V004

    Data.gov (United States)

    National Aeronautics and Space Administration — ML2HCN is the EOS Aura Microwave Limb Sounder (MLS) standard product for hydrogen cyanide derived from radiances measured primarily by the 190 GHz radiometer. The...

  4. Bima Array Detections of HCN in Comets Linear (C/2002 T7) and Neat (C/2001 Q4)

    Science.gov (United States)

    Friedel, D. N.; Remijan, A.; Snyder, L. E.; AHearn, M. F.; Blake, Geoffrey A.; dePater, Imke; Dickel, H. R.; Forster, J. R.; Hogerheijde, M. R.

    2004-01-01

    We present interferometric detections of HCN in comets LINEAR (C/2002 T7) and NEAT (C/2001 Q4) with the Berkeley-Illinois-Maryland Association (BIMA) Array in its D-configuration cross-correlation mode. We detected the HCN J = 1 - 0 emission line in both comets. With a 25".4 x 20".3 synthesized beam around Comet LINEAR, we found a total beam averaged HCN column density (assuming a rotation temperature of 146 K) of = 2.1(11)x 10(sup 13) cm(exp -2), and a HCN production rate of Q(HCN)=2.8(15)x 10(sup 27) s(exp -1). With a 21".3 x 17".5 synthesized beam around Comet NEAT, we found a total beam averaged HCN column density (assuming a rotation temperature of 107 K) of = 5.7(30) x 10(sup l2) cm(exp -2), and a HCN production rate of Q(HCN)=8.3(44) x 10(sup 26) s(exp -l) giving a production rate of HCN relative to H2O of approximately 0.09(5)%. The production rates relative to H2O and spatial extent of HCN are similar to previous comet observations.

  5. HCN observations of comets C/2013 R1 (Lovejoy) and C/2014 Q2 (Lovejoy)

    Science.gov (United States)

    Wirström, E. S.; Lerner, M. S.; Källström, P.; Levinsson, A.; Olivefors, A.; Tegehall, E.

    2016-04-01

    HCN J = 1-0 emission from the long-period comet C/2013 R1 (Lovejoy) was observed from the Onsala Space Observatory on multiple occasions during the month before its perihelion passage on December 22, 2013. We report detections for seven different dates, spanning heliocentric distances (Rh) decreasing from 0.94 to 0.82 au. Estimated HCN production rates are generally higher than previously reported for the same time period, but the implied increase in production rate with heliocentric distance, QHCN ∝ Rh-3.2, represent well the overall documented increase since it was first observed at Rh = 1.35. The implied mean HCN abundance relative to water in R1 Lovejoy is 0.2%. We also report on a detection of HCN with the new 3 mm receiver system at Onsala Space Observatory in comet C/2014 Q2 (Lovejoy) on January 14, 2015, when its heliocentric distance was 1.3 au. Relative to comet C/2013 R1 (Lovejoy), the HCN production rate of C/2014 Q2 (Lovejoy) was more than 5 times higher at similar heliocentric distances, and the implied HCN abundance relative to water 0.09%.

  6. Detection of Macromolecular Fractions in HCN Polymers Using Electrophoretic and Ultrafiltration Techniques.

    Science.gov (United States)

    Marín-Yaseli, Margarita R; Cid, Cristina; Yagüe, Ana I; Ruiz-Bermejo, Marta

    2017-02-01

    Elucidating the origin of life involves synthetic as well as analytical challenges. Herein, for the first time, we describe the use of gel electrophoresis and ultrafiltration to fractionate HCN polymers. Since the first prebiotic synthesis of adenine by Oró, HCN polymers have gained much interest in studies on the origins of life due to the identification of biomonomers and related compounds within them. Here, we demonstrate that macromolecular fractions with electrophoretic mobility can also be detected within HCN polymers. The migration of polymers under the influence of an electric field depends not only on their sizes (one-dimensional electrophoresis) but also their different isoelectric points (two-dimensional electrophoresis, 2-DE). The same behaviour was observed for several macromolecular fractions detected in HCN polymers. Macromolecular fractions with apparent molecular weights as high as 250 kDa were detected by tricine-SDS gel electrophoresis. Cationic macromolecular fractions with apparent molecular weights as high as 140 kDa were also detected by 2-DE. The HCN polymers synthesized were fractionated by ultrafiltration. As a result, the molecular weight distributions of the macromolecular fractions detected in the HCN polymers directly depended on the synthetic conditions used to produce these polymers. The implications of these results for prebiotic chemistry will be discussed. © 2017 Wiley-VHCA AG, Zurich, Switzerland.

  7. Axonal voltage-gated ion channels as pharmacological targets for pain

    DEFF Research Database (Denmark)

    Moldovan, Mihai; Alvarez, Susana; Romer Rosberg, Mette

    2013-01-01

    maladaptive leading to a persistent and debilitating pain state referred to as chronic pain corresponding to the clinical description of neuropathic/chronic inflammatory pain. There is little agreement to what causes peripheral chronic pain other than hyperactivity of the nociceptive DRG neurons which......-gated K(+) channels and blockers of hyperpolarization-activated cyclic nucleotide-gated channels that were found to reduce neuronal activity were also found to be effective in neuropathic and inflammatory pain states. The isoforms of these channels present on nociceptive axons have limited specificity....... The rationale for considering axonal voltage-gated ion channels as targets for pain treatment comes from the accumulating evidence that chronic pain states are associated with a dysregulation of these channels that could alter their specificity and make them more susceptible to pharmacological modulation...

  8. Organics Produced by Irradiation of Frozen and Liquid HCN Solutions: Implications for Chemical Evolution Studies

    Science.gov (United States)

    Colín-García, M.; Negrón-Mendoza, A.; Ramos-Bernal, S.

    2009-04-01

    Hydrogen cyanide (HCN), an important precursor of organic compounds, is widely present in extraterrestrial environments. HCN is also readily synthesized in prebiotic simulation experiments. To gain insight into the radiation chemistry of one of the most important and highly versatile constituents of cometary ices, we examined the behavior of over-irradiated frozen and liquid HCN solutions under ionizing radiation. The samples were exposed to gamma radiation at a dose range from 0 up to 419 kGy. Ultraviolet spectroscopy and gas chromatography were used to follow the process. The analyses confirmed that gamma-ray irradiation of liquid HCN solutions generates several organic products. Many of them are essential to life; we verified the presence of carboxylic acids (some of them members of the Krebs cycle) as well as free amino acids and urea. These are the first studies to reveal the presence of these compounds in experiments performed at low temperatures and bulk irradiation. Organic material was produced even at low temperatures and low radiation doses. This work strongly supports the presumption that, as a parent molecule, HCN played a central essential role in the process of chemical evolution on early Earth, comets, and other extraterrestrial environments.

  9. Experimental conditions affecting the kinetics of aqueous HCN polymerization as revealed by UV-vis spectroscopy.

    Science.gov (United States)

    Marín-Yaseli, Margarita R; Moreno, Miguel; de la Fuente, José L; Briones, Carlos; Ruiz-Bermejo, Marta

    2017-10-12

    HCN polymerization is one of the most important and fascinating reactions in prebiotic chemistry, and interest in HCN polymers in the field of materials science is growing. However, little is known about the kinetics of the HCN polymerization process. In the present study, a first approach to the kinetics of two sets of aqueous HCN polymerizations, from NH4CN and NaCN, at middle temperatures between 4 and 38°C, has been carried out. For each series, the presence of air and salts in the reaction medium has been systematically explored. A previous kinetic analysis was conducted during the conversion of the insoluble black HCN polymers obtained as gel fractions in these precipitation polymerizations for a reaction of one month, where a limit conversion was achieved at the highest polymerization temperature. The kinetic description of the gravimetric data for this complex system shows a clear change in the linear dependence with the polymerization temperature for the reaction from NH4CN, besides a relevant catalytic effect of ammonium, in comparison with those data obtained from the NaCN series. These results also demonstrated the notable influence of air, oxygen, and the saline medium in HCN polymer formation. Similar conclusions were reached when the sol fractions were monitored by UV-vis spectroscopy, and a Hill type correlation was used to describe the polymerization profiles obtained. This technique was chosen because it provides an easy, prompt and fast method to follow the evolution of the liquid or continuous phase of the process under study. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Experimental conditions affecting the kinetics of aqueous HCN polymerization as revealed by UV-vis spectroscopy

    Science.gov (United States)

    Marín-Yaseli, Margarita R.; Moreno, Miguel; de la Fuente, José L.; Briones, Carlos; Ruiz-Bermejo, Marta

    2018-02-01

    HCN polymerization is one of the most important and fascinating reactions in prebiotic chemistry, and interest in HCN polymers in the field of materials science is growing. However, little is known about the kinetics of the HCN polymerization process. In the present study, a first approach to the kinetics of two sets of aqueous HCN polymerizations, from NH4CN and NaCN, at middle temperatures between 4 and 38 °C, has been carried out. For each series, the presence of air and salts in the reaction medium has been systematically explored. A previous kinetic analysis was conducted during the conversion of the insoluble black HCN polymers obtained as gel fractions in these precipitation polymerizations for a reaction of one month, where a limit conversion was achieved at the highest polymerization temperature. The kinetic description of the gravimetric data for this complex system shows a clear change in the linear dependence with the polymerization temperature for the reaction from NH4CN, besides a relevant catalytic effect of ammonium, in comparison with those data obtained from the NaCN series. These results also demonstrated the notable influence of air, oxygen, and the saline medium in HCN polymer formation. Similar conclusions were reached when the sol fractions were monitored by UV-vis spectroscopy, and a Hill type correlation was used to describe the polymerization profiles obtained. This technique was chosen because it provides an easy, prompt and fast method to follow the evolution of the liquid or continuous phase of the process under study.

  11. HCN channels are a novel therapeutic target for cognitive dysfunction in Neurofibromatosis type 1.

    NARCIS (Netherlands)

    Omrani, A.; Van der Vaart, A.; Mientjes, E.; Woerden, G.M.; Hojjati, M.R.; Li, K.W.; Gutmann, D.H.; Levelt, C.N.; Smit, A.B.; Silva, A.J.; Kushner, S.A.; Elgersma, Y.

    2015-01-01

    Cognitive impairments are a major clinical feature of the common neurogenetic disease neurofibromatosis type 1 (NF1). Previous studies have demonstrated that increased neuronal inhibition underlies the learning deficits in NF1, however, the molecular mechanism underlying this cell-type specificity

  12. HCN channels are a novel therapeutic target for cognitive dysfunction in Neurofibromatosis type 1

    NARCIS (Netherlands)

    Omrani, A; van der Vaart, T; Mientjes, E; van Woerden, G M; Hojjati, M R; Li, K W; Gutmann, D H; Levelt, C N; Smit, A B; Silva, A J; Kushner, S A; Elgersma, Y

    2015-01-01

    Cognitive impairments are a major clinical feature of the common neurogenetic disease neurofibromatosis type 1 (NF1). Previous studies have demonstrated that increased neuronal inhibition underlies the learning deficits in NF1, however, the molecular mechanism underlying this cell-type specificity

  13. High Accuracy ab Initio Calculations of Rotational-Vibrational Levels of the HCN/HNC System.

    Science.gov (United States)

    Makhnev, Vladimir Yu; Kyuberis, Aleksandra A; Zobov, Nikolai F; Lodi, Lorenzo; Tennyson, Jonathan; Polyansky, Oleg L

    2018-02-08

    Highly accurate ab initio calculations of vibrational and rotational-vibrational energy levels of the HCN/HNC (hydrogen cyanide/hydrogen isocyanide) isomerising system are presented for several isotopologues. All-electron multireference configuration interaction (MRCI) electronic structure calculations were performed using basis sets up to aug-cc-pCV6Z on a grid of 1541 geometries. The ab initio energies were used to produce an analytical potential energy surface (PES) describing the two minima simultaneously. An adiabatic Born-Oppenheimer diagonal correction (BODC) correction surface as well as a relativistic correction surface were also calculated. These surfaces were used to compute vibrational and rotational-vibrational energy levels up to 25 000 cm -1 which reproduce the extensive set of experimentally known HCN/HNC levels with a root-mean-square deviation σ = 1.5 cm -1 . We studied the effect of nonadiabatic effects by introducing opportune radial and angular corrections to the nuclear kinetic energy operator. Empirical determination of two nonadiabatic parameters results in observed energies up to 7000 cm -1 for four HCN isotopologues (HCN, DCN, H 13 CN, and HC 15 N) being reproduced with σ = 0.37 cm -1 . The height of the isomerization barrier, the isomerization energy and the dissociation energy were computed using a number of models; our best results are 16 809.4, 5312.8, and 43 729 cm -1 , respectively.

  14. Photodissociation of HCN and HNC isomers in the 7-10 eV energy range

    Energy Technology Data Exchange (ETDEWEB)

    Chenel, Aurelie; Roncero, Octavio, E-mail: octavio.roncero@csic.es [Instituto de Física Fundamental (IFF-CSIC), C.S.I.C., Serrano 123, 28006 Madrid (Spain); Aguado, Alfredo [Departamento de Química Física Aplicada (UAM), Unidad Asociada a IFF-CSIC, Facultad de Ciencias Módulo 14, Universidad Autónoma de Madrid, 28049 Madrid (Spain); Agúndez, Marcelino; Cernicharo, José [Instituto de Ciencia de Materiales de Madrid, CSIC, C/ Sor Juana Inés de la Cruz 3, 28049 Cantoblanco (Spain)

    2016-04-14

    The ultraviolet photoabsorption spectra of the HCN and HNC isomers have been simulated in the 7-10 eV photon energy range. For this purpose, the three-dimensional adiabatic potential energy surfaces of the 7 lowest electronic states, and the corresponding transition dipole moments, have been calculated, at multireference configuration interaction level. The spectra are calculated with a quantum wave packet method on these adiabatic potential energy surfaces. The spectra for the 3 lower excited states, the dissociative electronic states, correspond essentially to predissociation peaks, most of them through tunneling on the same adiabatic state. The 3 higher electronic states are bound, hereafter electronic bound states, and their spectra consist of delta lines, in the adiabatic approximation. The radiative lifetime towards the ground electronic states of these bound states has been calculated, being longer than 10 ns in all cases, much longer that the characteristic predissociation lifetimes. The spectra of HCN is compared with the available experimental and previous theoretical simulations, while in the case of HNC there are no previous studies to our knowledge. The spectrum for HNC is considerably more intense than that of HCN in the 7-10 eV photon energy range, which points to a higher photodissociation rate for HNC, compared to HCN, in astrophysical environments illuminated by ultraviolet radiation.

  15. Real-time monitoring of hydrogen cyanide (HCN) and ammonia (NH3) emitted by Pseudomonas aeruginosa

    NARCIS (Netherlands)

    Neerincx, A.H.; Mandon, J.; Ingen, J. van; Arslanov, D.D.; Mouton, J.W.; Harren, F.J.; Merkus, P.J.F.M.; Cristescu, S.M.

    2015-01-01

    We present the real-time monitoring of hydrogen cyanide (HCN) production from Pseudomonas aeruginosa (P. aeruginosa) strains in vitro, using laser-based photoacoustic spectroscopy. Simultaneously, the production of ammonia (NH3) was measured, and the influence of different factors (e.g. the medium,

  16. Characterization by immunocytochemistry of ionic channels in Helix aspersa suboesophageal brain ganglia neurons.

    Science.gov (United States)

    Azanza, M J; Pérez-Castejón, C; Pes, N; Pérez-Bruzón, R N; Aisa, J; Junquera, C; Maestú, C; Lahoz, M; Martínez-Ciriano, C; Vera-Gil, A; Del Moral, A

    2008-04-01

    The aim of this work was to characterize several ionic channels in nervous cells of the suboesophageal visceral, left and right parietal, and left and right pleural brain ganglia complex of the snail Helix aspersa by immunocytochemistry. We have studied the immunostaining reaction for a wide panel of eleven polyclonal antibodies raised against mammal antigens as follows: voltage-gated-Na+ channel; voltage-gated-delayed-rectifier-K+ channel; SK2-small-conductance-Ca2+-dependent-K+ channel apamin sensitive; SK3 potassium channel; charybdotoxin-sensitive voltage-dependent potassium channel; BKCa-maxi-conductance-Ca2+-dependent-K+ channel; hyperpolarization-activated cyclic nucleotide-gated potassium channel 4; G-protein-activated inwardly rectifying potassium channel GIRK2 and voltage-gated-calcium of L, N and P/Q type channels. Our results show positive reaction in neurons, but neither in glia cells nor in processes in the Helix suboesophageal ganglia. Our results suggest the occurrence of molecules in Helix neurons sharing antigenic determinants with mammal ionic channels. The reaction density and distribution of immunoreactive staining within neurons is specific for each one of the antisera tested. The studies of co-localization of immunoreaction, on alternate serial sections of the anterior right parietal ganglion, have shown for several recognized mapped neurons that they can simultaneously be expressed among two and seven different ionic protein channels. These results are considered a key structural support for the interpretation of Helix aspersa neuron electrophysiological activity.

  17. The Role of Potassium Channels in the Temperature Control of Stomatal Aperture.

    Science.gov (United States)

    Ilan, N.; Moran, N.; Schwartz, A.

    1995-07-01

    We used the patch-clamp technique to examine the effect of temperature (13-36[deg]C) on the depolarization-activated K channels (KD channels) and on the hyperpolarization-activated channels (KH channels) in the plasma membrane of Vicia faba guard-cell protoplasts. The steady-state whole-cell conductance of both K channel types increased with temperature up to 20[deg]C. However, whereas the whole-cell conductance of the KH channels increased further and saturated at 28[deg]C, that of KD channels decreased at higher temperatures. The unitary conductance of both channel types increased with temperature like the rate of diffusion in water (temperature quotient of approximately 1.5), constituting the major contribution to the conductance increase in the whole cells. The mean number of available KH channels was not affected significantly by temperature, but the mean number of available KD channels increased significantly between 13 and 20[deg]C and declined drastically above 20[deg]C. This decrease and the reduced steady-state voltage-dependent probability of opening of the KD channels above 28[deg]C (because of a shift of voltage dependence by +21 mV) account for the depression of the whole-cell KD conductance at the higher temperatures. This may be a basic mechanism by which leaves of well-watered plants keep their stomata open during heat stress to promote cooling by transpiration.

  18. HCN production and hydroxynitrile lyase: a natural activity in plants and a renewed biotechnological interest.

    Science.gov (United States)

    Kassim, Muhammad Arshad; Rumbold, Karl

    2014-02-01

    Over 3,000 plant species are cyanogenic. Cyanogenesis is defined as the hydroxynitrile lyase catalysed release of a cyanide group in the form of HCN and the corresponding aldehyde or ketone. When a plant is attacked, HCN released is a self defence mechanism. A special characteristic of enzymatic reactions is that all enzymatic reactions are reversible-hydroxynitrile lyases can also be used for the synthesis of enantiomerically pure cyanohydrins which are of great importance in industry. This article presents a comprehensive review of the role of hydroxynitrile lyases, both in nature and industry, and an insightful. Areas covered include: history, discovery and natural sources of the hydroxynitrile lyase. Molecular cloning for mass production of this enzyme, including detailed information about several successful recombinant hydroxynitrile lyases is also included.

  19. Navigating the Chemical Space of HCN Polymerization and Hydrolysis: Guiding Graph Grammars by Mass Spectrometry Data

    Directory of Open Access Journals (Sweden)

    Peter F. Stadler

    2013-09-01

    Full Text Available Polymers of hydrogen cyanide and their hydrolysis products constitute a plausible, but still poorly understood proposal for early prebiotic chemistry on Earth. HCN polymers are generated by the interplay of more than a dozen distinctive reaction mechanisms and form a highly complex mixture. Here we use a computational model based on graph grammars as a means of exploring the chemical spaces of HCN polymerization and hydrolysis. A fundamental issue is to understand the combinatorial explosion inherent in large, complex chemical systems. We demonstrate that experimental data, here obtained by mass spectrometry, and computationally predicted free energies together can be used to guide the exploration of the chemical space and makes it feasible to investigate likely pathways and chemical motifs even in potentially open-ended chemical systems.

  20. 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.

  1. Photoacoustic Detection of New Bands of HCN between 11 390 and 13 020 cm(-1).

    Science.gov (United States)

    Lecoutre; Rohart; Huet; Maki

    2000-09-01

    A laser photoacoustic technique has been used to measure the absorption spectrum of HCN in the region from 11 390 to 13 020 cm(-1) with a resolution that is limited by the Doppler- and pressure-broadened linewidth. This is a very sensitive technique that has allowed us to measure very weak bands with a small volume of gas. These measurements provide the rovibrational constants for a number of newly observed vibrational energy levels. Copyright 2000 Academic Press.

  2. EXTENDED HCN AND HCO{sup +} EMISSION IN THE STARBURST GALAXY M82

    Energy Technology Data Exchange (ETDEWEB)

    Salas, P.; Galaz, G. [Instituto de Astrofísica, Facultad de Física, Pontificia Universidad Católica de Chile, Av. Vicua Mackenna 4860, 782-0436 Macul, Santiago (Chile); Salter, D.; Herrera-Camus, R.; Bolatto, A. D. [Department of Astronomy and Laboratory for Millimeter-Wave Astronomy, University of Maryland, College Park, MD 20742 (United States); Kepley, A. [National Radio Astronomy Observatory, 520 Edgemont Road, Charlottesville, VA 22903-2475 (United States)

    2014-12-20

    We mapped 3 mm continuum and line emission from the starburst galaxy M82 using the Combined Array for Research in Millimeter-wave Astronomy. We targeted the HCN, HCO{sup +}, HNC, CS, and HC{sub 3}N lines, but here we focus on the HCN and HCO{sup +} emission. The map covers a field of 1.'2 with an ≈5'' resolution. The HCN and HCO{sup +} observations are short spacings corrected. The molecular gas in M82 had been previously found to be distributed in a molecular disk, coincident with the central starburst, and a galactic scale outflow which originates in the central starburst. With the new short spacings-corrected maps we derive some of the properties of the dense molecular gas in the base of the outflow. From the HCN and HCO{sup +} J = (1-0) line emission, and under the assumptions of the gas being optically thin and in local thermodynamic equilibrium, we place lower limits on the amount of dense molecular gas in the base of the outflow. The lower limits are 7 × 10{sup 6} M {sub ☉} and 21 × 10{sup 6} M {sub ☉}, or ≳ 2% of the total molecular mass in the outflow. The kinematics and spatial distribution of the dense gas outside the central starburst suggests that it is being expelled through chimneys. Assuming a constant outflow velocity, the derived outflow rate of dense molecular gas is ≥0.3 M {sub ☉} yr{sup –1}, which would lower the starburst lifetime by ≥5%. The energy required to expel this mass of dense gas is (1-10) × 10{sup 52} erg.

  3. Descriptor‐Based Analysis Applied to HCN Synthesis from NH3 and CH4

    DEFF Research Database (Denmark)

    Grabow, Lars C.; Studt, Felix; Abild‐Pedersen, Frank

    2011-01-01

    A trendy volcano: By the example of HCN synthesis from NH3 and CH4, it is demonstrated how scaling relations for intermediates and transition states provide a basis for the prediction of trends in heterogeneous catalysis (see logarithmic turnover frequency, TOF). These trends include not only the...... the activity but also selectivity and the dominant reaction mechanism. This general approach can be applied to a large number of catalytic systems....

  4. United States Historical Climatology Network (US HCN) monthly temperature and precipitation data

    Energy Technology Data Exchange (ETDEWEB)

    Daniels, R.C. [ed.] [Univ. of Tennessee, Knoxville, TN (United States). Energy, Environment and Resources Center; Boden, T.A. [ed.] [Oak Ridge National Lab., TN (United States); Easterling, D.R.; Karl, T.R.; Mason, E.H.; Hughes, P.Y.; Bowman, D.P. [National Climatic Data Center, Asheville, NC (United States)

    1996-01-11

    This document describes a database containing monthly temperature and precipitation data for 1221 stations in the contiguous United States. This network of stations, known as the United States Historical Climatology Network (US HCN), and the resulting database were compiled by the National Climatic Data Center, Asheville, North Carolina. These data represent the best available data from the United States for analyzing long-term climate trends on a regional scale. The data for most stations extend through December 31, 1994, and a majority of the station records are serially complete for at least 80 years. Unlike many data sets that have been used in past climate studies, these data have been adjusted to remove biases introduced by station moves, instrument changes, time-of-observation differences, and urbanization effects. These monthly data are available free of charge as a numeric data package (NDP) from the Carbon Dioxide Information Analysis Center. The NDP includes this document and 27 machine-readable data files consisting of supporting data files, a descriptive file, and computer access codes. This document describes how the stations in the US HCN were selected and how the data were processed, defines limitations and restrictions of the data, describes the format and contents of the magnetic media, and provides reprints of literature that discuss the editing and adjustment techniques used in the US HCN.

  5. THE VARIABILITY OF HCN IN TITAN’S UPPER ATMOSPHERE AS IMPLIED BY THE CASSINI ION-NEUTRAL MASS SPECTROMETER MEASUREMENTS

    Energy Technology Data Exchange (ETDEWEB)

    Cui, J.; Cao, Y.-T. [National Astronomical Observatories, Chinese Academy of Sciences, Beijing 100012 (China); Lavvas, P. P. [Groupe de Spectroscopie Moleculaire et Atmospherique, Universite de Reims, Champagne-Ardenne, CNRS UMR F-7331 (France); Koskinen, T. T. [Lunar and Planetary Laboratory, University of Arizona, Tucson, AZ 85721 (United States)

    2016-07-20

    HCN is an important constituent in Titan’s upper atmosphere, serving as the main coolant in the local energy budget. In this study, we derive the HCN abundance at the altitude range of 960–1400 km, combining the Ion-Neutral Mass Spectrometer data acquired during a large number of Cassini flybys with Titan. Typically, the HCN abundance declines modestly with increasing altitude and flattens to a near constant level above 1200 km. The data reveal a tendency for dayside depletion of HCN, which is clearly visible below 1000 km but weakens with increasing altitude. Despite the absence of convincing anti-correlation between HCN volume mixing ratio and neutral temperature, we argue that the variability in HCN abundance makes an important contribution to the large temperature variability observed in Titan’s upper atmosphere.

  6. Effects of acidic pH on voltage-gated ion channels in rat trigeminal mesencephalic nucleus neurons.

    Science.gov (United States)

    Han, Jin-Eon; Cho, Jin-Hwa; Choi, In-Sun; Kim, Do-Yeon; Jang, Il-Sung

    2017-03-01

    The effects of acidic pH on several voltage-dependent ion channels, such as voltage-dependent K + and Ca 2+ channels, and hyperpolarization-gated and cyclic nucleotide-activated cation (HCN) channels, were examined using a whole-cell patch clamp technique on mechanically isolated rat mesencephalic trigeminal nucleus neurons. The application of a pH 6.5 solution had no effect on the peak amplitude of voltage-dependent K + currents. A pH 6.0 solution slightly, but significantly inhibited the peak amplitude of voltage-dependent K + currents. The pH 6.0 also shifted both the current-voltage and conductance-voltage relationships to the depolarization range. The application of a pH 6.5 solution scarcely affected the peak amplitude of membrane currents mediated by HCN channels, which were profoundly inhibited by the general HCN channel blocker Cs + (1 mM). However, the pH 6.0 solution slightly, but significantly inhibited the peak amplitude of HCN-mediated currents. Although the pH 6.0 solution showed complex modulation of the current-voltage and conductance-voltage relationships, the midpoint voltages for the activation of HCN channels were not changed by acidic pH. On the other hand, voltage-dependent Ca 2+ channels were significantly inhibited by an acidic pH. The application of an acidic pH solution significantly shifted the current-voltage and conductance-voltage relationships to the depolarization range. The modulation of several voltage-dependent ion channels by an acidic pH might affect the excitability of mesencephalic trigeminal nucleus neurons, and thus physiological functions mediated by the mesencephalic trigeminal nucleus could be affected in acidic pH conditions.

  7. Multifrequency electron spin resonance detection of solid-state organic free radicals in HCN polymer and a Titan tholin.

    Science.gov (United States)

    Budil, David E; Roebber, John L; Liebman, Shirley A; Matthews, Clifford N

    2003-01-01

    Macromolecules derived from hydrogen cyanide (HCN) may be major components of the dark matter observed in bodies in the outer Solar System, which include comets and asteroids. HCN oligomers and polymers are readily formed at room temperature and react with water to produce polypeptides and alpha-amino acids or undergo pyrolysis to produce nitrogen heterocycles. Electron spin resonance (ESR) spectroscopy shows that HCN polymer mixtures contain a significant amount of long-lived organic free radicals that are primarily carbon-based. For comparison, we have also examined samples of tholins produced from experimental analogs of Titan aerosols, which has been shown by trace organic analysis to consist partly of HCN polymer. The "Titan tholin" exhibits at least two ESR signals that can be assigned to nitrogen- and carbon-centered radicals, although heating the sample eliminates the nitrogen centers and increases the signal from the carbon centers. This result suggests that the nitrogen-centered radicals may be thermodynamically less stable, but are kinetically trapped during the spark-discharge reactions that produce tholins from mixtures of gases such as methane and nitrogen. The results strongly support previous proposals of free radical mechanisms for HCN polymerization.

  8. Seasonal and interannual variations in HCN amounts in the upper troposphere and lower stratosphere observed by MIPAS

    Science.gov (United States)

    Glatthor, N.; Höpfner, M.; Stiller, G. P.; von Clarmann, T.; Funke, B.; Lossow, S.; Eckert, E.; Grabowski, U.; Kellmann, S.; Linden, A.; Walker, K. A.; Wiegele, A.

    2015-01-01

    We present a HCN climatology of the years 2002-2012, derived from FTIR limb emission spectra measured with the Michelson Interferometer for Passive Atmospheric Sounding (MIPAS) on the ENVISAT satellite, with the main focus on biomass burning signatures in the upper troposphere and lower stratosphere. HCN is an almost unambiguous tracer of biomass burning with a tropospheric lifetime of 5-6 months and a stratospheric lifetime of about 2 years. The MIPAS climatology is in good agreement with the HCN distribution obtained by the spaceborne ACE-FTS experiment and with airborne in situ measurements performed during the INTEX-B campaign. The HCN amounts observed by MIPAS in the southern tropical and subtropical upper troposphere have an annual cycle peaking in October-November, i.e. 1-2 months after the maximum of southern hemispheric fire emissions. The probable reason for the time shift is the delayed onset of deep convection towards austral summer. Because of overlap of varying biomass burning emissions from South America and southern Africa with sporadically strong contributions from Indonesia, the size and strength of the southern hemispheric plume have considerable interannual variations, with monthly mean maxima at, for example, 14 km between 400 and more than 700 pptv. Within 1-2 months after appearance of the plume, a considerable portion of the enhanced HCN is transported southward to as far as Antarctic latitudes. The fundamental period of HCN variability in the northern upper troposphere is also an annual cycle with varying amplitude, which in the tropics peaks in May after and during the biomass burning seasons in northern tropical Africa and southern Asia, and in the subtropics peaks in July due to trapping of pollutants in the Asian monsoon anticyclone (AMA). However, caused by extensive biomass burning in Indonesia and by northward transport of part of the southern hemispheric plume, northern HCN maxima also occur around October/November in several years

  9. A widely tunable, near-infrared laser-based trace gas sensor for hydrogen cyanide (HCN) detection in exhaled breath

    Science.gov (United States)

    Azhar, M.; Mandon, J.; Neerincx, A. H.; Liu, Z.; Mink, J.; Merkus, P. J. F. M.; Cristescu, S. M.; Harren, F. J. M.

    2017-11-01

    A compact, cost-effective sensor is developed for detection of hydrogen cyanide (HCN) in exhaled breath within seconds. For this, an off-axis integrated cavity output spectroscopy setup is combined with a widely tunable compact near-infrared laser (tunability 1527-1564 nm). For HCN a detection sensitivity has been obtained of 8 ppbv in nitrogen (within 1 s), equal to a noise equivalent absorption sensitivity of 1.9 × 10-9 cm-1 Hz-1/2. With this sensor we demonstrated the presence of HCN in exhaled breath; its detection could be a good indicator for bacterial lung infection. Due to its compact, cost-effective and user-friendly design, this laser-based sensor has the potential to be implemented in future clinical applications.

  10. VizieR Online Data Catalog: CO and HCN observations of circumstellar envelopes (Loup+ 1993)

    Science.gov (United States)

    Loup, C.; Forveille, T.; Omont, A.; Paul, J. F.

    1997-06-01

    We have searched the literature for all observations of the 12CO(1-0), 12CO(2-1), and HCN(1-0) lines in circumstellar envelopes of late type stars published between January 1985 and September 1992. We report data for 1361 observations (stellar velocity, expansion velocity, peak intensity, integrated area, noise level). This CO-HCN sample now contains 444 sources. 184 are identified as oxygen-rich, 205 as carbon-rich, and there are 9 S stars. About 85% of the sources are AGB stars. There are 32 planetary nebulae and about thirty post-AGB stars candidates. Besides results of millimeter observations, we also list identifications, coordinates, IRAS data, chemical and spectral types for every source. For AGB stars, we have estimated (or compiled) bolometric fluxes and distances for 349 sources, and mass loss rates deduced from CO results for 324 sources, taking into account the influence of the CO photodissociation radius. We also list mass loss rates derived from detailed models of CO emission which we could find in the literature. (7 data files).

  11. The effects of the hydrogen addition on the HCN profiles in fuel-rich-premixed, burner-stabilized C1-C3 alkane flames

    NARCIS (Netherlands)

    Sepman, A. V.; Mokhov, A. V.; Levinsky, H. B.

    2011-01-01

    The effects of hydrogen addition on HCN formation and consumption in fuel-rich, burnerstabilized methane, ethane and propane flames are reported. The HCN mole fraction was measured using quartz-microprobe sampling followed by direct absorption spectroscopy. Experiments were performed at equivalence

  12. Ab initio treatment of the chemical reaction precursor complex Br(2P)-HCN. 1. Adiabatic and diabatic potential surfaces

    NARCIS (Netherlands)

    Fishchuk, A.V.; Merritt, J.M.; Avoird, A. van der

    2007-01-01

    The three adiabatic potential surfaces of the Br(P-2)-HCN complex that correlate to the P-2 ground state of the Br atom were calculated ab initio. With the aid of a geometry-dependent diabatic mixing angle, also calculated ab initio, these adiabatic potential surfaces were transformed into a set of

  13. Highly abundant HCN in the inner hot envelope of GL 2591 : probing the birth of a hot core?

    NARCIS (Netherlands)

    Boonman, A. M. S.; Stark, R.; Tak, F. F. S. van der; Dishoeck, E. F.; Schafer, F.; Lange, G de; Laauwen, W. M.; van der Wal, P.B.

    2004-01-01

    Published in: Astrophys. J. 553 (2001) L63-L68 citations recorded in [Science Citation Index] Abstract: We present observations of the v2=0 and vibrationally excited v2=1 J=9-8 rotational lines of HCN at 797 GHz toward the deeply embedded massive young stellar object GL 2591, which provide the

  14. Diode laser absorption measurement and analysis of HCN in atmospheric-pressure, fuel-rich premixed methane/air flames

    NARCIS (Netherlands)

    Gersen, Sander; Mokhov, A. V.; Levinsky, H. B.

    2008-01-01

    Measurements of HCN in flat, fuel-rich premixed methane/air flames at atmospheric pressure are reported. Quartz-microprobe sampling followed by wavelength modulation absorption spectroscopy with second harmonic detection was used to obtain an overall measurement uncertainty of better than 20% for

  15. cardiomyocyte-like cells after being co-cultured with cardiomyocytes

    Directory of Open Access Journals (Sweden)

    Jie FAN

    2014-01-01

    Full Text Available Objective To explore the gap junction function and pacing function transformed myocardial cells, rat bone marrow mesenchymal stem cells (BMSCs transfected by hyperpolarization activated cyclic nucleotide-gated cation channel 4 (HCN4 gene were co-cultured with neonatal rat cardiomyocytes (CM. Methods After being labelled with DAPI, neonatal rat CM were co-cultured with BMSCs, HCN4+ BMSCs or HCN4– BMSCs for 4 days, respectively. The spontaneous beating frequency of cells in each group was then detected, and the anatomical location of two types of cells was observed by fluorescence microscopy. Western blotting was used to detect the expression of connexin 43 (Cx43, and the intercellular gap junction was observed by transmission electron microscopy. Results The spontaneous beating rate of ventricular myocardium was significantly higher after being cultured. The anatomical location of BMSCs was found to be adjacent to CM under fluorescence microscope. Western blotting showed that Cx43 expression was significantly higher in HCN4+ MSC co-cultured with CM group than in HCN4– BMSCs cultured with CM group. Transmission electron microscopy revealed that HCN4+ BMSCs formed to be interlaced with adjacent CM. Conclusion The rat BMSCs transfected by HCN4 gene may establish an effective electro-mechanical connection with cardiomyocytes, the spontaneous pacing function is close to that of CM, and the result provides an experimental basis for promoting biological pacemaker therapy. DOI: 10.11855/j.issn.0577-7402.2013.12.02

  16. Observation of the Formation of 0-π Pulses in Rotation Spectra of HCN and HBr

    Science.gov (United States)

    Chesnokov, E. N.; Kubarev, V. V.; Koshlyakov, P. V.

    We present the first experimental study of the formation of 0-π pulses in the far infrared region. Experiments were made in rotation spectra of HCN and HBr molecules using a Novosibirsk terahertz free electron laser (NovoFEL) as a source of optical pulses and ultra-fast Schottky diode as detector. Transformation of the shape of 0-π pulses was explored within a wide range of optical density. Throughout the range of experimental conditions, the observed pulse shape is well described by the analytical formula of Grisp (Phys. Rev. A 1 (1970) 1604). The observed effect can be used for time-domain measurements of the oscillator strength of the absorption line.

