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Sample records for channels modulate pre

  1. Equalization of Skin Effect Loss Dominated Channels using Pulse-Width Modulation (PWM) Pre-Emphasis

    NARCIS (Netherlands)

    Schrader, J.H.R.; Klumperink, Eric A.M.; Visschers, J.L.; Nauta, Bram

    2005-01-01

    A digital transmitter pre-emphasis technique is presented that is based on pulse-width modulation, instead of finite impulse response (FIR) filtering. The technique fits well to future high-speed low-voltage CMOS processes. A 0.13μm CMOS transmitter achieves more than 5Gb/s (2-PAM) over 25m of

  2. Coolant channel module CCM

    International Nuclear Information System (INIS)

    Hoeld, Alois

    2007-01-01

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

  3. XPM-induced degradation of multilevel phase modulated channel caused by neighboring NRZ modulated channels

    DEFF Research Database (Denmark)

    Jensen, Jesper Bevensee; Schiellerup, G.; Peucheret, Christophe

    2008-01-01

    The impact of XPM from NRZ modulated channels on an 8-level phase modulated channel in a WDM system was investigated. Requirements on launch power are found. 400 km transmission was achieved with negligible penalty.......The impact of XPM from NRZ modulated channels on an 8-level phase modulated channel in a WDM system was investigated. Requirements on launch power are found. 400 km transmission was achieved with negligible penalty....

  4. BK channel modulators: a comprehensive overview

    DEFF Research Database (Denmark)

    Nardi, Antonio; Olesen, Søren-Peter

    2008-01-01

    channels as a potentially attractive target, the design and synthesis of potent and selective BK modulators continue based on novel chemical ideas. A comprehensive overview of BK channel modulators is therefore timely and important to the current medicinal chemist for review, summary, and classification...

  5. Monolithically integrated 8-channel WDM reflective modulator

    NARCIS (Netherlands)

    Stopinski, S.T.; Malinowski, M.; Piramidowicz, R.; Smit, M.K.; Leijtens, X.J.M.

    2013-01-01

    In this work the design and characterization of a monolithically integrated photonic circuit acting as a reflective modulator for eight WDM channels is presented. The chip was designed and fabricated in a generic integration technology

  6. 12-channel flash-ADC FASTBUS module

    International Nuclear Information System (INIS)

    Kuznetsov, A.A.; Rychenkov, V.I.; Sen'ko, V.A.; Sidorov, A.V.

    1992-01-01

    The slave module intended for digitizing the shape of single signals in 12-channels at once, is described. The module is designed on the base of FADC integrated circuits KR1107PV5A and memory chips K1500RU073. Resolution is 6 bit with up to 90 MHz sampling frequency. 5 refs.; 3 figs

  7. Power module assemblies with staggered coolant channels

    Science.gov (United States)

    Herron, Nicholas Hayden; Mann, Brooks S; Korich, Mark D

    2013-07-16

    A manifold is provided for supporting a power module assembly with a plurality of power modules. The manifold includes a first manifold section. The first face of the first manifold section is configured to receive the first power module, and the second face of the first manifold section defines a first cavity with a first baseplate thermally coupled to the first power module. The first face of the second manifold section is configured to receive the second power module, and the second face of the second manifold section defines a second cavity with a second baseplate thermally coupled to the second power module. The second face of the first manifold section and the second face of the second manifold section are coupled together such that the first cavity and the second cavity form a coolant channel. The first cavity is at least partially staggered with respect to second cavity.

  8. Spatial Modulation in the Underwater Acoustic Communication Channel

    National Research Council Canada - National Science Library

    Kilfoyle, Daniel

    2000-01-01

    .... The technique, termed spatial modulation, seeks to control the spatial distribution of signal energy such that multiple parallel communication channels are supported by the single, physical ocean channel...

  9. Single channel speech enhancement in the modulation domain: New insights in the modulation channel selection framework

    DEFF Research Database (Denmark)

    Boldt, Jesper B.; Bertelsen, Andreas Thelander; Gran, Fredrik

    2015-01-01

    Recently, the ideal binary mask has been introduced in the modulation domain by extending the ideal channel selection method to modulation channel selection [1]. This new method shows substantial improvement in speech intelligibility but less than its predecessor despite the higher complexity. Here......, we extend the previous finding from [1] and provide a more direct comparison of binary masking in the modulation domain with binary masking in the time-frequency domain. Subjective and objective evaluations are performed and provide additional insight into modulation domain processing....

  10. Calcium homeostasis modulator (CALHM) ion channels.

    Science.gov (United States)

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

    2016-03-01

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

  11. HCN Channels Modulators: The Need for Selectivity

    Science.gov (United States)

    Romanelli, Maria Novella; Sartiani, Laura; Masi, Alessio; Mannaioni, Guido; Manetti, Dina; Mugelli, Alessandro; Cerbai, Elisabetta

    2016-01-01

    Hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels, the molecular correlate of the hyperpolarization-activated current (If/Ih), are membrane proteins which play an important role in several physiological processes and various pathological conditions. In the Sino Atrial Node (SAN) HCN4 is the target of ivabradine, a bradycardic agent that is, at the moment, the only drug which specifically blocks If. Nevertheless, several other pharmacological agents have been shown to modulate HCN channels, a property that may contribute to their therapeutic activity and/or to their side effects. HCN channels are considered potential targets for developing drugs to treat several important pathologies, but a major issue in this field is the discovery of isoform-selective compounds, owing to the wide distribution of these proteins into the central and peripheral nervous systems, heart and other peripheral tissues. This survey is focused on the compounds that have been shown, or have been designed, to interact with HCN channels and on their binding sites, with the aim to summarize current knowledge and possibly to unveil useful information to design new potent and selective modulators. PMID:26975509

  12. Electrophysiological characterisation of KCNQ channel modulators

    DEFF Research Database (Denmark)

    Schrøder, R.L

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

  13. Pharmacological modulation of SK3 channels

    DEFF Research Database (Denmark)

    Grunnet, M; Jespersen, Thomas; Angelo, K

    2001-01-01

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

  14. Modulation of TRP channels by resveratrol and other stilbenoids

    Directory of Open Access Journals (Sweden)

    Yu Lina

    2013-02-01

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

  15. Modulation of ERG channels by XE991

    DEFF Research Database (Denmark)

    Elmedyb, Pernille; Calloe, Kirstine; Schmitt, Nicole

    2007-01-01

    In neuronal tissue, KCNQ2-5 channels conduct the physiologically important M-current. In some neurones, the M-current may in addition be conducted partly by ERG potassium channels, which have widely overlapping expression with the KCNQ channel subunits. XE991 and linopiridine are known to be stan......In neuronal tissue, KCNQ2-5 channels conduct the physiologically important M-current. In some neurones, the M-current may in addition be conducted partly by ERG potassium channels, which have widely overlapping expression with the KCNQ channel subunits. XE991 and linopiridine are known...... to be standard KCNQ potassium channel blockers. These compounds have been used in many different tissues as specific pharmacological tools to discern native currents conducted by KCNQ channels from other potassium currents. In this article, we demonstrate that ERG1-2 channels are also reversibly inhibited by XE......991 in the micromolar range (EC(50) 107 microM for ERG1). The effect has been characterized in Xenopus laevis oocytes expressing ERG1-2 and in the mammalian HEK293 cell line stably expressing ERG1 channels. The IC(50) values for block of KCNQ channels by XE991 range 1-65 microM. In conclusion, great...

  16. Adaptive Combined Source and Channel Decoding with Modulation ...

    African Journals Online (AJOL)

    In this paper, an adaptive system employing combined source and channel decoding with modulation is proposed for slow Rayleigh fading channels. Huffman code is used as the source code and Convolutional code is used for error control. The adaptive scheme employs a family of Convolutional codes of different rates ...

  17. PIP2 modulation of slick and slack K+ channels

    DEFF Research Database (Denmark)

    Tejada, Maria de los Angeles; Jensen, Lars Jørn; Klærke, Dan Arne

    2012-01-01

    Slick and Slack are members of the Slo family of high-conductance potassium channels. These channels are activated by Na(+) and Cl(-) and are highly expressed in the CNS, where they are believed to contribute to the resting membrane potential of neurons and the control of excitability. Herein, we...... provide evidence that Slick and Slack channels are regulated by the phosphoinositide PIP(2). Two stereoisomers of PIP(2) were able to exogenously activate Slick and Slack channels expressed in Xenopus oocytes, and in addition, it is shown that Slick and Slack channels are modulated by endogenous PIP(2......). The activating effect of PIP(2) appears to occur by direct interaction with lysine 306 in Slick and lysine 339 in Slack, located at the proximal C-termini of both channels. Overall, our data suggest that PIP(2) is an important regulator of Slick and Slack channels, yet it is not involved in the recently...