  17. PENGARUH LAMA PERENDAMAN KORO BENGU (Mucuna pruriens DALAM AIR KAPUR (Ca(OH2 TERHADAP KADAR ASAM SIANIDA (HCN

    Directory of Open Access Journals (Sweden)

    Arif Nurmawan Toro

    2014-03-01

    Full Text Available Latar belakang: Masyarakat Indonesia masih menitikberatkan pada komoditas kacang kedelai sebagai sumber utama protein, sedangkan pemanfaatan komoditas lain seperti koro benguk masih sangat minim. Minimnya pemanfaatan koro benguk ini karena di dalamnya terkandung senyawa alami berupa glokusida sianogenik yang dapat mengalami hidrolisis enzimatis menjadi asam sianida (HCN yang bersifat racun. Karena asam sianida bersifat asam yang sangat mudah larut dalam air, maka dilakukan perendaman menggunakan air kapur (Ca(OH2 bersifat basa yang dirasa cukup efektif menetralkan HCN dalam koro benguk.   Tujuan Penelitian: Mengetahui pengaruh lama perendaman koro benguk dalam air kapur terhadap kadar asam sianida dan mengetahui apakah air kapur lebih efektif dibandingkan air biasa dalam menetralkan HCN koro benguk.   Metode Penelitian: Penelitian dengan desain post test with control group. Obyek penelitian ini adalah koro benguk varietas benguk putih berumur 4-6 bulan yang diperoleh di Dusun Nogosari, Desa Purwosari, Kecamatan Girimulyo, Kabupaten Kulon Progo, DIY yang dilakukan perendaman dalam air sebagai kelompok kontrol dan air kapur 100 mg/L sebagai kelompok perlakuan selama 12, 24 dan 36 jam kemudian dilakukan destilasi. Destilat direaksikan dengan asam pikrat 1% kemudia diukur kadar HCN secara spektrofotometri.   Hasil: Kadar HCN  koro benguk pada perendaman dalam air selama 12 jam adalah 20,736 mg/kg, selama 24 jam adalah 19,348 mg/kg dan selama 36 jam adalah 16,786 mg/kg. Sedangkan kadar HCN pada perendaman air kapur 100 mg/L selama 12 jam adalah 19,020 mg/kg, selama 24 jam adalah 1,635 mg/kg dan selama 36 jam adalah 9,307 mg/kg. Hasil Uji ANOVA satu jalan pada kelompok perlakuan didapatkan nilai signifikansi 0.000 (p< 0.05.   Kesimpulan: Ada pengaruh bermakna lama perendaman koro benguk dalam air kapur terhadap kadar asam sianida. Perendaman dalam air kapur terbukti lebih efektif menetralkan asam sianida koro benguk dibandingkan perendaman dalam

  18. ALMA IMAGING OF HCN, CS, AND DUST IN ARP 220 AND NGC 6240

    Energy Technology Data Exchange (ETDEWEB)

    Scoville, Nick; Manohar, Swarnima; Murchikova, Lena [California Institute of Technology, MC 249-17, 1200 East California Boulevard, Pasadena, CA 91125 (United States); Sheth, Kartik [North American ALMA Science Center, National Radio Astronomy Observatory, 520 Edgemont Road, Charlottesville, VA 22901 (United States); Walter, Fabian; Zschaechner, Laura [Max-Planck-Institut fur Astronomie, Konigstuhl 17, D-69117 Heidelberg (Germany); Yun, Min [Department of Astronomy, University of Massachusetts, Amherst, MA 01003 (United States); Koda, Jin [Department of Physics and Astronomy, Stony Brook University, Stony Brook, NY 11794 (United States); Sanders, David; Barnes, Joshua [Institute for Astronomy, 2680 Woodlawn Drive, University of Hawaii, Honolulu, Hawaii, HI 96822 (United States); Thompson, Todd [Department of Astronomy, The Ohio State University, 140 West 18th Avenue, Columbus, OH 43210 (United States); Robertson, Brant; Tacconi, Linda; Narayanan, Desika [Department of Astronomy and Steward Observatory, University of Arizona, Tucson AZ 85721 (United States); Genzel, Reinhard; Davies, Richard [Max-Planck-Institut fur extraterrestrische Physik (MPE), Giessenbachstrasse, D-85748 Garching (Germany); Hernquist, Lars [Harvard-Smithsonian Center for Astrophysics, 60 Garden Street, Cambridge, MA 02138 (United States); Brown, Robert [National Radio Astronomy Observatory, 520 Edgemont Road, Charlottesville, VA 22901 (United States); Hayward, Christopher C. [TAPIR 350-17, California Institute of Technology, 1200 East California Boulevard, Pasadena, CA 91125 (United States); Kartaltepe, Jeyhan [National Optical Astronomy Observatory, 950 North Cherry Avenue, Tucson, AZ 85719 (United States); and others

    2015-02-10

    We report ALMA Band 7 (350 GHz) imaging at 0.''4-0.''6 resolution and Band 9 (696 GHz) at ∼0.''25 resolution of the luminous IR galaxies Arp 220 and NGC 6240. The long wavelength dust continuum is used to estimate interstellar medium masses for Arp 220 east and west and NGC 6240 of 1.9, 4.2, and 1.6 × 10{sup 9} M {sub ☉}within radii of 69, 65, and 190 pc. The HCN emission was modeled to derive the emissivity distribution as a function of radius and the kinematics of each nuclear disk, yielding dynamical masses consistent with the masses and sizes derived from the dust emission. In Arp 220, the major dust and gas concentrations are at radii less than 50 pc in both counter-rotating nuclear disks. The thickness of the disks in Arp 220 estimated from the velocity dispersion and rotation velocities are 10-20 pc and the mean gas densities are n{sub H{sub 2}}∼10{sup 5} cm{sup –3} at R <50 pc. We develop an analytic treatment for the molecular excitation (including photon trapping), yielding volume densities for both the HCN and CS emission with n {sub H2} ∼ 2 × 10{sup 5} cm{sup –3}. The agreement of the mean density from the total mass and size with that required for excitation suggests that the volume is essentially filled with dense gas, i.e., it is not cloudy or like swiss cheese.

  19. Development of an HCN dual laser for the interferometer on EAST

    Science.gov (United States)

    Li, Gen; Wei, Xuechao; Liu, Haiqing; Shen, Junjie; Jie, Yinxian; Lian, Hui; Zeng, Long; Zou, Zhiyong; Zhang, Jibo; Wang, Shouxin

    2017-08-01

    A two-color continuous wave (CW) discharge-pumped far-infrared (FIR) hydrogen cyanide (HCN) laser was developed as the source of an interferometer for measuring the line-averaged electron density in the Experimental Advanced Superconducting Tokamak (EAST). The output power of the dual laser system was about 120 mW from each laser on the 337 μm (0.89 THz) line. The polarization of each output beam was fixed using thin tungsten filaments and oscillated in the EH11 mode. Different megahertz intermediate frequencies (IF) and a slight frequency offset (˜1 MHz) were generated in this system to replace the traditional rotating grating with ˜10 kHz IF, and this can improve the time resolution of the interferometer significantly. The experimental result showed that different IF signals were obtained by successfully adjusting the cavity length. In particular, the beat frequency was captured at ˜1.3 MHz by a Schottky mixer when the length of the resonant cavities was changed by 5 μm by an automatic adjustment system. In order to study the character of IF, a long time record of the IF signal was carried out, and the IF signal could be stabilized for a few minutes in the range of 2 MHz to 3 MHz. A real-time IF stability control system was initially designed for long pulse discharge experiments on the EAST. The ˜MHz frequency response and good phase sensitivity of the dual laser HCN interferometer will allow the system to track fast density profiles and resolve fast MHD events, such as tearing/neoclassical tearing, disruptions, etc. Contributed paper, published as part of the Proceedings of the 3rd Domestic Electromagnetic Plasma Diagnostics Workshop, September 2016, Hefei, China.

  20. Kandungan Protein dan HCN “Wikau Maombo” Hasil Fermentasi Umbi Ubi Kayu Pahit (Manihot aipi Phol Menggunakan Beberapa Isolat Mikroorganisme Lokal

    Directory of Open Access Journals (Sweden)

    Nurhayani H. Muhiddin

    2015-01-01

    Full Text Available Penelitian bertujuan untuk mengetahui perubahan kandungan protein dan HCN umbi ubi kayu pahit melalui fermentasi beberapa isolat mikroorganisme lokal menjadi “Wikau Maombo” dan mengetahui isolat mikroorganisme yang menghasilkan “Wikau Maombo” terbaik. Penelitian menggunakan metode eksperimental dengan teknik fermentasi substrat padat. Inokulum yang digunakan adalah biakan murni sebanyak 35 isolat mikroorganisme lokal hasil isolasi dari “Wikau Maombo” yang terfermentasi secara tradisional. Hasil penelitian menunjukkan bahwa semua perlakuan isolat mikroorganisme memberikan pengaruh yang tidak berbeda nyata terhadap perubahan kadar protein dan berbeda nyata terhadap kadar HCN “Wikau Maombo” dibandingkan kontrol. Kontrol umbi ubi kayu segar (KS mengandung kadar protein sebesar 0,7221% dan HCN sebesar 103,8352 ppm. Produk “Wikau Maombo” berkualitas baik dari hasil fermentasi isolat bakteri M (FM mengandung protein 0,8805% dan HCN 23,0555 ppm. Produk “Wikau Maombo” hasil fermentasi isolat kapang KpC (FKpC mengandung protein 0,6505% dan HCN 25,7719 ppm, sedang hasil fermentasi isolat khamir HC (FHC mengandung protein 0,7608% dan HCN 25,7447 ppm.Kata kunci: Umbi Kayu Pahit, Fermentasi, Mikroorganisme Lokal, Protein, HCN.

  1. Large-scale upper tropospheric pollution observed by MIPAS HCN and C2H6 global distributions

    Directory of Open Access Journals (Sweden)

    A. Linden

    2009-12-01

    Full Text Available We present global upper tropospheric HCN and C2H6 amounts derived from MIPAS/ENVISAT limb emission spectra. HCN and C2H6 are retrieved in the spectral regions 715.5–782.7 cm−1 and 811.5–835.7 cm−1, respectively. The datasets consist of 54 days between September 2003 and March 2004. This period covers the peak and decline of the southern hemispheric biomass burning period and some months thereafter. HCN is a nearly unambiguous tracer of biomass burning with an assumed tropospheric lifetime of several months. Indeed, the most significant feature in the MIPAS HCN dataset is an upper tropospheric plume of enhanced values caused by southern hemispheric biomass burning, which in September and October 2003 extended from tropical South America over Africa, Australia to the Southern Pacific. The spatial extent of this plume agrees well with the MOPITT CO distribution of September 2003. Further there is good agreement with the shapes and mixing ratios of the southern hemispheric HCN and C2H6 fields measured by the ACE experiment between September and November 2005. The MIPAS HCN plume extended from the lowermost observation height of 8 km up to about 16 km altitude, with maximum values of 500–600 pptv in October 2003. It was still clearly visible in December 2003, but had strongly decreased by March 2004, confirming the assumed tropospheric lifetime. The main sources of C2H6 are production and transmission of fossil fuels, followed by biofuel use and biomass burning. The C2H6 distribution also clearly reflected the southern hemispheric biomass burning plume and its seasonal variation, with maximum amounts of 600–700 pptv. Generally there was good spatial overlap between the southern hemispheric distributions of both pollution tracers, except for the region between Peru and the mid-Pacific. Here C2H6was considerably enhanced, whereas the HCN amounts were low. Backward trajectory calculations suggested that industrial pollution was responsible

  2. Large-scale upper tropospheric pollution observed by MIPAS HCN and C2H6 global distributions

    Science.gov (United States)

    Glatthor, N.; von Clarmann, T.; Stiller, G. P.; Funke, B.; Koukouli, M. E.; Fischer, H.; Grabowski, U.; Höpfner, M.; Kellmann, S.; Linden, A.

    2009-12-01

    We present global upper tropospheric HCN and C2H6 amounts derived from MIPAS/ENVISAT limb emission spectra. HCN and C2H6 are retrieved in the spectral regions 715.5-782.7 cm-1 and 811.5-835.7 cm-1, respectively. The datasets consist of 54 days between September 2003 and March 2004. This period covers the peak and decline of the southern hemispheric biomass burning period and some months thereafter. HCN is a nearly unambiguous tracer of biomass burning with an assumed tropospheric lifetime of several months. Indeed, the most significant feature in the MIPAS HCN dataset is an upper tropospheric plume of enhanced values caused by southern hemispheric biomass burning, which in September and October 2003 extended from tropical South America over Africa, Australia to the Southern Pacific. The spatial extent of this plume agrees well with the MOPITT CO distribution of September 2003. Further there is good agreement with the shapes and mixing ratios of the southern hemispheric HCN and C2H6 fields measured by the ACE experiment between September and November 2005. The MIPAS HCN plume extended from the lowermost observation height of 8 km up to about 16 km altitude, with maximum values of 500-600 pptv in October 2003. It was still clearly visible in December 2003, but had strongly decreased by March 2004, confirming the assumed tropospheric lifetime. The main sources of C2H6 are production and transmission of fossil fuels, followed by biofuel use and biomass burning. The C2H6 distribution also clearly reflected the southern hemispheric biomass burning plume and its seasonal variation, with maximum amounts of 600-700 pptv. Generally there was good spatial overlap between the southern hemispheric distributions of both pollution tracers, except for the region between Peru and the mid-Pacific. Here C2H6was considerably enhanced, whereas the HCN amounts were low. Backward trajectory calculations suggested that industrial pollution was responsible for the elevated C2H6

  3. Airborne measurements of CO2, CH4 and HCN in boreal biomass burning plumes

    Science.gov (United States)

    O'Shea, Sebastian J.; Bauguitte, Stephane; Muller, Jennifer B. A.; Le Breton, Michael; Archibald, Alex; Gallagher, Martin W.; Allen, Grant; Percival, Carl J.

    2013-04-01

    Biomass burning plays an important role in the budgets of a variety of atmospheric trace gases and particles. For example, fires in boreal Russia have been linked with large growths in the global concentrations of trace gases such as CO2, CH4 and CO (Langenfelds et al., 2002; Simpson et al., 2006). High resolution airborne measurements of CO2, CH4 and HCN were made over Eastern Canada onboard the UK Atmospheric Research Aircraft FAAM BAe-146 from 12 July to 4 August 2011. These observations were made as part of the BORTAS project (Quantifying the impact of BOReal forest fires on Tropospheric oxidants over the Atlantic using Aircraft and Satellites). Flights were aimed at transecting and sampling the outflow from the commonly occurring North American boreal forest fires during the summer months and to investigate and identify the chemical composition and evolution of these plumes. CO2 and CH4 dry air mole fractions were determined using an adapted system based on a Fast Greenhouse Gas Analyser (FGGA, Model RMT-200) from Los Gatos Research Inc, which uses the cavity enhanced absorption spectroscopy technique. In-flight calibrations revealed a mean accuracy of 0.57 ppmv and 2.31 ppbv for 1 Hz observations of CO2 and CH4, respectively, during the BORTAS project. During these flights a number of fresh and photochemically-aged plumes were identified using simultaneous HCN measurements. HCN is a distinctive and useful marker for forest fire emissions and it was detected using chemical ionisation mass spectrometry (CIMS). In the freshest plumes, strong relationships were found between CH4, CO2 and other tracers for biomass burning. From this we were able to estimate that 8.5 ± 0.9 g of CH4 and 1512 ± 185 g of CO2 were released into the atmosphere per kg of dry matter burnt. These emission factors are in good agreement with estimates from previous studies and can be used to calculate budgets for the region. However for aged plumes the correlations between CH4 and other

  4. In-Situ Measurements of HCN and CH3CN in the Pacific Troposphere: Sources, Sinks, and Comparisons with Spectroscopic Observations

    Science.gov (United States)

    Singh, Hanwant B.; Salas, L.; Herlth, D.; Czech, E.; Viezee, W.; Li, Q.; Jacob, D. J.; Blake, D.; Sachse, G.; Harward, C. N.; hide

    2002-01-01

    We report the first in-situ measurements of hydrogen cyanide (HCN) and acetonitrile (CH3CN) from the Pacific troposphere (0-12 km) obtained during the NASA/Trace-P mission (Feb.-April, 2001). Mean HCN and CH3CN mixing ratios of 243 (+/-118) ppt and 149 (+/-56) ppt respectively, were measured. The in-situ observations correspond to a total HCN column of 4.4-4.9 x 10(exp 15) molec. cm(exp -2) and a CH3CN column of 2.8-3.0 x 10(exp 15) molec. cm(exp -2). This HCN column is in good agreement with available spectroscopic observations. The atmospheric concentrations of HCN and CH3CN were greatly influenced by outflow of pollution from Asia. There is a linear relationship between the mixing ratios of HCN and CH3CN, and in turn these are well correlated with tracers of biomass combustion (e.g. CH3Cl, CO). Relative enhancements with respect to known tracers of biomass combustion within selected plumes in the free troposphere, and pollution episodes in the boundary layer allow an estimation of a global biomass burning source of 0.8+/-0.4 Tg (N)/y for HCN and 0.4+/-0.1 Tg (N)/y for CH3CN. In comparison, emissions from automobiles and industry are quite small (in the MBL (Marine Boundary Layer). Using, a simple box model, the observed gradients across the top of the MBL are used to derive an oceanic flux of 6.7 x 10(exp -15) g (N) cm(exp -2)/s for HCN and 4.8 x 10(exp -15) g (N) cm(exp -2)/s for CH3CN. An air-sea exchange model is used to conclude that this flux can be maintained if the oceans are under-saturated in HCN and CH3CN by 23% and 17%, respectively. It is inferred that oceanic loss is a dominant sink for these nitrites, and they deposit some 1.3 Tg (N) of nitrogen annually to the oceans. Assuming reaction with OH radicals and loss to the oceans as the major removal processes, a mean atmospheric residence time of 4.7 months for HCN and 5.1 months for CH3CN is calculated. A global budget analysis shows that the sources and sinks of HCN and CH3CN are roughly in balance

  5. First-principle study of structural, electronic, vibrational and magnetic properties of HCN adsorbed graphene doped with Cr, Mn and Fe

    Energy Technology Data Exchange (ETDEWEB)

    Shi, Li Bin, E-mail: slb0813@sohu.com; Wang, Yong Ping; Dong, Hai Kuan

    2015-02-28

    Graphical abstract: - Highlights: • Cr, Mn and Fe doped graphene is more active to adsorb HCN molecule than pristine graphene. • The conductivity of Fe and Mn doped graphene hardly changes after adsorption HCN molecule. • The conductivity of Cr doped graphene can be affected significantly due to HCN adsorption. • The Cr, Mn and Fe may destroy the long range order in graphene. • Phonon density of states suggests that Cr doped graphene is stable. - Abstract: The adsorption energy, electronic structure, lattice vibration and magnetic properties of Cr, Mn and Fe doped graphene with and without HCN adsorption are investigated by the first principles based on density functional theory. The physisorption and chemisorption have been identified. In the paper, Cr-NG, Mn-NG and Fe-NG denote HCN adsorption on Cr, Mn and Fe doped graphene with N atom toward the adsorption site. It is found that the adsorption energy is −1.36 eV for Fe-NG, −0.60 eV for Mn-NG and −0.86 eV for Cr-NG. The Cr-NG will convert from half-metallic behavior to semiconductor after adsorbing HCN molecule, which indicates that the conductivity changes significantly. Phonon density of states (PDOS) shows that the long range order in graphene can be destroyed by doping Fe, Mn and Cr. The imaginary frequency mode in PDOS suggests that Fe and Mn doped graphene is unstable, while Cr doped graphene is stable. The electronic properties are sensitive toward adsorbing HCN, indicating that Cr doped graphene is a promising sensor for detecting HCN molecule. This study provides a useful basis for understanding of a wide variety of physical properties on graphene.

  6. The photolysis of NH3 in the presence of substituted acetylenes - A possible source of oligomers and HCN on Jupiter

    Science.gov (United States)

    Ferris, James P.; Jacobson, Richard R.; Guillemin, Jean C.

    1992-01-01

    An NMR spectral study is presently conducted of NH3 photolysis in the presence of substituted acetylenes with NMR spectra and gas chromatography. Quantum yields and percentage conversions to products are reported. It is shown that acetylenic hydrocarbons generated during methane photolysis in Jupiter's stratosphere can react with radicals formed by NH3 photolysis to yield nonvolatile, yellow-brown polymers, alkylnitriles, and in due course, HCN, as observed on Jupiter.

  7. In-Situ Measurements of HCN and CH3CN In the Pacific Troposphere: Sources, Sinks, and Comparisons with Satellite Observations

    Science.gov (United States)

    Singh, Hanwant B.; Salas, L.; Herlth, D.; Viezee, W.; Jacob, D.; Blake, D.; Sachse, G.; Hipskind, R. Stephen (Technical Monitor)

    2002-01-01

    A new capillary gas chromatographic method using a Reduction Gas Detector was developed to measure HCN and CH3CN in the remote troposphere. This instrumental configuration was deployed for the very first time in the Trace-P field mission performed during the spring of 2001. The NASA DC-8 aircraft afforded an opportunity to measure HCN and CH3CN in polluted and pristine environments over the Pacific to a maximum altitude of 12 km. These are some of the first in situ measurements of the distribution of HCN and CH3CN over the Pacific. Large background concentrations of both nitriles were found to be present and significant variability was observed. The abundance of HCN and CH3CN was strongly impacted by outflow of pollution from Asia. In general there appeared to be a direct but nonlinear relationship between the mixing ratios of HCN and CH3CN. The vertical structure of these chemicals shows direct evidence of the presence of a significant oceanic sink. These observations will be compared with the column content HCN data from satellites and other available measurements. A large body of data have been collected and are being analyzed, both statistically and with the help of models, to better understand the sources and sinks of these nitriles. These results will be presented.

  8. CN radical hydrogenation from solid H2 reactions, an alternative way of HCN formation in the interstellar medium

    Science.gov (United States)

    Borget, Fabien; Müller, Sandra; Grote, Dirk; Theulé, Patrice; Vinogradoff, Vassilissa; Chiavassa, Thierry; Sander, Wolfram

    2017-02-01

    Context. Molecular hydrogen (H2) is the most abundant molecule of the interstellar medium (ISM) in gas phase and it has been assumed to exist in solid state or as coating on grains. Aims: Our goal is to show that solid H2 can act as a hydrogenation agent, reacting with CN radicals to form HCN. Methods: In a H2 matrix, we studied the hydrogenation of the CN radical generated from the vacuum ultraviolet photolysis (VUV-photolysis) of C2N2 at 3.8 K. We modified the wavelengths and the host gas in order to be sure that CN radicals can abstract H from H2 molecules. Results: HCN monomers, dimers, and oligomers have been characterised by Fourier transform infrared spectroscopy (FTIR). H2CN as well as CN radicals have also been clearly observed during the photolysis performed at 3.8 K. Conclusions: H2 is a hydrogenation reagent towards CN radicals producing HCN. This type of reaction should be taken into account for the reactivity at low temperature in contaminated H2 ice macro-particles (CHIMPs), H2 flakes or in the first sublayers of grains where solid H2 has accumulated.

  9. Measurements of hydrogen cyanide (HCN) and acetylene (C2H2) from the Infrared Atmospheric Sounding Interferometer (IASI)

    Science.gov (United States)

    Duflot, V.; Hurtmans, D.; Clarisse, L.; R'honi, Y.; Vigouroux, C.; De Mazière, M.; Mahieu, E.; Servais, C.; Clerbaux, C.; Coheur, P.-F.

    2013-04-01

    Hydrogen cyanide (HCN) and acetylene (C2H2) are ubiquitous atmospheric trace gases with medium lifetime, which are frequently used as indicators of combustion sources and as tracers for atmospheric transport and chemistry. Because of their weak infrared absorption, overlapped by the CO2 Q branch near 720 cm-1, nadir sounders have up to now failed to measure these gases routinely. Taking into account CO2 line mixing, we provide for the first time extensive measurements of HCN and C2H2 total columns at Reunion Island (21° S, 55° E) and Jungfraujoch (46° N, 8° E) in 2009-2010 using observations from the Infrared Atmospheric Sounding Interferometer (IASI). A first order comparison with local ground-based Fourier transform infraRed (FTIR) measurements has been carried out allowing tests of seasonal consistency which is reasonably captured, except for HCN at Jungfraujoch. The IASI data shows a greater tendency to high C2H2 values. We also examine a nonspecific biomass burning plume over austral Africa and show that the emission ratios with respect to CO agree with previously reported values.

  10. Measurements of hydrogen cyanide (HCN and acetylene (C2H2 from the Infrared Atmospheric Sounding Interferometer (IASI

    Directory of Open Access Journals (Sweden)

    V. Duflot

    2013-04-01

    Full Text Available Hydrogen cyanide (HCN and acetylene (C2H2 are ubiquitous atmospheric trace gases with medium lifetime, which are frequently used as indicators of combustion sources and as tracers for atmospheric transport and chemistry. Because of their weak infrared absorption, overlapped by the CO2 Q branch near 720 cm−1, nadir sounders have up to now failed to measure these gases routinely. Taking into account CO2 line mixing, we provide for the first time extensive measurements of HCN and C2H2 total columns at Reunion Island (21° S, 55° E and Jungfraujoch (46° N, 8° E in 2009–2010 using observations from the Infrared Atmospheric Sounding Interferometer (IASI. A first order comparison with local ground-based Fourier transform infraRed (FTIR measurements has been carried out allowing tests of seasonal consistency which is reasonably captured, except for HCN at Jungfraujoch. The IASI data shows a greater tendency to high C2H2 values. We also examine a nonspecific biomass burning plume over austral Africa and show that the emission ratios with respect to CO agree with previously reported values.

  11. Reinterpreting the infrared spectrum of H + HCN: Methylene amidogen radical and its coproducts.

    Science.gov (United States)

    Wiens, Avery E; Copan, Andreas V; Rossomme, Elliot C; Aroeira, Gustavo J R; Bernstein, Olivia M; Agarwal, Jay; Schaefer, Henry F

    2018-01-07

    The methylene amidogen radical (H2CN) plays a role in high-energy material combustion and extraterresterial atmospheres. Recent theoretical work has struggled to match experimental assignments for its CN and antisymmetric CH2 stretching frequencies (ν2 and ν5), which were reported to occur at 1725 and 3103 cm-1. Herein, we compute the vibrational energy levels of this molecule by extrapolating quadruples-level coupled-cluster theory to the complete basis limit and adding corrections for vibrational anharmonicity. This level of theory predicts that ν2 and ν5 should occur at 1646 and 2892 cm-1, at odds with the experimental assignments. To investigate the possibility of defects in our theoretical treatment, we analyze the sensitivity of our approach to each of its contributing approximations. Our analysis suggests that the observed deviation from experiment is too large to be explained as an accumulation of errors, leading us to conclude that these transitions were misassigned. To help resolve this discrepancy, we investigate possible byproducts of the H + HCN reaction, which was the source of H2CN in the original experiment. In particular, we predict vibrational spectra for cis-HCNH, trans-HCNH, and H2CNH using high-level coupled-cluster computations. Based on these results, we reassign the transition at 1725 cm-1 to ν3 of trans-HCNH, yielding excellent agreement. Supporting this identification, we assign a known contaminant peak at 886 cm-1 to ν5 of the same conformer. Our computations suggest that the peak observed at 3103 cm-1, however, does not belong to any of the aforementioned species. To facilitate further investigation, we use structure and bonding arguments to narrow the range of possible candidates. These arguments lead us to tentatively put forth formaldazine [(H2CN)2] as a suggestion for further study, which we support with additional computations.

  12. Passivation of Si-based structures in HCN and KCN solutions

    Energy Technology Data Exchange (ETDEWEB)

    Pincik, Emil, E-mail: emil.pincik@savba.sk [Institute of Physics SAS, Dubravska cesta 9, 845 11 Bratislava (Slovakia); Kobayashi, Hikaru [ISIR of Osaka University, and CREST, Japan Science and Technology Organization, 8-1 Mihogaoka, Ibaraki, Osaka 567-0047 (Japan); Rusnak, Jaroslav [Institute of Physics SAS, Dubravska cesta 9, 845 11 Bratislava (Slovakia); Takahashi, Masao [ISIR of Osaka University, and CREST, Japan Science and Technology Organization, 8-1 Mihogaoka, Ibaraki, Osaka 567-0047 (Japan); Mikula, Milan [Faculty of Chemical and Food Technology of SUT, Radlinskeho 9, 812 37 Bratislava (Slovakia); Kim, Woo Byoung [ISIR of Osaka University, and CREST, Japan Science and Technology Organization, 8-1 Mihogaoka, Ibaraki, Osaka 567-0047 (Japan); Kucera, Michal [Institute of Electrical Engineering SAS, Dubravska cesta 9, 841 04 Bratislava (Slovakia); Brunner, Robert [Institute of Physics SAS, Dubravska cesta 9, 845 11 Bratislava (Slovakia); Jurecka, Stanislav [DEF FEE University of Zilina, kpt. Nalepku 1390, 03101 Liptovsky Mikulas (Slovakia)

    2012-08-15

    The contribution deals with passivation of surfaces of c-Si and 6H-SiC by formation of very thin SiO{sub 2} films in boiling HNO{sub 3} solutions and by passivation of a-Si based double and triple layer structures deposited on Corning glass and c-Si by KCN solutions. The structures are investigated by spectroscopic ellipsometry, charge version of DLTS, C-V, FTIR-DRIFT, and by photoluminescence measuremets at 6 K. Newly developed 2nd generation of MOS structures prepared on c-Si with an approx. 3 nm SiO{sub 2} layer gives typical density of interface defect states of 5 Multiplication-Sign 10{sup 10} eV{sup -1} cm{sup -2}. Real part of complex refractive index of approx. 3 nm thick SiO{sub 2} layers is about 1.75. Application of HCN solutions to structure approx. 3 nm SiO{sub 2}/Si (applied as the last technological step) leads to remarkable lowering of absorbance in wavelength region 4000 cm{sup -1}-2500 cm{sup -1}. This result indicates a decrease of number of non- radiation transitions in the surface region of oxide/Si structures. Such structures have also the lowest density of interface defect states (observed by Q-DLTS). Application of boiling KCN solutions considerably increases amplitudes of photoluminescence signals coming from different double and triple a-Si based layers deposited on Corning glass. We relate this effect predominantly with reduction of non-radiation transitions in excited region of amorphous structures - with passivation of corresponding defect states in a-Si structures in boiling KCN solutions.

  13. Reduction of nitrogen compounds in oceanic basement and its implications for HCN formation and abiotic organic synthesis

    Directory of Open Access Journals (Sweden)

    Neubeck Anna

    2009-10-01

    Full Text Available Abstract Hydrogen cyanide is an excellent organic reagent and is central to most of the reaction pathways leading to abiotic formation of simple organic compounds containing nitrogen, such as amino acids, purines and pyrimidines. Reduced carbon and nitrogen precursor compounds for the synthesis of HCN may be formed under off-axis hydrothermal conditions in oceanic lithosphere in the presence of native Fe and Ni and are adsorbed on authigenic layer silicates and zeolites. The native metals as well as the molecular hydrogen reducing CO2 to CO/CH4 and NO3-/NO2- to NH3/NH4+ are a result of serpentinization of mafic rocks. Oceanic plates are conveyor belts of reduced carbon and nitrogen compounds from the off-axis hydrothermal environments to the subduction zones, where compaction, dehydration, desiccation and diagenetic reactions affect the organic precursors. CO/CH4 and NH3/NH4+ in fluids distilled out of layer silicates and zeolites in the subducting plate at an early stage of subduction will react upon heating and form HCN, which is then available for further organic reactions to, for instance, carbohydrates, nucleosides or even nucleotides, under alkaline conditions in hydrated mantle rocks of the overriding plate. Convergent margins in the initial phase of subduction must, therefore, be considered the most potent sites for prebiotic reactions on Earth. This means that origin of life processes are, perhaps, only possible on planets where some kind of plate tectonics occur.

  14. Detection of CO and HCN in the coma of Jupiter-family comet 41P/Tuttle-Giacobini-Kresak

    Science.gov (United States)

    Wierzchos, Kacper; Womack, Maria

    2017-10-01

    Comets are divided into taxonomical groups determined largely by their orbits. Short-period Jupiter Family comets (JFCs) are thought to have formed in a trans-Neptunian disk ˜30 - 100 AU (Kuiper Belt) and then migrated inward (Edgeworth 1949, Kuiper 1951, Duncan et al. 1988). This different classification may be correlated with chemical abundance variations, and super-volatile species like CO can serve as an indicator of the thermal processes to which the precometary ices that led to comets where exposed (DiSainti et al. 2007). The close approach to Earth of comet 41P on the perihelion passage of 2017 was an excellent opportunity to probe the usually well-hidden inner coma of this Jupiter-family comet. We searched for CO (J=2-1) and HCN (J=3-2) emission with the Arizona Radio Observatory (ARO) 10-m Sub-millimeter Telescope (SMT) on 2017 April 1-2, when the comet was 1.1 AU from the Sun and 0.14 AU from Earth. We report the detection of both CO and HCN emission 13 days before perihelion and present column densities and production rates. We also discuss implications for Jupiter-family comets. The SMT is operated by the ARO, the Steward Observatory, and the University of Arizona, with support through the NSF University Radio Observatories program (AST-1140030). M.W. acknowledges support from NSF grant AST-1615917.

  15. Pacemaker current inhibition in experimental human cardiac sympathetic activation: a double-blind, randomized, crossover study.

    Science.gov (United States)

    Schroeder, C; Heusser, K; Zoerner, A A; Großhennig, A; Wenzel, D; May, M; Sweep, F C G J; Mehling, H; Luft, F C; Tank, J; Jordan, J

    2014-06-01

    Hyperpolarization-activated, cyclic nucleotide-gated 4 (HCN4) channels comprise the final pathway for autonomic heart rate (HR) regulation. We hypothesized that HCN4 inhibition could reverse autonomic imbalance in a human model of cardiac sympathetic activation. Nineteen healthy men ingested oral metoprolol+reboxetine, ivabradine+reboxetine, or placebo+reboxetine in a double-blind, randomized, crossover fashion. We assessed HR, blood pressure (BP), stroke volume, and cardiac output during rest and profound orthostatic stress. HR variability, BP variability, and baroreflex sensitivity were analyzed. Metoprolol, but not ivabradine, decreased resting HR and BP. Ivabradine attenuated the HR increase to orthostatic stress, albeit to a lesser extent than metoprolol. Stroke volume and cardiac output at a given HR were significantly lower with metoprolol. Unlike metoprolol, ivabradine did not affect HR variability, BP variability, or baroreflex sensitivity. Ivabradine attenuates sympathetic influences on HR at the sinus node level, leaving myocardial sympathetic activation unopposed. Reversal of parasympathetic dysfunction by ivabradine appears limited.

  16. Nitrogen and hydrogen fractionation in high-mass star-forming cores from observations of HCN and HNC

    Science.gov (United States)

    Colzi, L.; Fontani, F.; Caselli, P.; Ceccarelli, C.; Hily-Blant, P.; Bizzocchi, L.

    2018-02-01

    The ratio between the two stable isotopes of nitrogen, 14N and 15N, is well measured in the terrestrial atmosphere ( 272), and for the pre-solar nebula ( 441, deduced from the solar wind). Interestingly, some pristine solar system materials show enrichments in 15N with respect to the pre-solar nebula value. However, it is not yet clear if and how these enrichments are linked to the past chemical history because we have only a limited number of measurements in dense star-forming regions. In this respect, dense cores, which are believed to be the precursors of clusters and also contain intermediate- and high-mass stars, are important targets because the solar system was probably born within a rich stellar cluster, and such clusters are formed in high-mass star-forming regions. The number of observations in such high-mass dense cores has remained limited so far. In this work, we show the results of IRAM-30 m observations of the J = 1-0 rotational transition of the molecules HCN and HNC and their 15N-bearing counterparts towards 27 intermediate- and high-mass dense cores that are divided almost equally into three evolutionary categories: high-mass starless cores, high-mass protostellar objects, and ultra-compact HII regions. We have also observed the DNC(2-1) rotational transition in order to search for a relation between the isotopic ratios D/H and 14N/15N. We derive average 14N/15N ratios of 359 ± 16 in HCN and of 438 ± 21 in HNC, with a dispersion of about 150-200. We find no trend of the 14N/15N ratio with evolutionary stage. This result agrees with what has been found for N2H+ and its isotopologues in the same sources, although the 14N/15N ratios from N2H+ show a higher dispersion than in HCN/HNC, and on average, their uncertainties are larger as well. Moreover, we have found no correlation between D/H and 14N/15N in HNC. These findings indicate that (1) the chemical evolution does not seem to play a role in the fractionation of nitrogen, and that (2) the

  17. Cooperative effects of noncovalent bonds to the Br atom of halogen-bonded H3N...BrZ and HCN...BrZ (Z = F, Br) complexes.

    Science.gov (United States)

    McDowell, Sean A C; Joseph, Jerelle A

    2012-08-21

    A series of complexes formed between halogen-bonded H(3)N/HCN...BrZ (Z = Br, F) dimers and H(3)N/HCN...BrZ...XY (XY = HF, ClF, BeH(2), LiF) trimers were investigated at the MP2 and B3LYP levels of theory using a 6-31++G(d,p) basis set. Optimized structures, interaction energies, and other properties of interest were obtained. The addition of XY to the H(3)N/HCN...BrZ dyad leads to enhanced intermolecular binding with respect to the isolated monomers. This enhanced binding receives contributions from the electrostatic and inductive forces between the constituent pairs, with, in some instances, substantial three-body non-additive contributions to the binding energy. It was found that the XY = LiF interaction causes the greatest distortion of the H(3)N/HCN...BrZ halogen bond from the preferred linear orientation and also provides the strongest binding energy via the nonadditive energy.

  18. Theoretical insight into the BH3·HCN adsorption on the Co(100) and Co(110) surfaces as hydrogen storage.

    Science.gov (United States)

    Zhao, He; Ren, Fu-de; Wang, Yan-Hong

    2017-04-01

    Fifteen configurations and adsorption energies of the adsorption sites of BH3∙∙∙HCN on Co(100) and Co(110) surfaces were investigated using the density functional theory. The results show that after BH3∙∙∙HCN is adsorbed, although there is no general behavior for the H∙∙∙H distances, the adsorption energies of BH3∙∙∙HCN are always far stronger than those of H2 on Co surfaces, suggesting that the dihydrogen-bonded complex, one kind of prospective material for reversible hydrogen storage, can be tightly adsorbed on the surfaces of metals. Thus, the attempts to store the significant amounts of H2 can be successful by the way that the dihydrogen-bonded complexes are adsorbed on the surfaces of metals. The stability and binding mechanism was analyzed by the Mulliken charge population and reduced density gradients (RDGs) methods. Graphical Abstract BH3···HCN adsorption on Co surface.

  19. Cooperativity between the dihydrogen bond and the NHC hydrogen bond in LiH-(HCN)n Complexes.

    Science.gov (United States)

    Li, Qing-Zhong; Hu, Ting; An, Xiu-Lin; Gong, Bao-An; Cheng, Jian-Bo

    2008-09-15

    The cooperativity between the dihydrogen bond and the NHC hydrogen bond in LiH-(HCN)(n) (n=2 and 3) complexes is investigated at the MP2 level of theory. The bond lengths, dipole moments, and energies are analyzed. It is demonstrated that synergetic effects are present in the complexes. The cooperativity contribution of the dihydrogen bond is smaller than that of the NHC hydrogen bond. The three-body energy in systems involving different types of hydrogen bonds is larger than that in the same hydrogen-bonded systems. NBO analyses indicate that orbital interaction, charge transfer, and bond polarization are mainly responsible for the cooperativity between the two types of hydrogen bonds.

  20. Searching for Faint Traces of CO(2-1) and HCN(4-3) Gas In Debris Disks

    Science.gov (United States)

    Stafford Lambros, Zachary; Hughes, A. Meredith

    2018-01-01

    The surprising presence of molecular gas in the debris disks around main sequence stars provides an opportunity to study the dissipation of primordial gas and, potentially, the composition of gas in other solar systems. Molecular gas is not expected to survive beyond the pre-main sequence phase, and it is not yet clear whether the gas is a remnant of the primordial protoplanetary material or whether the gas, like the dust, is second-generation material produced by collisional or photodesorption from planetesimals, exocomets, or the icy mantles of dust grains. Here we present two related efforts to characterize the prevalence and properties of gas in debris disks. First, we place the lowest limits to date on the CO emission from an M star debris disk, using 0.3" resolution observations of CO(2-1) emission from the AU Mic system with the Atacama Large Millimeter/submillimeter Array (ALMA). We place a 3-sigma upper limit on the integrated flux of 0.39 Jy km/s, corresponding to a maximum CO mass of 5e10-6 (Earth Masses) if the gas is in LTE. We also present the results of an ALMA search for HCN(4-3) emission from the prototypical gas-rich debris disk around 49 Ceti at a spatial resolution of 0.3". Despite hosting one of the brightest CO-rich debris disks yet discovered, our observations of 49 Ceti also yield a low upper limit of 0.057 Jy km/s in the HCN line, leaving CO as the only molecule clearly detected in emission from a debris disk. We employ several methods of detecting faint line emission from debris disks, including a model based on Keplerian kinematics as well as a spectral shifting method previously used to detect faint CO emission from the Fomalhaut debris disk, and compare our results.

  1. Homogeneous formation of NO and N{sub 2}O from the oxidation of HCN and NH{sub 3} at 600--1000 C

    Energy Technology Data Exchange (ETDEWEB)

    Wargadalam, V.J.; Loeffler, G.; Winter, F.; Hofbauer, H.

    2000-03-01

    The oxidation of HCN and NH{sub 3} with CO, CH{sub 4}, or H{sub 2} addition has been studied in the temperature range between 600 to 1,000 C. In most of the tests 10% oxygen was used. The experiments were carried out under well-defined conditions in a flow tube reactor made of quartz glass. The effects of NO addition and oxygen level have been tested. To study the importance of O/H radicals in the reaction mechanism and to confirm previous studies, iodine was added in some tests. A detailed chemical kinetic model was used to analyze the experimental data. In general, the model and experimental results are in good agreement. The results show that under the conditions tested CO significantly promotes NO and N{sub 2}O formation during HCN oxidation. During NH{sub 3} oxidation carbon-containing gaseous species such as CO and CH{sub 4} are important to promote homogeneous NO formation. In the system with CH{sub 4} addition, the conversion of HCN to N{sub 2}O is lower compared to the other systems. In the HCN/NO/CO/O{sub 2} system NO reduction starts at 700 C and the maximum reduction of approx. 40% is obtained at 800 C. For the NH{sub 3}/NO/CO/O{sub 2} system the reduction starts at 750 C and the maximum reduction is 50% at 800 C. Iodine addition shifts the oxidation of HCN, NO, and N{sub 2}O formation as well as NO reduction to higher temperatures. Under the conditions tested, it was found that iodine mainly enhances the recombination of the O-radicals. No effect on NO formation was found in the HCN/CH{sub 4}/O{sub 2} system when oxygen was increased from 6% to 10%, but when oxygen was increased from 2% to 6% NO formation decreased. The role of hydrocarbon radicals in the destruction of NO is likely to become important at low oxygen concentrations (2%) and at high temperatures (1,000 C).

  2. Homogeneous formation of NO and N{sub 2}O from the oxidation of HCN and NH{sub 3} at 600-1000{degree}C

    Energy Technology Data Exchange (ETDEWEB)

    Wargadalam, V.J.; Loeffler, G.; Winter, F.; Hofbauer, H. [Vienna University of Technology, Vienna (Austria). Inst. of Chemical Engineering, Fuel Technology and Environmental Technology

    2000-03-01

    The oxidation of HCN and NH{sub 3} with CO, CH{sub 4} or H{sub 2} addition was studied at temperatures between 600 to 1000{degree}C. In most of the tests 10% oxygen was used. The experiments were carried out under well-defined conditions in a flow tube reactor made of quartz glass. The effects of NO addition and oxygen level were tested. To study the importance of O/H radicals in the reaction mechanism and to confirm previous studies, iodine was added in some tests. A chemical kinetic model was used to analyze the experimental data. The model and experimental results are in good agreement. The results show that under the conditions tested CO significantly promotes NO and N{sub 2}O formation during HCN oxidation. During NH{sub 3} oxidation carbon-containing gaseous species such as CO and CH{sub 4} are important in promoting homogeneous NO formation. In the system with CH{sub 4} addition, the conversion of HCN to N{sub 2}O is lower compared to the other systems. In the HCN/NO/CO/O{sub 2} system NO reduction starts at 700{degree}C and the maximum reduction of approx. 40% is obtained at 800{degree}C. For the NH{sub 3}/NO/CO/O{sub 2} system the reduction starts at 75{degree}C and the maximum reduction is 50% at 800{degree}C. Iodine addition shifts the oxidation of HCN, NO, and N{sub 2}O formation as well as NO reduction to higher temperatures. Under the conditions tested, it was found that iodine mainly enhances the recombination of the O-radicals. No effect on NO formation was found in the HCN/CH{sub 4}/O{sub 2} system when oxygen was increased from 6% to 10%, but when oxygen was increased from 2% to 6% NO formation decreased. The role of hydrocarbon radicals in the destruction of NO is likely to become important at low oxygen concentrations (2%) and at high temperatures (1000{degree}C). 47 refs., 9 figs., 2 tabs.

  3. A theoretical study of hydrogen complexes of the XH-pi type between propyne and HF, HCL or HCN.

    Science.gov (United States)

    Tavares, Alessandra M; da Silva, Washington L V; Lopes, Kelson C; Ventura, Elizete; Araújo, Regiane C M U; do Monte, Silmar A; da Silva, João Bosco P; Ramos, Mozart N

    2006-05-15

    The present manuscript reports a systematic investigation of the basis set dependence of some properties of hydrogen-bonded (pi type) complexes formed by propyne and a HX molecule, where X=F, Cl and CN. The calculations have been performed at Hartree-Fock, MP2 and B3LYP levels. Geometries, H-bond energies and vibrational have been considered. The more pronounced effects on the structural parameters of the isolated molecules, as a result of complexation, are verified on RCtriple bondC and HX bond lengths. As compared to double-zeta (6-31G**), triple-zeta (6-311G**) basis set leads to an increase of RCtriple bondC bond distance, at all three computational levels. In the case where diffuse functions are added to both hydrogen and 'heavy' atoms, the effect is more pronounced. The propyne-HX structural parameters are quite similar to the corresponding parameters of acetylene-HX complexes, at all levels. The largest difference is obtained for hydrogen bond distance, RH, with a smaller value for propyne-HX complex, indicating a stronger bond. Concerning the electronic properties, the results yield the following ordering for H-bond energies, DeltaE: propynecdots, three dots, centeredHF>propynecdots, three dots, centeredHCl>propynecdots, three dots, centeredHCN. It is also important to point out that the inclusion of BSSE and zero-point energies (ZPE) corrections cause significant changes on DeltaE. The smaller effect of ZPE is obtained for propynecdots, three dots, centeredHCN at HF/6-311++G** level, while the greatest difference is obtained at MP2/6-31G** level for propynecdots, three dots, centeredHF system. Concerning the IR vibrational it was obtained that larger shift can be associated with stronger hydrogen bonds. The more pronounced effect on the normal modes of the isolated molecule after the complexation is obtained for HX stretching frequency, which is shifted downward.

  4. Hydrogen constituents of the mesosphere inferred from positive ions - H2O, CH4, H2CO, H2O2, and HCN

    Science.gov (United States)

    Kopp, E.

    1990-01-01

    The concentrations in the mesosphere of H2O, CH4, H2CO, H2O2, and HCN were inferred from data on positive ion compositions, obtained from one mid-latitude and four high-latitude rocket flights. The inferred concentrations were found to agree only partially with the ground-based microwave measurements and/or model prediction by Garcia and Solomon (1985). The CH4 concentration was found to vary between 70 and 4 ppb in daytime and 900 and 100 ppbv at night, respectively. Unexpectedly high H2CO concentrations were obtained, with H2CO/H2O ratios between 0.0006 and 0.1, and a mean HCN volume mixing ratio of 6 x 10 to the -10th was inferred.

  5. Trends and variations in CO, C2H6, and HCN in the Southern Hemisphere point to the declining anthropogenic emissions of CO and C2H6

    Directory of Open Access Journals (Sweden)

    N. B. Jones

    2012-08-01

    Full Text Available We analyse the carbon monoxide (CO, ethane (C2H6 and hydrogen cyanide (HCN partial columns (from the ground to 12 km derived from measurements by ground-based solar Fourier Transform Spectroscopy at Lauder, New Zealand (45° S, 170° E, and at Arrival Heights, Antarctica (78° S, 167° E, from 1997 to 2009. Significant negative trends are calculated for all species at both locations, based on the daily-mean observed time series, namely CO (−0.94 ± 0.47% yr−1, C2H6 (−2.37 ± 1.18% yr−1 and HCN (−0.93 ± 0.47% yr−1 at Lauder and CO (−0.92 ± 0.46% yr−1, C2H6 (−2.82 ± 1.37% yr−1 and HCN (−1.41 ± 0.71% yr−1 at Arrival Heights. The uncertainties reflect the 95% confidence limits. However, the magnitudes of the trends are influenced by the anomaly associated with the 1997–1998 El Niño Southern Oscillation event at the beginning of the time series reported. We calculate trends for each month from 1997 to 2009 and find negative trends for all months. The largest monthly trends of CO and C2H6 at Lauder, and to a lesser degree at Arrival Heights, occur during austral spring during the Southern Hemisphere tropical and subtropical biomass burning period. For HCN, the largest monthly trends occur in July and August at Lauder and around November at Arrival Heights. The correlations between CO and C2H6 and between CO and HCN at Lauder in September to November, when the biomass burning maximizes, are significantly larger that those in other seasons. A tropospheric chemistry-climate model is used to simulate CO, C2H6, and HCN partial columns for the period of 1997–2009, using interannually varying biomass burning emissions from GFED3 and annually periodic but seasonally varying emissions from both biogenic and anthropogenic sources. The model-simulated partial columns of these species compare well with the measured partial columns and the model accurately reproduces seasonal cycles of all three species at both locations. However

  6. 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.

  7. Postmortem review and genetic analysis in sudden infant death syndrome: an 11-year review.

    Science.gov (United States)

    Evans, Angharad; Bagnall, Richard D; Duflou, Johan; Semsarian, Christopher

    2013-09-01

    Sudden infant death syndrome (SIDS) is the unexpected death of a child younger than 1 year that remains unexplained after thorough evaluation. The possibility of an underlying primary arrhythmogenic disorder has been proposed as a potential cause of SIDS. This study sought to review SIDS deaths and to perform genetic analysis in key genes that may contribute to sudden death. From 2000 to 2010, all postmortem records from the Department of Forensic Medicine in Sydney, Australia, were reviewed. Cases that gave the cause of death as "SIDS" or "undetermined" but consistent with SIDS were included. In a subset of cases, the hyperpolarization-activated cyclic nucleotide (HCN)-gated channel family of genes (HCN2 and HCN4) was analyzed. A total of 226 SIDS cases were identified; 61% were male, 41% occurred while bed sharing, and there was a peak in deaths between 2 and 4 months old. The incidence did not decrease over the study period. In a subgroup of SIDS cases (n = 46), genetic analysis identified 2 likely pathogenic variants (2/46; 4%). A novel nonsynonymous variant, HCN4-Ala195Val, predicted to be pathogenic, was identified in a female infant who died at age 4 months. A female infant aged 5 weeks carried a rare nonsynonymous variant, HCN4-Val759Ile, which is similar to previously described variants associated with cardiac arrhythmias. In conclusion, the incidence of SIDS remains constant, with no apparent decline in the last decade. The underlying cause of SIDS remains largely unknown. Mutations in cardiac ion channel genes including rare nonsynonymous HCN gene variants may play a role in the pathogenesis of some SIDS cases. Copyright © 2013 Elsevier Inc. All rights reserved.

  8. Intrinsic oscillatory activity arising within the electrically coupled AII amacrine–ON cone bipolar cell network is driven by voltage-gated Na+ channels

    Science.gov (United States)

    Trenholm, Stuart; Borowska, Joanna; Zhang, Jiawei; Hoggarth, Alex; Johnson, Kyle; Barnes, Steven; Lewis, Timothy J; Awatramani, Gautam B

    2012-01-01

    In the rd1 mouse model for retinal degeneration, the loss of photoreceptors results in oscillatory activity (∼10–20 Hz) within the remnant electrically coupled network of retinal ON cone bipolar and AII amacrine cells. We tested the role of hyperpolarization-activated currents (Ih), voltage-gated Na+ channels and gap junctions in mediating such oscillatory activity. Blocking Ih (1 mm Cs+) hyperpolarized the network and augmented activity, while antagonizing voltage-dependent Na+ channels (1 μm TTX) abolished oscillatory activity in the AII amacrine–ON cone bipolar cell network. Voltage-gated Na+ channels were only observed in AII amacrine cells, implicating these cells as major drivers of activity. Pharmacologically uncoupling the network (200 μm meclofenamic acid (MFA)) blocked oscillations in all cells indicating that Na+ channels exert their influence over multiple cell types within the network. In wt retina, occluding photoreceptor inputs to bipolar cells (10 μm NBQX and 50 μm l-AP4) resulted in a mild (∼10 mV) hyperpolarization and the induction of oscillatory activity within the AII amacrine–ON cone bipolar cell network. These oscillations had similar properties to those observed in rd1 retina, suggesting that no major degeneration-induced network rewiring is required to trigger spontaneous oscillations. Finally, we constructed a simplified computational model that exhibited Na+ channel-dependent network oscillations. In this model, mild heterogeneities in channel densities between individual neurons reproduced our experimental findings. These results indicate that TTX-sensitive Na+ channels in AII amacrine cells trigger degeneration-induced network oscillations, which provide a persistent synaptic drive to downstream remnant neurons, thus appearing to replace photoreceptors as the principal drivers of retinal activity. PMID:22393249

  9. Intrinsic oscillatory activity arising within the electrically coupled AII amacrine-ON cone bipolar cell network is driven by voltage-gated Na+ channels.

    Science.gov (United States)

    Trenholm, Stuart; Borowska, Joanna; Zhang, Jiawei; Hoggarth, Alex; Johnson, Kyle; Barnes, Steven; Lewis, Timothy J; Awatramani, Gautam B

    2012-05-15

    In the rd1 mouse model for retinal degeneration, the loss of photoreceptors results in oscillatory activity (∼10–20 Hz) within the remnant electrically coupled network of retinal ON cone bipolar and AII amacrine cells. We tested the role of hyperpolarization-activated currents (I(h)), voltage-gated Na(+) channels and gap junctions in mediating such oscillatory activity. Blocking I(h) (1 mm Cs(+)) hyperpolarized the network and augmented activity, while antagonizing voltage-dependent Na(+) channels (1 μm TTX) abolished oscillatory activity in the AII amacrine-ON cone bipolar cell network. Voltage-gated Na(+) channels were only observed in AII amacrine cells, implicating these cells as major drivers of activity. Pharmacologically uncoupling the network (200 μm meclofenamic acid (MFA)) blocked oscillations in all cells indicating that Na(+) channels exert their influence over multiple cell types within the network. In wt retina, occluding photoreceptor inputs to bipolar cells (10 μm NBQX and 50 μm l-AP4) resulted in a mild (∼10 mV) hyperpolarization and the induction of oscillatory activity within the AII amacrine-ON cone bipolar cell network. These oscillations had similar properties to those observed in rd1 retina, suggesting that no major degeneration-induced network rewiring is required to trigger spontaneous oscillations. Finally, we constructed a simplified computational model that exhibited Na(+) channel-dependent network oscillations. In this model, mild heterogeneities in channel densities between individual neurons reproduced our experimental findings. These results indicate that TTX-sensitive Na(+) channels in AII amacrine cells trigger degeneration-induced network oscillations, which provide a persistent synaptic drive to downstream remnant neurons, thus appearing to replace photoreceptors as the principal drivers of retinal activity.

  10. Structural Insights into the Functional Role of the Hcn Sub-domain of the Receptor-Binding Domain of the Botulinum Neurotoxin Mosaic Serotype C/D

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yanfeng; Gardberg, Anna; Edwards, Tom E.; Sankaran, Banumathi; Robinson, Howard; Varnum, Susan M.; Buchko, Garry W.

    2013-07-01

    Botulinum neurotoxin (BoNT), the causative agent of the deadly neuroparalytic disease botulism, is the most poisonous protein known for humans. Produced by different strains of the anaerobic bacterium Clostridium botulinum, BoNT effects cellular intoxication via a multistep mechanism executed by the three modules of the activated protein. Endocytosis, the first step of cellular intoxication, is triggered by the ~50 kDa, heavy-chain receptor-binding module (HCR) that is specific for a ganglioside and a protein receptor on neuronal cell surfaces. This dual receptor recognition mechanism between BoNT and the host cell’s membrane is well documented and occurs via specific intermolecular interactions with the C-terminal sub-domain, Hcc, of BoNT-HCR. The N-terminal sub-domain of BoNT-HCR, Hcn, comprises ~50% of BoNT-HCR and adopts a B-sheet jelly roll fold. While suspected in assisting cell surface recognition, no unambiguous function for the Hcn sub-domain in BoNT has been indentified. To obtain insights into the potential function of the Hcn sub-domain in BoNT, the first crystal structure of a BoNT with an organic ligand bound to the Hcn sub-domain has been obtained. Here, we describe the crystal structure of BoNT/CD-HCR determined at 1.70 Å resolution with a tetraethylene glycol (PG4) molecule bound in an hydrophobic cleft between B-strands in the B-sheet jelly fold roll of the Hcn sub-domain. The molecule is completely engulfed in the cleft, making numerous hydrophobic (Y932, S959, W966, and D1042) and hydrophilic (S935, W977, L979, N1013, and I1066) contacts with the protein’s side chain and backbone that may mimic in vivo interactions with the phospholipid membranes on neuronal cell surfaces. A sulfate ion was also observed bound to residues T1176, D1177, K1196, and R1243 in the Hcc sub-domain of BoNT/CD-HCR. In the crystal structure of a similar protein, BoNT/D-HCR, a sialic acid

  11. Dual effects of amiodarone on pacemaker currents in hypertrophied ventricular myocytes isolated from spontaneously hypertensive rats.

    Science.gov (United States)

    Li, Hongxia; Zhou, Yafeng; Jiang, Bin; Zhao, Xin; Li, Xun; Yang, Xiangjun; Jiang, Wenping

    2014-09-01

    The pacemaker current If conducted by hyperpolarization-activated cyclic nucleotide-gated (HCN) channels plays a critical role in the regulation of cardiac automaticity, with If density increased in hypertrophied ventricular myocytes. Amiodarone, a highly effective anti-arrhythmic agent, blocks human HCN currents and native If under normal conditions. To determine the effects of amiodarone under pathological conditions, we monitored If under after both acute (0.01, 0.1, 1, 10 and 100 μmol/L) and chronic (10 μmol/L) amiodarone treatment in ventricular myocytes from spontaneously hypertensive rats (SHR) with left ventricular hypertrophy using the whole-cell patch-clamp technique. The If current density was significantly greater in SHR ventricular myocytes than in cells from healthy normotensive control Wistar-Kyoto (WKY) rats. Acute application of amiodarone significantly decreased If density in myocytes from both SHR and WKY rats. The inhibition was concentration dependent with an IC50 of 4.9 ± 1.2 and 6.9 ± 1.3 μmol/L in myocytes from SHR and WKY rats, respectively. Amiodarone increased the activation and deactivation times of If in myocytes from SHR, although it did not alter the relationship of voltage-dependent activation and the reversal potential of If in myocytes from SHR. Chronic exposure of myocytes from SHR to amiodarone potently inhibited If and downregulated HCN2 and HCN4, the major channel subtypes underlying native If , at both the mRNA and protein level. These findings indicate that amiodarone inhibits If under hypertrophied conditions through dual mechanisms: (i) direct channel blockade of If currents; and (ii) indirect suppression via negative regulation of HCN channel gene expression. These unique properties of amiodarone may contribute to its anti-arrhythmic properties under pathological conditions. © 2014 Wiley Publishing Asia Pty Ltd.

  12. Chemical content of the circumstellar envelope of the oxygen-rich AGB star R Doradus. Non-LTE abundance analysis of CO, SiO, and HCN

    Science.gov (United States)

    Van de Sande, M.; Decin, L.; Lombaert, R.; Khouri, T.; de Koter, A.; Wyrowski, F.; De Nutte, R.; Homan, W.

    2018-01-01

    Context. The stellar outflows of low- to intermediate-mass stars are characterised by a rich chemistry. Condensation of molecular gas species into dust grains is a key component in a chain of physical processes that leads to the onset of a stellar wind. In order to improve our understanding of the coupling between the micro-scale chemistry and macro-scale dynamics, we need to retrieve the abundance of molecules throughout the outflow. Aims: Our aim is to determine the radial abundance profile of SiO and HCN throughout the stellar outflow of R Dor, an oxygen-rich AGB star with a low mass-loss rate. SiO is thought to play an essential role in the dust-formation process of oxygen-rich AGB stars. The presence of HCN in an oxygen-rich environment is thought to be due to non-equilibrium chemistry in the inner wind. Methods: We analysed molecular transitions of CO, SiO, and HCN measured with the APEX telescope and all three instruments on the Herschel Space Observatory, together with data available in the literature. Photometric data and the infrared spectrum measured by ISO-SWS were used to constrain the dust component of the outflow. Using both continuum and line radiative transfer methods, a physical envelope model of both gas and dust was established. We performed an analysis of the SiO and HCN molecular transitions in order to calculate their abundances. Results: We have obtained an envelope model that describes the dust and the gas in the outflow, and determined the abundance of SiO and HCN throughout the region of the stellar outflow probed by our molecular data. For SiO, we find that the initial abundance lies between 5.5 × 10-5 and 6.0 × 10-5 with respect to H2. The abundance profile is constant up to 60 ± 10 R∗, after which it declines following a Gaussian profile with an e-folding radius of 3.5 ± 0.5 × 1013 cm or 1.4 ± 0.2 R∗. For HCN, we find an initial abundance of 5.0 × 10-7 with respect to H2. The Gaussian profile that describes the decline

  13. 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

  14. Development of selective catalytic oxidation (SCO) for NH{sub 3} and HCN removal from gasification gas; Selektiivisen katalyyttisen hapetusprosessin (SCO) kehittaeminen kaasutuskaasun NH{sub 3}:n ja HCN:n poistoon

    Energy Technology Data Exchange (ETDEWEB)

    Leppaelahti, J.; Koljonen, T.; Heiskanen, K. [VTT Energy, Espoo (Finland)

    1997-10-01

    In gasification, reactive nitrogen compounds (mainly NH{sub 3} and HCN) are formed from fuel nitrogen. If the gas containing NH{sub 3} is burned, a high NO{sub x} emission may be formed. The content of nitrogen compounds of the hot gasification gas could be reduced in Selective Catalytic Oxidation (SCO) process. In this process small amounts of reactive oxidisers are injected into the gas in order to convert NH{sub 3} to N{sub 2}. The utilization of SCO process together with low NO{sub x} burners in advanced gasification power stations might offer an alternative for flue gas treatment technologies like SCR (Selective Catalytic Reduction). In the earlier research, conditions were found, where oxidizers reacted selectively with ammonia in the gasification gas. Highest ammonia reduction took place in the aluminium oxide bed in the presence of NO and O{sub 2}. The aim of this study is to examine the reaction mechanism in order to be able to further evaluate the development possibilities of this kind process. The effect of composition and the amount of added oxidizer, the content of combustible gas components, space velocity, pressure and temperature will be studied. The experiments are carried out with the laboratory scale high pressure flow reactor of VTT Energy. Kinetic modelling of the experimental results is carried out in co-operation with the combustion chemistry group of Aabo Akademi. The aim of the modelling work is to bring insight to the gas-phase reactions that are important for the SCO-process. (orig.)

  15. Revisiting the Lamotrigine-Mediated Effect on Hippocampal GABAergic Transmission

    Directory of Open Access Journals (Sweden)

    Yu-Yin Huang

    2016-07-01

    Full Text Available Lamotrigine (LTG is generally considered as a voltage-gated sodium (Nav channel blocker. However, recent studies suggest that LTG can also serve as a hyperpolarization-activated cyclic nucleotide-gated (HCN channel enhancer and can increase the excitability of GABAergic interneurons (INs. Perisomatic inhibitory INs, predominantly fast-spiking basket cells (BCs, powerfully inhibit granule cells (GCs in the hippocampal dentate gyrus. Notably, BCs express abundant Nav channels and HCN channels, both of which are able to support sustained action potential generation. Using whole-cell recording in rat hippocampal slices, we investigated the net LTG effect on BC output. We showed that bath application of LTG significantly decreased the amplitude of evoked compound inhibitory postsynaptic currents (IPSCs in GCs. In contrast, simultaneous paired recordings from BCs to GCs showed that LTG had no effect on both the amplitude and the paired-pulse ratio of the unitary IPSCs, suggesting that LTG did not affect GABA release, though it suppressed cell excitability. In line with this, LTG decreased spontaneous IPSC (sIPSC frequency, but not miniature IPSC frequency. When re-examining the LTG effect on GABAergic transmission in the cornus ammonis region 1 (CA1 area, we found that LTG markedly inhibits both the excitability of dendrite-targeting INs in the stratum oriens and the concurrent sIPSCs recorded on their targeting pyramidal cells (PCs without significant hyperpolarization-activated current (Ih enhancement. In summary, LTG has no effect on augmenting Ih in GABAergic INs and does not promote GABAergic inhibitory output. The antiepileptic effect of LTG is likely through Nav channel inhibition and the suppression of global neuronal network activity.

  16. On Shor's Channel Extension and Constrained Channels

    Science.gov (United States)

    Holevo, A. S.; Shirokov, M. E.

    Several equivalent formulations of the additivity conjecture for constrained channels, which formally is substantially stronger than the unconstrained additivity, are given. To this end a characteristic property of the optimal ensemble for such a channel is derived, generalizing the maximal distance property. It is shown that the additivity conjecture for constrained channels holds true for certain nontrivial classes of channels. After giving an algebraic formulation for Shor's channel extension, its main asymptotic property is proved. It is then used to show that additivity for two constrained channels can be reduced to the same problem for unconstrained channels, and hence, ``global'' additivity for channels with arbitrary constraints is equivalent to additivity without constraints.

  17. Rapid State-Dependent Alteration in Kv3 Channel Availability Drives Flexible Synaptic Signaling Dependent on Somatic Subthreshold Depolarization.

    Science.gov (United States)

    Rowan, Matthew J M; Christie, Jason M

    2017-02-21

    In many neurons, subthreshold depolarization in the soma can transiently increase action-potential (AP)-evoked neurotransmission via analog-to-digital facilitation. The mechanisms underlying this form of short-term synaptic plasticity are unclear, in part, due to the relative inaccessibility of the axon to direct physiological interrogation. Using voltage imaging and patch-clamp recording from presynaptic boutons of cerebellar stellate interneurons, we observed that depolarizing somatic potentials readily spread into the axon, resulting in AP broadening, increased spike-evoked Ca(2+) entry, and enhanced neurotransmission strength. Kv3 channels, which drive AP repolarization, rapidly inactivated upon incorporation of Kv3.4 subunits. This leads to fast susceptibility to depolarization-induced spike broadening and analog facilitation independent of Ca(2+)-dependent protein kinase C signaling. The spread of depolarization into the axon was attenuated by hyperpolarization-activated currents (Ih currents) in the maturing cerebellum, precluding analog facilitation. These results suggest that analog-to-digital facilitation is tempered by development or experience in stellate cells. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  18. Rapid State-Dependent Alteration in Kv3 Channel Availability Drives Flexible Synaptic Signaling Dependent on Somatic Subthreshold Depolarization

    Directory of Open Access Journals (Sweden)

    Matthew J.M. Rowan

    2017-02-01

    Full Text Available In many neurons, subthreshold depolarization in the soma can transiently increase action-potential (AP-evoked neurotransmission via analog-to-digital facilitation. The mechanisms underlying this form of short-term synaptic plasticity are unclear, in part, due to the relative inaccessibility of the axon to direct physiological interrogation. Using voltage imaging and patch-clamp recording from presynaptic boutons of cerebellar stellate interneurons, we observed that depolarizing somatic potentials readily spread into the axon, resulting in AP broadening, increased spike-evoked Ca2+ entry, and enhanced neurotransmission strength. Kv3 channels, which drive AP repolarization, rapidly inactivated upon incorporation of Kv3.4 subunits. This leads to fast susceptibility to depolarization-induced spike broadening and analog facilitation independent of Ca2+-dependent protein kinase C signaling. The spread of depolarization into the axon was attenuated by hyperpolarization-activated currents (Ih currents in the maturing cerebellum, precluding analog facilitation. These results suggest that analog-to-digital facilitation is tempered by development or experience in stellate cells.

  19. Unnatural amino acid photo-crosslinking of the IKs channel complex demonstrates a KCNE1:KCNQ1 stoichiometry of up to 4:4.

    Science.gov (United States)

    Murray, Christopher I; Westhoff, Maartje; Eldstrom, Jodene; Thompson, Emely; Emes, Robert; Fedida, David

    2016-01-23

    Cardiac repolarization is determined in part by the slow delayed rectifier current (IKs), through the tetrameric voltage-gated ion channel, KCNQ1, and its β-subunit, KCNE1. The stoichiometry between α and β-subunits has been controversial with studies reporting either a strict 2 KCNE1:4 KCNQ1 or a variable ratio up to 4:4. We used IKs fusion proteins linking KCNE1 to one (EQ), two (EQQ) or four (EQQQQ) KCNQ1 subunits, to reproduce compulsory 4:4, 2:4 or 1:4 stoichiometries. Whole cell and single-channel recordings showed EQQ and EQQQQ to have increasingly hyperpolarized activation, reduced conductance, and shorter first latency of opening compared to EQ - all abolished by the addition of KCNE1. As well, using a UV-crosslinking unnatural amino acid in KCNE1, we found EQQQQ and EQQ crosslinking rates to be progressively slowed compared to KCNQ1, which demonstrates that no intrinsic mechanism limits the association of up to four β-subunits within the IKs complex.

  20. The influence of zinc hydroxystannate on reducing toxic gases (CO, NO{sub x} and HCN) generation and fire hazards of thermoplastic polyurethane composites

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Bibo; Sheng, Haibo [State Key Laboratory of Fire Science, University of Science and Technology of China, Anhui 230026 (China); Shi, Yongqian [State Key Laboratory of Fire Science, University of Science and Technology of China, Anhui 230026 (China); Suzhou Key Laboratory of Urban Public Safety, Suzhou Institute for Advanced Study, University of Science and Technology of China, Jiangsu, Suzhou 215123 (China); Song, Lei [State Key Laboratory of Fire Science, University of Science and Technology of China, Anhui 230026 (China); Zhang, Yan [State Key Laboratory of Fire Science, University of Science and Technology of China, Anhui 230026 (China); Suzhou Key Laboratory of Urban Public Safety, Suzhou Institute for Advanced Study, University of Science and Technology of China, Jiangsu, Suzhou 215123 (China); Hu, Yuan, E-mail: yuanhu@ustc.edu.cn [State Key Laboratory of Fire Science, University of Science and Technology of China, Anhui 230026 (China); Suzhou Key Laboratory of Urban Public Safety, Suzhou Institute for Advanced Study, University of Science and Technology of China, Jiangsu, Suzhou 215123 (China); Hu, Weizhao, E-mail: hwz1988@ustc.edu.cn [State Key Laboratory of Fire Science, University of Science and Technology of China, Anhui 230026 (China)

    2016-08-15

    Highlights: • The ZnHS could significantly enhance the mechanical properties of the TPU composites. • ZnHS has excellent smoke suppression and reduction the HRR for TPU composites. • ZnHS shows significant decrease in CO, HCN, NO{sub x} for TPU composites. • These improvements are due to charring and catalytic degradation the toxic gases. - Abstract: A uniform zinc hydroxystannate (ZnHS) microcube was synthesized to reduce toxicity and fire hazards of thermoplastic polyurethane (TPU) composites using ammonium polyphosphate as a flame retardant agent. The structure, morphology and thermal properties of ZnHS were characterized by X-ray diffraction, transmission electron microscopy and thermogravimetric analysis, respectively. Smoke suppression properties and synergistic flame retardant effect of ZnHS on flame retardant TPU composites were intensively investigated by smoke density test, cone calorimeter test, and thermalgravimetric analysis. Thermogravimetric analysis/infrared spectrometry and tube furnace were employed to evaluate the toxic gases (CO, NO{sub x} and HCN) of TPU composites. The incorporation of ZnHS into TPU matrix effectively improved the fire safety and restrained the smoke density, which is attributed to that the char residue catalyzed by ZnHS enhanced barrier effect that reduced peak heat release rate, total heat release, smoke particles and organic volatiles during combustion. Furthermore, the ZnHS synergist demonstrated high efficiency in catalytic degradation of the toxic gases, which obviously decreased total volatiled product and toxic volatiles evolved, such as the CO, HCN and NO{sub x}, indicating suppressed toxicity of the TPU composites.

  1. Molecular Reconnaissance of the β Pictoris Gas Disk with the SMA: A Low HCN/(CO+CO2) Outgassing Ratio and Predictions for Future Surveys

    Science.gov (United States)

    Matrà, L.; Wilner, D. J.; Öberg, K. I.; Andrews, S. M.; Loomis, R. A.; Wyatt, M. C.; Dent, W. R. F.

    2018-02-01

    The exocometary origin of CO gas has been confirmed in several extrasolar Kuiper belts, with CO ice abundances consistent with solar system comets. We here present a molecular survey of the β Pictoris belt with the Submillimeter Array (SMA), reporting upper limits for CN, HCN, HCO+, N2H+, and H2CO, as well as for H2S, CH3OH, SiO, and DCN from archival ALMA data. Nondetections can be attributed to rapid molecular photodissociation due to the A-star’s strong UV flux. CN is the longest lasting and most easily detectable molecule after CO in this environment. We update our nonlocal thermodynamic equilibrium excitation model to include UV fluorescence, finding it plays a key role in CO and CN excitation, and we use it to turn the SMA CN/CO flux ratio constraint into an upper limit of value is consistent with, but at the low end of, the broad range observed in solar system comets. If sublimation dominates outgassing, then this low value may be caused by decreased outgassing for the less volatile molecule HCN compared to CO. If instead UV photodesorption or collisional vaporization of unbound grains dominates outgassing, then this low ratio of rates would imply a low ice abundance ratio, which would in turn indicate a variation in cometary cyanide abundances across planetary systems. To conclude, we make predictions for future molecular surveys and show that CN and HCN should be readily detectable with ALMA around β Pictoris for solar-system-like exocometary compositions.

  2. The cardiac sodium channel displays differential distribution in the conduction system and transmural heterogeneity in the murine ventricular myocardium.

    Science.gov (United States)

    Remme, C A; Verkerk, A O; Hoogaars, W M H; Aanhaanen, W T J; Scicluna, B P; Annink, C; van den Hoff, M J B; Wilde, A A M; van Veen, T A B; Veldkamp, M W; de Bakker, J M T; Christoffels, V M; Bezzina, C R

    2009-09-01

    Cardiac sodium channels are responsible for conduction in the normal and diseased heart. We aimed to investigate regional and transmural distribution of sodium channel expression and function in the myocardium. Sodium channel Scn5a mRNA and Na(v)1.5 protein distribution was investigated in adult and embryonic mouse heart through immunohistochemistry and in situ hybridization. Functional sodium channel availability in subepicardial and subendocardial myocytes was assessed using patch-clamp technique. Adult and embryonic (ED14.5) mouse heart sections showed low expression of Na(v)1.5 in the HCN4-positive sinoatrial and atrioventricular nodes. In contrast, high expression levels of Na(v)1.5 were observed in the HCN4-positive and Cx43-negative AV or His bundle, bundle branches and Purkinje fibers. In both ventricles, a transmural gradient was observed, with a low Na(v)1.5 labeling intensity in the subepicardium as compared to the subendocardium. Similar Scn5a mRNA expression patterns were observed on in situ hybridization of embryonic and adult tissue. Maximal action potential upstroke velocity was significantly lower in subepicardial myocytes (mean +/- SEM 309 +/- 32 V/s; n = 14) compared to subendocardial myocytes (394 +/- 32 V/s; n = 11; P channel availability in subepicardium compared to subendocardium. Scn5a and Na(v)1.5 show heterogeneous distribution patterns within the cardiac conduction system and across the ventricular wall. This differential distribution of the cardiac sodium channel may have profound consequences for conduction disease phenotypes and arrhythmogenesis in the setting of sodium channel disease.

  3. Transcriptional Remodeling of Ion Channel Subunits by Flow Adaptation in Human Coronary Artery Endothelial Cells

    Science.gov (United States)

    Kefaloyianni, Eirini; Coetzee, William A.

    2011-01-01

    Endothelial cells (ECs) are constantly exposed to blood flow-induced shear forces in the vessels and this is a major determinant of endothelial function. Ion channels have a major role in endothelial function and in the control of vascular tone. We hypothesized that shear force is a general regulator of ion channel expression, which will have profound effects on endothelial function. We examined this hypothesis using large-scale quantitative real-time RT-PCR. Human coronary artery ECs were exposed to two levels of flow-induced shear stress for 24 h, while control cells were grown under static conditions. The expression of ion channel subunits was compared between control and flow-adapted cells. We used primers against 55 ion channel and exchanger subunits and were able to detect 54 subunits. Five dyn/cm2 of shear induced downregulation of 1 (NCX1) and upregulation of 18 subunits, including KCa2.2, KCa2.3, CX37, Kv1.5 and HCN2. Fifteen dyn/cm2 of shear stress induced the expression of 30 ion channel subunits, including KCa2.3, KCa2.2, CX37, Kir2.3 and KCa3.1. Our data demonstrate that substantial remodeling of endothelial ion channel subunit expression occurs with flow adaptation and suggest that altered ion channel expression may significantly contribute to vascular pathology associated with flow-induced alterations. PMID:21389733

  4. Opposite effects of the S4-S5 linker and PIP2 on voltage-gated channel function: KCNQ1/KCNE1 and other channels

    Directory of Open Access Journals (Sweden)

    Frank S Choveau

    2012-07-01

    Full Text Available Voltage-gated potassium (Kv channels are tetramers, each subunit presenting six transmembrane segments (S1-S6, with each S1-S4 segments forming a voltage-sensing domain (VSD and the four S5-S6 forming both the conduction pathway and its gate. S4 segments control the opening of the intracellular activation gate in response to changes in membrane potential. Crystal structures of several voltage-gated ion channels in combination with biophysical and mutagenesis studies highlighted the critical role of the S4-S5 linker (S4S5L and of the S6 C-terminal part (S6T in the coupling between the VSD and the activation gate. Several mechanisms have been proposed to describe the coupling at a molecular scale. This review summarizes the mechanisms suggested for various voltage-gated ion channels, including a mechanism that we described for KCNQ1, in which S4S5L is acting like a ligand binding to S6T to stabilize the channel in a closed state. As discussed in this review, this mechanism may explain the reverse response to depolarization in HCN-like channels. As opposed to S4S5L, the phosphoinositide, phosphatidylinositol 4,5-bisphosphate (PIP2, stabilizes KCNQ1 channel in an open state. Many other ion channels (not only voltage-gated require PIP2 to function properly, confirming its crucial importance as an ion channel co-factor. This is highlighted in cases in which an altered regulation of ion channels by PIP2 leads to channelopathies, as observed for KCNQ1. This review summarizes the state of the art on the two regulatory mechanisms that are critical for KCNQ1 and other voltage-gated channels function (PIP2 and S4-S5L, and assesses their potential physiological and pathophysiological roles.