  18. Pre-attentive and attentive vision module

    NARCIS (Netherlands)

    Nyamsuren, Enkhbold; Taatgen, Niels A.

    This paper introduces a new vision module, called PAAV, developed for the cognitive architecture ACT-R. Unlike ACT-R's default vision module that was originally developed for top-down perception only, PAAV was designed to model a wide range of tasks, such as visual search and scene viewing, where

  19. Cholesterol modulates Orai1 channel function

    Czech Academy of Sciences Publication Activity Database

    Derler, I.; Jardin, I.; Stathopulos, P.B.; Muik, M.; Fahrner, M.; Zayats, Vasilina; Pandey, Saurabh Kumar; Poteser, M.; Lackner, B.; Absolonova, M.; Schindl, R.; Groschner, K.; Ettrich, Rüdiger; Ikura, M.; Romanin, Ch.

    2016-01-01

    Roč. 9, č. 412 (2016), ra10 ISSN 1945-0877 R&D Projects: GA ČR GA13-21053S Institutional support: RVO:61388971 Keywords : ACTIVATES CRAC CHANNELS * OPERATED CA2+ ENTRY * PLASMA-MEMBRANE Subject RIV: CE - Biochemistry Impact factor: 6.494, year: 2016

  20. Pre-experiment testing of the Multi Channel Systems 16-channel preamplifier CPA16

    International Nuclear Information System (INIS)

    Patin, J B; Stoyer, M A; Moody, K J; Friensehner, A V

    2003-01-01

    The 16-channel preamplifier model CPA16 from Multi Channel Systems was studied. The CPA16 preamplifier/amplifier module is a candidate to be used as the preamplifiers and amplifiers for the focal plane detectors of the Mass Analyzer of Super Heavy Atoms (MASHA). The equipment used to test the CPA16, the results of testing the CPA16 with a pulser, a mixed 229 Th/ 148 Gd source and a 252 Cf source, and a summary of the results will be presented

  1. Thermally modulated biomolecule transport through nanoconfined channels.

    Science.gov (United States)

    Liu, Lei; Zhu, Lizhong

    2015-01-01

    In this work, a nanofluidic device containing both a feed cell and a permeation cell linked by nanopore arrays has been fabricated, which is employed to investigate thermally controlled biomolecular transporting properties through confined nanochannels. The ionic currents modulated by the translocations of goat antibody to human immunoglobulin G (IgG) or bovine serum albumin (BSA) are recorded and analyzed. The results suggest that the modulation effect decreases with the electrolyte concentration increasing, while the effects generated by IgG translocation are more significant than that generated by BSA translocation. More importantly, there is a maximum decreasing value in each modulated current curve with biomolecule concentration increasing for thermally induced intermolecular collision. Furthermore, the turning point for the maximum shifts to lower biomolecule concentrations with the system temperature rising (from 4°C to 45°C), and it is mainly determined by the temperature in the feed cell if the temperature difference exists in the two separated cells. These findings are expected to be valuable for the future design of novel sensing device based on nanopore and/or nanopore arrays.

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

    Science.gov (United States)

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

    2017-10-01

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

  3. Development of a 64-channel 100 ps TDC module

    International Nuclear Information System (INIS)

    Liu Xiaohua; An Qi; Liu Shubin; Su Hong; Zhan Wenlong

    2009-01-01

    Multi-wire drift chamber at external target experiment in HIRFL-CSR measures drift time of charged particles to obtain the track information. A 64-channel TDC module hosting high density connectors and high performance TDC chips (HPTDC) are used to perform the time digitization. Data of the module is transferred to computer through PXI bus. The test results show that a 100 ps resolution has been achieved. (authors)

  4. PIP₂ modulation of Slick and Slack K⁺ channels.

    Science.gov (United States)

    de los Angeles Tejada, Maria; Jensen, Lars Jørn; Klaerke, Dan A

    2012-07-27

    Slick and Slack are members of the Slo family of high-conductance potassium channels. These channels are activated by Na(+) and Cl(-) and are highly expressed in the CNS, where they are believed to contribute to the resting membrane potential of neurons and the control of excitability. Herein, we provide evidence that Slick and Slack channels are regulated by the phosphoinositide PIP(2). Two stereoisomers of PIP(2) were able to exogenously activate Slick and Slack channels expressed in Xenopus oocytes, and in addition, it is shown that Slick and Slack channels are modulated by endogenous PIP(2). The activating effect of PIP(2) appears to occur by direct interaction with lysine 306 in Slick and lysine 339 in Slack, located at the proximal C-termini of both channels. Overall, our data suggest that PIP(2) is an important regulator of Slick and Slack channels, yet it is not involved in the recently described cell volume sensitivity of Slick channels, since mutated PIP(2)-insensitive Slick channels retained their sensitivity to cell volume. Copyright © 2012 Elsevier Inc. All rights reserved.

  5. Development of a compact 25-channel preamplifier module for Si-pad detectors of the BARC-CPDA

    International Nuclear Information System (INIS)

    Inkar, A.; John, Bency; Vind, R.P.; Kinage, L.; Jangale, R.V.; Biswas, D.C.; Nayak, B.K.

    2011-01-01

    The BARC Charged Particle Detector Array modules use indigenously developed Si pad detectors as their first element. Total number of charge sensitive pre-amplifiers required for the Si-pad detectors is 250. One of the main ideas here is a layout of five pre-amplifiers connected with one Si-pad detector (called a bank of preamplifiers). In the present work, a 25-channel pre-amplifier module that can cater to 5 independent Si-pad detectors, or a five-bank module, has been developed. This module uses pre-amp hybrid chips A1422H from CAEN S.p.A. and is housed in a double width NIM standard box. The module has been tested for performance using proton and ''7Li beams from FOTIA facility, Trombay

  6. Gabapentin Modulates HCN4 Channel Voltage-Dependence

    Directory of Open Access Journals (Sweden)

    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.

  7. Effect of Potassium Channel Modulators on Morphine Withdrawal in Mice

    Directory of Open Access Journals (Sweden)

    Vikas Seth

    2010-01-01

    Full Text Available The present study was conducted to investigate the effect of potassium channel openers and blockers on morphine withdrawal syndrome. Mice were rendered dependent on morphine by subcutaneous injection of morphine; four hours later, withdrawal was induced by using an opioid antagonist, naloxone. Mice were observed for 30 minutes for the withdrawal signs ie, the characteristic jumping, hyperactivity, urination and diarrhea. ATP-dependent potassium (K + ATP channel modulators were injected intraperitoneally (i.p. 30 minutes before the naloxone. It was found that a K + ATP channel opener, minoxidil (12.5–50 mg/kg i.p., suppressed the morphine withdrawal significantly. On the other hand, the K + ATP channel blocker glibenclamide (12.5–50 mg/kg i.p. caused a significant facilitation of the withdrawal. Glibenclamide was also found to abolish the minoxidil's inhibitory effect on morphine withdrawal. The study concludes that K + ATP channels play an important role in the genesis of morphine withdrawal and K + ATP channel openers could be useful in the management of opioid withdrawal. As morphine opens K + ATP channels in neurons, the channel openers possibly act by mimicking the effects of morphine on neuronal K + currents.

  8. Reconfigurable WDM-PON empowered by a low-cost 8-channel directly modulated laser module

    Science.gov (United States)

    Zhang, Yi-ming; Liu, Yu; Zhang, Zhi-ke; Zhao, Ze-ping; Tian, Ye; Zhu, Ning-hua

    2017-11-01

    A 10 Gbit/s 16-km-long reconfigurable wavelength-division-multiplexing passive optical network (WDM-PON) is presented empowered by a low-cost multi-channel directly modulated laser (DML) module. Compared with the case using discrete devices in conventional scheme, the proposed DML module provides a cost-effective solution with reduced complexity. The clear eye diagram and the bit error rate ( BER) of less than 2×10-7 with a sensitivity of -7 dBm are obtained. Due to the special packaging design, the crosstalk between channels under condition of simultaneous operation can be negligible.