  5. A new ab initio potential energy surface for the collisional excitation of HCN by para- and ortho-H{sub 2}

    Energy Technology Data Exchange (ETDEWEB)

    Denis-Alpizar, Otoniel, E-mail: otonieldenisalpizar@gmail.com [Université de Bordeaux, ISM, CNRS UMR 5255, 33405 Talence Cedex (France); Departamento de Física, Universidad de Matanzas, Matanzas 40100 (Cuba); Kalugina, Yulia [LOMC - UMR 6294, CNRS-Université du Havre, 25 rue Philippe Lebon, BP 540, 76058, Le Havre (France); Department of Optics and Spectroscopy, Tomsk State University, 36 Lenin av., Tomsk 634050 (Russian Federation); Stoecklin, Thierry [Université de Bordeaux, ISM, CNRS UMR 5255, 33405 Talence Cedex (France); Vera, Mario Hernández [LOMC - UMR 6294, CNRS-Université du Havre, 25 rue Philippe Lebon, BP 540, 76058, Le Havre (France); Instituto Superior de Tecnologías y Ciencias Aplicadas, Quinta de Los Molinos, Plaza, La Habana 10600 (Cuba); Lique, François, E-mail: francois.lique@univ-lehavre.fr [Departamento de Física, Universidad de Matanzas, Matanzas 40100 (Cuba)

    2013-12-14

    We present a new four-dimensional potential energy surface for the collisional excitation of HCN by H{sub 2}. Ab initio calculations of the HCN–H{sub 2} van der Waals complex, considering both molecules as rigid rotors, were carried out at the explicitly correlated coupled cluster with single, double, and perturbative triple excitations [CCSD(T)-F12a] level of theory using an augmented correlation-consistent triple zeta (aVTZ) basis set. The equilibrium structure is linear HCN–H{sub 2} with the nitrogen pointing towards H{sub 2} at an intermolecular separation of 7.20 a{sub 0}. The corresponding well depth is −195.20 cm{sup −1}. A secondary minimum of −183.59 cm{sup −1} was found for a T-shape configuration with the H of HCN pointing to the center of mass of H{sub 2}. We also determine the rovibrational energy levels of the HCN–para-H{sub 2} and HCN–ortho-H{sub 2} complexes. The calculated dissociation energies for the para and ortho complexes are 37.79 cm{sup −1} and 60.26 cm{sup −1}, respectively. The calculated ro-vibrational transitions in the HCN–H{sub 2} complex are found to agree by more than 0.5% with the available experimental data, confirming the accuracy of the potential energy surface.

  6. Possible selective formation of CNC/sup +/ and CCN/sup +/ in the interstellar reactions of C/sup +/ with HCN and HNC/sup +/

    Energy Technology Data Exchange (ETDEWEB)

    Haese, N.N.; Woods, R.C.

    1981-05-15

    The molecular structures of CNC/sup +/ and CCN/sup +/ have been determined by double zeta self-consistent field (SCF) calculations. Their standard heats of formation are theoretically estimated to be 372 +- 20 and 421 +- 25 kcal mol/sup -1/, respectively, the latter determined by double zeta plus polarization SCF-CI (configuration interaction) calculation of the isomerization energy for CNC/sup +/..-->..CCN/sup +/. Using these results, the available appearance potential data for these ions in the mass spectra of HC/sub 3/N and C/sub 2/N/sub 2/ can be explained by simple reactions, and the numerical agreement between the corresponding experimental and theoretical heats of formation is excellent. With this thermochemical information and mechanistic considerations of C/sup +/ reactions with HCN and HNC, we propose that CNC/sup +/ may be selectively made from HCN, and CCN/sup +/ from HNC, and that this selectivity may play an important role in the chemistry of the interstellar medium. For the polar isomer CCN/sup +/ we report an SCF prediction of its rotational constant (11.93 +- 0.5 GHz) and a higher-level (CI) calculation of its electric dipole moment (2.50 +- 0.2 debye) and nitrogen nuclear quadrupole coupling constant (-4.95 +- 0.5 MHz).

  7. Dendritic distributions of Ih channels in experimentally-derived multi-compartment models of oriens-lacunosum/moleculare (O-LM hippocampal interneurons

    Directory of Open Access Journals (Sweden)

    Vladislav eSekulic

    2015-02-01

    Full Text Available The O-LM cell type mediates feedback inhibition onto hippocampal pyramidal cells and gates information flow in the CA1. Its functions depend on the presence of voltage-gated channels (VGCs, which affect its integrative properties and response to synaptic input. Given the challenges associated with determining densities and distributions of VGCs on interneuron dendrites, we take advantage of computational modeling to consider different possibilities. In this work, we focus on hyperpolarization-activated channels (h-channels in O-LM cells. While h-channels are known to be present in O-LM cells, it is unknown whether they are present on their dendrites. In previous work, we used ensemble modeling techniques with experimental data to obtain insights into potentially important conductance balances. We found that the best O-LM models that included uniformly distributed h-channels in the dendrites could not fully capture the sag response. This led us to examine activation kinetics and non-uniform distributions of h-channels in the present work. In tuning our models, we found that different kinetics and non-uniform distributions could better reproduce experimental O-LM cell responses. In contrast to CA1 pyramidal cells where higher conductance densities of h-channels occur in more distal dendrites, decreasing conductance densities of h-channels away from the soma were observed in O-LM models. Via an illustrative scenario, we showed that having dendritic h-channels clearly speeds up back-propagating action potentials in O-LM cells, unlike when h-channels are present only in the soma. Although the present results were morphology-dependent, our work shows that it should be possible to determine the distributions and characteristics of O-LM cells with recordings and morphologies from the same cell. We hypothesize that h-channels are distributed in O-LM cell dendrites and endow them with particular synaptic integration properties that shape information flow

  8. GLI3 repressor controls functional development of the mouse ureter

    Science.gov (United States)

    Cain, Jason E.; Islam, Epshita; Haxho, Fiona; Blake, Joshua; Rosenblum, Norman D.

    2011-01-01

    Obstructive and nonobstructive forms of hydronephrosis (increased diameter of the renal pelvis and calyces) and hydroureter (dilatation of the ureter) are the most frequently detected antenatal abnormalities, yet the underlying molecular mechanisms are largely undefined. Hedgehog (Hh) proteins control tissue patterning and cell differentiation by promoting GLI-dependent transcriptional activation and by inhibiting the processing of GLI3 to a transcriptional repressor. Genetic mutations that generate a truncated GLI3 protein similar in size to the repressor in humans with Pallister-Hall syndrome (PHS; a disorder whose characteristics include renal abnormalities) and hydroureter implicate Hh-dependent signaling in ureter morphogenesis and function. Here, we determined that Hh signaling controls 2 cell populations required for the initiation and transmission of coordinated ureter contractions. Tissue-specific inactivation of the Hh cell surface effector Smoothened (Smo) in the renal pelvic and upper ureteric mesenchyme resulted in nonobstructive hydronephrosis and hydroureter characterized by ureter dyskinesia. Mutant mice had reduced expression of markers of cell populations implicated in the coordination of unidirectional ureter peristalsis (specifically, Kit and hyperpolarization-activation cation–3 channel [Hcn3]), but exhibited normal epithelial and smooth muscle cell differentiation. Kit deficiency in a mouse model of PHS suggested a pathogenic role for GLI3 repressor in Smo-deficient embryos; indeed, genetic inactivation of Gli3 in Smo-deficient mice rescued their hydronephrosis, hydroureter, Kit and Hcn3 expression, and ureter peristalsis. Together, these data demonstrate that Hh signaling controls Kit and Hcn3 expression and ureter peristalsis. PMID:21339645

  9. Preserved Autonomic Cardiovascular Regulation With Cardiac Pacemaker Inhibition: A Crossover Trial Using High-Fidelity Cardiovascular Phenotyping.

    Science.gov (United States)

    Heusser, Karsten; Tank, Jens; Brinkmann, Julia; Schroeder, Christoph; May, Marcus; Großhennig, Anika; Wenzel, Daniela; Diedrich, André; Sweep, Fred C G J; Mehling, Heidrun; Luft, Friedrich C; Jordan, Jens

    2016-01-13

    Sympathetic and parasympathetic influences on heart rate (HR), which are governed by baroreflex mechanisms, are integrated at the cardiac sinus node through hyperpolarization-activated cyclic nucleotide-gated channels (HCN4). We hypothesized that HCN4 blockade with ivabradine selectively attenuates HR and baroreflex HR regulation, leaving baroreflex control of muscle sympathetic nerve activity intact. We treated 21 healthy men with 2×7.5 mg ivabradine or placebo in a randomized crossover fashion. We recorded electrocardiogram, blood pressure, and muscle sympathetic nerve activity at rest and during pharmacological baroreflex testing. Ivabradine reduced normalized HR from 65.9±8.1 to 58.4±6.2 beats per minute (P<0.001) with unaffected blood pressure and muscle sympathetic nerve activity. On ivabradine, cardiac and sympathetic baroreflex gains and blood pressure responses to vasoactive drugs were unchanged. Ivabradine aggravated bradycardia during baroreflex loading. HCN4 blockade with ivabradine reduced HR, leaving physiological regulation of HR and muscle sympathetic nerve activity as well as baroreflex blood pressure buffering intact. Ivabradine could aggravate bradycardia during parasympathetic activation. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00865917. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  10. 12C/13C and 14N/15N isotopic ratios in HCN in the middle atmosphere of Titan from Cassini/CIRS data

    Science.gov (United States)

    Mathé, Christophe; Vinatier, Sandrine; Bézard, Bruno; Nixon, Conor A.

    2017-10-01

    Our study aims at constraining the 12C/13C and 14N/15N isotopic ratios in HCN, the most abundant nitrile in Titan’s atmosphere, which can provide information on physical and chemical process occurring during the formation and/or destruction of this molecule.Over the last decade, several estimations of the 12C/13C and 14N/15N isotopic ratios in HCN were performed from ground-based, Herschel and Cassini observations (Bézard et al,2014). The 14N/15N ratio lies in the range 56-76, which corresponds to half of the 14N/15N ratio in N2 (major N-bearing molecule in Titan’s atmosphere). This nitrogen isotopic fractionation mostly originates from the photodissociation of N2 (Liang et al, 2007). The 12C/13C ratio lies in the range 75-108, in agreement with the 12C/13C ratio in CH4 (major C-bearing molecule). Recent disk-averaged ALMA observations indicate 12C/13C and 14N/15N ratios equal to ˜90 and ˜72, respectively (Molter et al, 2016).Vinatier et al (2007) derived 14N/15N and 12C/13C ratios in two different regions (equator and north pole) from Cassini/CIRS (Composite InfraRed Spectrometer) observations at the beginning of the Cassini mission. 14N/15N was similar for both latitudes while the 12C/13C ratio displayed a possible enhancement at the equator.We present here a new study of the 12C/13C and 14N/15N isotopic ratios in HCN from CIRS. We analyzed limb observations (0.5 cm-1 resolution) from northern winter to early spring at poles, mid-latitudes and equator in order to investigate potential spatial and seasonal changes of these isotopic ratios in Titan’s middle atmosphere. These preliminary results will be presented and compared with previous observations.References:Bézard et al., Cambrigde University Press, 2014Liang et al., The Astrophysical Jounral Letters, 2007Molter et al., The Astronomical Journal, 2016Vinatier et al., Icarus, 2007

  11. In silico determination of the effect of multi-target drugs on calcium dynamics signaling network underlying sea urchin spermatozoa motility.

    Directory of Open Access Journals (Sweden)

    Jesús Espinal-Enríquez

    Full Text Available The motility of spermatozoa of both Lytechinus pictus and Strongylocentrotus purpuratus sea urchin species is modulated by the egg-derived decapeptide speract via an oscillatory [Ca2+]-dependent signaling pathway. Comprehension of this pathway is hence directly related to the understanding of regulated sperm swimming. Niflumic acid (NFA, a nonsteroidal anti-inflammatory drug alters several ion channels. Though unspecific, NFA profoundly affects how sea urchin sperm respond to speract, increasing the [Ca2+]i oscillation period, amplitude, peak and average level values of the responses in immobilized and swimming cells. A previous logical network model we developed for the [Ca2+] dynamics of speract signaling cascade in sea urchin sperm allows integrated dissection of individual and multiple actions of NFA. Among the channels affected by NFA are: hyperpolarization-activated and cyclic nucleotide gated Na+ channels (HCN, [Ca2+]-dependent Cl- channels (CaCC and [Ca2+]-dependent K+ channels (CaKC, all present in the sea urchin genome. Here, using our model we investigated the effect of blocking in silico HCN and CaCC channels suggested by experiments. Regarding CaKC channels, arguments can be provided for either their blockage or activation by NFA. Our study yielded two scenarios compliant with experimental observations: i under CaKC inhibition, this [Ca2+]-dependent K+ channel should be different from the Slo1 channel and ii under activation of the CaKC channel, another [Ca2+] channel not considered previously in the network is required, such as the pH-dependent CatSper channel. Additionally, our findings predict cause-effect relations resulting from a selective inhibition of those channels. Knowledge of these relations may be of consequence for a variety of electrophysiological studies and have an impact on drug related investigations. Our study contributes to a better grasp of the network dynamics and suggests further experimental work.

  12. 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,

  13. Convergent and reciprocal modulation of a leak K+ current and Ih by an inhalational anaesthetic and neurotransmitters in rat brainstem motoneurones

    Science.gov (United States)

    Sirois, Jay E; Lynch, Carl; Bayliss, Douglas A

    2002-01-01

    anaesthetic actions resulting from effects on either TASK or hyperpolarization-activated cyclic nucleotide-gated (HCN) channels in motoneurones, and perhaps at other CNS sites, can be modulated by prevailing neurotransmitter tone. PMID:12068035

  14. Channel nut tool

    Science.gov (United States)

    Olson, Marvin

    2016-01-12

    A method, system, and apparatus for installing channel nuts includes a shank, a handle formed on a first end of a shank, and an end piece with a threaded shaft configured to receive a channel nut formed on the second end of the shaft. The tool can be used to insert or remove a channel nut in a channel framing system and then removed from the channel nut.

  15. [Memory and potassium channels].

    Science.gov (United States)

    Solntseva, E I; Bukanova, Iu V; Skrebitskiĭ, V G

    2003-01-01

    The K(+)-channels of the surface membrane play a crucial role in the generation of electrical activity of a neuron. There is a large diversity of the K(+)-channels that depends on a great number (over 200) of genes encoding channels proteins. An evolutionary conservation of channel's proteins is determined. The K(+)-channels were found to have a great importance in the memory processes. It was shown on different model systems that K(+)-current of the surface membrane decreases during the learning. The antagonists of K(+)-channels were found to improve the learning and memory. It was revealed in electrophysiological experiments that K(+)-channels antagonists can either themselves induce a long-term synaptic potentiation or intensify the synaptic potentiation induced by a tetanization. The disfunction of K(+)-channels is believed to be an important link in the mechanisms of memory disturbances. In animal mutants with K(+)-channels disfunction, learning and memory are deficient. In behavioral experiments, the use of K(+)-channels openers make the learning worse. Amnesia caused by cerebral ischemia is explained by strong activity of K(+)-channels which not only inhibits neuronal excitement but also causes neurodegeneration. The question on the K(+)-channels involvement into pathophysiology of Alzheimer's disease is discussed. Neurotoxic peptide beta-amyloid, which is supposed to be involved into mechanisms of Alzheimer's disease, modulates K(+)-channels function. The effect of beta-amyloid depends on the subtype of K(+)-channels: A-channels are inhibited, and KDR-channels, on the contrary, become stronger. The effect of the cognitive enhancers (vinpocetine, piracetam, tacrine, linopirdine) on K(+)-current also depends on the subtype of K(+)-channels. Slow-inactivating K(+)-currents (IDR, IK(Ca), IM) are inhibited in the presence of these drugs, while fast-in-activating K(+)-current (A-current) remains unchanged or even increases.

  16. Hadamard quantum broadcast channels

    Science.gov (United States)

    Wang, Qingle; Das, Siddhartha; Wilde, Mark M.

    2017-10-01

    We consider three different communication tasks for quantum broadcast channels, and we determine the capacity region of a Hadamard broadcast channel for these various tasks. We define a Hadamard broadcast channel to be such that the channel from the sender to one of the receivers is entanglement-breaking and the channel from the sender to the other receiver is complementary to this one. As such, this channel is a quantum generalization of a degraded broadcast channel, which is well known in classical information theory. The first communication task we consider is classical communication to both receivers, the second is quantum communication to the stronger receiver and classical communication to other, and the third is entanglement-assisted classical communication to the stronger receiver and unassisted classical communication to the other. The structure of a Hadamard broadcast channel plays a critical role in our analysis: The channel to the weaker receiver can be simulated by performing a measurement channel on the stronger receiver's system, followed by a preparation channel. As such, we can incorporate the classical output of the measurement channel as an auxiliary variable and solve all three of the above capacities for Hadamard broadcast channels, in this way avoiding known difficulties associated with quantum auxiliary variables.

  17. USACE Navigation Channels 2012

    Data.gov (United States)

    California Department of Resources — This dataset represents both San Francisco and Los Angeles District navigation channel lines. All San Francisco District channel lines were digitized from CAD files...

  18. Calcium channel blocker overdose

    Science.gov (United States)

    ... 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 to ...

  19. Ion channel transcript expression at the rabbit atrioventricular conduction axis.

    Science.gov (United States)

    Greener, Ian D; Tellez, James O; Dobrzynski, Halina; Yamamoto, Mitsuru; Graham, Gillian M; Billeter, Rudi; Boyett, Mark R

    2009-06-01

    Little is known about the distribution of gap junctions and ion channels in the atrioventricular node, even though the physiology and pathology of the atrioventricular node is ultimately dependent on them. The abundance of 30 transcripts for markers, gap junctions, ion channels, and Ca(2+)-handling proteins in different regions of the rabbit atrioventricular node (nodal extension and proximal and distal penetrating bundle of His as well as atrial and ventricular muscle) was measured using a novel quantitative polymerase chain reaction technique and in situ hybridization. The expression profile of the nodal extension (slow pathway into penetrating bundle) was similar to that of the sinoatrial node. For example, in the nodal extension, in contrast to the atrial muscle and as expected for a slowly conducting tissue with pacemaker activity, there was no or reduced expression of Cx43, Na(v)1.5, Ca(v)1.2, K(v)1.4, KChIP2, and RYR3 and high expression of Ca(v)1.3 and HCN4. The expression profile of the penetrating bundle was less specialized. In situ hybridization revealed a transitional zone with reduced expression of Cx43, Na(v)1.5, and KChIP2 that may form the fast pathway into the penetrating bundle. At the atrioventricular node, the expression of gap junctions and ion channels in the nodal extension (slow pathway) and a transitional zone (putative fast pathway) as well as the penetrating bundle (output pathway) is specialized and heterogeneous and roughly matches the electrophysiology of the different regions.

  20. Channel morphology [Chapter 5

    Science.gov (United States)

    Jonathan W. Long; Alvin L. Medina; Daniel G. Neary

    2012-01-01

    Channel morphology has become an increasingly important subject for analyzing the health of rivers and associated fish populations, particularly since the popularization of channel classification and assessment methods. Morphological data can help to evaluate the flows of sediment and water that influence aquatic and riparian habitat. Channel classification systems,...

  1. 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...

  2. Boreal forest fire emissions in fresh Canadian smoke plumes: C1-C10 volatile organic compounds (VOCs, CO2, CO, NO2, NO, HCN and CH3CN

    Directory of Open Access Journals (Sweden)

    M. Yang

    2011-07-01

    Full Text Available Boreal regions comprise about 17 % of the global land area, and they both affect and are influenced by climate change. To better understand boreal forest fire emissions and plume evolution, 947 whole air samples were collected aboard the NASA DC-8 research aircraft in summer 2008 as part of the ARCTAS-B field mission, and analyzed for 79 non-methane volatile organic compounds (NMVOCs using gas chromatography. Together with simultaneous measurements of CO2, CO, CH4, CH2O, NO2, NO, HCN and CH3CN, these measurements represent the most comprehensive assessment of trace gas emissions from boreal forest fires to date. Based on 105 air samples collected in fresh Canadian smoke plumes, 57 of the 80 measured NMVOCs (including CH2O were emitted from the fires, including 45 species that were quantified from boreal forest fires for the first time. After CO2, CO and CH4, the largest emission factors (EFs for individual species were formaldehyde (2.1 ± 0.2 g kg−1, followed by methanol, NO2, HCN, ethene, α-pinene, β-pinene, ethane, benzene, propene, acetone and CH3CN. Globally, we estimate that boreal forest fires release 2.4 ± 0.6 Tg C yr−1 in the form of NMVOCs, with approximately 41 % of the carbon released as C1-C2 NMVOCs and 21 % as pinenes. These are the first reported field measurements of monoterpene emissions from boreal forest fires, and we speculate that the pinenes, which are relatively heavy molecules, were detected in the fire plumes as the result of distillation of stored terpenes as the vegetation is heated. Their inclusion in smoke chemistry models is expected to improve model predictions of secondary organic aerosol (SOA formation. The fire-averaged EF of dichloromethane or CH2Cl2, (6.9 ± 8.6 × 10−4 g kg−1, was not significantly different from zero and supports recent findings that its global biomass burning source appears to have been overestimated. Similarly, we found no evidence for emissions of chloroform (CHCl3 or methyl

  3. Stepwise association of hydrogen cyanide and acetonitrile with the benzene radical cation: structures and binding energies of (C6H6•+)(HCN)n, n = 1-6, and (C6H6•+)(CH3CN)n, n = 1-4, clusters.

    Science.gov (United States)

    Hamid, Ahmed M; Soliman, Abdel-Rahman; El-Shall, M Samy

    2013-02-14

    Equilibrium thermochemical measurements using the ion mobility drift cell technique have been utilized to investigate the binding energies and entropy changes associated with the stepwise association of HCN and CH(3)CN molecules with the benzene radical cation in the C(6)H(6)(•+)(HCN)(n) and C(6)H(6)(•+)(CH(3)CN)(n) clusters with n = 1-6 and 1-4, respectively. The binding energy of CH(3)CN to the benzene cation (14 kcal/mol) is stronger than that of HCN (9 kcal/mol) mostly due to a stronger ion-dipole interaction because of the large dipole moment of acetonitrile (3.9 D). However, HCN can form hydrogen bonds with the hydrogen atoms of the benzene cation (CH(δ+)···NCH) and linear hydrogen bonding chains involving HCN···HCN interaction. HCN molecules tend to form externally solvated structures with the benzene cation where the ion is hydrogen bonded to the exterior of HCN chains. For the C(6)H(6)(•+)(CH(3)CN)(n) clusters, internally solvated structures are formed where the acetonitrile molecules are directly interacting with the benzene cation through ion-dipole and hydrogen bonding interactions. The lack of formation of higher clusters with n > 4, in contrast to HCN, suggests the formation of a solvent shell at n = 4, which is attributed to steric interactions among the acetonitrile molecules attached to the benzene cation and to the presence of the blocking CH(3) groups, both effects make the addition of more than four acetonitrile molecules less favorable.

  4. Voltage-gated sodium channels in taste bud cells

    Directory of Open Access Journals (Sweden)

    Williams Mark E

    2009-03-01

    Full Text Available Abstract Background Taste bud cells transmit information regarding the contents of food from taste receptors embedded in apical microvilli to gustatory nerve fibers innervating basolateral membranes. In particular, taste cells depolarize, activate voltage-gated sodium channels, and fire action potentials in response to tastants. Initial cell depolarization is attributable to sodium influx through TRPM5 in sweet, bitter, and umami cells and an undetermined cation influx through an ion channel in sour cells expressing PKD2L1, a candidate sour taste receptor. The molecular identity of the voltage-gated sodium channels that sense depolarizing signals and subsequently initiate action potentials coding taste information to gustatory nerve fibers is unknown. Results We describe the molecular and histological expression profiles of cation channels involved in electrical signal transmission from apical to basolateral membrane domains. TRPM5 was positioned immediately beneath tight junctions to receive calcium signals originating from sweet, bitter, and umami receptor activation, while PKD2L1 was positioned at the taste pore. Using mouse taste bud and lingual epithelial cells collected by laser capture microdissection, SCN2A, SCN3A, and SCN9A voltage-gated sodium channel transcripts were expressed in taste tissue. SCN2A, SCN3A, and SCN9A were expressed beneath tight junctions in subsets of taste cells. SCN3A and SCN9A were expressed in TRPM5 cells, while SCN2A was expressed in TRPM5 and PKD2L1 cells. HCN4, a gene previously implicated in sour taste, was expressed in PKD2L1 cells and localized to cell processes beneath the taste pore. Conclusion SCN2A, SCN3A and SCN9A voltage-gated sodium channels are positioned to sense initial depolarizing signals stemming from taste receptor activation and initiate taste cell action potentials. SCN2A, SCN3A and SCN9A gene products likely account for the tetrodotoxin-sensitive sodium currents in taste receptor cells.

  5. Impaired Dendritic Expression and Plasticity of h-Channels in the fmr1−/y Mouse Model of Fragile X Syndrome

    Directory of Open Access Journals (Sweden)

    Darrin H. Brager

    2012-03-01

    Full Text Available Despite extensive research into both synaptic and morphological changes, surprisingly little is known about dendritic function in fragile X syndrome (FXS. We found that the dendritic input resistance of CA1 neurons was significantly lower in fmr1−/y versus wild-type mice. Consistent with elevated dendritic Ih, voltage sag, rebound, and resonance frequency were significantly higher and temporal summation was lower in the dendrites of fmr1−/y mice. Dendritic expression of the h-channel subunit HCN1, but not HCN2, was higher in the CA1 region of fmr1−/y mice. Interestingly, whereas mGluR-mediated persistent decreases in Ih occurred in both wild-type and fmr1−/y mice, persistent increases in Ih that occurred after LTP induction in wild-type mice were absent in fmr1−/y mice. Thus, chronic upregulation of dendritic Ih in conjunction with impairment of homeostatic h-channel plasticity represents a dendritic channelopathy in this model of mental retardation and may provide a mechanism for the cognitive impairment associated with FXS.

  6. Ion channel pharmacology.

    Science.gov (United States)

    Camerino, Diana Conte; Tricarico, Domenico; Desaphy, Jean-François

    2007-04-01

    Because ion channels are involved in many cellular processes, drugs acting on ion channels have long been used for the treatment of many diseases, especially those affecting electrically excitable tissues. The present review discusses the pharmacology of voltage-gated and neurotransmitter-gated ion channels involved in neurologic diseases, with emphasis on neurologic channelopathies. With the discovery of ion channelopathies, the therapeutic value of many basic drugs targeting ion channels has been confirmed. The understanding of the genotype-phenotype relationship has highlighted possible action mechanisms of other empirically used drugs. Moreover, other ion channels have been pinpointed as potential new drug targets. With regards to therapy of channelopathies, experimental investigations of the intimate drug-channel interactions have demonstrated that channel mutations can either increase or decrease affinity for the drug, modifying its potential therapeutic effect. Together with the discovery of channel gene polymorphisms that may affect drug pharmacodynamics, these findings highlight the need for pharmacogenetic research to allow identification of drugs with more specific effects on channel isoforms or mutants, to increase efficacy and reduce side effects. With a greater understanding of channel genetics, structure, and function, together with the identification of novel primary and secondary channelopathies, the number of ion channel drugs for neurologic channelopathies will increase substantially.

  7. Characterization of mid-infrared emissions from C2H2, CO, CO2, and HCN-filled hollow fiber lasers

    Science.gov (United States)

    Jones, A. M.; Fourcade-Dutin, C.; Mao, C.; Baumgart, B.; Nampoothiri, A. V. V.; Campbell, N.; Wang, Y.; Benabid, F.; Rudolph, W.; Washburn, B. R.; Corwin, K. L.

    2012-02-01

    We have now demonstrated and characterized gas-filled hollow-core fiber lasers based on population inversion from acetylene (12C2H2) and HCN gas contained within the core of a kagome-structured hollow-core photonic crystal fiber. The gases are optically pumped via first order rotational-vibrational overtones near 1.5 μm using 1-ns pulses from an optical parametric amplifier. Transitions from the pumped overtone modes to fundamental C-H stretching modes in both molecules create narrow-band laser emissions near 3 μm. High gain resulting from tight confinement of the pump and laser light together with the active gas permits us to operate these lasers in a single pass configuration, without the use of any external resonator structure. A delay between the emitted laser pulse and the incident pump pulse has been observed and is shown to vary with pump pulse energy and gas pressure. Furthermore, we have demonstrated lasing beyond 4 μm from CO and CO2 using silver-coated glass capillaries, since fused silica based fibers do not transmit in this spectral region and chalcogenide fibers are not yet readily available. Studies of the laser pulse energy as functions of the pump pulse energy and gas pressure were performed. Efficiencies reaching ~ 20% are observed for both acetylene and CO2.

  8. FORMATION OF N{sub 3}, CH{sub 3}, HCN, AND HNC FROM THE FAR-UV PHOTOLYSIS OF CH{sub 4} IN NITROGEN ICE

    Energy Technology Data Exchange (ETDEWEB)

    Lo, Jen-Iu; Chou, Sheng-Lung; Peng, Yu-Chain; Lin, Meng-Yeh; Lu, Hsiao-Chi; Cheng, Bing-Ming, E-mail: bmcheng@nsrrc.org.tw [National Synchrotron Radiation Research Center, No. 101, Hsin-Ann Road, Hsinchu Science Park, Hsinchu 30076, Taiwan (China)

    2015-11-15

    The irradiation of pure solid N{sub 2} at 3 K with far-ultraviolet light from a synchrotron produced infrared absorption lines at 1657.7, 1655.6, and 1652.4 cm{sup −1} and an ultraviolet absorption line at 272.0 nm, which are characteristic of the product N{sub 3}. The threshold wavelength at which N{sub 3} was generated was 145.6 ± 2.9 nm, corresponding to an energy of 8.52 ± 0.17 eV. The photolysis of isotopically labeled {sup 15}N{sub 2} at 3 K consistently led to the formation of {sup 15}N{sub 3} with the same threshold wavelength of 145.6 ± 2.9 nm for its formation. The photolysis of CH{sub 4} in nitrogen ice in low concentrations also led to the formation of N{sub 3}, together with CH{sub 3}, HCN, and HNC, with the same threshold wavelength of 145.6 ± 2.9 nm. These results indicate that N{sub 3} radicals may play an important role in the photochemistry of nitrogen ices in astronomical environments.

  9. 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.

  10. FTIR time-series of biomass burning products (HCN, C2H6, C2H2, CH3OH, and HCOOH) at Reunion Island (21° S, 55° E) and comparisons with model data

    Science.gov (United States)

    Vigouroux, C.; Stavrakou, T.; Whaley, C.; Dils, B.; Duflot, V.; Hermans, C.; Kumps, N.; Metzger, J.-M.; Scolas, F.; Vanhaelewyn, G.; Müller, J.-F.; Jones, D. B. A.; Li, Q.; De Mazière, M.

    2012-11-01

    Reunion Island (21° S, 55° E), situated in the Indian Ocean at about 800 km east of Madagascar, is appropriately located to monitor the outflow of biomass burning pollution from Southern Africa and Madagascar, in the case of short-lived compounds, and from other Southern Hemispheric landmasses such as South America, in the case of longer-lived species. Ground-based Fourier transform infrared (FTIR) solar absorption observations are sensitive to a large number of biomass burning products. We present in this work the FTIR retrieval strategies, suitable for very humid sites such as Reunion Island, for hydrogen cyanide (HCN), ethane (C2H6), acetylene (C2H2), methanol (CH3OH), and formic acid (HCOOH). We provide their total columns time-series obtained from the measurements during August-October 2004, May-October 2007, and May 2009-December 2010. We show that biomass burning explains a large part of the observed seasonal and interannual variability of the chemical species. The correlations between the daily mean total columns of each of the species and those of CO, also measured with our FTIR spectrometer at Reunion Island, are very good from August to November (R ≥ 0.86). This allows us to derive, for that period, the following enhancement ratios with respect to CO: 0.0047, 0.0078, 0.0020, 0.012, and 0.0046 for HCN, C2H6, C2H2, CH3OH, and HCOOH, respectively. The HCN ground-based data are compared to the chemical transport model GEOS-Chem, while the data for the other species are compared to the IMAGESv2 model. We show that using the HCN/CO ratio derived from our measurements (0.0047) in GEOS-Chem reduces the underestimation of the modeled HCN columns compared with the FTIR measurements. The comparisons between IMAGESv2 and the long-lived species C2H6 and C2H2 indicate that the biomass burning emissions used in the model (from the GFED3 inventory) are probably underestimated in the late September-October period for all years of measurements, and especially in

  11. The Neural Noisy Channel

    OpenAIRE

    Yu, Lei; Blunsom, Phil; Dyer, Chris; Grefenstette, Edward; Kocisky, Tomas

    2016-01-01

    We formulate sequence to sequence transduction as a noisy channel decoding problem and use recurrent neural networks to parameterise the source and channel models. Unlike direct models which can suffer from explaining-away effects during training, noisy channel models must produce outputs that explain their inputs, and their component models can be trained with not only paired training samples but also unpaired samples from the marginal output distribution. Using a latent variable to control ...

  12. A simple quantum channel having superadditivity of channel capacity

    OpenAIRE

    Sasaki, Masahide; Kato, Kentaro; Izutsu, Masayuki; Hirota, Osamu

    1997-01-01

    When classical information is sent through a quantum channel of nonorthogonal states, there is a possibility that transmittable classical information exceeds a channel capacity in a single use of the initial channel by extending it into multi-product channel. In this paper, it is shown that this remarkable feature of a quantum channel, so-called superadditivity, appears even in as low as the third extended coding of the simplest binary input channel. A physical implementation of this channel ...

  13. TRP channels in schistosomes

    Directory of Open Access Journals (Sweden)

    Swarna Bais

    2016-12-01

    Full Text Available Praziquantel (PZQ is effectively the only drug currently available for treatment and control of schistosomiasis, a disease affecting hundreds of millions of people worldwide. Many anthelmintics, likely including PZQ, target ion channels, membrane protein complexes essential for normal functioning of the neuromusculature and other tissues. Despite this fact, only a few classes of parasitic helminth ion channels have been assessed for their pharmacological properties or for their roles in parasite physiology. One such overlooked group of ion channels is the transient receptor potential (TRP channel superfamily. TRP channels share a common core structure, but are widely diverse in their activation mechanisms and ion selectivity. They are critical to transducing sensory signals, responding to a wide range of external stimuli. They are also involved in other functions, such as regulating intracellular calcium and organellar ion homeostasis and trafficking. Here, we review current literature on parasitic helminth TRP channels, focusing on those in schistosomes. We discuss the likely roles of these channels in sensory and locomotor activity, including the possible significance of a class of TRP channels (TRPV that is absent in schistosomes. We also focus on evidence indicating that at least one schistosome TRP channel (SmTRPA has atypical, TRPV1-like pharmacological sensitivities that could potentially be exploited for future therapeutic targeting.

  14. Enhanced excitability of primary sensory neurons and altered gene expression of neuronal ion channels in dorsal root ganglion in paclitaxel-induced peripheral neuropathy.

    Science.gov (United States)

    Zhang, Haijun; Dougherty, Patrick M

    2014-06-01

    The mechanism of chemotherapy-induced peripheral neuropathy after paclitaxel treatment is not well understood. Given the poor penetration of paclitaxel into central nervous system, peripheral nervous system is most at risk. Intrinsic membrane properties of dorsal root ganglion neurons were studied by intracellular recordings. Multiple-gene real-time polymerase chain reaction array was used to investigate gene expression of dorsal root ganglion neuronal ion channels. Paclitaxel increased the incidence of spontaneous activity from 4.8 to 27.1% in large-sized and from 0 to 33.3% in medium-sized neurons. Paclitaxel decreased the rheobase (nA) from 1.6 ± 0.1 to 0.8 ± 0.1 in large-sized, from 1.5 ± 0.2 to 0.6 ± 0.1 in medium-sized, and from 1.6 ± 0.2 to 1.0 ± 0.1 in small-sized neurons. After paclitaxel treatment, other characteristics of membrane properties in each group remained the same except that Aδ neurons showed shorter action potential fall time (ms) (1.0 ± 0.2, n = 10 vs. 1.8 ± 0.3, n = 9, paclitaxel vs. vehicle). Meanwhile, real-time polymerase chain reaction array revealed an alteration in expression of some neuronal ion channel genes including up-regulation of hyperpolarization-activated cyclic nucleotide-gated channel 1 (fold change 1.76 ± 0.06) and Nav1.7 (1.26 ± 0.02) and down-regulation of Kir channels (Kir1.1, 0.73 ± 0.05, Kir3.4, 0.66 ± 0.06) in paclitaxel-treated animals. The increased neuronal excitability and the changes in gene expression of some neuronal ion channels in dorsal root ganglion may provide insight into the molecular and cellular basis of paclitaxel-induced neuropathy, which may lead to novel therapeutic strategies.

  15. DESIGN OF PARABOLIC CHANNELS

    Directory of Open Access Journals (Sweden)

    A. K. Alibekov

    2015-01-01

    Full Text Available The dependence of the apparent location of the hydraulic parameters of parabolic channels in earthen channel and volume of dredging required in their design and construction, on the basis of conditions to ensure the stability of the slope at the maximum water flow rate. 

  16. 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...

  17. 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...

  18. Athermalized channeled spectropolarimeter enhancement.

    Energy Technology Data Exchange (ETDEWEB)

    Jones, Julia Craven; Way, Brandyn Michael; Mercier, Jeffrey Alan; Hunt, Jeffery P.

    2013-09-01

    Channeled spectropolarimetry can measure the complete polarization state of light as a function of wavelength. Typically, a channeled spectropolarimeter uses high order retarders made of uniaxial crystal to amplitude modulate the measured spectrum with the spectrally-dependent Stokes polarization information. A primary limitation of conventional channeled spectropolarimeters is related to the thermal variability of the retarders. Thermal variation often forces frequent system recalibration, particularly for field deployed systems. However, implementing thermally stable retarders, made of biaxial crystal, results in an athermal channeled spectropolarimeter that relieves the need for frequent recalibration. This report presents experimental results for an anthermalized channeled spectropolarimeter prototype produced using potassium titanyl phosphate. The results of this prototype are compared to the current thermal stabilization state of the art. Finally, the application of the technique to the thermal infrared is studied, and the athermalization concept is applied to an infrared imaging spectropolarimeter design.

  19. 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....

  20. Extreme bosonic linear channels

    Science.gov (United States)

    Holevo, A. S.

    2013-02-01

    The set of all channels with a fixed input and output is convex. We first give a convenient formulation of the necessary and sufficient condition for a channel to be an extreme point of this set in terms of the complementary channel, a notion of great importance in quantum information theory. This formulation is based on the general approach to extremality of completely positive maps in an operator algebra in the spirit of Arveson. We then use this formulation to prove our main result: under certain nondegeneracy conditions, environmental purity is necessary and sufficient for the extremality of a bosonic linear (quasifree) channel. It hence follows that a Gaussian channel between finite-mode bosonic systems is extreme if and only if it has minimum noise.

  1. 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

  2. Free-energy relationships in ion channels activated by voltage and ligand

    Science.gov (United States)

    Chowdhury, Sandipan

    2013-01-01

    Many ion channels are modulated by multiple stimuli, which allow them to integrate a variety of cellular signals and precisely respond to physiological needs. Understanding how these different signaling pathways interact has been a challenge in part because of the complexity of underlying models. In this study, we analyzed the energetic relationships in polymodal ion channels using linkage principles. We first show that in proteins dually modulated by voltage and ligand, the net free-energy change can be obtained by measuring the charge-voltage (Q-V) relationship in zero ligand condition and the ligand binding curve at highly depolarizing membrane voltages. Next, we show that the voltage-dependent changes in ligand occupancy of the protein can be directly obtained by measuring the Q-V curves at multiple ligand concentrations. When a single reference ligand binding curve is available, this relationship allows us to reconstruct ligand binding curves at different voltages. More significantly, we establish that the shift of the Q-V curve between zero and saturating ligand concentration is a direct estimate of the interaction energy between the ligand- and voltage-dependent pathway. These free-energy relationships were tested by numerical simulations of a detailed gating model of the BK channel. Furthermore, as a proof of principle, we estimate the interaction energy between the ligand binding and voltage-dependent pathways for HCN2 channels whose ligand binding curves at various voltages are available. These emerging principles will be useful for high-throughput mutagenesis studies aimed at identifying interaction pathways between various regulatory domains in a polymodal ion channel. PMID:23250866

  3. Assay for calcium channels

    Energy Technology Data Exchange (ETDEWEB)

    Glossmann, H.; Ferry, D.R.

    1985-01-01

    This chapter focuses on biochemical assays for Ca/sup 2 +/-selective channels in electrically excitable membranes which are blocked in electrophysiological and pharmacological experiments by verapamil, 1,4-dihydropyridines, diltiazen (and various other drugs), as well as inorganic di- or trivalent cations. The strategy employed is to use radiolabeled 1,4-dihydropyridine derivatives which block calcium channels with ED/sub 50/ values in the nanomolar range. Although tritiated d-cis-diltiazem and verapamil can be used to label calcium channels, the 1,4-dihydropyridines offer numerous advantages. The various sections cover tissue specificity of channel labeling, the complex interactions of divalent cations with the (/sup 3/H)nimodipine-labeled calcium channels, and the allosteric regulation of (/sup 3/H)nimodipine binding by the optically pure enantiomers of phenylalkylamine and benzothiazepine calcium channel blockers. A comparison of the properties of different tritiated 1,4-dihydropyridine radioligands and the iodinated channel probe (/sup 125/I)iodipine is given.

  4. 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.

  5. 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 no sys...... no systematic overview exist of channel choice. We present a literature review of channel choice studies in government to citizen context identifying authors, countries, methods, concepts, units of analysis, and theories, and offer suggestionsfor future studies....

  6. Convex approximations of quantum channels

    Science.gov (United States)

    Sacchi, Massimiliano F.; Sacchi, Tito

    2017-09-01

    We address the problem of optimally approximating the action of a desired and unavailable quantum channel Φ having at our disposal a single use of a given set of other channels {Ψi} . The problem is recast to look for the least distinguishable channel from Φ among the convex set ∑ipiΨi , and the corresponding optimal weights {pi} provide the optimal convex mixing of the available channels {Ψi} . For single-qubit channels we study specifically cases where the available convex set corresponds to covariant channels or to Pauli channels, and the desired target map is an arbitrary unitary transformation or a generalized damping channel.

  7. 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.

  8. 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.

  9. 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.

  10. Imperfect Channel State Estimation

    Directory of Open Access Journals (Sweden)

    Tao Qin

    2010-01-01

    in a multiuser OFDM CR system. A simple back-off scheme is proposed, and simulation results are provided which show that the proposed scheme is very effective in mitigating the negative impact of channel estimation errors.

  11. 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...

  12. 28-Channel rotary transformer

    Science.gov (United States)

    Mclyman, W. T.

    1981-01-01

    Transformer transmits power and digital data across rotating interface. Array has many parallel data channels, each with potential l megabaud data rate. Ferrite-cored transformers are spaced along rotor; airgap between them reduces crosstalk.

  13. 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....

  14. Ion Channels in Leukocytes

    Science.gov (United States)

    1991-07-01

    state (170).-Single K, channel currents were blocked by gesting that the synthesis of new channel protein was external-Ba (2.5 mM) and, like whole...Hg, La, cells, NK cells, human 2M2, 267 nifedipine, and murine B-cells diltiazem, chlorpromazine , forskolin, trifluorperazine, noxiustoxin -K, (I...Cells that ultimately leads to an increase in DNA synthesis and cell division. T lymphocytes develop in the thymus and have both effector and

  15. 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...

  16. Interacting divided channel method for compound channel flow

    NARCIS (Netherlands)

    Huthoff, Freek; Roos, Pieter C.; Augustijn, Dionysius C.M.; Hulscher, Suzanne J.M.H.

    2008-01-01

    A new method to calculate flow in compound channels is proposed: the interacting divided channel method (IDCM), based on a new parametrization of the interface stress between adjacent flow compartments, typically between the main channel and floodplain of a two-stage channel. This expression is

  17. Five-Channel Infrared Laser Absorption Spectrometer for Combustion Product Monitoring Aboard Manned Spacecraft

    Science.gov (United States)

    Briggs, Ryan M.; Frez, Clifford; Borgentun, Carl E.; Bagheri, Mahmood; Forouhar, Siamak; May, Randy D.

    2014-01-01

    Continuous combustion product monitoring aboard manned spacecraft can prevent chronic exposure to hazardous compounds and also provides early detection of combustion events. As future missions extend beyond low-Earth orbit, analysis of returned environmental samples becomes impractical and safety monitoring should be performed in situ. Here, we describe initial designs of a five-channel tunable laser absorption spectrometer to continuously monitor combustion products with the goal of minimal maintenance and calibration over long-duration missions. The instrument incorporates dedicated laser channels to simultaneously target strong mid-infrared absorption lines of CO, HCl, HCN, HF, and CO2. The availability of low-power-consumption semiconductor lasers operating in the 2 to 5 micron wavelength range affords the flexibility to select absorption lines for each gas with maximum interaction strength and minimal interference from other gases, which enables the design of a compact and mechanically robust spectrometer with low-level sensitivity. In this paper, we focus primarily on absorption line selection based on the availability of low-power single-mode semiconductor laser sources designed specifically for the target wavelength range.

  18. Postsynaptic mechanisms underlying the excitatory action of histamine on medial vestibular nucleus neurons in rats

    Science.gov (United States)

    Zhang, Xiao-Yang; Yu, Lei; Zhuang, Qian-Xing; Peng, Shi-Yu; Zhu, Jing-Ning; Wang, Jian-Jun

    2013-01-01

    Background and Purpose Anti-histaminergic drugs have been widely used in the clinical treatment of vestibular disorders and most studies concentrate on their presynaptic actions. The present study investigated the postsynaptic effect of histamine on medial vestibular nucleus (MVN) neurons and the underlying mechanisms. Experimental Approach Histamine-induced postsynaptic actions on MVN neurons and the corresponding receptor and ionic mechanisms were detected by whole-cell patch-clamp recordings on rat brain slices. The distribution of postsynaptic histamine H1, H2 and H4 receptors was mapped by double and single immunostaining. Furthermore, the expression of mRNAs for H1, H2 and H4 receptors and for subtypes of Na+–Ca2+ exchangers (NCXs) and hyperpolarization-activated cyclic nucleotide-gated (HCN) channels was assessed by quantitative real-time RT-PCR. Key Results A marked postsynaptic excitatory effect, co-mediated by histamine H1 and H2 receptors, was involved in the histamine-induced depolarization of MVN neurons. Postsynaptic H1 and H2 rather than H4 receptors were co-localized in the same MVN neurons. NCXs contributed to the inward current mediated by H1 receptors, whereas HCN channels were responsible for excitation induced by activation of H2 receptors. Moreover, NCX1 and NCX3 rather than NCX2, and HCN1 rather than HCN2-4 mRNAs, were abundantly expressed in MVN. Conclusion and Implications NCXs coupled to H1 receptors and HCN channels linked to H2 receptors co-mediate the strong postsynaptic excitatory action of histamine on MVN neurons. These results highlight an active role of postsynaptic mechanisms in the modulation by central histaminergic systems of vestibular functions and suggest potential targets for clinical treatment of vestibular disorders. Linked Articles This article is part of a themed issue on Histamine Pharmacology Update. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2013.170.issue-1 PMID:23713466

  19. Channels with Hydrogen Peroxide

    Directory of Open Access Journals (Sweden)

    Isabella Appiah

    2012-01-01

    Full Text Available The uteri, spontaneously active or Ca2+ (6 mM induced, were allowed to equilibrate, and to inhibit voltage-gated potassium ( channels 1 mM 4-amino pyridine (4-AP was applied for 15 min before adding H2O2 .  H2O2 was added cumulatively: 2 μM, 20 μM, 200 μM, 400 μM, and 3 mM. Average time for H2O2 concentrations (2, 20, 200, and 400 μM to reach its full effect was 15 min. H2O2 3 mM had a prolonged effect and therefore was left to act for 30 min. Two-way ANOVA showed significant differences in time dependency between spontaneous and Ca2+-induced rat uteri after applying 3 mM H2O2 (type of contraction, , but not 400 μM H2O2 (. Our results indicate that H2O2 oxidises channel intracellular thiol groups and activates the channel, inducing relaxation. Cell antioxidative defence system quickly activates glutathione peroxidase (GSHPx defence mechanism but not catalase (CAT defence mechanism. Intracellular redox mechanisms repair the oxidised sites and again establish deactivation of channels, recuperating contractility. In conclusion, our results demonstrate that channels can be altered in a time-dependent manner by reversible redox-dependent intracellular alterations.

  20. MEMS in microfluidic channels.

    Energy Technology Data Exchange (ETDEWEB)

    Ashby, Carol Iris Hill; Okandan, Murat; Michalske, Terry A.; Sounart, Thomas L.; Matzke, Carolyn M.

    2004-03-01

    Microelectromechanical systems (MEMS) comprise a new class of devices that include various forms of sensors and actuators. Recent studies have shown that microscale cantilever structures are able to detect a wide range of chemicals, biomolecules or even single bacterial cells. In this approach, cantilever deflection replaces optical fluorescence detection thereby eliminating complex chemical tagging steps that are difficult to achieve with chip-based architectures. A key challenge to utilizing this new detection scheme is the incorporation of functionalized MEMS structures within complex microfluidic channel architectures. The ability to accomplish this integration is currently limited by the processing approaches used to seal lids on pre-etched microfluidic channels. This report describes Sandia's first construction of MEMS instrumented microfluidic chips, which were fabricated by combining our leading capabilities in MEMS processing with our low-temperature photolithographic method for fabricating microfluidic channels. We have explored in-situ cantilevers and other similar passive MEMS devices as a new approach to directly sense fluid transport, and have successfully monitored local flow rates and viscosities within microfluidic channels. Actuated MEMS structures have also been incorporated into microfluidic channels, and the electrical requirements for actuation in liquids have been quantified with an elegant theory. Electrostatic actuation in water has been accomplished, and a novel technique for monitoring local electrical conductivities has been invented.

  1. 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.

  2. FTIR time-series of biomass burning products (HCN, C2H6, C2H2, CH3OH, and HCOOH at Reunion Island (21° S, 55° E and comparisons with model data

    Directory of Open Access Journals (Sweden)

    D. B. A. Jones

    2012-11-01

    Full Text Available Reunion Island (21° S, 55° E, situated in the Indian Ocean at about 800 km east of Madagascar, is appropriately located to monitor the outflow of biomass burning pollution from Southern Africa and Madagascar, in the case of short-lived compounds, and from other Southern Hemispheric landmasses such as South America, in the case of longer-lived species. Ground-based Fourier transform infrared (FTIR solar absorption observations are sensitive to a large number of biomass burning products. We present in this work the FTIR retrieval strategies, suitable for very humid sites such as Reunion Island, for hydrogen cyanide (HCN, ethane (C2H6, acetylene (C2H2, methanol (CH3OH, and formic acid (HCOOH. We provide their total columns time-series obtained from the measurements during August–October 2004, May–October 2007, and May 2009–December 2010. We show that biomass burning explains a large part of the observed seasonal and interannual variability of the chemical species. The correlations between the daily mean total columns of each of the species and those of CO, also measured with our FTIR spectrometer at Reunion Island, are very good from August to November (R ≥ 0.86. This allows us to derive, for that period, the following enhancement ratios with respect to CO: 0.0047, 0.0078, 0.0020, 0.012, and 0.0046 for HCN, C2H6, C2H2, CH3OH, and HCOOH, respectively. The HCN ground-based data are compared to the chemical transport model GEOS-Chem, while the data for the other species are compared to the IMAGESv2 model. We show that using the HCN/CO ratio derived from our measurements (0.0047 in GEOS-Chem reduces the underestimation of the modeled HCN columns compared with the FTIR measurements. The comparisons between IMAGESv2 and the long-lived species C2H6 and C2H2 indicate that the biomass burning emissions used in the model (from the GFED3 inventory are probably underestimated in the late September–October period for all years of measurements, and

  3. 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.

  4. Nanoscale Vacuum Channel Transistor.

    Science.gov (United States)

    Han, Jin-Woo; Moon, Dong-Il; Meyyappan, M

    2017-04-12

    Vacuum tubes that sparked the electronics era had given way to semiconductor transistors. Despite their faster operation and better immunity to noise and radiation compared to the transistors, the vacuum device technology became extinct due to the high power consumption, integration difficulties, and short lifetime of the vacuum tubes. We combine the best of vacuum tubes and modern silicon nanofabrication technology here. The surround gate nanoscale vacuum channel transistor consists of sharp source and drain electrodes separated by sub-50 nm vacuum channel with a source to gate distance of 10 nm. This transistor performs at a low voltage (3 microamperes). The nanoscale vacuum channel transistor can be a possible alternative to semiconductor transistors beyond Moore's law.

  5. 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......- 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....... Understanding the structure/function relationship of TRPV4 is essential for future development of specific TRPV4 agonist for treatment of diseases causes by dysfunctional TRPV4. E.g. two inherited bone dysplasias have recently been demonstrated in humans to originate from TRPV4 mutations....

  6. Ionic Channels in Thunderclouds

    Science.gov (United States)

    Losseva, T. V.; Fomenko, A. S.; Nemtchinov, I. V.

    2007-12-01

    We proceed to study the formation and propagation of ionic channels in thunderclouds in the framework of the model of the corona discharge wave propagation (Fomenko A.S., Losseva T.V., Nemtchinov I.V. The corona discharge waves in thunderclouds and formation of ionic channels // 2004 Fall Meeting. EOS Trans. AGU. 2004. V. 85. ¹ 47. Suppl. Abstract AE23A-0835.). In this model we proposed a hypothesis that the structure of a thundercloud becomes nonuniform due to corona discharge on the drops and ice particles and formation of ionic channels with higher conductivity than the surrounding air. When the onset strength of corona discharge becomes smaller than the electric field strength the corona discharge increases concentrations of ions in a small part of the cloud (a hot spot). An additional charge at opposite ends of the hot spot forms due to polarization process. The increased electric field initiates corona discharge in other parts of the cloud on ice particles and water drops with smaller sizes. The corona discharge front moves as a wave with the velocity of the order of ion drift and formes a highly conductive channel. We model this non-stationary problem with Poisson equation which is solved simultaneously with a simplified set of kinetic equations for ions, small charged particles and electrons (at high electric fields), including ionization due to electronic impact, attachment and formation of positive ions. By applying 3D numerical simulations we obtain the parameters of formed ionic channels with respect to onset electric fields both from large particles (in hot spot) and from small particles (surrounding hot spot), microscopic currents from particles with different sizes and the external electric field in the cloud. The interaction of ionic channels is also investigated. This work was supported by Russian Foundation of Basic Research (Project No 07-05-00998-à).

  7. Aquaporins as gas channels.

    Science.gov (United States)

    Herrera, Marcela; Garvin, Jeffrey L

    2011-10-01

    Gas molecules play important roles in human physiology. Volatile substances produced by one cell often regulate neighboring cells in a paracrine fashion. While gaseous molecules have traditionally been thought to travel from cell to cell by free diffusion through the bilayer portion of the membrane, this does not explain their rapid physiological actions. The recent observations that: (1) water channels can transport other molecules besides water, and (2) aquaporins are often expressed in tissues where gas (but not water) transport is essential suggest that these channels conduct physiologically important gases in addition to water. This review summarizes recent findings on the role of aquaporins as gas transporters as well as their physiological significance.

  8. Sodium channels and pain.

    Science.gov (United States)

    Habib, Abdella M; Wood, John N; Cox, James J

    2015-01-01

    Human and mouse genetic studies have led to significant advances in our understanding of the role of voltage-gated sodium channels in pain pathways. In this chapter, we focus on Nav1.7, Nav1.8, Nav1.9 and Nav1.3 and describe the insights gained from the detailed analyses of global and conditional transgenic Nav knockout mice in terms of pain behaviour. The spectrum of human disorders caused by mutations in these channels is also outlined, concluding with a summary of recent progress in the development of selective Nav1.7 inhibitors for the treatment of pain.

  9. UMTS Common Channel Sensitivity Analysis

    DEFF Research Database (Denmark)

    Pratas, Nuno; Rodrigues, António; Santos, Frederico

    2006-01-01

    The UMTS common transport channels forward access channel (FACH) and the random access channel (RACH) are two of the three fundamental channels for a functional implementation of an UMTS network. Most signaling procedures, such as the registration procedure, make use of these channels...... 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....

  10. 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…

  11. 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.

  12. Learning in Tactile Channels

    Science.gov (United States)

    Gescheider, George A.; Wright, John H.

    2012-01-01

    Vibrotactile intensity-discrimination thresholds for sinusoidal stimuli applied to the thenar eminence of the hand declined as a function of practice. However, improvement was confined to the tactile information-processing channel in which learning had occurred. Specifically, improvements in performance with training within the Pacinian-corpuscle…

  13. Same-Single-Cell Analysis of Pacemaker-Specific Markers in Human Induced Pluripotent Stem Cell-Derived Cardiomyocyte Subtypes Classified by Electrophysiology.

    Science.gov (United States)

    Yechikov, Sergey; Copaciu, Raul; Gluck, Jessica M; Deng, Wenbin; Chiamvimonvat, Nipavan; Chan, James W; Lieu, Deborah K

    2016-11-01

    Insights into the expression of pacemaker-specific markers in human induced pluripotent stem cell (hiPSC)-derived cardiomyocyte subtypes can facilitate the enrichment and track differentiation and maturation of hiPSC-derived pacemaker-like cardiomyocytes. To date, no study has directly assessed gene expression in each pacemaker-, atria-, and ventricular-like cardiomyocyte subtype derived from hiPSCs since currently the subtypes of these immature cardiomyocytes can only be identified by action potential profiles. Traditional acquisition of action potentials using patch-clamp recordings renders the cells unviable for subsequent analysis. We circumvented these issues by acquiring the action potential profile of a single cell optically followed by assessment of protein expression through immunostaining in that same cell. Our same-single-cell analysis for the first time revealed expression of proposed pacemaker-specific markers-hyperpolarization-activated cyclic nucleotide-modulated (HCN)4 channel and Islet (Isl)1-at the protein level in all three hiPSC-derived cardiomyocyte subtypes. HCN4 expression was found to be higher in pacemaker-like hiPSC-derived cardiomyocytes than atrial- and ventricular-like subtypes but its downregulation over time in all subtypes diminished the differences. Isl1 expression in pacemaker-like hiPSC-derived cardiomyocytes was initially not statistically different than the contractile subtypes but did become statistically higher than ventricular-like cells with time. Our observations suggest that although HCN4 and Isl1 are differentially expressed in hiPSC-derived pacemaker-like relative to ventricular-like cardiomyocytes, these markers alone are insufficient in identifying hiPSC-derived pacemaker-like cardiomyocytes. Stem Cells 2016;34:2670-2680. © 2016 AlphaMed Press.

  14. Same-Single-Cell Analysis of Pacemaker-Specific Markers in Human Induced Pluripotent Stem Cell-Derived Cardiomyocyte Subtypes Classified by Electrophysiology

    Science.gov (United States)

    Yechikov, Sergey; Copaciu, Raul; Gluck, Jessica M.; Deng, Wenbin; Chiamvimonvat, Nipavan; Chan, James W.; Lieu, Deborah K.

    2018-01-01

    Insights into the expression of pacemaker-specific markers in human induced pluripotent stem cell (hiPSC)-derived cardiomyocyte subtypes can facilitate the enrichment and track differentiation and maturation of hiPSC-derived pacemaker-like cardiomyocytes. To date, no study has directly assessed gene expression in each pacemaker-, atria-, and ventricular-like cardiomyocyte subtype derived from hiPSCs since currently the subtypes of these immature cardiomyocytes can only be identified by action potential profiles. Traditional acquisition of action potentials using patch-clamp recordings renders the cells unviable for subsequent analysis. We circumvented these issues by acquiring the action potential profile of a single cell optically followed by assessment of protein expression through immunostaining in that same cell. Our same-single-cell analysis for the first time revealed expression of proposed pacemaker-specific markers—hyperpolarization-activated cyclic nucleotide-modulated (HCN)4 channel and Islet (Isl)1—at the protein level in all three hiPSC-derived cardiomyocyte subtypes. HCN4 expression was found to be higher in pacemaker-like hiPSC-derived cardiomyocytes than atrial- and ventricular-like subtypes but its downregulation over time in all subtypes diminished the differences. Isl1 expression in pacemaker-like hiPSC-derived cardiomyocytes was initially not statistically different than the contractile subtypes but did become statistically higher than ventricular-like cells with time. Our observations suggest that although HCN4 and Isl1 are differentially expressed in hiPSC-derived pacemaker-like relative to ventricular-like cardiomyocytes, these markers alone are insufficient in identifying hiPSC-derived pacemaker-like cardiomyocytes. PMID:27434649

  15. Congestive Heart Failure Leads to Prolongation of the PR Interval and Atrioventricular Junction Enlargement and Ion Channel Remodelling in the Rabbit

    Science.gov (United States)

    Nikolaidou, Theodora; Cai, Xue J.; Stephenson, Robert S.; Yanni, Joseph; Lowe, Tristan; Atkinson, Andrew J.; Jones, Caroline B.; Sardar, Rida; Corno, Antonio F.; Dobrzynski, Halina; Withers, Philip J.; Jarvis, Jonathan C.; Hart, George; Boyett, Mark R.

    2015-01-01

    Heart failure is a major killer worldwide. Atrioventricular conduction block is common in heart failure; it is associated with worse outcomes and can lead to syncope and bradycardic death. We examine the effect of heart failure on anatomical and ion channel remodelling in the rabbit atrioventricular junction (AVJ). Heart failure was induced in New Zealand rabbits by disruption of the aortic valve and banding of the abdominal aorta resulting in volume and pressure overload. Laser micro-dissection and real-time polymerase chain reaction (RT-PCR) were employed to investigate the effects of heart failure on ion channel remodelling in four regions of the rabbit AVJ and in septal tissues. Investigation of the AVJ anatomy was performed using micro-computed tomography (micro-CT). Heart failure animals developed first degree heart block. Heart failure caused ventricular myocardial volume increase with a 35% elongation of the AVJ. There was downregulation of HCN1 and Cx43 mRNA transcripts across all regions and downregulation of Cav1.3 in the transitional tissue. Cx40 mRNA was significantly downregulated in the atrial septum and AVJ tissues but not in the ventricular septum. mRNA abundance for ANP, CLCN2 and Navβ1 was increased with heart failure; Nav1.1 was increased in the inferior nodal extension/compact node area. Heart failure in the rabbit leads to prolongation of the PR interval and this is accompanied by downregulation of HCN1, Cav1.3, Cx40 and Cx43 mRNAs and anatomical enlargement of the entire heart and AVJ. PMID:26509807

  16. 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.

  17. Intracellular ion channels and cancer

    OpenAIRE

    Luigi eLeanza; Lucia eBiasutto; Antonella eManago; Erich eGulbins; Mario eZoratti; Ildikò eSzabò

    2013-01-01

    Several types of channels play a role in the maintenance of ion homeostasis in subcellular organelles including endoplasmatic reticulum, nucleus, lysosome, endosome, and mitochondria. Here we give a brief overview of the contribution of various mitochondrial and other organellar channels to cancer cell proliferation or death. Much attention is focused on channels involved in intracellular calcium signaling and on ion fluxes in the ATP-producing organelle mitochondria. Mitochondrial K+ channel...

  18. ``Just Another Distribution Channel?''

    Science.gov (United States)

    Lemstra, Wolter; de Leeuw, Gerd-Jan; van de Kar, Els; Brand, Paul

    The telecommunications-centric business model of mobile operators is under attack due to technological convergence in the communication and content industries. This has resulted in a plethora of academic contributions on the design of new business models and service platform architectures. However, a discussion of the challenges that operators are facing in adopting these models is lacking. We assess these challenges by considering the mobile network as part of the value system of the content industry. We will argue that from the perspective of a content provider the mobile network is ‘just another’ distribution channel. Strategic options available for the mobile communication operators are to deliver an excellent distribution channel for content delivery or to move upwards in the value chain by becoming a content aggregator. To become a mobile content aggregator operators will have to develop or acquire complementary resources and capabilities. Whether this strategic option is sustainable remains open.

  19. Lipid Ion Channels

    CERN Document Server

    Heimburg, Thomas

    2010-01-01

    The interpretation electrical phenomena in biomembranes is usually based on the assumption that the experimentally found discrete ion conduction events are due to a particular class of proteins called ion channels while the lipid membrane is considered being an inert electrical insulator. The particular protein structure is thought to be related to ion specificity, specific recognition of drugs by receptors and to macroscopic phenomena as nerve pulse propagation. However, lipid membranes in their chain melting regime are known to be highly permeable to ions, water and small molecules, and are therefore not always inert. In voltage-clamp experiments one finds quantized conduction events through protein-free membranes in their melting regime similar to or even undistinguishable from those attributed to proteins. This constitutes a conceptual problem for the interpretation of electrophysiological data obtained from biological membrane preparations. Here, we review the experimental evidence for lipid ion channels...

  20. 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....

  1. Micro-channel plate detector

    Science.gov (United States)

    Elam, Jeffrey W.; Lee, Seon W.; Wang, Hsien -Hau; Pellin, Michael J.; Byrum, Karen; Frisch, Henry J.

    2015-09-22

    A method and system for providing a micro-channel plate detector. An anodized aluminum oxide membrane is provided and includes a plurality of nanopores which have an Al coating and a thin layer of an emissive oxide material responsive to incident radiation, thereby providing a plurality of radiation sensitive channels for the micro-channel plate detector.

  2. 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).

  3. Totally Asynchronous Interference Channels

    CERN Document Server

    Moshksar, Kamyar

    2010-01-01

    This paper addresses an interference channel consisting of $\\mathbf{n}$ active users sharing $u$ frequency sub-bands. Users are asynchronous meaning there exists a mutual delay between their transmitted codes. A stationary model for interference is considered by assuming the starting point of an interferer's data is uniformly distributed along the codeword of any user. The spectrum is divided to private and common bands each containing $v_{\\mathrm{p}}$ and $v_{\\mathrm{c}}$ frequency sub-bands respectively. We consider a scenario where all transmitters are unaware of the number of active users and the channel gains. The optimum $v_{\\mathrm{p}}$ and $v_{\\mathrm{c}}$ are obtained such that the so-called outage capacity per user is maximized. If $\\Pr\\{\\mathbf{n}\\leq 2\\}=1$, upper and lower bounds on the mutual information between the input and output of the channel for each user are derived using a genie-aided technique. The proposed bounds meet each other as the code length grows to infinity yielding a closed ex...

  4. Intracellular ion channels and cancer.

    Science.gov (United States)

    Leanza, Luigi; Biasutto, Lucia; Managò, Antonella; Gulbins, Erich; Zoratti, Mario; Szabò, Ildikò

    2013-09-03

    Several types of channels play a role in the maintenance of ion homeostasis in subcellular organelles including endoplasmatic reticulum, nucleus, lysosome, endosome, and mitochondria. Here we give a brief overview of the contribution of various mitochondrial and other organellar channels to cancer cell proliferation or death. Much attention is focused on channels involved in intracellular calcium signaling and on ion fluxes in the ATP-producing organelle mitochondria. Mitochondrial K(+) channels (Ca(2+)-dependent BKCa and IKCa, ATP-dependent KATP, Kv1.3, two-pore TWIK-related Acid-Sensitive K(+) channel-3 (TASK-3)), Ca(2+) uniporter MCU, Mg(2+)-permeable Mrs2, anion channels (voltage-dependent chloride channel VDAC, intracellular chloride channel CLIC) and the Permeability Transition Pore (MPTP) contribute importantly to the regulation of function in this organelle. Since mitochondria play a central role in apoptosis, modulation of their ion channels by pharmacological means may lead to death of cancer cells. The nuclear potassium channel Kv10.1 and the nuclear chloride channel CLIC4 as well as the endoplasmatic reticulum (ER)-located inositol 1,4,5-trisphosphate (IP3) receptor, the ER-located Ca(2+) depletion sensor STIM1 (stromal interaction molecule 1), a component of the store-operated Ca(2+) channel and the ER-resident TRPM8 are also mentioned. Furthermore, pharmacological tools affecting organellar channels and modulating cancer cell survival are discussed. The channels described in this review are summarized on Figure 1. Overall, the view is emerging that intracellular ion channels may represent a promising target for cancer treatment.

  5. Intracellular ion channels and cancer

    Directory of Open Access Journals (Sweden)

    Luigi eLeanza

    2013-09-01

    Full Text Available Several types of channels play a role in the maintenance of ion homeostasis in subcellular organelles including endoplasmatic reticulum, nucleus, lysosome, endosome and mitochondria. Here we give a brief overview of the contribution of various mitochondrial and other organellar channels to cancer cell proliferation or death. Much attention is focused on channels involved in intracellular calcium signaling and on ion fluxes in the ATP-producing organelle mitochondria. Mitochondrial K+ channels (Ca2+-dependent BKCa and IKCa, ATP-dependent KATP, Kv1.3, two-pore TWIK-related Acid-Sensitive K+ channel-3 (TASK-3, Ca2+ uniporter MCU, Mg2+-permeable Mrs2, anion channels (voltage-dependent chloride channel VDAC, intracellular chloride channel CLIC and the Permeability Transition Pore (MPTP contribute importantly to the regulation of function in this organelle. Since mitochondria play a central role in apoptosis, modulation of their ion channels by pharmacological means may lead to death of cancer cells. The nuclear potassium channel Kv10.1 and the nuclear chloride channel CLIC4 as well as the endoplasmatic reticulum (ER-located inositol 1,4,5-trisphosphate (IP3 receptor, the ER-located Ca2+ depletion sensor STIM1 (stromal interaction molecule 1, a component of the store-operated Ca2+ channel and the ER-resident TRPM8 are also mentioned. Furthermore, pharmacological tools affecting organellar channels and modulating cancer cell survival are discussed. The channels described in this review are summarized on Figure 1. Overall, the view is emerging that intracellular ion channels may represent a promising target for cancer treatment.

  6. Chemical Selectivity and Sensitivity of a 16-Channel Electronic Nose for Trace Vapour Detection

    Directory of Open Access Journals (Sweden)

    Drago Strle

    2017-12-01

    Full Text Available Good chemical selectivity of sensors for detecting vapour traces of targeted molecules is vital to reliable detection systems for explosives and other harmful materials. We present the design, construction and measurements of the electronic response of a 16 channel electronic nose based on 16 differential microcapacitors, which were surface-functionalized by different silanes. The e-nose detects less than 1 molecule of TNT out of 10+12 N2 molecules in a carrier gas in 1 s. Differently silanized sensors give different responses to different molecules. Electronic responses are presented for TNT, RDX, DNT, H2S, HCN, FeS, NH3, propane, methanol, acetone, ethanol, methane, toluene and water. We consider the number density of these molecules and find that silane surfaces show extreme affinity for attracting molecules of TNT, DNT and RDX. The probability to bind these molecules and form a surface-adsorbate is typically 10+7 times larger than the probability to bind water molecules, for example. We present a matrix of responses of differently functionalized microcapacitors and we propose that chemical selectivity of multichannel e-nose could be enhanced by using artificial intelligence deep learning methods.

  7. 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

  8. MITOCHONDRIAL BKCa CHANNEL

    OpenAIRE

    Enrique eBalderas; Jin eZhang; Enrico eStefani; Ligia eToro

    2015-01-01

    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, an...

  9. Improving virtual channel discrimination in a multi-channel context.

    Science.gov (United States)

    Srinivasan, Arthi G; Shannon, Robert V; Landsberger, David M

    2012-04-01

    Improving spectral resolution in cochlear implants is key to improving performance in difficult listening conditions (e.g. speech in noise, music, etc.). Current focusing might reduce channel interaction, thereby increasing spectral resolution. Previous studies have shown that combining current steering and current focusing reduces spread of excitation and improves virtual channel discrimination in a single-channel context. It is unclear whether the single-channel benefits from current focusing extend to a multi-channel context, in which the physical and perceptual interference of multiple stimulated channels might overwhelm the benefits of improved spectral resolution. In this study, signal discrimination was measured with and without current focusing, in the presence of competing stimuli on nearby electrodes. Results showed that signal discrimination was consistently better with current focusing than without, regardless of the amplitude of the competing stimuli. Therefore, combining current steering and current focusing may provide more effective spectral cues than are currently available.

  10. Cholesterol binding to ion channels

    Directory of Open Access Journals (Sweden)

    Irena eLevitan

    2014-02-01

    Full Text Available Numerous studies demonstrated that membrane cholesterol is a major regulator of ion channel function. The goal of this review is to discuss significant advances that have been recently achieved in elucidating the mechanisms responsible for cholesterol regulation of ion channels. The first major insight that comes from growing number of studies that based on the sterol specificity of cholesterol effects, show that several types of ion channels (nAChR, Kir, BK, TRPV are regulated by specific sterol-protein interactions. This conclusion is supported by demonstrating direct saturable binding of cholesterol to a bacterial Kir channel. The second major advance in the field is the identification of putative cholesterol binding sites in several types of ion channels. These include sites at locations associated with the well-known cholesterol binding motif CRAC and its reversed form CARC in nAChR, BK, and TRPV, as well as novel cholesterol binding regions in Kir channels. Notably, in the majority of these channels, cholesterol is suggested to interact mainly with hydrophobic residues in non-annular regions of the channels being embedded in between transmembrane protein helices. We also discuss how identification of putative cholesterol binding sites is an essential step to understand the mechanistic basis of cholesterol-induced channel regulation. Clearly, however, these are only the first few steps in obtaining a general understanding of cholesterol-ion channels interactions and their roles in cellular and organ functions.

  11. Channel Wall Landslides

    Science.gov (United States)

    2005-01-01

    [figure removed for brevity, see original site] The multiple landslides in this VIS image occur along a steep channel wall. Note the large impact crater in the context image. The formation of the crater may have initially weakened that area of the surface prior to channel formation. Image information: VIS instrument. Latitude -2.7, Longitude 324.8 East (35.2 West). 19 meter/pixel resolution. Note: this THEMIS visual image has not been radiometrically nor geometrically calibrated for this preliminary release. An empirical correction has been performed to remove instrumental effects. A linear shift has been applied in the cross-track and down-track direction to approximate spacecraft and planetary motion. Fully calibrated and geometrically projected images will be released through the Planetary Data System in accordance with Project policies at a later time. NASA's Jet Propulsion Laboratory manages the 2001 Mars Odyssey mission for NASA's Office of Space Science, Washington, D.C. The Thermal Emission Imaging System (THEMIS) was developed by Arizona State University, Tempe, in collaboration with Raytheon Santa Barbara Remote Sensing. The THEMIS investigation is led by Dr. Philip Christensen at Arizona State University. Lockheed Martin Astronautics, Denver, is the prime contractor for the Odyssey project, and developed and built the orbiter. Mission operations are conducted jointly from Lockheed Martin and from JPL, a division of the California Institute of Technology in Pasadena.

  12. Modeling Dubai City Artificial Channel

    Directory of Open Access Journals (Sweden)

    Elhakeem Mohamed

    2016-01-01

    Full Text Available Dubai’s new channel further enhances the urban-scape of the city offering new waterfront developments, transportation venues and diversified panoramas to the city. This paper performs a study to simulate the flow field in the proposed Dubai artificial channel using a 2D hydrodynamic model. The model predicts the flow depth and velocity in the channel, lagoons and bends. The model predictions show that the velocity is higher in the channel sections compared to the lagoons and bends sections. On the other hand, the water depth is lower in the channel sections compared to the lagoons and bends sections. Nonetheless, the velocities in the channel are within the accepted range that prevents boundary erosion and sediment deposition.

  13. 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.

  14. Single-channel kinetics of BK (Slo1) channels

    Science.gov (United States)

    Geng, Yanyan; Magleby, Karl L.

    2014-01-01

    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 five closed states on the upper tier and five 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. PMID:25653620

  15. Marketing channels and competitive advantage

    OpenAIRE

    Jovičić Dragoljub

    2005-01-01

    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 an...

  16. 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....

  17. Beyond the Manual Channel

    DEFF Research Database (Denmark)

    This collection of papers stems from the Sixth Workshop on the Representation and Processing of Sign Languages, held in May 2014 as a satellite to the Language Resources and Evaluation Conference in Reykjavik. While there has been occasional attention for sign languages at the main LREC conference......, 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...