  9. Zinc as Allosteric Ion Channel Modulator: Ionotropic Receptors as Metalloproteins

    Science.gov (United States)

    Peralta, Francisco Andrés; Huidobro-Toro, Juan Pablo

    2016-01-01

    Zinc is an essential metal to life. This transition metal is a structural component of many proteins and is actively involved in the catalytic activity of cell enzymes. In either case, these zinc-containing proteins are metalloproteins. However, the amino acid residues that serve as ligands for metal coordination are not necessarily the same in structural proteins compared to enzymes. While crystals of structural proteins that bind zinc reveal a higher preference for cysteine sulfhydryls rather than histidine imidazole rings, catalytic enzymes reveal the opposite, i.e., a greater preference for the histidines over cysteines for catalysis, plus the influence of carboxylic acids. Based on this paradigm, we reviewed the putative ligands of zinc in ionotropic receptors, where zinc has been described as an allosteric modulator of channel receptors. Although these receptors do not strictly qualify as metalloproteins since they do not normally bind zinc in structural domains, they do transitorily bind zinc at allosteric sites, modifying transiently the receptor channel’s ion permeability. The present contribution summarizes current information showing that zinc allosteric modulation of receptor channels occurs by the preferential metal coordination to imidazole rings as well as to the sulfhydryl groups of cysteine in addition to the carboxyl group of acid residues, as with enzymes and catalysis. It is remarkable that most channels, either voltage-sensitive or transmitter-gated receptor channels, are susceptible to zinc modulation either as positive or negative regulators. PMID:27384555

  10. Modulation of epithelial sodium channel in human alveolar epithelial ...

    African Journals Online (AJOL)

    Modulation of epithelial sodium channel in human alveolar epithelial cells by lipoxin A4 through AhR-cAMP-dependent pathway. Bi-Huan Cheng1,2, Li-Wei Pan2, Sheng-Rong Zhang3, Bin-Yu Ying2, Ben-Ji. Wang2, Guo-Liang Lin2 and Shi-Fang Ding1*. 1Department of Critical Care Medicine, Qilu Hospital of Shandong ...

  11. Modulated Hawking radiation and a nonviolent channel for information release

    OpenAIRE

    Giddings, Steven B.

    2014-01-01

    Unitarization of black hole evaporation requires that quantum information escapes a black hole; an important question is to identify the mechanism or channel by which it does so. Accurate counting of black hole states via the Bekenstein–Hawking entropy would indicate this information should be encoded in radiation with average energy flux matching Hawking's. Information can be encoded with no change in net flux via fine-grained modulation of the Hawking radiation. In an approximate effective ...

  12. L-Type Calcium Channels Modulation by Estradiol.

    Science.gov (United States)

    Vega-Vela, Nelson E; Osorio, Daniel; Avila-Rodriguez, Marco; Gonzalez, Janneth; García-Segura, Luis Miguel; Echeverria, Valentina; Barreto, George E

    2017-09-01

    Voltage-gated calcium channels are key regulators of brain function, and their dysfunction has been associated with multiple conditions and neurodegenerative diseases because they couple membrane depolarization to the influx of calcium-and other processes such as gene expression-in excitable cells. L-type calcium channels, one of the three major classes and probably the best characterized of the voltage-gated calcium channels, act as an essential calcium binding proteins with a significant biological relevance. It is well known that estradiol can activate rapidly brain signaling pathways and modulatory/regulatory proteins through non-genomic (or non-transcriptional) mechanisms, which lead to an increase of intracellular calcium that activate multiple kinases and signaling cascades, in the same way as L-type calcium channels responses. In this context, estrogens-L-type calcium channels signaling raises intracellular calcium levels and activates the same signaling cascades in the brain probably through estrogen receptor-independent modulatory mechanisms. In this review, we discuss the available literature on this area, which seems to suggest that estradiol exerts dual effects/modulation on these channels in a concentration-dependent manner (as a potentiator of these channels in pM concentrations and as an inhibitor in nM concentrations). Indeed, estradiol may orchestrate multiple neurotrophic responses, which open a new avenue for the development of novel estrogen-based therapies to alleviate different neuropathologies. We also highlight that it is essential to determine through computational and/or experimental approaches the interaction between estradiol and L-type calcium channels to assist these developments, which is an interesting area of research that deserves a closer look in future biomedical research.

  13. Performance analysis of OFDM modulation on indoor broadband PLC channels

    Science.gov (United States)

    Antonio Cortés, José; Díez, Luis; Cañete, Francisco Javier; Sánchez-Martínez, Juan José; Entrambasaguas, José Tomás

    2011-12-01

    Indoor broadband power-line communications is a suitable technology for home networking applications. In this context, orthogonal frequency-division multiplexing (OFDM) is the most widespread modulation technique. It has recently been adopted by the ITU-T Recommendation G.9960 and is also used by most of the commercial systems, whose number of carriers has gone from about 100 to a few thousands in less than a decade. However, indoor power-line channels are frequency-selective and exhibit periodic time variations. Hence, increasing the number of carriers does not always improves the performance, since it reduces the distortion because of the frequency selectivity, but increases the one caused by the channel time variation. In addition, the long impulse response of power-line channels obliges to use an insufficient cyclic prefix. Increasing its value reduces the distortion, but also the symbol rate. Therefore, there are optimum values for both modulation parameters. This article evaluates the performance of an OFDM system as a function of the number of carriers and the cyclic prefix length, determining their most appropriate values for the indoor power-line scenario. This task must be accomplished by means of time-consuming simulations employing a linear time-varying filtering, since no consensus on a tractable statistical channel model has been reached yet. However, this study presents a simpler procedure in which the distortion because of the frequency selectivity is computed using a time-invariant channel response, and an analytical expression is derived for the one caused by the channel time variation.

  14. Eight-Channel Digital Signal Processor and Universal Trigger Module

    Science.gov (United States)

    Skulski, Wojtek; Wolfs, Frank

    2003-04-01

    A 10-bit, 8-channel, 40 megasamples per second digital signal processor and waveform digitizer DDC-8 (nicknamed Universal Trigger Module) is presented. The digitizer features 8 analog inputs, 1 analog output for a reconstructed analog waveform, 16 NIM logic inputs, 8 NIM logic outputs, and a pool of 16 TTL logic lines which can be individually configured as either inputs or outputs. The first application of this device is to enhance the present trigger electronics for PHOBOS at RHIC. The status of the development and the first results are presented. Possible applications of the new device are discussed. Supported by the NSF grant PHY-0072204.

  15. Calcium channel modulation as a target in chronic pain control.

    Science.gov (United States)

    Patel, Ryan; Montagut-Bordas, Carlota; Dickenson, Anthony H

    2018-06-01

    Neuropathic pain remains poorly treated for large numbers of patients, and little progress has been made in developing novel classes of analgesics. To redress this issue, ziconotide (Prialt™) was developed and approved as a first-in-class synthetic version of ω-conotoxin MVIIA, a peptide blocker of Ca v 2.2 channels. Unfortunately, the impracticalities of intrathecal delivery, low therapeutic index and severe neurological side effects associated with ziconotide have restricted its use to exceptional circumstances. Ziconotide exhibits no state or use-dependent block of Ca v 2.2 channels; activation state-dependent blockers were hypothesized to circumvent the side effects of state-independent blockers by selectively targeting high-frequency firing of nociceptive neurones in chronic pain states, thus alleviating aberrant pain but not affecting normal sensory transduction. Unfortunately, numerous drugs, including state-dependent calcium channel blockers, have displayed efficacy in preclinical models but have subsequently been disappointing in clinical trials. In recent years, it has become more widely acknowledged that trans-aetiological sensory profiles exist amongst chronic pain patients and may indicate similar underlying mechanisms and drug sensitivities. Heterogeneity amongst patients, a reliance on stimulus-evoked endpoints in preclinical studies and a failure to utilize translatable endpoints, all are likely to have contributed to negative clinical trial results. We provide an overview of how electrophysiological and operant-based assays provide insight into sensory and affective aspects of pain in animal models and how these may relate to chronic pain patients in order to improve the bench-to-bedside translation of calcium channel modulators. This article is part of a themed section on Recent Advances in Targeting Ion Channels to Treat Chronic Pain. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175

  16. Intracellular calcium modulation of voltage-gated sodium channels in ventricular myocytes

    NARCIS (Netherlands)

    Casini, Simona; Verkerk, Arie O.; van Borren, Marcel M. G. J.; van Ginneken, Antoni C. G.; Veldkamp, Marieke W.; de Bakker, Jacques M. T.; Tan, Hanno L.

    2009-01-01

    AIMS: Cardiac voltage-gated sodium channels control action potential (AP) upstroke and cell excitability. Intracellular calcium (Ca(i)(2+)) regulates AP properties by modulating various ion channels. Whether Ca(i)(2+) modulates sodium channels in ventricular myocytes, is unresolved. We studied

  17. Experimental Results and Issues on Equalization for Nonlinear Memory Channel: Pre-Cursor Enhanced Ram-DFE Canceler

    Science.gov (United States)

    Yuan, Lu; LeBlanc, James

    1998-01-01

    This thesis investigates the effects of the High Power Amplifier (HPA) and the filters over a satellite or telemetry channel. The Volterra series expression is presented for the nonlinear channel with memory, and the algorithm is based on the finite-state machine model. A RAM-based algorithm operating on the receiver side, Pre-cursor Enhanced RAM-FSE Canceler (PERC) is developed. A high order modulation scheme , 16-QAM is used for simulation, the results show that PERC provides an efficient and reliable method to transmit data on the bandlimited nonlinear channel. The contribution of PERC algorithm is that it includes both pre-cursors and post-cursors as the RAM address lines, and suggests a new way to make decision on the pre-addresses. Compared with the RAM-DFE structure that only includes post- addresses, the BER versus Eb/NO performance of PERC is substantially enhanced. Experiments are performed for PERC algorithms with different parameters on AWGN channels, and the results are compared and analyzed. The investigation of this thesis includes software simulation and hardware verification. Hardware is setup to collect actual TWT data. Simulation on both the software-generated data and the real-world data are performed. Practical limitations are considered for the hardware collected data. Simulation results verified the reliability of the PERC algorithm. This work was conducted at NMSU in the Center for Space Telemetering and Telecommunications Systems in the Klipsch School of Electrical and Computer Engineering Department.

  18. Pre-charging of module capacitors of MMC when the module ...

    Indian Academy of Sciences (India)

    Shamkant D Joshi

    The module capacitors need to be pre-charged, to power the control circuit. The problem faced while ... It consists of three legs to share a common DC link voltage. Each of these legs has ... Consider the stability of a system with only one capacitor with negative ..... number of wires because separate wires are not required for.

  19. Modulation of cardiac ryanodine receptor channels by alkaline earth cations.

    Directory of Open Access Journals (Sweden)

    Paula L Diaz-Sylvester

    Full Text Available Cardiac ryanodine receptor (RyR2 function is modulated by Ca(2+ and Mg(2+. To better characterize Ca(2+ and Mg(2+ binding sites involved in RyR2 regulation, the effects of cytosolic and luminal earth alkaline divalent cations (M(2+: Mg(2+, Ca(2+, Sr(2+, Ba(2+ were studied on RyR2 from pig ventricle reconstituted in bilayers. RyR2 were activated by M(2+ binding to high affinity activating sites at the cytosolic channel surface, specific for Ca(2+ or Sr(2+. This activation was interfered by Mg(2+ and Ba(2+ acting at low affinity M(2+-unspecific binding sites. When testing the effects of luminal M(2+ as current carriers, all M(2+ increased maximal RyR2 open probability (compared to Cs(+, suggesting the existence of low affinity activating M(2+-unspecific sites at the luminal surface. Responses to M(2+ vary from channel to channel (heterogeneity. However, with luminal Ba(2+or Mg(2+, RyR2 were less sensitive to cytosolic Ca(2+ and caffeine-mediated activation, openings were shorter and voltage-dependence was more marked (compared to RyR2 with luminal Ca(2+or Sr(2+. Kinetics of RyR2 with mixtures of luminal Ba(2+/Ca(2+ and additive action of luminal plus cytosolic Ba(2+ or Mg(2+ suggest luminal M(2+ differentially act on luminal sites rather than accessing cytosolic sites through the pore. This suggests the presence of additional luminal activating Ca(2+/Sr(2+-specific sites, which stabilize high P(o mode (less voltage-dependent and increase RyR2 sensitivity to cytosolic Ca(2+ activation. In summary, RyR2 luminal and cytosolic surfaces have at least two sets of M(2+ binding sites (specific for Ca(2+ and unspecific for Ca(2+/Mg(2+ that dynamically modulate channel activity and gating status, depending on SR voltage.

  20. Effect of potassium channel modulators in mouse forced swimming test

    Science.gov (United States)

    Galeotti, Nicoletta; Ghelardini, Carla; Caldari, Bernardetta; Bartolini, Alessandro

    1999-01-01

    The effect of intracerebroventricular (i.c.v.) administration of different potassium channel blockers (tetraethylammonium, apamin, charybdotoxin, gliquidone), potassium channel openers (pinacidil, minoxidil, cromakalim) and aODN to mKv1.1 on immobility time was evaluated in the mouse forced swimming test, an animal model of depression. Tetraethylammonium (TEA; 5 μg per mouse i.c.v.), apamin (3 ng per mouse i.c.v.), charybdotoxin (1 μg per mouse i.c.v.) and gliquidone (6 μg per mouse i.c.v.) administered 20 min before the test produced anti-immobility comparable to that induced by the tricyclic antidepressants amitriptyline (15 mg kg−1 s.c.) and imipramine (30 mg kg−1 s.c.). By contrast pinacidil (10–20 μg per mouse i.c.v.), minoxidil (10–20 μg per mouse i.c.v.) and cromakalim (20–30 μg per mouse i.c.v.) increased immobility time when administered in the same experimental conditions. Repeated administration of an antisense oligonucleotide (aODN) to the mKv1.1 gene (1 and 3 nmol per single i.c.v. injection) produced a dose-dependent increase in immobility time of mice 72 h after the last injection. At day 7, the increasing effect produced by aODN disappeared. A degenerate mKv1.1 oligonucleotide (dODN), used as control, did not produce any effect in comparison with saline- and vector-treated mice. At the highest effective dose, potassium channels modulators and the mKv1.1 aODN did not impair motor coordination, as revealed by the rota rod test, nor did they modify spontaneous motility as revealed by the Animex apparatus. These results suggest that modulation of potassium channels plays an important role in the regulation of immobility time in the mouse forced swimming test. PMID:10323599

  1. Microvillar ion channels: cytoskeletal modulation of ion fluxes.

    Science.gov (United States)

    Lange, K

    2000-10-21

    The recently presented theory of microvillar Ca(2+)signaling [Lange, K. (1999) J. Cell. Physiol.180, 19-35], combined with Manning's theory of "condensed counterions" in linear polyelectrolytes [Manning, G. S. (1969). J. Chem. Phys.51, 924-931] and the finding of cable-like ion conductance in actin filaments [Lin, E. C. & Cantiello, H. F. (1993). Biophys. J.65, 1371-1378], allows a systematic interpretation of the role of the actin cytoskeleton in ion channel regulation. Ion conduction through actin filament bundles of microvilli exhibits unique nonlinear transmission properties some of which closely resemble that of electronic semiconductors: (1) bundles of microfilaments display significant resistance to cation conduction and (2) this resistance is decreased by supply of additional energy either as thermal, mechanical or electromagnetic field energy. Other transmission properties, however, are unique for ionic conduction in polyelectrolytes. (1) Current pulses injected into the filaments were transformed into oscillating currents or even into several discrete charge pulses closely resembling that of single-channel recordings. Discontinuous transmission is due to the existence of counterion clouds along the fixed anionic charge centers of the polymer, each acting as an "ionic capacitor". (2) The conductivity of linear polyelectrolytes strongly decreases with the charge number of the counterions; thus, Ca(2+)and Mg(2+)are effective modulator of charge transfer through linear polyelectrolytes. Field-dependent formation of divalent cation plugs on either side of the microvillar conduction line may generate the characteristic gating behavior of cation channels. (3) Mechanical movement of actin filament bundles, e.g. bending of hair cell microvilli, generates charge translocations along the filament structure (mechano-electrical coupling). (4) Energy of external fields, by inducing molecular dipoles within the polyelectrolyte matrix, can be transformed into mechanical

  2. Sigma-1 Receptor Plays a Negative Modulation on N-type Calcium Channel

    Directory of Open Access Journals (Sweden)