  18. The emergence of two anti-phase oscillatory neural populations in a computational model of the Parkinsonian globus pallidus

    Directory of Open Access Journals (Sweden)

    Robert John Merrison-Hort

    2013-12-01

    Full Text Available Experiments in rodent models of Parkinson's Disease have demonstrated a prominent increase of oscillatory firing patterns in neurons within the Parkinsonian globus pallidus (GP which may underlie some of the motor symptoms of the disease. There are two main pathways from the cortex to GP: via the striatum and via the subthalamic nucleus (STN, but it is not known how these inputs sculpt the pathological pallidal firing patterns. To study this we developed a novel neural network model of conductance-based spiking pallidal neurons with cortex-modulated input from STN neurons. Our results support the hypothesis that entrainment occurs primarily via the subthalamic pathway. We find that as a result of the interplay between excitatory input from the STN and mutual inhibitory coupling between GP neurons, a homogeneous population of GP neurons demonstrates a self-organising dynamical behaviour where two groups of neurons emerge: one spiking in-phase with the cortical rhythm and the other in anti-phase. This finding mirrors what is seen in recordings from the GP of rodents that have had Parkinsonism induced via brain lesions. Our model also includes downregulation of Hyperpolarization-activated Cyclic Nucleotide-gated (HCN channels in response to burst firing of GP neurons, since this has been suggested as a possible mechanism for the emergence of Parkinsonian activity. We found that the downregulation of HCN channels provides even better correspondence with experimental data but that it is not essential in order for the two groups of oscillatory neurons to appear. We discuss how the influence of inhibitory striatal input will strengthen our results.

  19. 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

  20. The EMBL-EBI channel.

    Science.gov (United States)

    McEntyre, Jo; Birney, Ewan

    2016-01-01

    This editorial introduces the EMBL-EBI channel in F1000Research. The aims of the channel are to present EMBL-EBI outputs and collate research published on F1000Research contributed, in whole or in part, EMBL-EBI researchers.

  1. FMCG companies specific distribution channels

    National Research Council Canada - National Science Library

    Ioana Barin

    2009-01-01

    ... 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.

  2. 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.

  3. The Orange Juice Distribution Channels

    African Journals Online (AJOL)

    is to provide a general overview about the agents in the European marketing channels of the FCOJ, focusing on the final juice consumers, retailing, food service and the beverage industry. The framework for this part is build up of the marketing channel concepts and functions (Stern et al., 1996; Berman,. 1996; Rosembloom ...

  4. Hydrodynamic instability of meandering channels

    Science.gov (United States)

    Ali, Sk Zeeshan; Dey, Subhasish

    2017-12-01

    In this paper, we explore the hydrodynamic instability of meandering channels driven by the turbulent flow. The governing equations of channel dynamics with suitable boundary conditions are closed with the fluid and granular constitutive relationships. A regular expansion of the fundamental variables is employed to linearize the parent equations by superimposing the perturbations on the basic unperturbed flow. The channel dynamics reveal a resonance phenomenon which occurs when the key variables fall in the vicinity of the distinct critical values. The resonance phenomenon preserves its distinctive signature in different flow regimes which are guided by the characteristic values of the shear Reynolds number. The hydrodynamic analysis indicates that the fluid friction and the volumetric sediment flux play a decisive role to characterize the channel instability in different flow regimes. The growths of azimuthal velocity perturbation in phase with curvature, bed topography perturbation, bend amplification rate, and meander propagation speed in different flow regimes are investigated by varying the meander wavenumber, Shields number, channel aspect ratio, and relative roughness number. The analysis is capable to capture the effects of grain size on azimuthal velocity perturbation, bed topography perturbation, bend amplification rate, and meandering propagation speed over a wide range of shear Reynolds numbers. The variations of resonant wavenumbers in different flow regimes with the Shields number, channel aspect ratio, and relative roughness number are addressed. For a specific flow regime, the upstream and downstream migrations of meandering channels are typically governed by the Shields number, channel aspect ratio, and relative roughness number.

  5. Capacity of quantum Gaussian channels

    Science.gov (United States)

    Holevo, A. S.; Sohma, M.; Hirota, O.

    1999-03-01

    The aim of this paper is to give explicit calculation of the classical capacity of quantum Gaussian channels, in particular, involving squeezed states. The calculation is based on a general formula for the entropy of a quantum Gaussian state, which is of independent interest, and on the recently proved coding theorem for quantum communication channels.

  6. 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.

  7. Hydroxychloroquine reduces heart rate by modulating the hyperpolarization-activated current If: Novel electrophysiological insights and therapeutic potential.

    Science.gov (United States)

    Capel, Rebecca A; Herring, Neil; Kalla, Manish; Yavari, Arash; Mirams, Gary R; Douglas, Gillian; Bub, Gil; Channon, Keith; Paterson, David J; Terrar, Derek A; Burton, Rebecca-Ann B

    2015-10-01

    Bradycardic agents are of interest for the treatment of ischemic heart disease and heart failure, as heart rate is an important determinant of myocardial oxygen consumption. The purpose of this study was to investigate the propensity of hydroxychloroquine (HCQ) to cause bradycardia. We assessed the effects of HCQ on (1) cardiac beating rate in vitro (mice); (2) the "funny" current (If) in isolated guinea pig sinoatrial node (SAN) myocytes (1, 3, 10 µM); (3) heart rate and blood pressure in vivo by acute bolus injection (rat, dose range 1-30 mg/kg), (4) blood pressure and ventricular function during feeding (mouse, 100 mg/kg/d for 2 wk, tail cuff plethysmography, anesthetized echocardiography). In mouse atria, spontaneous beating rate was significantly (P rate (17% ± 6%, 1 μM dose) and a dose-dependent reduction in If (13% ± 3% at 1 µM; 19% ± 2% at 3 µM). Effects were also observed on L-type calcium ion current (ICaL) (12% ± 4% reduction) and rapid delayed rectifier potassium current (IKr) (35% ± 4%) at 3 µM. Intravenous HCQ decreased heart rate in anesthetized rats (14.3% ± 1.1% at 15mg/kg; n = 6) without significantly reducing mean arterial blood pressure. In vivo feeding studies in mice showed no significant change in systolic blood pressure nor left ventricular function. We have shown that HCQ acts as a bradycardic agent in SAN cells, in atrial preparations, and in vivo. HCQ slows the rate of spontaneous action potential firing in the SAN through multichannel inhibition, including that of If. Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

  8. Channel Aggregation Schemes for Cognitive Radio Networks

    Science.gov (United States)

    Lee, Jongheon; So, Jaewoo

    This paper proposed three channel aggregation schemes for cognitive radio networks, a constant channel aggregation scheme, a probability distribution-based variable channel aggregation scheme, and a residual channel-based variable channel aggregation scheme. A cognitive radio network can have a wide bandwidth if unused channels in the primary networks are aggregated. Channel aggregation schemes involve either constant channel aggregation or variable channel aggregation. In this paper, a Markov chain is used to develop an analytical model of channel aggregation schemes; and the performance of the model is evaluated in terms of the average sojourn time, the average throughput, the forced termination probability, and the blocking probability. Simulation results show that channel aggregation schemes can reduce the average sojourn time of cognitive users by increasing the channel occupation rate of unused channels in a primary network.

  9. Voltage-gated Proton Channels

    Science.gov (United States)

    DeCoursey, Thomas E.

    2014-01-01

    Voltage-gated proton channels, HV1, have vaulted from the realm of the esoteric into the forefront of a central question facing ion channel biophysicists, namely the mechanism by which voltage-dependent gating occurs. This transformation is the result of several factors. Identification of the gene in 2006 revealed that proton channels are homologues of the voltage-sensing domain of most other voltage-gated ion channels. Unique, or at least eccentric, properties of proton channels include dimeric architecture with dual conduction pathways, perfect proton selectivity, a single-channel conductance ~103 smaller than most ion channels, voltage-dependent gating that is strongly modulated by the pH gradient, ΔpH, and potent inhibition by Zn2+ (in many species) but an absence of other potent inhibitors. The recent identification of HV1 in three unicellular marine plankton species has dramatically expanded the phylogenetic family tree. Interest in proton channels in their own right has increased as important physiological roles have been identified in many cells. Proton channels trigger the bioluminescent flash of dinoflagellates, facilitate calcification by coccolithophores, regulate pH-dependent processes in eggs and sperm during fertilization, secrete acid to control the pH of airway fluids, facilitate histamine secretion by basophils, and play a signaling role in facilitating B-cell receptor mediated responses in B lymphocytes. The most elaborate and best-established functions occur in phagocytes, where proton channels optimize the activity of NADPH oxidase, an important producer of reactive oxygen species. Proton efflux mediated by HV1 balances the charge translocated across the membrane by electrons through NADPH oxidase, minimizes changes in cytoplasmic and phagosomal pH, limits osmotic swelling of the phagosome, and provides substrate H+ for the production of H2O2 and HOCl, reactive oxygen species crucial to killing pathogens. PMID:23798303

  10. 47 CFR 95.7 - Channel sharing.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 5 2010-10-01 2010-10-01 false Channel sharing. 95.7 Section 95.7... SERVICES General Mobile Radio Service (GMRS) § 95.7 Channel sharing. (a) Channels or channel pairs (one 462... and use of channels to reduce interference and to make the most effective use of the facilities. (b...

  11. Convergence of estuarine channels

    Science.gov (United States)

    Dronkers, Job

    2017-07-01

    Tide-dominated coastal plain estuaries have typically up-estuary convergent tidal channels. Analysis of estuarine characteristics indicates a dependence of the convergence length on relative tidal amplitude, relative intertidal area and river flow velocity. In order to explain these relationships we investigate a condition for continuity of net sediment transport throughout the estuary, corresponding to morphodynamic equilibrium. We show, by using an analytical solution of the tidal equations, that this condition is equivalent to a condition on the convergence length. This condition is evaluated for 21 estuaries in different regions of the world. It appears that the convergence length determined in this way can explain observed convergence lengths for the considered set of estuaries. The dependence of the convergence length on different estuarine characteristics is analysed by solving the fully coupled hydro-morphodynamic equations. We show that this dependence limits the range of variation of the tidal velocity amplitude. The analysis provides insight in the morphological response of estuaries to human interventions. The condition can easily be evaluated to yield an estimate of this response.

  12. Dual axial channel heat pipe

    Energy Technology Data Exchange (ETDEWEB)

    Alario, J.P.; Haslett, R.A.; Kosson, R.L.

    1984-09-11

    A heat pipe comprising an elongated sealed metallic envelope having at least a pair of longitudinal channels extending along the length thereof. One of the channels is for the circulation of the vapor phase of the working medium in operation and the other for the liquid phase and capillary means are provided to furnish fluid communication therebetween. Dedicated vapor and liquid channels result in low viscous pressure drops, the capillary communication means and circumferential grooving in the vapor channel provide high capillary pressure differences, and circumferential grooving is provided to furnish the high evaporation and condensation film coefficients required. To support higher heat fluxes, wicking can be used to augment the capillary flow from the liquid channel. To support higher evaporator heat flux without the need for wicking means, the heat pipe can be provided with more than one liquid channel, each communicating with the vapor channel by capillary means. The heat pipe can be provided with an integral fin or equivalent means for rejection of heat by radiation to ambient or for attachment to a source of heat in the evaporator region thereof.

  13. Thermally stable imaging channeled spectropolarimetry

    Science.gov (United States)

    Craven-Jones, Julia; Way, Brandyn M.; Hunt, Jeff; Kudenov, Michael W.; Mercier, Jeffrey A.

    2013-09-01

    Channeled spectropolarimetry can measure the complete polarization state of light as a function of wavelength. Typically, a channeled spectropolarimeter uses high order retarders made of uniaxial crystal to amplitude modulate the measured spectrum with the spectrally-dependent Stokes polarization information. A primary limitation of conventional channeled spectropolarimeters is related to the thermal variability of the retarders. Thermal variation often forces frequent system recalibration, particularly for field deployed systems. However, implementing thermally stable retarders results in an athermal channeled spectropolarimeter that relieves the need for frequent recalibration. Past work has addressed this issue by developing athermalized retarders using two or more uniaxial crystals. Recently, a retarder made of biaxial KTP and cut at a thermally insensitive angle was used to produce an athermal channeled spectropolarimeter. This paper presents the results of the biaxial crystal system and compares the two thermal stabilization techniques in the context of producing an imaging thermally stable channeled spectropolarimeter. A preliminary design for a snapshot imaging channeled spectropolarimeter is also presented.

  14. Ion Channels in Brain Metastasis.

    Science.gov (United States)

    Klumpp, Lukas; Sezgin, Efe C; Eckert, Franziska; Huber, Stephan M

    2016-09-08

    Breast cancer, lung cancer and melanoma exhibit a high metastatic tropism to the brain. Development of brain metastases severely worsens the prognosis of cancer patients and constrains curative treatment options. Metastasizing to the brain by cancer cells can be dissected in consecutive processes including epithelial-mesenchymal transition, evasion from the primary tumor, intravasation and circulation in the blood, extravasation across the blood-brain barrier, formation of metastatic niches, and colonization in the brain. Ion channels have been demonstrated to be aberrantly expressed in tumor cells where they regulate neoplastic transformation, malignant progression or therapy resistance. Moreover, many ion channel modulators are FDA-approved drugs and in clinical use proposing ion channels as druggable targets for future anti-cancer therapy. The present review article aims to summarize the current knowledge on the function of ion channels in the different processes of brain metastasis. The data suggest that certain channel types involving voltage-gated sodium channels, ATP-release channels, ionotropic neurotransmitter receptors and gap junction-generating connexins interfere with distinct processes of brain metastazation.

  15. Ion Channels in Brain Metastasis

    Directory of Open Access Journals (Sweden)

    Lukas Klumpp

    2016-09-01

    Full Text Available Breast cancer, lung cancer and melanoma exhibit a high metastatic tropism to the brain. Development of brain metastases severely worsens the prognosis of cancer patients and constrains curative treatment options. Metastasizing to the brain by cancer cells can be dissected in consecutive processes including epithelial–mesenchymal transition, evasion from the primary tumor, intravasation and circulation in the blood, extravasation across the blood–brain barrier, formation of metastatic niches, and colonization in the brain. Ion channels have been demonstrated to be aberrantly expressed in tumor cells where they regulate neoplastic transformation, malignant progression or therapy resistance. Moreover, many ion channel modulators are FDA-approved drugs and in clinical use proposing ion channels as druggable targets for future anti-cancer therapy. The present review article aims to summarize the current knowledge on the function of ion channels in the different processes of brain metastasis. The data suggest that certain channel types involving voltage-gated sodium channels, ATP-release channels, ionotropic neurotransmitter receptors and gap junction-generating connexins interfere with distinct processes of brain metastazation.

  16. Landslide-channel feedbacks amplify flood response and channel erosion

    Science.gov (United States)

    Bennett, Georgina; Kean, Jason; Rengers, Francis; Ryan, Sandra; Rathburn, Sara

    2017-04-01

    Flood stream power is amplified in mountainous catchments by channel confinement and steep slopes, generating widespread channel erosion and causing significant challenges for flood risk management. Approaches to predicting flood channel response include identification of stream power thresholds. However, in a mountainous catchment in Colorado, USA, we find that stream power, estimated from the pre-storm DEM, was not a good predictor of channel flood response and that landslide-channel feedbacks better explain the observed pattern of channel erosion. The North St Vrain is a 250 km2 catchment in the Colorado Front Range. It was among several catchments impacted by a 1000 yr prolonged rainfall event in September 2013, which generated a 200 yr flood and >100 landslides in the catchment. We estimated peak discharge and stream power using radar-based rainfall data, wherein the rainfall was converted to a discharge based on the upstream drainage area and assuming no infiltration (a reasonable assumption after 3 days of heavy rainfall). Measured high water marks in key reaches were used to calculate a field-based estimate of peak discharge. These discharge estimates were compared with spatial erosion estimates, calculated using the differenced pre- and post-flood LiDAR DEMs. We found that the onset of profound channel erosion was determined by the formation and failure of an in-channel dam. The dam, composed of debris flow and tributary sediment input, was sufficiently large (˜150,000 m3) to temporarily overwhelm channel transport capacity even during flood. Our field-based estimate of peak discharge downstream of the dam is more than 2 times greater than our rainfall-based estimate, which suggests a dam burst event occurred. Further downstream we observe additional channel reaches in which erosion was amplified by landslide and tributary sediment input, either through the formation and failure of dams or potentially through sediment bulking alone. These findings imply

  17. Marine Toxins Targeting Ion Channels

    Directory of Open Access Journals (Sweden)

    Hugo R. Arias

    2006-04-01

    Full Text Available Abstract: This introductory minireview points out the importance of ion channels for cell communication. The basic concepts on the structure and function of ion channels triggered by membrane voltage changes, the so-called voltage-gated ion channels (VGICs, as well as those activated by neurotransmitters, the so-called ligand-gated ion channel (LGICs, are introduced. Among the most important VGIC superfamiles, we can name the voltage-gated Na+ (NaV, Ca2+ (CaV, and K+ (KV channels. Among the most important LGIC super families, we can include the Cys-loop or nicotinicoid, the glutamate-activated (GluR, and the ATP-activated (P2XnR receptor superfamilies. Ion channels are transmembrane proteins that allow the passage of different ions in a specific or unspecific manner. For instance, the activation of NaV, CaV, or KV channels opens a pore that is specific for Na+, Ca2+, or K+, respectively. On the other hand, the activation of certain LGICs such as nicotinic acetylcholine receptors, GluRs, and P2XnRs allows the passage of cations (e.g., Na+, K+, and/or Ca2+, whereas the activation of other LGICs such as type A γ-butyric acid and glycine receptors allows the passage of anions (e.g., Cl− and/or HCO3−. In this regard, the activation of NaV and CaV as well as ligand-gated cation channels produce membrane depolarization, which finally leads to stimulatory effects in the cell, whereas the activation of KV as well as ligand-gated anion channels induce membrane hyperpolarization that finally leads to inhibitory effects in the cell. The importance of these ion channel superfamilies is emphasized by considering their physiological functions throughout the body as well as their pathophysiological implicance in several neuronal diseases. In this regard, natural molecules, and especially marine toxins, can be potentially used as modulators (e.g., inhibitors or prolongers of ion channel functions to treat or to alleviate a specific

  18. 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.

  19. ACE Strategy with Virtual Channels

    Directory of Open Access Journals (Sweden)

    T. Tichy

    2008-12-01

    Full Text Available Cochlear implant is an electronic device, which can mediate hearing sensations to profoundly deaf people. Contemporary cochlear implants are sophisticated electronic devices; however, their performance could still be improved. This paper describes an experiment we made in that direction: additional 21 virtual channels were implemented by sequential stimulation of adjacent intracochlear electrodes, and the ACE strategy with virtual channels (ACEv, Advanced Combination Encoder strategy with virtual channels for the Nucleus® 24 Cochlear Implant System was created and verified in a clinical test with four patients.

  20. Catalytic reaction in confined flow channel

    Energy Technology Data Exchange (ETDEWEB)

    Van Hassel, Bart A.

    2016-03-29

    A chemical reactor comprises a flow channel, a source, and a destination. The flow channel is configured to house at least one catalytic reaction converting at least a portion of a first nanofluid entering the channel into a second nanofluid exiting the channel. The flow channel includes at least one turbulating flow channel element disposed axially along at least a portion of the flow channel. A plurality of catalytic nanoparticles is dispersed in the first nanofluid and configured to catalytically react the at least one first chemical reactant into the at least one second chemical reaction product in the flow channel.

  1. Charge‐selective claudin channels

    National Research Council Canada - National Science Library

    Krug, Susanne M; Günzel, Dorothee; Conrad, Marcel P; Lee, In‐Fah M; Amasheh, Salah; Fromm, Michael; Yu, Alan S. L

    2012-01-01

    Claudins are the main determinants of barrier properties of the tight junction. Many claudins have been shown to act by tightening the paracellular pathway, but several function as paracellular channels...

  2. Kinetic ELISA in microfluidic channels

    National Research Council Canada - National Science Library

    Yanagisawa, Naoki; Dutta, Debashis

    2011-01-01

    In this article, we describe the kinetic ELISA of Blue Tongue and Epizootic Hemorrhagic Disease viral antibodies in microfluidic channels by monitoring the rate of generation of the enzyme reaction...

  3. Wireless Communication over Dispersive Channels

    NARCIS (Netherlands)

    Fang, K.

    2010-01-01

    Broadband wireless communication systems require high transmission rates, where the bandwidth of the transmitted signal is larger than the channel coherence bandwidth. This gives rise to time dispersion of the transmitted symbols or frequency-selectivity with different frequency components

  4. Biophysics of BK Channel Gating.

    Science.gov (United States)

    Pantazis, A; Olcese, R

    2016-01-01

    BK channels are universal regulators of cell excitability, given their exceptional unitary conductance selective for K(+), joint activation mechanism by membrane depolarization and intracellular [Ca(2+)] elevation, and broad expression pattern. In this chapter, we discuss the structural basis and operational principles of their activation, or gating, by membrane potential and calcium. We also discuss how the two activation mechanisms interact to culminate in channel opening. As members of the voltage-gated potassium channel superfamily, BK channels are discussed in the context of archetypal family members, in terms of similarities that help us understand their function, but also seminal structural and biophysical differences that confer unique functional properties. © 2016 Elsevier Inc. All rights reserved.

  5. 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.

  6. Potassium Channels in Neurofbromatosis-1

    National Research Council Canada - National Science Library

    Chen, Mingkui

    2006-01-01

    .... We were the first to investigate potential mechanisms of cognitive impairment in NF-1 at the molecular level involving potassium channels, and demonstrated a possible mechanism for the learning deficits seen in NF1...

  7. Skeletal Muscle Na+ Channel Disorders

    OpenAIRE

    Dina eSimkin; Saïd eBendahhou

    2011-01-01

    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 impo...

  8. Magnetically suspended virtual divergent channel

    Energy Technology Data Exchange (ETDEWEB)

    Yamane, Ryuichiro [Kokushikan University, 4-28-1 Setagaya, Setagaya-ku, Tokyo 154-8515 (Japan)]. E-mail: yamane@kokushikan.ac.jp; Oshiama, Shuzo [Tokyo Institute of Technology, 2-12-1 Ookayama, Meguro-ku, Tokyo 152-8552 (Japan); Park, Myeong-Kwan [Pusan National University, 30 Changjeon-dong, Kumjeong-ku, Pusan 609-735 (Korea, Republic of)

    2005-03-15

    Two permanent magnets are set face-to-face and inclined with each other to produce the long cuspidal magnetic field. The diamagnetic liquid is levitated and flows through it without contact with the solid walls as if it is in the virtual divergent channel. Analysis is made on the shape of the virtual channel, and the results are compared with the experimental ones. The divergence angle increases with the increase in the inclination of the magnets.

  9. Central neural alterations predominate in an insect model of nociceptive sensitization.

    Science.gov (United States)

    Tabuena, Dennis R; Solis, Allan; Geraldi, Ken; Moffatt, Christopher A; Fuse, Megumi

    2017-04-01

    Many organisms respond to noxious stimuli with defensive maneuvers. This is noted in the hornworm, Manduca sexta, as a defensive strike response. After tissue damage, organisms typically display sensitized responses to both noxious or normally innocuous stimuli. To further understand this phenomenon, we used novel in situ and in vitro preparations based on paired extracellular nerve recordings and videography to identify central and peripheral nerves responsible for nociception and sensitization of the defensive behavior in M. sexta. In addition, we used the in vivo defensive strike response threshold assayed with von Frey filaments to examine the roles that N-methyl-D-aspartate receptor (NMDAR) and hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels play in this nociceptive sensitization using the inhibitors MK-801 and AP5 (NMDAR), and ivabradine and ZD7288 (HCN). Using our new preparations, we found that afferent activity evoked by noxious pinch in these preparations was conveyed to central ganglia by axons in the anterior- and lateral-dorsal nerve branches, and that sensitization induced by tissue damage was mediated centrally. Furthermore, sensitization was blocked by all inhibitors tested except the inactive isomer L-AP5, and reversed by ivabradine both in vivo and in vitro. Our findings suggest that M. sexta's sensitization occurs through central signal amplification. Due to the relatively natural sensitization method and conserved molecular actions, we suggest that M. sexta may be a valuable model for studying the electrophysiological properties of nociceptive sensitization and potentially related conditions such as allodynia and hyperalgesia in a comparative setting that offers unique experimental advantages. J. Comp. Neurol. 525:1176-1191, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  10. Analyzing and Modeling the Dysfunction of Inhibitory Neurons in Alzheimer's Disease.

    Directory of Open Access Journals (Sweden)

    Carlos Perez

    Full Text Available Alzheimer's disease (AD is characterized by the abnormal proteolytic processing of amyloid precursor protein, resulting in increased production of a self-aggregating form of beta amyloid (Aβ. Several lines of work on AD patients and transgenic mice with high Aβ levels exhibit altered rhythmicity, aberrant neuronal network activity and hyperexcitability reflected in clusters of hyperactive neurons, and spontaneous epileptic activity. Recent studies highlight that abnormal accumulation of Aβ changes intrinsic properties of inhibitory neurons, which is one of the main reasons underlying the impaired network activity. However, specific cellular mechanisms leading to interneuronal dysfunction are not completely understood. Using extended Hodgkin-Huxley (HH formalism in conjunction with patch-clamp experiments, we investigate the mechanisms leading to the impaired activity of interneurons. Our detailed analysis indicates that increased Na+ leak explains several observations in inhibitory neurons, including their failure to reliably produce action potentials, smaller action potential amplitude, increased resting membrane potential, and higher membrane depolarization in response to a range of stimuli in a model of APPSWE/PSEN1DeltaE9 (APdE9 AD mice as compared to age-matched control mice. While increasing the conductance of hyperpolarization activated cyclic nucleotide-gated (HCN ion channel could account for most of the observations, the extent of increase required to reproduce these observations render such changes unrealistic. Furthermore, increasing the conductance of HCN does not account for the observed changes in depolarizability of interneurons from APdE9 mice as compared to those from NTG mice. None of the other pathways tested could lead to all observations about interneuronal dysfunction. Thus we conclude that upregulated sodium leak is the most likely source of impaired interneuronal function.

  11. Channel and Timeslot Co-Scheduling with Minimal Channel Switching for Data Aggregation in MWSNs

    OpenAIRE

    Sanggil Yeoum; Byungseok Kang; Jinkyu Lee; Hyunseung Choo

    2017-01-01

    Collision-free transmission and efficient data transfer between nodes can be achieved through a set of channels in multichannel wireless sensor networks (MWSNs). While using multiple channels, we have to carefully consider channel interference, channel and time slot (resources) optimization, channel switching delay, and energy consumption. Since sensor nodes operate on low battery power, the energy consumed in channel switching becomes an important challenge. In this paper, we propose channel...

  12. 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...

  13. 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....

  14. 18 CFR 1304.303 - Channel excavation.

    Science.gov (United States)

    2010-04-01

    ... 18 Conservation of Power and Water Resources 2 2010-04-01 2010-04-01 false Channel excavation... Activities on TVA Flowage Easement Shoreland § 1304.303 Channel excavation. (a) Channel excavation of... encourage owners of flowage easement property to adopt the standards for channel excavation applicable to...

  15. Therapeutic approaches to ion channel diseases.

    Science.gov (United States)

    Camerino, Diana Conte; Desaphy, Jean-François; Tricarico, Domenico; Pierno, Sabata; Liantonio, Antonella

    2008-01-01

    More than 400 genes are known that encode ion channel subunits. In addition, alternative splicing and heteromeric assembly of different subunits increase tremendously the variety of ion channels. Such many channels are needed to accomplish very complex cellular functions, whereas dysfunction of ion channels are key events in many pathological processes. The recent discovery of ion channelopathies, which, in its more stringent definition, encloses monogenic disorders due to mutations in ion channel genes, has largely contributed to our understanding of the function of the various channel subtypes and of the role of ion channels in multigenic or acquired diseases. Last but not least, ion channels are the main targets of many drugs already used in the clinics. Most of these drugs were introduced in therapy based on the experience acquired quite empirically, and many were discovered afterward to target ion channels. Now, intense research is being conducted to develop new drugs acting selectively on ion channel subtypes and aimed at the understanding of the intimate drug-channel interaction. In this review, we first focus on the pharmacotherapy of ion channel diseases, which includes many drugs targeting ion channels. Then, we describe the molecular pharmacology of ion channels, including the more recent advancement in drug development. Among the newest aspect of ion channel pharmacology, we draw attention to how polymorphisms or mutations in ion channel genes may modify sensitivity to drugs, opening the way toward the development of pharmacogenetics.

  16. Electrophysiological characterisation of KCNQ channel modulators

    DEFF Research Database (Denmark)

    Schrøder, R.L

    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...

  17. 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

  18. 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

  19. Geometry-based channel modelling of MIMO channels in comparison with channel sounder measurements

    Directory of Open Access Journals (Sweden)

    G. Del Galdo

    2004-01-01

    Full Text Available In this paper we propose a flexible geometrybased propagation model for wireless communications developed at Ilmenau University of Technology. The IlmProp comprises a geometrical representation of the environment surrounding the experiment and a precise representation of the transmitting and receiving antennas. The IlmProp is capable of simulating Multi-User MIMO scenarios and includes a complete collection of tools to analyze the synthetic channels. In order to assess the potentials as well as the limits of our channel simulator we reconstruct the scenario encountered in a recent measurement campaign at Ilmenau University of Technology leading to synthetic data sets similar to the ones actually measured. The measurements have been collected with the RUSK MIMO multi-dimensional channel sounder. From the comparisons of the two channel matrices it is possible to derive useful information to improve the model itself and to better understand the physical origins of small-scale fading. In particular the effects of the different parameters on the synthetic channel have been studied in order to assess the sensibility of the model. This analysis shows that the correct positioning of a small number of scatterers is enough to achieve frequency selectiveness as well as specific traits of the channel statistics. The size of the scattering clusters, the number of scatterers per cluster, and the Rician K-factor can be modified in order to tune the channel statistics at will. To obtain higher levels of time variance, moving scatterers or time dependent reflection coefficients must be introduced.

  20. On stimulated resonance radiation by channeled particles

    Science.gov (United States)

    Dabagov, S. B.; Kalashnikov, N. P.

    2017-07-01

    The channeled particles undergo quasiperiodic transverse bound motion along main crystallographic directions at either 1D planar or 2D axial channeling. This motion is accompanied by spontaneous radiation known as channeling radiation due to projectile's transmission between discrete quantum states. In this work we have presented preliminary evaluation of the processes of resonance scattering of external electromagnetic field when the external frequency becomes close to the channeled particle transition energies that might be of the source for induced radiation at channeling.

  1. Channels of Monetary Transmission in the CIS

    OpenAIRE

    Jamilov, Rustam

    2012-01-01

    Twenty years have passed since the breakdown of the Soviet Union, and it is time to draw a concluding line for monetary policy efficiency in the Commonwealth of Independent States (CIS). We propose a comprehensive treatment of the subject for nine members of the CIS for the period of 2000-2009. Four transmission channels are investigated: interest rate channel, exchange rate channel, bank lending channel, and monetary channel. First, we design a VAR framework for each CIS member-state and inv...

  2. Insect sodium channels and insecticide resistance

    OpenAIRE

    Dong, Ke

    2007-01-01

    Voltage-gated sodium channels are essential for the generation and propagation of action potentials (i.e., electrical impulses) in excitable cells. Although most of our knowledge about sodium channels is derived from decades of studies of mammalian isoforms, research on insect sodium channels is revealing both common and unique aspects of sodium channel biology. In particular, our understanding of the molecular dynamics and pharmacology of insect sodium channels has advanced greatly in recent...

  3. adequacy of drainage channels f drainage channels in a small

    African Journals Online (AJOL)

    eobe

    analysis, construction and maintenance of drainage c. Keywords: Keywords: Time of concentration, ... nwamba of Civil Engineering Department, University of Nigeria Nsuk. F DRAINAGE CHANNELS IN A SMALL URBAN .... The assessment of extreme precipitation is an important problem in hydrologic risk analysis and.

  4. Lubiprostone: a chloride channel activator.

    Science.gov (United States)

    Lacy, Brian E; Levy, L Campbell

    2007-04-01

    In January 2006 the Food and Drug Administration approved lubiprostone for the treatment of chronic constipation in men and women aged 18 and over. Lubiprostone is categorized as a prostone, a bicyclic fatty acid metabolite of prostaglandin E1. Lubiprostone activates a specific chloride channel (ClC-2) in the gastrointestinal (GI) tract to enhance intestinal fluid secretion, which increases GI transit and improves symptoms of constipation. This article reviews the role of chloride channels in the GI tract, describes the structure, function, and pharmacokinetics of lubiprostone, and discusses clinically important data on this new medication.

  5. 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...

  6. 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.

  7. 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.

  8. Higgs in Bosonic channel (CMS)

    CERN Document Server

    Gori, Valentina

    2015-01-01

    All the investigated properties result to be fully consistent with the SM predictions: the signal strength and the signal strength modifiers are consistent with unity in all the bosonic channels considered; the hypothesis of a scalar particle is strongly favored, ag...

  9. 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

  10. 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

  11. 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.

  12. Hidden systematics of fission channels

    Directory of Open Access Journals (Sweden)

    Schmidt Karl-Heinz

    2013-12-01

    Full Text Available It is a common procedure to describe the fission-fragment mass distributions of fissioning systems in the actinide region by a sum of at least 5 Gaussian curves, one for the symmetric component and a few additional ones, together with their complementary parts, for the asymmetric components. These components have been attributed to the influence of fragment shells, e.g. in the statistical scission-point model of Wilkins, Steinberg and Chasman. They have also been associated with valleys in the potential-energy landscape between the outer saddle and the scission configuration in the multi-channel fission model of Brosa. When the relative yields, the widths and the mean mass-asymmetry values of these components are fitted to experimental data, the mass distributions can be very well reproduced. Moreover, these fission channels are characterised by specific values of charge polarisation, total kinetic energy and prompt-neutron yields. The present contribution investigates the systematic variation of the characteristic fission-channel properties as a function of the composition and the excitation energy of the fissioning system. The mean position of the asymmetric fission channels in the heavy fragment is almost constant in atomic number. The deformation of the nascent fragments at scission, which is the main source of excitation energy of the separated fission fragments ending up in prompt-neutron emission, is found to be a unique function of Z for the light and the heavy fragment of the asymmetric fission channels. A variation of the initial excitation energy of the fissioning system above the fission saddle is only seen in the neutron yield of the heavy fragment. The charge polarisation in the two most important asymmetric fission channels is found to be constant and to appreciably exceed the macroscopic value. The variation of the relative yields and of the positions of the fission channels as a function of the composition and excitation energy

  13. 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.

  14. Subspace Based Blind Sparse Channel Estimation

    DEFF Research Database (Denmark)

    Hayashi, Kazunori; Matsushima, Hiroki; Sakai, Hideaki

    2012-01-01

    The paper proposes a subspace based blind sparse channel estimation method using 1–2 optimization by replacing the 2–norm minimization in the conventional subspace based method by the 1–norm minimization problem. Numerical results confirm that the proposed method can significantly improve...... the estimation accuracy for the sparse channel, while achieving the same performance as the conventional subspace method when the channel is dense. Moreover, the proposed method enables us to estimate the channel response with unknown channel order if the channel is sparse enough....

  15. 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.

  16. Broadening of spectral lines of CO2, N2O , H2CO, HCN, and H2S by pressure of gases dominant in planetary atmospheres (H2, He and CO2)

    Science.gov (United States)

    Samuels, Shanelle; Gordon, Iouli; Tan, Yan

    2018-01-01

    HITRAN1,2 is a compilation of spectroscopic parameters that a variety of computer codes use to predict and simulate the transmission and emission of light in planetary atmospheres. The goal of this project is to add to the potential of the HITRAN database towards the exploration of the planetary atmospheres by including parameters describing broadening of spectral lines by H2, CO2, and He. These spectroscopic data are very important for the study of the hydrogen and helium-rich atmospheres of gas giants as well as rocky planets with volcanic activities, including Venus and Mars, since their atmospheres are dominated by CO2. First step in this direction was accomplished by Wilzewski et al.3 where this was done for SO2, NH3, HF, HCl, OCS and C2H2. The molecules investigated in this work were CO2, N2O, H2CO, HCN and H2S. Line-broadening coefficients, line shifts and temperature-dependence exponents for transitions of these molecules perturbed by H2, CO2 and He have been assembled from available peer-reviewed experimental and theoretical sources. The data was evaluated and the database was populated with these data and their extrapolations/interpolations using semi-empirical models that were developed to this end.Acknowledgements: Financial support from NASA PDART grant NNX16AG51G and the Smithsonian Astrophysical Observatory Latino Initiative Program from the Latino Initiatives Pool, administered by the Smithsonian Latino Center is gratefully acknowledged.References: 1. HITRAN online http://hitran.org/2. Gordon, I.E., Rothman, L.S., Hill, C., Kochanov, R.V., Tan, Y., et al., 2017. The HITRAN2016 Molecular Spectroscopic Database. J. Quant. Spectrosc. Radiat. Transf. doi:10.1016/j.jqsrt.2017.06.0383. Wilzewski, J.S., Gordon, I.E., Kochanov, R. V., Hill, C., Rothman, L.S., 2016. H2, He, and CO2 line-broadening coefficients, pressure shifts and temperature-dependence exponents for the HITRAN database. Part 1: SO2, NH3, HF, HCl, OCS and C2H2. J. Quant. Spectrosc. Radiat

  17. 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....

  18. BK channel modulators: a comprehensive overview

    DEFF Research Database (Denmark)

    Nardi, Antonio; Olesen, Søren-Peter

    2008-01-01

    the notion that the channel represents an innovative and promising drug target. However, after more than ten years of intense research effort both in academia and industry, scientists have yet to witness the approval of a single BK channel modulator for clinical use. On the contrary, three BK openers...... and blockers 4) Marketed and/or investigational drugs with BK-modulating side properties and structural analogues 5) Naturally-occurring BK channel openers and structural analogues 6) Synthetic BK channel openers. This review is intended to provide readers with current opinion on the BK channel as a drug......The large Ca(2+)-activated K(+) channel (BK channel) reflects per excellence the dilemma of the molecular target driven drug discovery process. Significant experimental evidence suggests that the BK channels play a pivotal and specific role in many pathophysiological conditions supporting...

  19. 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,

  20. 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

  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.

  2. 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...

  3. The additivity problem and constrained quantum channels

    Science.gov (United States)

    Holevo, A. S.

    2005-06-01

    We give formulations of the famous additivity conjecture for several important quantities characterizing quantum channel and prove their global equivalence to the additivity of the classical capacity of a channel under input constrains (like mean energy constrain).

  4. 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

  5. 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.

  6. 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.

  7. Ion coordination in the amphotericin B channel

    OpenAIRE

    Khutorsky, V

    1996-01-01

    The antifungal polyene antibiotic amphotericin B forms channels in lipid membranes that are permeable to ions, water, and nonelectrolytes. Anion, cation, and ion pair coordination in the water-filled pore of the "barrel" unit of the channels was studied by molecular dynamics simulations. Unlike the case of the gramicidin A channel, the water molecules do not create a single-file configuration in the pore, and some cross sections of the channel contain three or four water molecules. Both the a...