    Kang Zhang

    2017-05-01

    Full Text Available The sigma-1 receptor is a 223 amino acids molecular chaperone with a single transmembrane domain. It is resident to eukaryotic mitochondrial-associated endoplasmic reticulum and plasma membranes. By chaperone-mediated interactions with ion channels, G-protein coupled receptors and cell-signaling molecules, the sigma-1 receptor performs broad physiological and pharmacological functions. Despite sigma-1 receptors have been confirmed to regulate various types of ion channels, the relationship between the sigma-1 receptor and N-type Ca2+ channel is still unclear. Considering both sigma-1 receptors and N-type Ca2+ channels are involved in intracellular calcium homeostasis and neurotransmission, we undertake studies to explore the possible interaction between these two proteins. In the experiment, we confirmed the expression of the sigma-1 receptors and the N-type calcium channels in the cholinergic interneurons (ChIs in rat striatum by using single-cell reverse transcription-polymerase chain reaction (scRT-PCR and immunofluorescence staining. N-type Ca2+ currents recorded from ChIs in the brain slice of rat striatum was depressed when sigma-1 receptor agonists (SKF-10047 and Pre-084 were administrated. The inhibition was completely abolished by sigma-1 receptor antagonist (BD-1063. Co-expression of the sigma-1 receptors and the N-type calcium channels in Xenopus oocytes presented a decrease of N-type Ca2+ current amplitude with an increase of sigma-1 receptor expression. SKF-10047 could further depress N-type Ca2+ currents recorded from oocytes. The fluorescence resonance energy transfer (FRET assays and co-immunoprecipitation (Co-IP demonstrated that sigma-1 receptors and N-type Ca2+ channels formed a protein complex when they were co-expressed in HEK-293T (Human Embryonic Kidney -293T cells. Our results revealed that the sigma-1 receptors played a negative modulation on N-type Ca2+ channels. The mechanism for the inhibition of sigma-1 receptors on

  3. Modulated Hawking radiation and a nonviolent channel for information release

    International Nuclear Information System (INIS)

    Giddings, Steven B.

    2014-01-01

    Unitarization of black hole evaporation requires that quantum information escapes a black hole; an important question is to identify the mechanism or channel by which it does so. Accurate counting of black hole states via the Bekenstein–Hawking entropy would indicate this information should be encoded in radiation with average energy flux matching Hawking's. Information can be encoded with no change in net flux via fine-grained modulation of the Hawking radiation. In an approximate effective field theory description, couplings to the stress tensor of the black hole atmosphere that depend on the internal state of the black hole are a promising alternative for inducing such modulation. These can be picturesquely thought of as due to state-dependent metric fluctuations in the vicinity of the horizon. Such couplings offer the prospect of emitting information without extra energy flux, and can be shown to do so at linear order in the couplings, with motivation given for possible extension of this result to higher orders. The potential advantages of such couplings to the stress tensor thus extend beyond their universality, which is helpful in addressing constraints from black hole mining

  4. Modulated Hawking radiation and a nonviolent channel for information release

    Energy Technology Data Exchange (ETDEWEB)

    Giddings, Steven B., E-mail: giddings@physics.ucsb.edu

    2014-11-10

    Unitarization of black hole evaporation requires that quantum information escapes a black hole; an important question is to identify the mechanism or channel by which it does so. Accurate counting of black hole states via the Bekenstein–Hawking entropy would indicate this information should be encoded in radiation with average energy flux matching Hawking's. Information can be encoded with no change in net flux via fine-grained modulation of the Hawking radiation. In an approximate effective field theory description, couplings to the stress tensor of the black hole atmosphere that depend on the internal state of the black hole are a promising alternative for inducing such modulation. These can be picturesquely thought of as due to state-dependent metric fluctuations in the vicinity of the horizon. Such couplings offer the prospect of emitting information without extra energy flux, and can be shown to do so at linear order in the couplings, with motivation given for possible extension of this result to higher orders. The potential advantages of such couplings to the stress tensor thus extend beyond their universality, which is helpful in addressing constraints from black hole mining.

  5. Entrance channel systematics of pre-scission neutron multiplicities

    International Nuclear Information System (INIS)

    Shareef, M.; Prasad, E.; Chatterjee, A.

    2016-01-01

    Statistical model analysis has been performed for the available neutron multiplicity (ν_p_r_e) data in the literature. Larger ν_p_r_e values for more symmetric reactions have been observed in comparison with asymmetric reactions forming the same compound nucleus, in most cases. A reverse trend has also been noticed in a few cases. A systematic entrance channel dependence of fission timescale is brought out in this work. Fission timescales calculated using the experimental ν_p_r_e values fall into two distinct groups according to the entrance channel mass asymmetry of the reaction with respect to the Businaro-Gallone critical mass asymmetry. The difference in the delay between these two groups ranges between 20 and 100 zs, which is larger than that reported in some cases. (orig.)

  6. Neutron flux monitoring with pre-startup channels in FBTR [Paper No.:E6

    International Nuclear Information System (INIS)

    Nagaraj, C.P.; Ramakrishnan, R.; Subha Rao, R.; Pillai, C.P.; Muralikrishan, G.; Raghavan, K.

    1993-01-01

    The pre-start up instrumentation system using boron lined proportional counters has been well designed and the counters have been rigorously tested. This system in conjunction with the regular start-up channels (with more than 3 decades overlap) covers the start up measurement range adequately and provides necessary indications, interlocks and trips on low count rate, high count rate and doubling time to ensure safety. The pre-startup channels have been operational. The reactor trip on LOG NO due to count rate on start-up channels less than 3 cps is automatically inhibited with the higher count rate obtained on the pre-startup channels. With this and log CRM readings from PSU well on scale has facilitated smooth and safe reactor start ups even with low shutdown count rates. (author). 5 figs

  7. Pre-Amplifier Module for Laser Inertial Confinement Fusion

    Energy Technology Data Exchange (ETDEWEB)

    Heebner, J E; Bowers, M W

    2008-02-06

    The Pre-Amplifier Modules (PAMs) are the heart of the National Ignition Facility (NIF), providing most of the energy gain for the most energetic laser in the world. Upon completion, NIF will be the only laboratory in which scientists can examine the fusion processes that occur inside stars, supernovae, and exploding nuclear weapons and that may someday serve as a virtually inexhaustible energy source for electricity. Consider that in a fusion power plant 50 cups of water could provide the energy comparable to 2 tons of coal. Of paramount importance for achieving laser-driven fusion ignition with the least energy input is the synchronous and symmetric compression of the target fuel--a condition known as laser power balance. NIF's 48 PAMs thus must provide energy gain in an exquisitely stable and consistent manner. While building one module that meets performance requirements is challenging enough, our design has already enabled the construction and fielding of 48 PAMs that are stable, uniform, and interchangeable. PAM systems are being tested at the University of Rochester's Laboratory for Laser Energetics, and the Atomic Weapons Enterprise of Great Britain has purchased the PAM power system.

  8. Performance of Pre-processing Schemes with Imperfect Channel State Information

    DEFF Research Database (Denmark)

    Christensen, Søren Skovgaard; Kyritsi, Persa; De Carvalho, Elisabeth

    2006-01-01

    Pre-processing techniques have several benefits when the CSI is perfect. In this work we investigate three linear pre-processing filters, assuming imperfect CSI caused by noise degradation and channel temporal variation. Results indicate, that the LMMSE filter achieves the lowest BER and the high......Pre-processing techniques have several benefits when the CSI is perfect. In this work we investigate three linear pre-processing filters, assuming imperfect CSI caused by noise degradation and channel temporal variation. Results indicate, that the LMMSE filter achieves the lowest BER...... and the highest SINR when the CSI is perfect, whereas the simple matched filter may be a good choice when the CSI is imperfect. Additionally the results give insight into the inherent trade-off between robustness against CSI imperfections and spatial focusing ability....

  9. Research on channel characteristics of differential multi pulse position modulation without background noise

    Science.gov (United States)

    Gao, Zhuo; Zhan, Weida; Sun, Quan; Hao, Ziqiang

    2018-04-01

    Differential multi-pulse position modulation (DMPPM) is a new type of modulation technology. There is a fast transmission rate, high bandwidth utilization, high modulation rate characteristics. The study of DMPPM modulation has important scientific value and practical significance. Channel capacity is one of the important indexes to measure the communication capability of communication system, and studying the channel capacity of DMPPM without background noise is the key to analyze the characteristics of DMPPM. The DMPPM theoretical model is established. The symbol structure of DMPPM with guard time slot is analyzed, and the channel capacity expression of DMPPM is deduced. Simulation analysis by MATLAB. The curves of unit channel capacity and capacity efficiency at different pulse and photon counting rates are analyzed. The results show that DMPPM is more advantageous than multi-pulse position modulation (MPPM), and is more suitable for future wireless optical communication system.

  10. Optical transmission modules for multi-channel superconducting quantum interference device readouts

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jin-Mok, E-mail: jmkim@kriss.re.kr; Kwon, Hyukchan; Yu, Kwon-kyu; Lee, Yong-Ho; Kim, Kiwoong [Brain Cognition Measurement Center, Korea Research Institute of Standards and Science, Daejeon 305-600 (Korea, Republic of)

    2013-12-15

    We developed an optical transmission module consisting of 16-channel analog-to-digital converter (ADC), digital-noise filter, and one-line serial transmitter, which transferred Superconducting Quantum Interference Device (SQUID) readout data to a computer by a single optical cable. A 16-channel ADC sent out SQUID readouts data with 32-bit serial data of 8-bit channel and 24-bit voltage data at a sample rate of 1.5 kSample/s. A digital-noise filter suppressed digital noises generated by digital clocks to obtain SQUID modulation as large as possible. One-line serial transmitter reformed 32-bit serial data to the modulated data that contained data and clock, and sent them through a single optical cable. When the optical transmission modules were applied to 152-channel SQUID magnetoencephalography system, this system maintained a field noise level of 3 fT/√Hz @ 100 Hz.

  11. MIMO Intensity-Modulation Channels: Capacity Bounds and High SNR Characterization

    KAUST Repository

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

    2016-01-01

    The capacity of MIMO intensity modulation channels is studied. The nonnegativity of the transmit signal (intensity) poses a challenge on the precoding of the transmit signal, which limits the applicability of classical schemes in this type

  12. Pre-stimulus BOLD-network activation modulates EEG spectral activity during working memory retention

    Directory of Open Access Journals (Sweden)

    Mara eKottlow

    2015-05-01

    Full Text Available Working memory (WM processes depend on our momentary mental state and therefore exhibit considerable fluctuations. Here, we investigate the interplay of task-preparatory and task-related brain activity as represented by pre-stimulus BOLD-fluctuations and spectral EEG from the retention periods of a visual WM task. Visual WM is used to maintain sensory information in the brain enabling the performance of cognitive operations and is associated with mental health.We tested 22 subjects simultaneously with EEG and fMRI while performing a visuo-verbal Sternberg task with two different loads, allowing for the temporal separation of preparation, encoding, retention and retrieval periods.Four temporally coherent networks - the default mode network (DMN, the dorsal attention, the right and the left WM network - were extracted from the continuous BOLD data by means of a group ICA. Subsequently, the modulatory effect of these networks’ pre-stimulus activation upon retention-related EEG activity in the theta, alpha and beta frequencies was analyzed. The obtained results are informative in the context of state-dependent information processing.We were able to replicate two well-known load-dependent effects: the frontal-midline theta increase during the task and the decrease of pre-stimulus DMN activity. As our main finding, these two measures seem to depend on each other as the significant negative correlations at frontal-midline channels suggested. Thus, suppressed pre-stimulus DMN levels facilitated later task related frontal midline theta increases. In general, based on previous findings that neuronal coupling in different frequency bands may underlie distinct functions in WM retention, our results suggest that processes reflected by spectral oscillations during retention seem not only to be online synchronized with activity in different attention-related networks but are also modulated by activity in these networks during preparation intervals.

  13. MIMO Intensity-Modulation Channels: Capacity Bounds and High SNR Characterization

    KAUST Repository

    Chaaban, Anas

    2016-10-01

    The capacity of MIMO intensity modulation channels is studied. The nonnegativity of the transmit signal (intensity) poses a challenge on the precoding of the transmit signal, which limits the applicability of classical schemes in this type of channels. To resolve this issue, capacity lower bounds are developed by using precoding-free schemes. This is achieved by channel inversion or QR decomposition to convert the MIMO channel to a set of parallel channels. The achievable rate of a DC-offset SVD based scheme is also derived as a benchmark. Then, a capacity upper bound is derived and is shown to coincide with the achievable rate of the QR decomposition based scheme at high SNR, consequently characterizing the high-SNR capacity of the channel. The high-SNR gap between capacity and the achievable rates of the channel inversion and the DC-offset SVD based schemes is also characterized. Finally, the ergodic capacity of the channel is also briefly discussed.

  14. 5-HT1A receptors modulate small-conductance Ca2+-activated K+ channels

    DEFF Research Database (Denmark)

    Grunnet, Morten; Jespersen, Thomas; Perrier, Jean-François

    2004-01-01

    Small-conductance calcium-activated potassium channels (SK) are responsible for the medium afterhyperpolarisation (mAHP) following action potentials in neurons. Here we tested the ability of serotonin (5-HT) to modulate the activity of SK channels by coexpressing 5-HT1A receptors with different...

  15. Adaptive Modulation for a Downlink Multicast Channel in OFDMA Systems

    DEFF Research Database (Denmark)

    Wang, Haibo; Schwefel, Hans-Peter; Toftegaard, Thomas Skjødeberg

    2007-01-01

    In this paper we focus on adaptive modulation strategies for multicast service in orthogonal frequency division multiple access systems. A reward function has been defined as the optimization target, which includes both the average user throughput and bit error rate. We also developed an adaptive...... modulation strategy, namely local best reward strategy, to maximize this reward function. The performance of different modulation strategies are compared in different SNR distribution scenarios, and the optimum strategy in each scenario is suggested....

  16. TASK Channels on Basal Forebrain Cholinergic Neurons Modulate Electrocortical Signatures of Arousal by Histamine.

    Science.gov (United States)

    Vu, Michael T; Du, Guizhi; Bayliss, Douglas A; Horner, Richard L

    2015-10-07

    Basal forebrain cholinergic neurons are the main source of cortical acetylcholine, and their activation by histamine elicits cortical arousal. TWIK-like acid-sensitive K(+) (TASK) channels modulate neuronal excitability and are expressed on basal forebrain cholinergic neurons, but the role of TASK channels in the histamine-basal forebrain cholinergic arousal circuit is unknown. We first expressed TASK channel subunits and histamine Type 1 receptors in HEK cells. Application of histamine in vitro inhibited the acid-sensitive K(+) current, indicating a functionally coupled signaling mechanism. We then studied the role of TASK channels in modulating electrocortical activity in vivo using freely behaving wild-type (n = 12) and ChAT-Cre:TASK(f/f) mice (n = 12), the latter lacking TASK-1/3 channels on cholinergic neurons. TASK channel deletion on cholinergic neurons significantly altered endogenous electroencephalogram oscillations in multiple frequency bands. We then identified the effect of TASK channel deletion during microperfusion of histamine into the basal forebrain. In non-rapid eye movement sleep, TASK channel deletion on cholinergic neurons significantly attenuated the histamine-induced increase in 30-50 Hz activity, consistent with TASK channels contributing to histamine action on basal forebrain cholinergic neurons. In contrast, during active wakefulness, histamine significantly increased 30-50 Hz activity in ChAT-Cre:TASK(f/f) mice but not wild-type mice, showing that the histamine response depended upon the prevailing cortical arousal state. In summary, we identify TASK channel modulation in response to histamine receptor activation in vitro, as well as a role of TASK channels on cholinergic neurons in modulating endogenous oscillations in the electroencephalogram and the electrocortical response to histamine at the basal forebrain in vivo. Attentive states and cognitive function are associated with the generation of γ EEG activity. Basal forebrain

  17. G-protein-coupled inward rectifier potassium channels involved in corticostriatal presynaptic modulation.

    Science.gov (United States)

    Meneses, David; Mateos, Verónica; Islas, Gustavo; Barral, Jaime

    2015-09-01

    Presynaptic modulation has been associated mainly with calcium channels but recent data suggests that inward rectifier potassium channels (K(IR)) also play a role. In this work we set to characterize the role of presynaptic K(IR) channels in corticostriatal synaptic transmission. We elicited synaptic potentials in striatum by stimulating cortical areas and then determined the synaptic responses of corticostriatal synapsis by using paired pulse ratio (PPR) in the presence and absence of several potassium channel blockers. Unspecific potassium channels blockers Ba(2+) and Cs(+) reduced the PPR, suggesting that these channels are presynaptically located. Further pharmacological characterization showed that application of tertiapin-Q, a specific K(IR)3 channel family blocker, also induced a reduction of PPR, suggesting that K(IR)3 channels are present at corticostriatal terminals. In contrast, exposure to Lq2, a specific K(IR)1.1 inward rectifier potassium channel, did not induce any change in PPR suggesting the absence of these channels in the presynaptic corticostriatal terminals. Our results indicate that K(IR)3 channels are functionally expressed at the corticostriatal synapses, since blockage of these channels result in PPR decrease. Our results also help to explain how synaptic activity may become sensitive to extracellular signals mediated by G-protein coupled receptors. A vast repertoire of receptors may influence neurotransmitter release in an indirect manner through regulation of K(IR)3 channels. © 2015 Wiley Periodicals, Inc.