  8. Chloride channels in toad skin

    DEFF Research Database (Denmark)

    Larsen, Erik Hviid; Rasmussen, B E

    1982-01-01

    A study of the voltage and time dependence of a transepithelial Cl- current in toad skin (Bufo bufo) by the voltage-clamp method leads to the conclusion that potential has a dual role for Cl- transport. One is to control the permeability of an apical membrane Cl-pathway, the other is to drive Cl-......- transport through open channels does not obey the constant-field equation....

  9. 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......, we describe the meaning of each data dimension along with the background and motivation for their inclusion. Finally, we present feedback provided by the users (31 individuals) of the visualization....

  10. Channeled and microactiviation of materials

    Energy Technology Data Exchange (ETDEWEB)

    Maggiore, C.J.; Blacic, J.D.; Blondiaux, G.; Debrun, J.L.; Ali, M.H.; Mathez, E.; Misdaq, M.A.; Valladon, M.

    1988-01-01

    Charged particle activation analysis can be combined with channeling to determine lattice location of impurities at the trace level in single crystal samples. It can also be used with a nuclear microprobe to measure impurities at trace levels in small or spatially inhomogeneous samples. Examples of these extensions of activation analysis to realistic samples are carbon determination in organometallic vapor phase epitaxial layers of GaAlAs on GaAs and oxygen determination in diamonds. 5 refs., 2 figs.

  11. Adaptive RAC codes employing statistical channel evaluation ...

    African Journals Online (AJOL)

    In time varying channels the noise and interference vary randomly. Forward error correction codes (FEC) on such channels are designed to cater for the worst possible state and require a large amount of redundancy at all time. This means that when the channel is relatively noiseless, excessive error control power and ...

  12. 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

  13. 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...

  14. 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…

  15. Genetic control of sodium channel function

    NARCIS (Netherlands)

    Tan, Hanno L.; Bezzina, Connie R.; Smits, Jeroen P. P.; Verkerk, Arie O.; Wilde, Arthur A. M.

    2003-01-01

    Sodium ion (Na) influx through cardiac Na channels triggers the action potential in cells of the working myocardium and the specialized conduction system. Na channels thus act as key molecular determinants of cardiac excitability and impulse propagation. Na channel dysfunction may cause

  16. Comments on Ionization Cooling Channel Characteristics

    Energy Technology Data Exchange (ETDEWEB)

    Neuffer, David [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States). Fermilab Center for Particle Astrophysics

    2013-12-04

    Ionization cooling channels with a wide variety of characteristics and cooling properties are being developed. These channels can produce cooling performances that are largely consistent with the ionization cooling theory developed previously. In this paper we review ionization cooling theory, discuss its application to presently developing cooling channels, and discuss criteria for optimizing cooling.

  17. 47 CFR 76.57 - Channel positioning.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 4 2010-10-01 2010-10-01 false Channel positioning. 76.57 Section 76.57... CABLE TELEVISION SERVICE Carriage of Television Broadcast Signals § 76.57 Channel positioning. (a) At... obligations, a cable operator shall carry such signal on the cable system channel number on which the local...

  18. 33 CFR 117.147 - Cerritos Channel.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Cerritos Channel. 117.147 Section... DRAWBRIDGE OPERATION REGULATIONS Specific Requirements California § 117.147 Cerritos Channel. (a) The draw of... immediately. Channel 13 (156.65 MHZ) or other assigned frequencies may be used. (b) The draw of the Henry Ford...

  19. Functional Expression of Drosophila para Sodium Channels

    Science.gov (United States)

    Warmke, Jeffrey W.; Reenan, Robert A.G.; Wang, Peiyi; Qian, Su; Arena, Joseph P.; Wang, Jixin; Wunderler, Denise; Liu, Ken; Kaczorowski, Gregory J.; Ploeg, Lex H.T. Van der; Ganetzky, Barry; Cohen, Charles J.

    1997-01-01

    The Drosophila para sodium channel α subunit was expressed in Xenopus oocytes alone and in combination with tipE, a putative Drosophila sodium channel accessory subunit. Coexpression of tipE with para results in elevated levels of sodium currents and accelerated current decay. Para/TipE sodium channels have biophysical and pharmacological properties similar to those of native channels. However, the pharmacology of these channels differs from that of vertebrate sodium channels: (a) toxin II from Anemonia sulcata, which slows inactivation, binds to Para and some mammalian sodium channels with similar affinity (Kd ≅ 10 nM), but this toxin causes a 100-fold greater decrease in the rate of inactivation of Para/TipE than of mammalian channels; (b) Para sodium channels are >10-fold more sensitive to block by tetrodotoxin; and (c) modification by the pyrethroid insecticide permethrin is >100-fold more potent for Para than for rat brain type IIA sodium channels. Our results suggest that the selective toxicity of pyrethroid insecticides is due at least in part to the greater affinity of pyrethroids for insect sodium channels than for mammalian sodium channels. PMID:9236205

  20. Entanglement-assisted capacity of constrained channels

    Science.gov (United States)

    Holevo, A. S.

    2003-07-01

    In this paper we fil a gap in previous work by proving the conjectured formula for the antanglement-assisted capacity of quantum channel with additive input constraint (such as Bosonic Gaussian channel). The main tools are the coding theorem for classical-quantum constrained channels and a finite dimensional approximation of the input density operators for the entanglement-assisted capacity.

  1. 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.

  2. Animal Model Selection for Inhalational HCN Exposure

    Science.gov (United States)

    2016-08-01

    phosphate pathway by decreasing the rate of glycolysis, and inhibition of the tricarboxylic acid cycle with marked metabolic acidosis (Ballantyne... Canine 100 NA Pritchard, 2007; WHO, 2004 Swine 3404 1 McNamara, 1976 1466 3 607 10 688 90 NHP 96-2171 (87-196 ppm ) 30 Purser et al, 1984...pulmonary studies (Laboratory Animal Medicine, 2002, 1984; Biology and Diseases of the Ferret, 1998). Canine The dog is commonly used in safety

  3. The use of service channels by citizens in the Netherlands: implications for multi-channel management

    NARCIS (Netherlands)

    Pieterson, Willem Jan; Ebbers, Wolfgang E.

    2008-01-01

    Many governmental organizations are changing their service channel management strategies to multi-channel management. However, very few empirical studies exist that explore how these multi-channel strategies should be shaped. In this article we test a number of hypotheses on citizens' channel use

  4. Sodium channels and mammalian sensory mechanotransduction.

    OpenAIRE

    Raouf, R.; Rugiero, F.; Kiesewetter, H.; Hatch, R.; Hummler, E; Nassar, M. A.; Wang, F.; Wood, J.N.

    2012-01-01

    Abstract Background Members of the degenerin/epithelial (DEG/ENaC) sodium channel family are mechanosensors in C elegans, and Nav1.7 and Nav1.8 voltage-gated sodium channel knockout mice have major deficits in mechanosensation. β and γENaC sodium channel subunits are present with acid sensing ion channels (ASICs) in mammalian sensory neurons of the dorsal root ganglia (DRG). The extent to which epithelial or voltage-gated sodium channels are involved in transduction of mechanical stimuli is u...

  5. Geometry-based channel modelling of MIMO channels in comparison with channel sounder measurements

    OpenAIRE

    G. Del Galdo; M. Haardt; C. Schneider

    2004-01-01

    In this paper we propose a flexible geometrybased propagation model for wireless communications developed at Ilmenau University of Technology. The IlmProp comprises a geometrical representation of the environment surrounding the experiment and a precise representation of the transmitting and receiving antennas. The IlmProp is capable of simulating Multi-User MIMO scenarios and includes a complete collection of tools to analyze the synthetic channels. In order to assess...

  6. A Reliable Channel Reservation based Multi-channel MAC Protocol with A Single Transceiver

    OpenAIRE

    Bo Yang; Bo Li; Zhongjiang Yan; Mao Yang; Xiaoya Zuo

    2015-01-01

    The multi-channel MAC protocols have been proposed recently to improve the network capacity by accommodating more concurrent transmissions. In this paper, we propose a distributed multi-channel MAC protocol using reliable multiple channel reservation with only a single transceiver. Specifically, the control handshake information is reserved to be re-broadcasted over the control channel to address the multi-channel hidden terminal problem. Besides, by reserving multiple data transmission oppor...

  7. [Topology of the mitochondrial potassium ion channels].

    Science.gov (United States)

    Laskowski, Michał; Kulawiak, Bogusz

    In the inner mitochondrial membrane several potassium channels have been identified whose activation lead to cytoprotection during ischemic event. It was found that activation of mitochondrial large conductance calcium activated potassium channel (mitoBKCa) and ATP regulated potassium channel (mitoKATP) preserves brain and heart muscle cells against ischemia/reperfusion induced damage. However the detailed cytoprotection mechanism remains unclear. Similarly, the molecular structures and protein interactions of the mitochondrial potassium channels are still unknown. In this article, we summarize the current knowledge of the mitoKATP and mitoBKCa channels topology. Different aspects of this topic are discussed like import and assembly of the channel subunits and biophysical properties of mitochondrial compartments. Additionally, the consequences of different topology models on the cytoprotective function of the mitochondrial potassium channels were analyzed.

  8. Cardiovascular KATP channels and advanced aging.

    Science.gov (United States)

    Yang, Hua-Qian; Subbotina, Ekaterina; Ramasamy, Ravichandran; Coetzee, William A

    2016-01-01

    With advanced aging, there is a decline in innate cardiovascular function. This decline is not general in nature. Instead, specific changes occur that impact the basic cardiovascular function, which include alterations in biochemical pathways and ion channel function. This review focuses on a particular ion channel that couple the latter two processes, namely the KATP channel, which opening is promoted by alterations in intracellular energy metabolism. We show that the intrinsic properties of the KATP channel changes with advanced aging and argue that the channel can be further modulated by biochemical changes. The importance is widespread, given the ubiquitous nature of the KATP channel in the cardiovascular system where it can regulate processes as diverse as cardiac function, blood flow and protection mechanisms against superimposed stress, such as cardiac ischemia. We highlight questions that remain to be answered before the KATP channel can be considered as a viable target for therapeutic intervention.

  9. Post-Translational Modifications of TRP Channels

    Science.gov (United States)

    Voolstra, Olaf; Huber, Armin

    2014-01-01

    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. PMID:24717323

  10. 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.

  11. 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...

  12. 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...

  13. Propagation Characterization and MIMO Channel-Modelling for 3G

    DEFF Research Database (Denmark)

    Schumacher, Laurent; Berger, Lars Torsten; Ramiro-Moreno, Juan

    2004-01-01

    This paper presents a survey of MIMO channel models, distinguishing between determinsistic and stochastic channel models.......This paper presents a survey of MIMO channel models, distinguishing between determinsistic and stochastic channel models....

  14. Opening the shaker K+ channel with hanatoxin.

    Science.gov (United States)

    Milescu, Mirela; Lee, Hwa C; Bae, Chan Hyung; Kim, Jae Il; Swartz, Kenton J

    2013-02-01

    Voltage-activated ion channels open and close in response to changes in membrane voltage, a property that is fundamental to the roles of these channels in electrical signaling. Protein toxins from venomous organisms commonly target the S1-S4 voltage-sensing domains in these channels and modify their gating properties. Studies on the interaction of hanatoxin with the Kv2.1 channel show that this tarantula toxin interacts with the S1-S4 domain and inhibits opening by stabilizing a closed state. Here we investigated the interaction of hanatoxin with the Shaker Kv channel, a voltage-activated channel that has been extensively studied with biophysical approaches. In contrast to what is observed in the Kv2.1 channel, we find that hanatoxin shifts the conductance-voltage relation to negative voltages, making it easier to open the channel with membrane depolarization. Although these actions of the toxin are subtle in the wild-type channel, strengthening the toxin-channel interaction with mutations in the S3b helix of the S1-S4 domain enhances toxin affinity and causes large shifts in the conductance-voltage relationship. Using a range of previously characterized mutants of the Shaker Kv channel, we find that hanatoxin stabilizes an activated conformation of the voltage sensors, in addition to promoting opening through an effect on the final opening transition. Chimeras in which S3b-S4 paddle motifs are transferred between Kv2.1 and Shaker Kv channels, as well as experiments with the related tarantula toxin GxTx-1E, lead us to conclude that the actions of tarantula toxins are not simply a product of where they bind to the channel, but that fine structural details of the toxin-channel interface determine whether a toxin is an inhibitor or opener.

  15. 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.

  16. 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.

  17. Multicarrier chaotic communications in multipath fading channels without channel estimation

    Science.gov (United States)

    Wang, Shilian; Zhang, Zhili

    2015-01-01

    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.

  18. Conductive Channel for Energy Transmission

    Science.gov (United States)

    Apollonov, Victor V.

    2011-11-01

    For many years the attempts to create conductive channels of big length were taken in order to study the upper atmosphere and to settle special tasks, related to energy transmission. There upon the program of creation of "Impulsar" represents a great interest, as this program in a combination with high-voltage high repetition rate electrical source can be useful to solve the above mentioned problems (N. Tesla ideas for the days of high power lasers). The principle of conductive channel production can be shortly described as follows. The "Impulsar"—laser jet engine vehicle—propulsion take place under the influence of powerful high repetition rate pulse-periodic laser radiation. In the experiments the CO2—laser and solid state Nd:YAG laser systems had been used. Active impulse appears thanks to air breakdown (30 km), placed in the vicinity of the focusing mirror-acceptor of the breakdown waves. With each pulse of powerful laser the device rises up, leaving a bright and dense trace of products with high degree of ionization and metallization by conductive nano-particles due to ablation. Conductive dust plasma properties investigation in our experiments was produced by two very effective approaches: high power laser controlled ablation and by explosion of wire. Experimental and theoretical results of conductive canal modeling will be presented. The estimations show that with already experimentally demonstrated figures of specific thrust impulse the lower layers of the Ionosphere can be reached in several ten seconds that is enough to keep the high level of channel conductivity and stability with the help of high repetition rate high voltage generator. Some possible applications for new technology are highlighted.

  19. Precipitation patterns during channel flow

    Science.gov (United States)

    Jamtveit, B.; Hawkins, C.; Benning, L. G.; Meier, D.; Hammer, O.; Angheluta, L.

    2013-12-01

    Mineral precipitation during channelized fluid flow is widespread in a wide variety of geological systems. It is also a common and costly phenomenon in many industrial processes that involve fluid flow in pipelines. It is often referred to as scale formation and encountered in a large number of industries, including paper production, chemical manufacturing, cement operations, food processing, as well as non-renewable (i.e. oil and gas) and renewable (i.e. geothermal) energy production. We have studied the incipient stages of growth of amorphous silica on steel plates emplaced into the central areas of the ca. 1 meter in diameter sized pipelines used at the hydrothermal power plant at Hellisheidi, Iceland (with a capacity of ca 300 MW electricity and 100 MW hot water). Silica precipitation takes place over a period of ca. 2 months at approximately 120°C and a flow rate around 1 m/s. The growth produces asymmetric ca. 1mm high dendritic structures ';leaning' towards the incoming fluid flow. A novel phase-field model combined with the lattice Boltzmann method is introduced to study how the growth morphologies vary under different hydrodynamic conditions, including non-laminar systems with turbulent mixing. The model accurately predicts the observed morphologies and is directly relevant for understanding the more general problem of precipitation influenced by turbulent mixing during flow in channels with rough walls and even for porous flow. Reference: Hawkins, C., Angheluta, L., Hammer, Ø., and Jamtveit, B., Precipitation dendrites in channel flow. Europhysics Letters, 102, 54001

  20. Magnetohydrodynamic (MHD) channel corner seal

    Science.gov (United States)

    Spurrier, Francis R.

    1980-01-01

    A corner seal for an MHD duct includes a compressible portion which contacts the duct walls and an insulating portion which contacts the electrodes, sidewall bars and insulators. The compressible portion may be a pneumatic or hydraulic gasket or an open-cell foam rubber. The insulating portion is segmented into a plurality of pieces of the same thickness as the electrodes, insulators and sidewall bars and aligned therewith, the pieces aligned with the insulator being of a different size from the pieces aligned with the electrodes and sidewall bars to create a stepped configuration along the corners of the MHD channel.

  1. Hydraulic jumps in a channel

    DEFF Research Database (Denmark)

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

    2009-01-01

    '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...... for a supercritical one-dimensional boundary layer flow, but we find that the surface slope is up to an order of magnitude larger than expected and independent of flow rate. We explain this as an effect of turbulent fluctuations creating an enhanced eddy viscosity, and we model the results in terms of Prandtl...

  2. Channel function reconstitution and re-animation: a single-channel strategy in the postcrystal age

    Science.gov (United States)

    Oiki, Shigetoshi

    2015-01-01

    The most essential properties of ion channels for their physiologically relevant functions are ion-selective permeation and gating. Among the channel species, the potassium channel is primordial and the most ubiquitous in the biological world, and knowledge of this channel underlies the understanding of features of other ion channels. The strategy applied to studying channels changed dramatically after the crystal structure of the potassium channel was resolved. Given the abundant structural information available, we exploited the bacterial KcsA potassium channel as a simple model channel. In the postcrystal age, there are two effective frameworks with which to decipher the functional codes present in the channel structure, namely reconstitution and re-animation. Complex channel proteins are decomposed into essential functional components, and well-examined parts are rebuilt for integrating channel function in the membrane (reconstitution). Permeation and gating are dynamic operations, and one imagines the active channel by breathing life into the ‘frozen’ crystal (re-animation). Capturing the motion of channels at the single-molecule level is necessary to characterize the behaviour of functioning channels. Advanced techniques, including diffracted X-ray tracking, lipid bilayer methods and high-speed atomic force microscopy, have been used. Here, I present dynamic pictures of the KcsA potassium channel from the submolecular conformational changes to the supramolecular collective behaviour of channels in the membrane. These results form an integrated picture of the active channel and offer insights into the processes underlying the physiological function of the channel in the cell membrane. PMID:25833254

  3. Use of navigation channels by Lake Sturgeon: Does channelization increase vulnerability of fish to ship strikes?

    Science.gov (United States)

    Hondorp, Darryl W.; Bennion, David; Roseman, Edward; Holbrook, Christopher; Boase, James C.; Chiotti, Justin A.; Thomas, Michael V.; Wills, Todd C.; Drouin, Richard; Kessel, Steven T.; Krueger, Charles C.

    2017-01-01

    Channelization for navigation and flood control has altered the hydrology and bathymetry of many large rivers with unknown consequences for fish species that undergo riverine migrations. In this study, we investigated whether altered flow distributions and bathymetry associated with channelization attracted migrating Lake Sturgeon (Acipenser fulvescens) into commercial navigation channels, potentially increasing their exposure to ship strikes. To address this question, we quantified and compared Lake Sturgeon selection for navigation channels vs. alternative pathways in two multi-channel rivers differentially affected by channelization, but free of barriers to sturgeon movement. Acoustic telemetry was used to quantify Lake Sturgeon movements. Under the assumption that Lake Sturgeon navigate by following primary flow paths, acoustic-tagged Lake Sturgeon in the more-channelized lower Detroit River were expected to choose navigation channels over alternative pathways and to exhibit greater selection for navigation channels than conspecifics in the less-channelized lower St. Clair River. Consistent with these predictions, acoustic-tagged Lake Sturgeon in the more-channelized lower Detroit River selected the higher-flow and deeper navigation channels over alternative migration pathways, whereas in the less-channelized lower St. Clair River, individuals primarily used pathways alternative to navigation channels. Lake Sturgeon selection for navigation channels as migratory pathways also was significantly higher in the more-channelized lower Detroit River than in the less-channelized lower St. Clair River. We speculated that use of navigation channels over alternative pathways would increase the spatial overlap of commercial vessels and migrating Lake Sturgeon, potentially enhancing their vulnerability to ship strikes. Results of our study thus demonstrated an association between channelization and the path use of migrating Lake Sturgeon that could prove important for

  4. Microwave line-of-sight channel measurements, channel modelling, and application of channel models to digital radio performance prediction, publications

    Science.gov (United States)

    Haeggman, S. G.

    1991-06-01

    Seven scientific papers published during 1978 to 1990 are reviewed. The papers constitute the basis for a PhD. The titles of the 7 papers are as follows: Time domain observation of microwave multipath propagation and estimation of channel model parameters; Microwave channel model parameters from pulse propagation measurements; The use of simple channel models in the analysis of 16 QAM radio links; Multipath outage probability for QAM systems with interference; Planning of propagation measurements for characterization of digital radio link channels; Measurement and statistical characterization of two 40 MHz line of sight radio channels at 6.2 GHz; and Effects on bandwidth on microwave line of sight channel modeling and digital radio performance prediction.

  5. A Perspective on the MIMO Wiretap Channel

    KAUST Repository

    Oggier, Frederique

    2015-10-01

    A wiretap channel is a communication channel between a transmitter Alice and a legitimate receiver Bob, in the presence of an eavesdropper Eve. The goal of communication is to achieve reliability between Alice and Bob, but also confidentiality despite Eve’s presence. Wiretap channels are declined in all kinds of flavors, depending on the underlying channels used by the three players: discrete memoryless channels, additive Gaussian noise channels, or fading channels, to name a few. In this survey, we focus on the case where the three players use multiple-antenna channels with Gaussian noise to communicate. After summarizing known results for multiple-input–multiple-output (MIMO) channels, both in terms of achievable reliable data rate (capacity) and code design, we introduce the MIMO wiretap channel. We then state the MIMO wiretap capacity, summarize the idea of the proof(s) behind this result, and comment on the insights given by the proofs on the physical meaning of the secrecy capacity. We finally discuss design criteria for MIMO wiretap codes.

  6. 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.

  7. Transient Receptor Potential Channels in the Vasculature

    Science.gov (United States)

    Earley, Scott; Brayden, Joseph E.

    2015-01-01

    The mammalian genome encodes 28 distinct members of the transient receptor potential (TRP) superfamily of cation channels, which exhibit varying degrees of selectivity for different ionic species. Multiple TRP channels are present in all cells and are involved in diverse aspects of cellular function, including sensory perception and signal transduction. Notably, TRP channels are involved in regulating vascular function and pathophysiology, the focus of this review. TRP channels in vascular smooth muscle cells participate in regulating contractility and proliferation, whereas endothelial TRP channel activity is an important contributor to endothelium-dependent vasodilation, vascular wall permeability, and angiogenesis. TRP channels are also present in perivascular sensory neurons and astrocytic endfeet proximal to cerebral arterioles, where they participate in the regulation of vascular tone. Almost all of these functions are mediated by changes in global intracellular Ca2+ levels or subcellular Ca2+ signaling events. In addition to directly mediating Ca2+ entry, TRP channels influence intracellular Ca2+ dynamics through membrane depolarization associated with the influx of cations or through receptor- or store-operated mechanisms. Dysregulation of TRP channels is associated with vascular-related pathologies, including hypertension, neointimal injury, ischemia-reperfusion injury, pulmonary edema, and neurogenic inflammation. In this review, we briefly consider general aspects of TRP channel biology and provide an in-depth discussion of the functions of TRP channels in vascular smooth muscle cells, endothelial cells, and perivascular cells under normal and pathophysiological conditions. PMID:25834234

  8. 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.

  9. Inertial (non-Darcian) channeled seepage flow

    Science.gov (United States)

    Foda, Mostafa A.

    1994-10-01

    A slow wave solution is identified for an infinite elastic medium intersected by a two-dimensional fluid channel. Because the wave speed is much slower than the medium's elastic shear wave, the response in the elastic medium is governed by elastostatics. The inertia of the wave is essentially focused in the fluid channel. Furthermore, wave damping is caused by fluid viscous friction on the channel in an elastic solid. It is proposed that these solutions may also be used in the case of a granular porous medium. The seepage channels would then represent a network of preferential flow paths. Therefore we would allow, in this case, the channel porosity to be different from the average granular porosity. For a strongly channel seepage flow or for a low channel porosity the solution is shown to approach that of a single-channel solution, giving rise to a slow propagating wave mode. On the other hand, for weak channeling or nearly `homogeneous' seepage flow the solution is shown to reproduce Biot's (1956) critically damped wave of the second kind. It is proposed that the resonance observed by Foda and Tzang (1994) are in the form of these strongly channeled wave modes.

  10. Human Slack Potassium Channel Mutations Increase Positive Cooperativity between Individual Channels

    Directory of Open Access Journals (Sweden)

    Grace E. Kim

    2014-12-01

    Full Text Available Disease-causing mutations in ion channels generally alter intrinsic gating properties such as activation, inactivation, and voltage dependence. We examined nine different mutations of the KCNT1 (Slack Na+-activated K+ channel that give rise to three distinct forms of epilepsy. All produced many-fold increases in current amplitude compared to the wild-type channel. This could not be accounted for by increases in the intrinsic open probability of individual channels. Rather, greatly increased opening was a consequence of cooperative interactions between multiple channels in a patch. The degree of cooperative gating was much greater for all of the mutant channels than for the wild-type channel, and could explain increases in current even in a mutant with reduced unitary conductance. We also found that the same mutation gave rise to different forms of epilepsy in different individuals. Our findings indicate that a major consequence of these mutations is to alter channel-channel interactions.

  11. KATP Channels in the Cardiovascular System.

    Science.gov (United States)

    Foster, Monique N; Coetzee, William A

    2016-01-01

    KATP channels are integral to the functions of many cells and tissues. The use of electrophysiological methods has allowed for a detailed characterization of KATP channels in terms of their biophysical properties, nucleotide sensitivities, and modification by pharmacological compounds. However, even though they were first described almost 25 years ago (Noma 1983, Trube and Hescheler 1984), the physiological and pathophysiological roles of these channels, and their regulation by complex biological systems, are only now emerging for many tissues. Even in tissues where their roles have been best defined, there are still many unanswered questions. This review aims to summarize the properties, molecular composition, and pharmacology of KATP channels in various cardiovascular components (atria, specialized conduction system, ventricles, smooth muscle, endothelium, and mitochondria). We will summarize the lessons learned from available genetic mouse models and address the known roles of KATP channels in cardiovascular pathologies and how genetic variation in KATP channel genes contribute to human disease. Copyright © 2016 the American Physiological Society.

  12. Phase rotation channel design with induction linacs

    CERN Document Server

    Fukui, Y

    2001-01-01

    Two models of the phase rotation channels of the neutrino factory were designed with a solenoid transport system and the induction linac acceleration system. One model has the one stage induction linac channel, and another model has two stages of the induction linac channels and an absorber and drift space in between them. Major figure of merits of the channel are the particle ratio of muons over primary protons, the momentum spread and the muon polarization correlation to the arrival time at the end of the phase rotation channel. The mu/proton ratios were 0.25 and 0.13 for the single stage and the double stage induction linac channels, respectively. The effective muon polarization, radicalradical, was 0.16 and the muon polarization correlation was 0.23/(100 ns) for the single stage induction linac model.

  13. Parameter estimation in channel network flow simulation

    Directory of Open Access Journals (Sweden)

    Han Longxi

    2008-03-01

    Full Text Available Simulations of water flow in channel networks require estimated values of roughness for all the individual channel segments that make up a network. When the number of individual channel segments is large, the parameter calibration workload is substantial and a high level of uncertainty in estimated roughness cannot be avoided. In this study, all the individual channel segments are graded according to the factors determining the value of roughness. It is assumed that channel segments with the same grade have the same value of roughness. Based on observed hydrological data, an optimal model for roughness estimation is built. The procedure of solving the optimal problem using the optimal model is described. In a test of its efficacy, this estimation method was applied successfully in the simulation of tidal water flow in a large complicated channel network in the lower reach of the Yangtze River in China.

  14. Distortion Exponent in MIMO Channels with Feedback

    CERN Document Server

    Gunduz, Deniz; Poor, H Vincent

    2009-01-01

    The transmission of a Gaussian source over a block-fading multiple antenna channel in the presence of a feedback link is considered. The feedback link is assumed to be an error and delay free link of capacity 1 bit per channel use. Under the short-term power constraint, the optimal exponential behavior of the end-to-end average distortion is characterized for all source-channel bandwidth ratios. It is shown that the optimal transmission strategy is successive refinement source coding followed by progressive transmission over the channel, in which the channel block is allocated dynamically among the layers based on the channel state using the feedback link as an instantaneous automatic repeat request (ARQ) signal.

  15. BK channel activators and their therapeutic perspectives

    Directory of Open Access Journals (Sweden)

    Bo Hjorth Bentzen

    2014-10-01

    Full Text Available The large conductance calcium- and voltage- activated K+ channel (KCa1.1, BK, MaxiK is ubiquitously expressed in the body, and holds the ability to integrate changes in intracellular calcium and membrane potential. This makes the BK channel an important negative feedback system linking increases in intracellular calcium to outward hyperpolarizing potassium currents. Consequently, the channel has many important physiological roles including regulation of smooth muscle tone, neurotransmitter release and neuronal excitability. Additionally, cardioprotective roles have been revealed in recent years. After a short introduction to the structure, function and regulation of BK channels, we review the small organic molecules activating BK channels and how these tool compounds have helped delineate the roles of BK channels in health and disease.

  16. Pore size matters for potassium channel conductance

    Science.gov (United States)

    Moldenhauer, Hans; Pincuntureo, Matías

    2016-01-01

    Ion channels are membrane proteins that mediate efficient ion transport across the hydrophobic core of cell membranes, an unlikely process in their absence. K+ channels discriminate K+ over cations with similar radii with extraordinary selectivity and display a wide diversity of ion transport rates, covering differences of two orders of magnitude in unitary conductance. The pore domains of large- and small-conductance K+ channels share a general architectural design comprising a conserved narrow selectivity filter, which forms intimate interactions with permeant ions, flanked by two wider vestibules toward the internal and external openings. In large-conductance K+ channels, the inner vestibule is wide, whereas in small-conductance channels it is narrow. Here we raise the idea that the physical dimensions of the hydrophobic internal vestibule limit ion transport in K+ channels, accounting for their diversity in unitary conductance. PMID:27619418

  17. BK channel activators and their therapeutic perspectives

    DEFF Research Database (Denmark)

    Bentzen, Bo Hjorth; Olesen, Søren-Peter; Rønn, Lars C B

    2014-01-01

    The large conductance calcium- and voltage-activated K(+) channel (KCa1.1, BK, MaxiK) is ubiquitously expressed in the body, and holds the ability to integrate changes in intracellular calcium and membrane potential. This makes the BK channel an important negative feedback system linking increases...... in intracellular calcium to outward hyperpolarizing potassium currents. Consequently, the channel has many important physiological roles including regulation of smooth muscle tone, neurotransmitter release and neuronal excitability. Additionally, cardioprotective roles have been revealed in recent years. After...... a short introduction to the structure, function and regulation of BK channels, we review the small organic molecules activating BK channels and how these tool compounds have helped delineate the roles of BK channels in health and disease....

  18. Export channel pricing management for integrated solutions

    OpenAIRE

    Roine, Henna; Sainio, Liisa-Maija; Saarenketo, Sami

    2012-01-01

    This article studies systems integrators' export channel pricing management for integrated solutions. We find support from our empirical case study for the notion that a systems integrator's export channel pricing strategy is multidimensional and dependent on international pricing environment and partner characteristics and that export partnerships have unique implications on a systems integrator's pricing process. The results show that giving up pricing control in export channel context may ...

  19. Dynamic study of milling low depth channels

    Directory of Open Access Journals (Sweden)

    Rosca Dorin Mircea

    2017-01-01

    Full Text Available This paper presents a study of dynamic aspects of the milling cutters used in particular case of low depth channels. A new calculation method was developed, taking into account the high variations of cutting forces during milling small depth channels with peripheral cutting tools. A new formula was established for the minimal value of channel depth that allows cutting process to be performed in conditions of dynamic stability.

  20. 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.

  1. State dependent dissociation of HERG channel inhibitors

    OpenAIRE

    Stork, D; Timin, E N; Berjukow, S; Huber, C.; Hohaus, A; Hering, S.; Auer, M.

    2007-01-01

    Background and purpose: Inhibition of HERG channels prolongs the ventricular action potential and the QT interval with the risk of torsade de pointes arrhythmias and sudden cardiac death. Many drugs induce greater inhibition of HERG channels when the cell membrane is depolarized frequently. The dependence of inhibition on the pulsing rate may yield different IC values at different frequencies and thus affect the quantification of HERG channel block. We systematically compared the kinetics of ...

  2. Analytical admittance characterization of high mobility channel

    Energy Technology Data Exchange (ETDEWEB)

    Mammeri, A. M.; Mahi, F. Z., E-mail: fati-zo-mahi2002@yahoo.fr [Institute of Science and Technology, University of Bechar (Algeria); Varani, L. [Institute of Electronics of the South (IES - CNRS UMR 5214), University of Montpellier (France)

    2015-03-30

    In this contribution, we investigate the small-signal admittance of the high electron mobility transistors field-effect channels under a continuation branching of the current between channel and gate by using an analytical model. The analytical approach takes into account the linearization of the 2D Poisson equation and the drift current along the channel. The analytical equations discuss the frequency dependence of the admittance at source and drain terminals on the geometrical transistor parameters.

  3. Pharmaceutical Distribution Market Channels in Poland

    OpenAIRE

    Agnieszka Woś

    2009-01-01

    Distribution on the pharmaceutical market in Poland is interesting and the most difficult sphere to manage. Numerous varied and specialized companies operating on the market cause that the processes of choosing middlemen in distribution channels are very complex. The hereby article presents the role and location of the companies operating within distribution channels on the pharmaceutical market. It draws attention to the development of non-pharmacy and non-wholesale sales channels.

  4. Information and Inventory in Distribution Channels

    OpenAIRE

    Ganesh Iyer; Chakravarthi Narasimhan; Rakesh Niraj

    2007-01-01

    We examine the trade-offs between demand information and inventory in a distribution channel. While better demand information has a positive direct effect for the manufacturer in improving the efficiency of holding inventory in a channel, it can also have the strategic effect of increasing retail prices and limiting the extraction of retail profits. Having inventory in the channel can help the manufacturer to manage retail pricing behavior while better extracting retail surplus. Thus, even if...

  5. [Synopsis about the hypothesis of "information channel" of channel-collateral system].

    Science.gov (United States)

    Chang, Xi-Lang

    2008-10-01

    The author of the present paper founded a theorem about the "incompleteness of single channel structure" (nerve, blood vessel, lymphatic, interspace, aperture, etc.) through quantitative and qualitative analysis about the economic information channel in the human body, which eliminates the probability of single channel structure in the information channel of channel (meridian)-collateral system. After comprehensive analysis on the current researches, the author puts forward a neodoxy, i.e., the body "information channel" structure of the channel-collateral system, mainly follows the distribution regularity of systemic statistics, and is not a single specific entity; various layers of the information channel in the main stems of the channel-collaterals are composed of optimized structure tissues. Hence, the structure of this information channel of channel-collateral system is an overall-optimized, sequential and compatible systemic structure. From this neodoxy, the author brings forward a working principle of channel-collaterals, which is supported theoretically by bio-auxology. The longitudinal distribution of the main stems of meridian-collaterals is considered to result from that in the process of the animal evolution, in the animals moving forward, the microscopic complicated movement of intracorporeal information and energy molecules is related to the forward macroscopic and non-uniform movement of organism in trans-measure. Its impulse and kinetic momentum forms a main vector in the longitudinal direction of the body (the direction of the main stem of channel-collaterals). In order to adapt to and utilize natural regularities, the main stems of the channel-collaterals gradually differentiate and evolve in the living organism, forming a whole system. The "hypothesis of biological origin of channel-collateral system" and "that of information channel of the channel-collaterals in the body" constitute a relatively complete theoretical system framework.

  6. KATP channel openers in the trigeminovascular system

    DEFF Research Database (Denmark)

    Ploug, K.B.; Amrutkar, D.V.; Baun, M.

    2012-01-01

    The ATP-sensitive K(+) (K(ATP)) channel openers levcromakalim and pinacidil are vasodilators that induce headache in healthy people. The neuropeptide calcitonin gene-related peptide (CGRP) induces headache in healthy people and migraine in migraineurs, potentially through a mechanism that involves...... opening of vascular or neuronal K(ATP) channels and mast cell degranulation. Using rat as a model, we studied the molecular presence of K(ATP) channels in the trigeminovascular system. Furthermore, we examined whether K(ATP) channel openers stimulate the in vitro release of CGRP and whether...

  7. Flow and sediment transport across oblique channels

    DEFF Research Database (Denmark)

    Hjelmager Jensen, Jacob; Madsen, Erik Østergaard; Fredsøe, Jørgen

    1998-01-01

    A 3D numerical investigation of flow across channels aligned obliquely to the main flow direction has been conducted. The applied numerical model solves the Reynolds-averaged Navier-Stokes equations using the k-ε model for turbulence closure on a curvilinear grid. Three momentum equations...... are solved, but the computational domain is 2D due to a uniformity along the channel alignment. Two important flow features arise when the flow crosses the channel: (i) the flow will be refracted in the direction of the channel alignment. This may be described by a depth-averaged model. (ii) due to shear...

  8. Achromatic Cooling Channel with Li Lenses

    Energy Technology Data Exchange (ETDEWEB)

    Balbekov, V. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States)

    2002-04-29

    A linear cooling channel with Li lenses, solenoids, and 201 MHz RF cavities is considered. A special lattice design is used to minimize chromatic aberrations by suppression of several betatron resonances. Transverse emittance of muon beam decreases from 2 mm to 0.5 mm at the channel of about 110 m length. Longitudinal heating is modest, therefore transmission of the channel is rather high: 96% without decay and 90% with decay. Minimal beam emittance achievable by similar channel estimated as about 0.25 mm at surface field of Li lenses 10 T.

  9. Customer Engagement Tool (Multi Channel Communication)

    Data.gov (United States)

    Social Security Administration — Add new infrastructure within SSA's Enterprise Architecture to allow interactions over multiple, yet to be defined, channels. Possibilities include: Provide a portal...

  10. Similarities between rivers and submarine channels

    Science.gov (United States)

    Balcerak, Ernie

    2013-02-01

    Scientists have long known that the width and depth of rivers follows a power law relationship with discharge. They have also noticed that submarine channels appear to be similar to terrestrial rivers, but there have not been many systematic comparisons of the relationships between submarine channel morphology and discharge. Konsoer et al. compared the width, depth, and slope of 177 submarine channels to those of 231 river cross sections. They found that submarine channels are up to an order of magnitude wider and deeper than the largest terrestrial rivers, but they exhibit a similar power law relationship between width and depth. For submarine channels that were similar in size to rivers, the authors found that submarine channels tend to be 1 to 2 orders of magnitude steeper than rivers. The authors also inferred values for sediment concentration in the turbidity currents in the channels and combined this with estimated mean flow velocities to look for a relationship between discharge and morphology in the channels. They found that like rivers, the width and depth of the submarine channels follow a power law scaling with discharge. (Journal of Geophysical Research-Earth Surface, doi:10.1029/2012JF002422, 2013)

  11. State dependent dissociation of HERG channel inhibitors.

    Science.gov (United States)

    Stork, D; Timin, E N; Berjukow, S; Huber, C; Hohaus, A; Auer, M; Hering, S

    2007-08-01

    Inhibition of HERG channels prolongs the ventricular action potential and the QT interval with the risk of torsade de pointes arrhythmias and sudden cardiac death. Many drugs induce greater inhibition of HERG channels when the cell membrane is depolarized frequently. The dependence of inhibition on the pulsing rate may yield different IC(50) values at different frequencies and thus affect the quantification of HERG channel block. We systematically compared the kinetics of HERG channel inhibition and recovery from block by 8 blockers at different frequencies. HERG channels were expressed heterologously in Xenopus oocytes and currents were measured with the two-electrode voltage clamp technique. Frequency-dependent block was observed for amiodarone, cisapride, droperidol and haloperidol (group 1) whereas bepridil, domperidone, E-4031 and terfenadine (group 2) induced similar pulse-dependent block at all frequencies. With the group 1 compounds, HERG channels recovered from block in the presence of drug (recovery being voltage-dependent). No substantial recovery from block was observed with the second group of compounds. Washing out of bepridil, domperidone, E-4031 and terfenadine was substantially augmented by frequent pulsing. Mutation D540K in the HERG channel (which exhibits reopening at negative voltages) facilitated recovery from block by these compounds at -140 mV. Drug molecules dissociate at different rates from open and closed HERG channels ('use-dependent' dissociation). Our data suggest that apparently 'trapped' drugs (group 2) dissociated from the open channel state whereas group 1 compounds dissociated from open and resting states.

  12. Sea Anemone Toxins Affecting Potassium Channels

    Science.gov (United States)

    Diochot, Sylvie; Lazdunski, Michel

    The great diversity of K+ channels and their wide distribution in many tissues are associated with important functions in cardiac and neuronal excitability that are now better understood thanks to the discovery of animal toxins. During the past few decades, sea anemones have provided a variety of toxins acting on voltage-sensitive sodium and, more recently, potassium channels. Currently there are three major structural groups of sea anemone K+ channel (SAK) toxins that have been characterized. Radioligand binding and electrophysiological experiments revealed that each group contains peptides displaying selective activities for different subfamilies of K+ channels. Short (35-37 amino acids) peptides in the group I display pore blocking effects on Kv1 channels. Molecular interactions of SAK-I toxins, important for activity and binding on Kv1 channels, implicate a spot of three conserved amino acid residues (Ser, Lys, Tyr) surrounded by other less conserved residues. Long (58-59 amino acids) SAK-II peptides display both enzymatic and K+ channel inhibitory activities. Medium size (42-43 amino acid) SAK-III peptides are gating modifiers which interact either with cardiac HERG or Kv3 channels by altering their voltage-dependent properties. SAK-III toxins bind to the S3C region in the outer vestibule of Kv channels. Sea anemones have proven to be a rich source of pharmacological tools, and some of the SAK toxins are now useful drugs for the diagnosis and treatment of autoimmune diseases.

  13. An experimental study of rip channel flow

    DEFF Research Database (Denmark)

    Drønen, Nils Kjetil; Karunarathna, H.; Fredsøe, Jørgen

    2002-01-01

    A laboratory study of the flow over a bar with a single rip channel has been performed. First, the well-known pattern of a bar circulation cell with a strong offshore-directed current out through the rip channel and a weaker onshore-directed return flow over the bar is documented. Then measurements...... of the three-dimensional structure of the flow in the area where the rip channel, the bar and the trough meet and well inside the rip channel are presented. These measurements reveal that 3D effects play an important role, and that a depth-integrated viewpoint may not always be sufficient for predicting...

  14. Channeling crystals for positron production

    Energy Technology Data Exchange (ETDEWEB)

    Decker, F.J.

    1991-05-01

    Particles traversing at small angles along a single crystal axis experience a collective scattering force of many crystal atoms. The enormous fields can trap the particles along an axis or plane, called channeling. High energy electrons are attracted by the positive nuclei and therefore produce strongly enhanced so called coherent bremsstrahlung and pair production. These effects could be used in a positron production target: A single tungsten crystal is oriented to the incident electron beam within 1 mrad. At 28 GeV/c the effective radiation length is with 0.9 mm about one quarter of the amorphous material. So the target length can be shorter, which yields a higher conversion coefficient and a lower emittance of the positron beam. This makes single crystals very interesting for positron production targets. 18 refs., 2 figs.

  15. Posttranslational Modification of Sodium Channels.

    Science.gov (United States)

    Pei, Zifan; Pan, Yanling; Cummins, Theodore R

    2017-10-26

    Voltage-gated sodium channels (VGSCs) are critical determinants of excitability. The properties of VGSCs are thought to be tightly controlled. However, VGSCs are also subjected to extensive modifications. Multiple posttranslational modifications that covalently modify VGSCs in neurons and muscle have been identified. These include, but are not limited to, phosphorylation, ubiquitination, palmitoylation, nitrosylation, glycosylation, and SUMOylation. Posttranslational modifications of VGSCs can have profound impact on cellular excitability, contributing to normal and abnormal physiology. Despite four decades of research, the complexity of VGSC modulation is still being determined. While some modifications have similar effects on the various VGSC isoforms, others have isoform-specific interactions. In addition, while much has been learned about how individual modifications can impact VGSC function, there is still more to be learned about how different modifications can interact. Here we review what is known about VGSC posttranslational modifications with a focus on the breadth and complexity of the regulatory mechanisms that impact VGSC properties.

  16. An information-guided channel-hopping scheme for block-fading channels with estimation errors

    KAUST Repository

    Yang, Yuli

    2010-12-01

    Information-guided channel-hopping technique employing multiple transmit antennas was previously proposed for supporting high data rate transmission over fading channels. This scheme achieves higher data rates than some mature schemes, such as the well-known cyclic transmit antenna selection and space-time block coding, by exploiting the independence character of multiple channels, which effectively results in having an additional information transmitting channel. Moreover, maximum likelihood decoding may be performed by simply decoupling the signals conveyed by the different mapping methods. In this paper, we investigate the achievable spectral efficiency of this scheme in the case of having channel estimation errors, with optimum pilot overhead for minimum meansquare error channel estimation, when transmitting over blockfading channels. Our numerical results further substantiate the robustness of the presented scheme, even with imperfect channel state information. ©2010 IEEE.

  17. Hysteresis in voltage-gated channels.

    Science.gov (United States)

    Villalba-Galea, Carlos A

    2017-03-04

    Ion channels constitute a superfamily of membrane proteins found in all living creatures. Their activity allows fast translocation of ions across the plasma membrane down the ion's transmembrane electrochemical gradient, resulting in a difference in electrical potential across the plasma membrane, known as the membrane potential. A group within this superfamily, namely voltage-gated channels, displays activity that is sensitive to the membrane potential. The activity of voltage-gated channels is controlled by the membrane potential, while the membrane potential is changed by these channels' activity. This interplay produces variations in the membrane potential that have evolved into electrical signals in many organisms. These signals are essential for numerous biological processes, including neuronal activity, insulin release, muscle contraction, fertilization and many others. In recent years, the activity of the voltage-gated channels has been observed not to follow a simple relationship with the membrane potential. Instead, it has been shown that the activity of voltage-gated channel displays hysteresis. In fact, a growing number of evidence have demonstrated that the voltage dependence of channel activity is dynamically modulated by activity itself. In spite of the great impact that this property can have on electrical signaling, hysteresis in voltage-gated channels is often overlooked. Addressing this issue, this review provides examples of voltage-gated ion channels displaying hysteretic behavior. Further, this review will discuss how Dynamic Voltage Dependence in voltage-gated channels can have a physiological role in electrical signaling. Furthermore, this review will elaborate on the current thoughts on the mechanism underlying hysteresis in voltage-gated channels.

  18. The Impact of New Communication Technologies and Channels on Historically Basic Channels of Communication

    Science.gov (United States)

    Schnell, Jim

    2005-01-01

    This article describes how new communication technologies and channels of communication are impacting historically basic channels of communication. This impact is described as being an incremental and evolutionary process rather than a blunt transition. A main theme stressed is that historically basic channels of communication, strongly grounded…

  19. Optimising the Quality of Experience during Channel Zapping : The Impact of Advertisements during Channel Zapping

    NARCIS (Netherlands)

    Kooij, R.E.; Klos, V.B.; Godana, B.E.; Nicolai, F.P.; Ahmed, O.K.

    2009-01-01

    Nowadays various digital television services are available. However, the user of these services experiences longer delays than the traditional analog TV while switching from channel to channel. The digital TV operator usually displays a black screen with the channel number during zapping. However,

  20. Innate immune response of channel catfish (Ictalurus punctatus) mannose-binding lectin to channel catfish virus

    Science.gov (United States)

    The channel catfish virus (CCV) is a pathogenic herpesvirus that infects channel catfish (Ictalurus punctatus) in pond aquaculture in the Southeast USA. The innate immune protein mannose-binding lectin (MBL) could play an important role in the innate response of channel catfish by binding to the CC...

  1. Pilot study on navigation channel regulation works in the North Channel, Yangtze estuary

    NARCIS (Netherlands)

    Gao, M.; Roelvink, J.A.

    2011-01-01

    It is estimated that the waterway in North Passage would not be able to meet the demand of shipping development soon and it is necessary to open a new deep navigation channel with a depth of 10 m in North Channel in the near future. A pilot study on the regulation of North Channel was proposed by

  2. Intrinsic properties and neuropharmacology of midline paraventricular thalamic nucleus neurons.

    Directory of Open Access Journals (Sweden)

    Miloslav eKolaj

    2014-04-01

    Full Text Available Neurons in the midline and intralaminar thalamic nuclei are components of an interconnected brainstem, limbic and prefrontal cortex neural network that is engaged during arousal, vigilance, motivated and addictive behaviors, and stress. To better understand the cellular mechanisms underlying these functions, here we review some of the recently characterized electrophysiological and neuropharmacological properties of neurons in the paraventricular thalamic nucleus (PVT, derived from whole cell patch clamp recordings in acute rat brain slice preparations. PVT neurons display firing patterns and ionic conductances (IT and IH that exhibit significant diurnal change. Their resting membrane potential is maintained by various ionic conductances that include inward rectifier (Kir, hyperpolarization-activated nonselective cation (HCN and TWIK-related acid sensitive (TASK K+ channels. Firing patterns are regulated by high voltage-activated (HVA and low voltage-activated (LVA Ca2+ conductances. Moreover, transient receptor potential (TRP-like nonselective cation channels together with Ca2+- and Na+-activated K+ conductances (KCa; KNa contribute to unique slow afterhyperpolarizing potentials (sAHPs that are generally not detectable in lateral thalamic or reticular thalamic nucleus neurons. We also report on receptor-mediated actions of GABA, glutamate, monoamines and several neuropeptides: arginine vasopressin, gastrin-releasing peptide, thyrotropin releasing hormone and the orexins (hypocretins. This review represents an initial survey of intrinsic and transmitter-sensitive ionic conductances that are deemed to be unique to this population of midline thalamic neurons, information that is fundamental to an appreciation of the role these thalamic neurons may play in normal central nervous system (CNS physiology and in CNS disorders that involve the dorsomedial thalamus.

  3. Developing laminar flow in curved rectangular channels

    NARCIS (Netherlands)

    De Vriend, H.J.

    1978-01-01

    As an intermediate step between earlier investigations on fully developed laminar flow in curved channels of shallow rectancular wet cross-section and the mathematical modeling of turbulent flow in river bends, a mathematical model of developing laminar flow in such channels is investigated. The

  4. Forbidden Channels and SIMP Dark Matter

    OpenAIRE

    Choi Soo-Min; Kang Yoo-Jin; Lee Hyun Min

    2018-01-01

    In this review, we focus on dark matter production from thermal freeze-out with forbidden channels and SIMP processes. We show that forbidden channels can be dominant to produce dark matter depending on the dark photon and / or dark Higgs mass compared to SIMP.

  5. Channel Effect Compensation in LSF Domain

    Directory of Open Access Journals (Sweden)

    An-Tze Yu

    2003-08-01

    Full Text Available This study addresses the problem of channel effect in the line spectrum frequency (LSF domain. LSF parameters are the popular speech features encoded in the bit stream for low bit-rate speech transmission. A method of channel effect compensation in LSF domain is of interest for robust speech recognition on mobile communication and Internet systems. If the bit error rate in the transmission of digital encoded speech is negligibly low, the channel distortion comes mainly from the microphone or the handset. When the speech signal is represented in terms of the phase of inverse filter derived from LP analysis, this channel distortion can be expressed in terms of the channel phase. Further derivation shows that the mean subtraction performed on the phase of inverse filter can minimize the channel effect. Based on this finding, an iterative algorithm is proposed to remove the bias on LSFs due to channel effect. The experiments on the simulated channel distorted speech and the real telephone speech are conducted to show the effectiveness of our proposed method. The performance of the proposed method is comparable to that of cepstral mean normalization (CMN in using cepstral coefficients.

  6. Resonant coherent excitation of channeled ions

    Energy Technology Data Exchange (ETDEWEB)

    Datz, S.; Moak, C.D.; Crawford, O.H.; Krause, H.F.; Dittner, P.F.; Gomez del Campo, J.; Biggerstaff, J.A.; Miller, P.D.; Hvelplund, P.; Knudsen, H.

    1978-03-27

    We have observed resonant excitation of swift channeled hydrogenlike ions (Z = 5 to Z = 9) and heliumlike F/sup 7 +/ which arises from a coherent periodic perturbation by the atoms in the bounding crystal rows. The resonance excitation was seen through the reduction in the transmission of fixed-charge-state ions through channels in thin crystals of Au and Ag.

  7. Physical Experiment of Englacial R-Channels

    Science.gov (United States)

    Prohaska, Yuri M.; Werder, Mauro A.; Farinotti, Daniel

    2017-04-01

    In 1972, Röthlisberger presented a theoretical study describing the evolution of pressurised en- and subglacial channels. The existence of these so-called R-channels has later been confirmed through field observations. To our knowledge, however, no physical experiment has ever been conducted to actually measure the properties of such channel flow in the laboratory. Here, we present a setup for such a laboratory experiment and preliminary results. The aim of our experiment is to measure the Darcy-Weisbach friction factor, the heat exchange rate between water and channel wall, and the Reynolds number. For our experiment, we produce transparent ice blocks of 1.6m length and a cross section of up to 25x25cm. A small metal tube is frozen into the ice block and removed before the experiment to create an initial R-channel. Pipes attached to flanges frozen into the ice block allow us to let water flow under pressurised conditions. Water pressure and temperature are measured at the inlet and outlet of the ice block whilst the evolution of the channel diameter is captured by photographic imaging. A magnetic flow meter measures the discharge. During a typical experiment, the diameter of the R-channel evolves from 1 to 6cm with flow speeds of up to 2m/s, the Reynolds number is around 10⁴, and the friction factor increases from about 0.024 to 0.12. This means that the channel evolves from hydraulically smooth to rough.

  8. Form and process in developing channels

    Science.gov (United States)

    Leslie M. Reid

    1988-01-01

    The topographic grain of a landscape is strongly influenced by the drainage density, and the drainage density reflects the balance between processes active on hillslopes and those in channels. This balance was explored by constructing sediment budgets for a sequence of stages in the development of a discontinuously incising channel.

  9. Dual-view flow channel visualization

    NARCIS (Netherlands)

    Hibara, A.; Kaxama, Y; Carlen, Edwin; van den Berg, Albert

    2014-01-01

    The concept of dual-view flow-channel visualization is proposed, where ordinary (top) and lateral images are available in a single view field. In order to obtain the top and lateral fluidic-channel images in a single view of the microscope observation, optical path lengths of these images were

  10. The Orange Juice Distribution Channel: Some Characteristics ...

    African Journals Online (AJOL)

    Several changes are taking place in the fruit juice distribution channels environment in Europe, a growing importance of food-service, the penetration of the global ... The framework for this part is build up of the marketing channel concepts and functions (Stern et al., 1996; Berman, 1996; Rosembloom, 1999), and data was ...

  11. Quantum Correlations Evolution Asymmetry in Quantum Channels

    Science.gov (United States)

    Li, Meng; Huang, Yun-Feng; Guo, Guang-Can

    2017-03-01

    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. Supported by the National Natural Science Foundation of China under Grant Nos. 61327901, 61490711, 61225025, 11474268, and the Fundamental Research Funds for the Central Universities under Grant No. WK2470000018

  12. Hydrodynamic blood plasma separation in microfluidic channels

    DEFF Research Database (Denmark)

    Jouvet, Lionel

    2010-01-01

    The separation of red blood cells from plasma flowing in microchannels is possible by biophysical effects such as the Zweifach–Fung bifurcation law. In the present study, daughter channels are placed alongside a main channel such that cells and plasma are collected separately. The device is aimed...

  13. Pharmacological modulation of SK3 channels

    DEFF Research Database (Denmark)

    Grunnet, M; Jespersen, Thomas; Angelo, K

    2001-01-01

    -frequency adaptation, pharmacological modulation of SK channels may be of significant clinical importance. Here we report the functional expression of SK3 in HEK293 and demonstrate a broad pharmacological profile for these channels. Brain slice studies commonly employ 4-aminopyridine (4-AP) to block voltage...

  14. Hardware Emulation of Wireless Communication Fading Channels

    Science.gov (United States)

    2011-01-01

    2009. [6] Elektrobit, “EB Propsim F8-advanced RF channel emulator,” Online: http://www.elektrobit.com, Jun. 2009. [7] A. Anastasopoulos and K.M. Chugg...digital transmission over WS- SUS channels,” IEEE Trans. Commun., vol. 43, no. 12, pp. 2907-2913, Dec. 1995. [15] A. Anastasopoulos and K.M. Chugg, “An

  15. REVIEW OF WIRELESS MIMO CHANNEL MODELS | Anioke ...

    African Journals Online (AJOL)

    The need to increase spectral efficiency has led to the design of multiple antenna systems for both transmit and receive sides otherwise known as MIMO. Channel modeling forms an integral part of this design. Therefore it is very important to investigate and understand existing MIMO channel models. This paper provides a ...

  16. Biology of the KCNQ1 Potassium Channel

    Directory of Open Access Journals (Sweden)

    Geoffrey W. Abbott

    2014-01-01

    Full Text Available Ion channels are essential for basic cellular function and for processes including sensory perception and intercellular communication in multicellular organisms. Voltage-gated potassium (Kv channels facilitate dynamic cellular repolarization during an action potential, opening in response to membrane depolarization to facilitate K+ efflux. In both excitable and nonexcitable cells other, constitutively active, K+ channels provide a relatively constant repolarizing force to control membrane potential, ion homeostasis, and secretory processes. Of the forty known human Kv channel pore-forming α subunits that coassemble in various combinations to form the fundamental tetrameric channel pore and voltage sensor module, KCNQ1 is unique. KCNQ1 stands alone in having the capacity to form either channels that are voltage-dependent and require membrane depolarization for activation, or constitutively active channels. In mammals, KCNQ1 regulates processes including gastric acid secretion, thyroid hormone biosynthesis, salt and glucose homeostasis, and cell volume and in some species is required for rhythmic beating of the heart. In this review, the author discusses the unique functional properties, regulation, cell biology, diverse physiological roles, and involvement in human disease states of this chameleonic K+ channel.

  17. Multi-Channel Maximum Likelihood Pitch Estimation

    DEFF Research Database (Denmark)

    Christensen, Mads Græsbøll

    2012-01-01

    In this paper, a method for multi-channel pitch estimation is proposed. The method is a maximum likelihood estimator and is based on a parametric model where the signals in the various channels share the same fundamental frequency but can have different amplitudes, phases, and noise characteristi...

  18. Privacy of a lossy bosonic memory channel

    OpenAIRE

    Ruggeri, G.; Mancini, S.

    2006-01-01

    We study the security of the information transmission between two honest parties realized through a lossy bosonic memory channel when losses are captured by a dishonest party. We then show that entangled inputs can enhance the private information of such a channel, which however does never overcome that of unentangled inputs in absence of memory.

  19. Sodium channels and mammalian sensory mechanotransduction.

    Science.gov (United States)

    Raouf, Ramin; Rugiero, Francois; Kiesewetter, Hannes; Hatch, Rachel; Hummler, Edith; Nassar, Mohammed A; Wang, Fan; Wood, John N

    2012-03-26

    Members of the degenerin/epithelial (DEG/ENaC) sodium channel family are mechanosensors in C elegans, and Nav1.7 and Nav1.8 voltage-gated sodium channel knockout mice have major deficits in mechanosensation. β and γENaC sodium channel subunits are present with acid sensing ion channels (ASICs) in mammalian sensory neurons of the dorsal root ganglia (DRG). The extent to which epithelial or voltage-gated sodium channels are involved in transduction of mechanical stimuli is unclear. Here we show that deleting β and γENaC sodium channels in sensory neurons does not result in mechanosensory behavioural deficits. We had shown previously that Nav1.7/Nav1.8 double knockout mice have major deficits in behavioural responses to noxious mechanical pressure. However, all classes of mechanically activated currents in DRG neurons are unaffected by deletion of the two sodium channels. In contrast, the ability of Nav1.7/Nav1.8 knockout DRG neurons to generate action potentials is compromised with 50% of the small diameter sensory neurons unable to respond to electrical stimulation in vitro. Behavioural deficits in Nav1.7/Nav1.8 knockout mice reflects a failure of action potential propagation in a mechanosensitive set of sensory neurons rather than a loss of primary transduction currents. DEG/ENaC sodium channels are not mechanosensors in mouse sensory neurons.

  20. Radio Channel Modeling in Body Area Networks

    NARCIS (Netherlands)

    An, L.; Bentum, Marinus Jan; Meijerink, Arjan; Scanlon, W.G.

    2009-01-01

    A body area network (BAN) is a network of bodyworn or implanted electronic devices, including wireless sensors which can monitor body parameters or to de- tect movements. One of the big challenges in BANs is the propagation channel modeling. Channel models can be used to understand wave propagation

  1. Radio channel modeling in body area networks

    NARCIS (Netherlands)

    An, L.; Bentum, Marinus Jan; Meijerink, Arjan; Scanlon, W.G.

    2010-01-01

    A body area network (BAN) is a network of bodyworn or implanted electronic devices, including wireless sensors which can monitor body parameters or to detect movements. One of the big challenges in BANs is the propagation channel modeling. Channel models can be used to understand wave propagation in

  2. 33 CFR 117.720 - Great Channel.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Great Channel. 117.720 Section 117.720 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY BRIDGES DRAWBRIDGE OPERATION REGULATIONS Specific Requirements New Jersey § 117.720 Great Channel. The draw of the...

  3. 33 CFR 117.1005 - Chincoteague Channel.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Chincoteague Channel. 117.1005 Section 117.1005 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY BRIDGES DRAWBRIDGE OPERATION REGULATIONS Specific Requirements Virginia § 117.1005 Chincoteague Channel. The draw of...

  4. Forbidden Channels and SIMP Dark Matter

    OpenAIRE

    Choi, Soo-Min; Kang, Yoo-Jin; Lee, Hyun Min

    2017-01-01

    In this review, we focus on dark matter production from thermal freeze-out with forbidden channels and SIMP processes. We show that forbidden channels can be dominant to produce dark matter depending on the dark photon and / or dark Higgs mass compared to SIMP.

  5. Route 66: Passively Breaking All GSM Channels

    DEFF Research Database (Denmark)

    Vejre, Philip S.; Bogdanov, Andrey

    2014-01-01

    impact in the field, only a small selection of its channels have been analyzed. In this paper, we perform a complete practical-complexity, ciphertext-only cryptanalysis of all 66 encoded GSM channels. Moreover, we present a new passive attack which recovers the encryption key by exploiting the location...

  6. Ion channel model development and validation

    Science.gov (United States)

    Nelson, Peter Hugo

    2010-03-01

    The structure of the KcsA ion channel selectivity filter is used to develop three simple models of ion channel permeation. The quantitative predictions of the knock-on model are tested by comparison with experimental data from single-channel recordings of the KcsA channel. By comparison with experiment, students discover that the knock-on model can't explain saturation of ion channel current as the concentrations of the bathing solutions are increased. By inverting the energy diagram, students derive the association-dissociation model of ion channel permeation. This model predicts non-linear Michaelis-Menten saturating behavior that requires students to perform non-linear least-squares fits to the experimental data. This is done using Excel's solver feature. Students discover that this simple model does an excellent job of explaining the qualitative features of ion channel permeation but cannot account for changes in voltage sensitivity. The model is then extended to include an electrical dissociation distance. This rapid translocation model is then compared with experimental data from a wide variety of ion channels and students discover that this model also has its limitations. Support from NSF DUE 0836833 is gratefully acknowledged.

  7. Atlantic water flow through the Faroese Channels

    Directory of Open Access Journals (Sweden)

    B. Hansen

    2017-11-01

    Full Text Available Through the Faroese Channels – the collective name for a system of channels linking the Faroe–Shetland Channel, Wyville Thomson Basin, and Faroe Bank Channel – there is a deep flow of cold waters from Arctic regions that exit the system as overflow through the Faroe Bank Channel and across the Wyville Thomson Ridge. The upper layers, in contrast, are dominated by warm, saline water masses from the southwest, termed Atlantic water. In spite of intensive research over more than a century, there are still open questions on the passage of these waters through the system with conflicting views in recent literature. Of special note is the suggestion that there is a flow of Atlantic water from the Faroe–Shetland Channel through the Faroe Bank Channel, which circles the Faroes over the slope region in a clockwise direction. Here, we combine the observational evidence from ship-borne hydrography, moored current measurements, surface drifter tracks, and satellite altimetry to address these questions and propose a general scheme for the Atlantic water flow through this channel system. We find no evidence for a continuous flow of Atlantic water from the Faroe–Shetland Channel to the Faroe Bank Channel over the Faroese slope. Rather, the southwestward-flowing water over the Faroese slope of the Faroe–Shetland Channel is totally recirculated within the combined area of the Faroe–Shetland Channel and Wyville Thomson Basin, except possibly for a small release in the form of eddies. This does not exclude a possible westward flow over the southern tip of the Faroe Shelf, but even including that, we estimate that the average volume transport of a Circum-Faroe Current does not exceed 0.5 Sv (1 Sv  =  106 m3 s−1. Also, there seems to be a persistent flow of Atlantic water from the western part of the Faroe Bank Channel into the Faroe–Shetland Channel that joins the Slope Current over the Scottish slope. These conclusions will affect

  8. Atlantic water flow through the Faroese Channels

    Science.gov (United States)

    Hansen, Bogi; Poulsen, Turið; Margretha Húsgarð Larsen, Karin; Hátún, Hjálmar; Østerhus, Svein; Darelius, Elin; Berx, Barbara; Quadfasel, Detlef; Jochumsen, Kerstin

    2017-11-01

    Through the Faroese Channels - the collective name for a system of channels linking the Faroe-Shetland Channel, Wyville Thomson Basin, and Faroe Bank Channel - there is a deep flow of cold waters from Arctic regions that exit the system as overflow through the Faroe Bank Channel and across the Wyville Thomson Ridge. The upper layers, in contrast, are dominated by warm, saline water masses from the southwest, termed Atlantic water. In spite of intensive research over more than a century, there are still open questions on the passage of these waters through the system with conflicting views in recent literature. Of special note is the suggestion that there is a flow of Atlantic water from the Faroe-Shetland Channel through the Faroe Bank Channel, which circles the Faroes over the slope region in a clockwise direction. Here, we combine the observational evidence from ship-borne hydrography, moored current measurements, surface drifter tracks, and satellite altimetry to address these questions and propose a general scheme for the Atlantic water flow through this channel system. We find no evidence for a continuous flow of Atlantic water from the Faroe-Shetland Channel to the Faroe Bank Channel over the Faroese slope. Rather, the southwestward-flowing water over the Faroese slope of the Faroe-Shetland Channel is totally recirculated within the combined area of the Faroe-Shetland Channel and Wyville Thomson Basin, except possibly for a small release in the form of eddies. This does not exclude a possible westward flow over the southern tip of the Faroe Shelf, but even including that, we estimate that the average volume transport of a Circum-Faroe Current does not exceed 0.5 Sv (1 Sv = 106 m3 s-1). Also, there seems to be a persistent flow of Atlantic water from the western part of the Faroe Bank Channel into the Faroe-Shetland Channel that joins the Slope Current over the Scottish slope. These conclusions will affect potential impacts from offshore activities in the

  9. Enhancement effects of martentoxin on glioma BK channel and BK channel (α+β1 subtypes.

    Directory of Open Access Journals (Sweden)

    Jie Tao

    Full Text Available BACKGROUND: BK channels are usually activated by membrane depolarization and cytoplasmic Ca(2+. Especially,the activity of BK channel (α+β4 can be modulated by martentoxin, a 37 residues peptide, with Ca(2+-dependent manner. gBK channel (glioma BK channel and BK channel (α+β1 possessed higher Ca(2+ sensitivity than other known BK channel subtypes. METHODOLOGY AND PRINCIPAL FINDINGS: The present study investigated the modulatory characteristics of martentoxin on these two BK channel subtypes by electrophysiological recordings, cell proliferation and Ca(2+ imaging. In the presence of cytoplasmic Ca(2+, martentoxin could enhance the activities of both gBK and BK channel (α+β1 subtypes in dose-dependent manner with EC(50 of 46.7 nM and 495 nM respectively, while not shift the steady-state activation of these channels. The enhancement ratio of martentoxin on gBK and BK channel (α+β1 was unrelated to the quantitative change of cytoplasmic Ca(2+ concentrations though the interaction between martentoxin and BK channel (α+β1 was accelerated under higher cytoplasmic Ca(2+. The selective BK pore blocker iberiotoxin could fully abolish the enhancement of these two BK subtypes induced by martentoxin, suggesting that the auxiliary β subunit might contribute to the docking for martentoxin. However, in the absence of cytoplasmic Ca(2+, the activity of gBK channel would be surprisingly inhibited by martentoxin while BK channel (α+β1 couldn't be affected by the toxin. CONCLUSIONS AND SIGNIFICANCE: Thus, the results shown here provide the novel evidence that martentoxin could increase the two Ca(2+-hypersensitive BK channel subtypes activities in a new manner and indicate that β subunit of these BK channels plays a vital role in this enhancement by martentoxin.

  10. Serial data transmission between redundant channels

    Science.gov (United States)

    Tulpule, Bhalchandra R. (Inventor); Binnall, Daniel G. (Inventor)

    1992-01-01

    Data is communicated between redundant channels formatted in blocks having an initial command word followed by a destination code, starting address and a variable number of data words including a word count. The blocks are transmitted between each channel and all of the channels over cross-channel data links, each channel receiving the data blocks and determining the validity thereof by counting the number of data words received and comparing that number to the word count transmitted for that block. An interrupt signal indicative of invalidity of a block is provided in the event of a miscompare. A stop address is generated for each block received for storage at the start address. A memory address is generated for each valid word received for storage in sequence starting immediately after the start address. The next block received has its start address placed immediately at the end of the previously received block.

  11. Stability of flowing open fluidic channels

    Directory of Open Access Journals (Sweden)

    Jue Nee Tan

    2013-02-01

    Full Text Available Open fluidic systems have a distinct advantage over enclosed channels in that the fluids exposed nature makes for easy external interaction, this finds uses in introduction of samples by adding liquid droplets or from the surrounding gaseous medium. This work investigates flowing open channels and films, which can potentially make use of the open section of the system as an external interface, before bringing the sample into an enclosed channel. Clearly, in this scenario a key factor is the stability of the flowing open fluid. The open channels investigated include a straight open channel defined by a narrow strip of solid surface, the edges of which allow large contact angle hysteresis, and a wider structure allowing for multiple inputs and outputs. A model is developed for fluid flow, and the findings used to describe the process of failure in both cases.

  12. Customers’ Perception regarding Assurance of Bancassurance Channel

    Directory of Open Access Journals (Sweden)

    Choudhury Mousumi

    2016-12-01

    Full Text Available Bancassurance has evolved as a strong distribution channel in India. Bancassurance means that the insurance company and the bank come together to offer insurance products from the counter of the banks to the bank’s customer. The present study attempts to analyse customers’ perception regarding assurance of bancassurance channel in providing insurance-related services. The study also tries to find out the impact of various demographic variables on customers’ perception regarding assurance of bancassurance channel. The study finds that customers consider bancassurance channel having high assurance in providing insurance services. It is also found in the study that there is no significant association between the demographic variables considered in the study and customers’ perception regarding assurance of bancassurance channel.

  13. Spiking neural P systems with multiple channels.

    Science.gov (United States)

    Peng, Hong; Yang, Jinyu; Wang, Jun; Wang, Tao; Sun, Zhang; Song, Xiaoxiao; Luo, Xiaohui; Huang, Xiangnian

    2017-11-01

    Spiking neural P systems (SNP systems, in short) are a class of distributed parallel computing systems inspired from the neurophysiological behavior of biological spiking neurons. In this paper, we investigate a new variant of SNP systems in which each neuron has one or more synaptic channels, called spiking neural P systems with multiple channels (SNP-MC systems, in short). The spiking rules with channel label are introduced to handle the firing mechanism of neurons, where the channel labels indicate synaptic channels of transmitting the generated spikes. The computation power of SNP-MC systems is investigated. Specifically, we prove that SNP-MC systems are Turing universal as both number generating and number accepting devices. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Quantum cryptography over non-Markovian channels

    Science.gov (United States)

    Thapliyal, Kishore; Pathak, Anirban; Banerjee, Subhashish

    2017-05-01

    A three-party scheme for secure quantum communication, namely controlled quantum dialogue (CQD), is analyzed under the influence of non-Markovian channels. By comparing with the corresponding Markovian cases, it is seen that the average fidelity can be maintained for relatively longer periods of time. Interestingly, a number of facets of quantum cryptography, such as quantum secure direct communication, deterministic secure quantum communication and their controlled counterparts, quantum dialogue, quantum key distribution, quantum key agreement, can be reduced from the CQD scheme. Therefore, the CQD scheme is analyzed under the influence of damping, dephasing and depolarizing non-Markovian channels, and subsequently, the effect of these non-Markovian channels on the other schemes of secure quantum communication is deduced from the results obtained for CQD. The damped non-Markovian channel causes a periodic revival in the fidelity, while fidelity is observed to be sustained under the influence of the dephasing non-Markovian channel.

  15. Indoor MIMO Channel Measurement and Modeling

    DEFF Research Database (Denmark)

    Nielsen, Jesper Ødum; Andersen, Jørgen Bach

    2005-01-01

    Forming accurate models of the multiple input multiple output (MIMO) channel is essential both for simulation as well as understanding of the basic properties of the channel. This paper investigates different known models using measurements obtained with a 16x32 MIMO channel sounder for the 5.8GHz...... band. The measurements were carried out in various indoor scenarios including both temporal and spatial aspects of channel changes. The models considered include the so-called Kronecker model, a model proposed by Weichselberger et. al., and a model involving the full covariance matrix, the most...... accurate model for Gaussian channels. For each of the environments different sizes of both the transmitter and receiver antenna arrays are investigated, 2x2 up to 16x32. Generally it was found that in terms of capacity cumulative distribution functions (CDFs) all models fit well for small array sizes...

  16. Convex decomposition of dimension-altering quantum channels

    Science.gov (United States)

    Wang, Dong-Sheng

    2016-11-01

    Quantum channels, which are completely positive and trace preserving mappings, can alter the dimension of a system, e.g. a quantum channel from a qubit to a qutrit. We study the convex set properties of dimension-altering quantum channels, and particularly the channel decomposition problem in terms of convex sum of extreme channels. We provide various quantum circuit representations of extreme and generalized extreme channels, which can be employed in an optimization to approximately decompose an arbitrary channel. Numerical simulations of low-dimensional channels are performed to demonstrate our channel decomposition scheme.

  17. Dissociation and the experience of channeling: narratives of Israeli women who practice channeling.

    Science.gov (United States)

    Stolovy, Tali; Lev-Wiesel, Rachel; Eisikovits, Zvi

    2015-01-01

    "Channeling" is a phenomenon in which people describe themselves as receiving messages from another personality or dimension of reality. Channeling is often regarded as dissociation, which is a disruption in the usually integrated functions of consciousness, memory, identity, or perception. This study explored the interface between channeling and dissociation through a phenomenological analysis. Qualitative data were obtained through interviews with 20 Israeli women who practice channeling. The analysis revealed 3 themes: dissociation, absorption, and control. The channelers' descriptions correspond with what is coined as "dissociative states" and enable an emic view of the etic definition of dissociation.

  18. Channel and Timeslot Co-Scheduling with Minimal Channel Switching for Data Aggregation in MWSNs

    Directory of Open Access Journals (Sweden)

    Sanggil Yeoum

    2017-05-01

    Full Text Available Collision-free transmission and efficient data transfer between nodes can be achieved through a set of channels in multichannel wireless sensor networks (MWSNs. While using multiple channels, we have to carefully consider channel interference, channel and time slot (resources optimization, channel switching delay, and energy consumption. Since sensor nodes operate on low battery power, the energy consumed in channel switching becomes an important challenge. In this paper, we propose channel and time slot scheduling for minimal channel switching in MWSNs, while achieving efficient and collision-free transmission between nodes. The proposed scheme constructs a duty-cycled tree while reducing the amount of channel switching. As a next step, collision-free time slots are assigned to every node based on the minimal data collection delay. The experimental results demonstrate that the validity of our scheme reduces the amount of channel switching by 17.5%, reduces energy consumption for channel switching by 28%, and reduces the schedule length by 46%, as compared to the existing schemes.

  19. The Zambezi Channel: A new perspective on submarine channel evolution at low latitudes

    Science.gov (United States)

    Wiles, E.; Green, A.; Watkeys, M.; Jokat, W.

    2017-06-01

    Submarine channels are not stand-alone systems. They are long-lived systems modified by imperceptibly slow processes and rapid gravity flows, in some part controlled by hinterland dynamics. The submarine Zambezi Channel, within the Mozambique Channel, receives sediment from the Zambezi River catchment which has a dynamic tectonic and morphological history. Using recently collected multibeam bathymetry and PARASOUND data we discuss the geomorphology of the Zambezi Channel. Results show this system to be distinct in geomorphologic character when compared to other low-latitude submarine channels, sharing similarities with high-latitude systems. We propose a new, source-to-sink, hypothesis for the evolution of the Zambezi Channel, taking in to consideration hinterland tectonics, palaeo-lake development, river capture and rapid gravity flows. This hypothesis accounts for the unique present-day anatomy of the Zambezi Channel within the dynamic framework of the systems regional setting.

  20. 33 CFR 165.1195 - Regulated Navigation Area; Humboldt Bay Bar Channel and Humboldt Bay Entrance Channel, Humboldt...

    Science.gov (United States)

    2010-07-01

    ...; Humboldt Bay Bar Channel and Humboldt Bay Entrance Channel, Humboldt Bay, California. 165.1195 Section 165... Channel and Humboldt Bay Entrance Channel, Humboldt Bay, California. (a) Location. The Regulated Navigation Area (RNA) includes all navigable waters of the Humboldt Bay Bar Channel and the Humboldt Bay...