  18. Ion channelling analysis of pre-amorphised silicon diodes using a nuclear microprobe

    International Nuclear Information System (INIS)

    Thornton, J.; Paus, K.C.

    1988-01-01

    Aligned and random ion channelling analysis was performed on p + n diode structures in silicon, with the Surrey nuclear microprobe. Three different types of diode were investigated, each pre-amorphised by a different ion (Si + , Ge + or Sn + ) before the p + region was formed by BF 2 + implantation. The ion channelling measurements are presented and compared with previously published electrical measurements on these diodes. Relatively large residual disorder and junction leakage currents were found for the Si + pre-amorphised diodes; however, all the diodes were leaky. The results are consistent with dislocation loops within the depletion regions of the diodes causing both the residual disorder and the large leakage currents. Cross-sectional transmission electron microscopy studies support this model. (author)

  19. Bladder contractility is modulated by Kv7 channels in pig detrusor

    DEFF Research Database (Denmark)

    Svalø, Julie; Bille, Michala; Parameswaran Theepakaran, Neeraja

    2013-01-01

    Kv7 channels are involved in smooth muscle relaxation, and accordingly we believe that they constitute potential targets for the treatment of overactive bladder syndrome. We have therefore used myography to examine the function of Kv7 channels in detrusor, i.e. pig bladder, with a view...... relaxation, suggesting that Kv7.2 and/or Kv7.4 channels constitute the subtypes that are relevant to bladder contractility. The effects of retigabine and ML213 were attenuated by pre-incubation with 10µM XE991 (Kv7.1-7.5 channel blocker) (P...

  20. Numerical study of mixed convection heat transfer enhancement in a channel with active flow modulation

    Science.gov (United States)

    Billah, Md. Mamun; Khan, Md Imran; Rahman, Mohammed Mizanur; Alam, Muntasir; Saha, Sumon; Hasan, Mohammad Nasim

    2017-06-01

    A numerical study of steady two dimensional mixed convention heat transfer phenomena in a rectangular channel with active flow modulation is carried out in this investigation. The flow in the channel is modulated via a rotating cylinder placed at the center of the channel. In this study the top wall of the channel is subjected to an isothermal low temperature while a discrete isoflux heater is positioned on the lower wall. The fluid flow under investigation is assumed to have a Prandtl number of 0.71 while the Reynolds No. and the Grashof No. are varied in wide range for four different situations such as: i) plain channel with no cylinder, ii) channel with stationary cylinder, iii) channel with clockwise rotating cylinder and iv) channel with counter clockwise rotating cylinder. The results obtained in this study are presented in terms of the distribution of streamlines, isotherms in the channel while the heat transfer process from the heat source is evaluated in terms of the local Nusselt number, average Nusselt number. The outcomes of this study also indicate that the results are strongly dependent on the type of configuration and direction of rotation of the cylinder and that the average Nusselt number value rises with an increase in Reynolds and Grashof numbers but the correlation between these parameters at higher values of Reynolds and Grashof numbers becomes weak.

  1. Optical integrated circuit of a 40-channel electrooptical LiNbO/sub 3/ modulator for data-processing devices

    Energy Technology Data Exchange (ETDEWEB)

    Bukreev, I.N.; Venediktov, V.V.; Gorbatovskii, M.V.; Demina, T.P.; Kashintsev, M.A.

    1988-06-01

    An optical integrated circuit for a 40-channel electrooptical phase modulator has been developed. The channel waveguides are prepared through Ti thermal diffusion into a Y-cut LiNbO/sub 3/ substrate. The half-wave voltage for each channel is 1.6 V at a modulating frequency bandwidth of 0-290 MHz. Results are presented from an experiment concerning the use of the modulator as an input device for the optical processing of radio signals.

  2. A 240-channel thick film multi-chip module for readout of silicon drift detectors

    International Nuclear Information System (INIS)

    Lynn, D.; Bellwied, R.; Beuttenmueller, R.; Caines, H.; Chen, W.; DiMassimo, D.; Dyke, H.; Elliott, D.; Grau, M.; Hoffmann, G.W.; Humanic, T.; Jensen, P.; Kleinfelder, S.A.; Kotov, I.; Kraner, H.W.; Kuczewski, P.; Leonhardt, B.; Li, Z.; Liaw, C.J.; LoCurto, G.; Middelkamp, P.; Minor, R.; Mazeh, N.; Nehmeh, S.; O'Conner, P.; Ott, G.; Pandey, S.U.; Pruneau, C.; Pinelli, D.; Radeka, V.; Rescia, S.; Rykov, V.; Schambach, J.; Sedlmeir, J.; Sheen, J.; Soja, B.; Stephani, D.; Sugarbaker, E.; Takahashi, J.; Wilson, K.

    2000-01-01

    We have developed a thick film multi-chip module for readout of silicon drift (or low capacitance ∼200 fF) detectors. Main elements of the module include a custom 16-channel NPN-BJT preamplifier-shaper (PASA) and a custom 16-channel CMOS Switched Capacitor Array (SCA). The primary design criteria of the module were the minimizations of the power (12 mW/channel), noise (ENC=490 e - rms), size (20.5 mmx63 mm), and radiation length (1.4%). We will discuss various aspects of the PASA design, with emphasis on the preamplifier feedback network. The SCA is a modification of an integrated circuit that has been previously described [1]; its design features specific to its application in the SVT (Silicon Vertex Tracker in the STAR experiment at RHIC) will be discussed. The 240-channel multi-chip module is a circuit with five metal layers fabricated in thick film technology on a beryllia substrate and contains 35 custom and commercial integrated circuits. It has been recently integrated with silicon drift detectors in both a prototype system assembly for the SVT and a silicon drift array for the E896 experiment at the Alternating Gradient Synchrotron at the Brookhaven National Laboratory. We will discuss features of the module's design and fabrication, report the test results, and emphasize its performance both on the bench and under experimental conditions

  3. Social exclusion modulates pre-reflective interpersonal body representation

    DEFF Research Database (Denmark)

    Ambrosini, Ettore; Blomberg, Olle; Mandrigin, Alisa

    2014-01-01

    social exclusion condition. The results were that the SAE that normally occurs when the mug is in the avatar’s reaching space is extinguished by the induced social exclusion. This indicates that judgments about one’s own social status modulate the effect of IBR.......Perception of an affordance is enhanced not only when the relevant object is located in one’s own peripersonal space, as compared to when it is located within extrapersonal space, but also when the object is located in another person’s peripersonal space (as measured by a Spatial Alignment Effect...... (SAE)). It has been suggested that this reflects the existence of an interpersonal body representation (IBR) that allows us to represent the perceptual states and action possibilities of others. Here, we address the question of whether IBR can be modulated by higher level/reflective social cognition...

  4. Stuttering adults' lack of pre-speech auditory modulation normalizes when speaking with delayed auditory feedback.

    Science.gov (United States)

    Daliri, Ayoub; Max, Ludo

    2018-02-01

    Auditory modulation during speech movement planning is limited in adults who stutter (AWS), but the functional relevance of the phenomenon itself remains unknown. We investigated for AWS and adults who do not stutter (AWNS) (a) a potential relationship between pre-speech auditory modulation and auditory feedback contributions to speech motor learning and (b) the effect on pre-speech auditory modulation of real-time versus delayed auditory feedback. Experiment I used a sensorimotor adaptation paradigm to estimate auditory-motor speech learning. Using acoustic speech recordings, we quantified subjects' formant frequency adjustments across trials when continually exposed to formant-shifted auditory feedback. In Experiment II, we used electroencephalography to determine the same subjects' extent of pre-speech auditory modulation (reductions in auditory evoked potential N1 amplitude) when probe tones were delivered prior to speaking versus not speaking. To manipulate subjects' ability to monitor real-time feedback, we included speaking conditions with non-altered auditory feedback (NAF) and delayed auditory feedback (DAF). Experiment I showed that auditory-motor learning was limited for AWS versus AWNS, and the extent of learning was negatively correlated with stuttering frequency. Experiment II yielded several key findings: (a) our prior finding of limited pre-speech auditory modulation in AWS was replicated; (b) DAF caused a decrease in auditory modulation for most AWNS but an increase for most AWS; and (c) for AWS, the amount of auditory modulation when speaking with DAF was positively correlated with stuttering frequency. Lastly, AWNS showed no correlation between pre-speech auditory modulation (Experiment II) and extent of auditory-motor learning (Experiment I) whereas AWS showed a negative correlation between these measures. Thus, findings suggest that AWS show deficits in both pre-speech auditory modulation and auditory-motor learning; however, limited pre

  5. Robust Automatic Modulation Classification Technique for Fading Channels via Deep Neural Network

    Directory of Open Access Journals (Sweden)

    Jung Hwan Lee

    2017-08-01

    Full Text Available In this paper, we propose a deep neural network (DNN-based automatic modulation classification (AMC for digital communications. While conventional AMC techniques perform well for additive white Gaussian noise (AWGN channels, classification accuracy degrades for fading channels where the amplitude and phase of channel gain change in time. The key contributions of this paper are in two phases. First, we analyze the effectiveness of a variety of statistical features for AMC task in fading channels. We reveal that the features that are shown to be effective for fading channels are different from those known to be good for AWGN channels. Second, we introduce a new enhanced AMC technique based on DNN method. We use the extensive and diverse set of statistical features found in our study for the DNN-based classifier. The fully connected feedforward network with four hidden layers are trained to classify the modulation class for several fading scenarios. Numerical evaluation shows that the proposed technique offers significant performance gain over the existing AMC methods in fading channels.

  6. Multiuser chirp modulation for underwater acoustic channel based on VTRM

    Directory of Open Access Journals (Sweden)

    Fei Yuan

    2017-05-01

    Full Text Available In this paper, an ascheme is proposed for multiuser underwater acoustic communication by using the multi-chirp rate signals. It differs from the well known TDMA (Time Division Multiple Access, FDMA (Frequency Division Multiple Access or CDMA (Code Division Multiple Access, by assigning each users with different chirp-rate carriers instead of the time, frequency or PN code. Multi-chirp rate signals can be separated from each other by FrFT (Fractional Fourier Transform, which can be regarded as the chirp-based decomposing, and superior to the match filter in the underwater acoustic channel. VTRM (Virtual Time Reverse Mirror is applied into the system to alleviate the ISI caused by the multipatch and make the equalization more simple. Results of computer simulations and pool experiments prove that the proposed multiuser underwater acoustic communication based on the multi-chirp rate exhibit well performance. Outfield experments carrie out in Xiamen Port show that using about 10 kHz bandwidth, four users could communicate at the same time with 425 bps with low BER and can match the UAC application.

  7. 80-Channel Multiplexer-Demultiplexer Module for DWDM Communications using Hybrid AWG -- Interleaver Technology

    Science.gov (United States)

    Rablau, Corneliu; Bredthauer, Lance

    2007-10-01

    Aside from the more traditional data, voice and e-mail communications, new bandwidth intensive applications in the larger consumer markets, such as music, digital pictures and movies, have led to an explosive increase in the demand for transmission capacity for optical communications networks. This has resulted in a widespread deployment of Dense Wavelength Division Multiplexing (DWDM) as a means of increasing the communications capacity by multiplexing and transmitting signals of different wavelengths (establishing multiple communication channels) through a single strand of fiber. We report on the design, assembly and characterization of a 50-GHz, 80-channel Mux-Demux module for DWDM systems. The module has been assembled from two commercially available 100 GHz, 40-channel Array Waveguide Grating (AWG) modules and a 50-GHz to 100-GHz interleaver. Relevant performance parameters such as insertion loss, channel uniformity, next-channel isolation (crosstalk) and integrated cross-talk are presented and discussed in contrast with the performance of other competing technologies such as Thin-Film-Filter-based Mux-Demux devices.

  8. Noise-based frequency offset modulation in wideband frequency-selective fading channels

    NARCIS (Netherlands)

    Meijerink, Arjan; Cotton, S.L.; Bentum, Marinus Jan; Scanlon, W.G.

    2009-01-01

    A frequency offset modulation scheme using wideband noise carriers is considered. The main advantage of such a scheme is that it enables fast receiver synchronization without channel adaptation, while providing robustness to multipath fading and in-band interference. This is important for low-power

  9. Tidal modulated flow and sediment flux through Wax Lake Delta distributary channels: Implications for delta development

    Directory of Open Access Journals (Sweden)

    K. Hanegan

    2015-03-01

    Full Text Available In this study, a Delft3D model of the Wax Lake Delta was developed to simulate flow and sediment flux through delta distributary channels. The model was calibrated for tidal constituents as well as velocity and sediment concentration across channel transects. The calibrated model was then used to simulate full spring–neap tidal cycles under constant low flow upstream boundary conditions, with grain size variation in suspended load represented using two sediment fractions. Flow and sediment flux results through distributary channel cross-sections were examined for spatial and temporal variability with the goal of characterizing the role of tides in sediment reworking and delta development. The Wax Lake Delta has prograded through channel extension, river mouth bar deposition, and channel bifurcation. Here we show that tidal modulation of currents influences suspended sand transport, and spatial acceleration through distributary channels at low tides is sufficient to suspend sand in distal reaches during lower flows. The basinward-increasing transport capacity in distributary channels indicates that erosive channel extension could be an important process, even during non-flood events.

  10. Study of multi-channel readout ASIC and its discrete module for particle detector

    International Nuclear Information System (INIS)

    Wang Ke; Fan Lei; Zhang Shengjun; Li Xian

    2013-01-01

    Recently, kinds of particle detectors have used Application Specific Integrated Circuits (ASIC) in their electronics readout systems, it is the key part for the whole system. This project designed a multi-channel readout ASIC for general detectors. The chip has Preamplifier, Shaper and Peak Detector embedded for easy readout. For each channel, signal which is preprocessed by a low-noise preamplifier is sent to the shaper to form a quasi-Gaussian pulse and keep its peak for readout. This chip and modules of individual Preamplifier, Shaper and Peak Detector have been manufactured and tested. The discrete modules work well, and the 6-channel chip NPRE 6 is ready for test in some particle detection system. (authors)

  11. Electroosmosis modulated biomechanical transport through asymmetric microfluidics channel

    Science.gov (United States)

    Jhorar, R.; Tripathi, D.; Bhatti, M. M.; Ellahi, R.

    2018-05-01

    This article addresses the electrokinetically modulated biomechanical transport through a two-dimensional asymmetric microchannel induced by peristaltic waves. Electrokinetic transport with peristaltic phenomena grabbed a significant attention due to its novel applications in engineering. Electrical fields also provide an excellent mode for regulating flows. The electrohydrodynamics problem is modified by means of Debye-Hückel linearization. Firstly, the governing flow problem is described by continuity and momentum equations in the presence of electrokinetic forces in Cartesian coordinates, then long wavelength and low/zero Reynolds ("neglecting the inertial forces") approximations are applied to modify the governing flow problem. The resulting differential equations are solved analytically in order to obtain exact solutions for velocity profile whereas the numerical integration is carried out to analyze the pumping characteristics. The physical behaviour of sundry parameters is discussed for velocity profile, pressure rise and volume flow rate. In particular, the behaviour of electro-osmotic parameter, phase difference, and Helmholtz-Smoluchowski velocity is examined and discussed. The trapping mechanism is also visualized by drawing streamlines against the governing parameters. The present study offers various interesting results that warrant further study on electrokinetic transport with peristalsis.

  12. Visualization of pre-set vortices in boundary layer flow over wavy surface in rectangular channel

    KAUST Repository

    Budiman, Alexander Christantho

    2014-12-04

    Abstract: Smoke-wire flow visualization is used to study the development of pre-set counter-rotating streamwise vortices in boundary layer flow over a wavy surface in a rectangular channel. The formation of the vortices is indicated by the vortical structures on the cross-sectional plane normal to the wavy surface. To obtain uniform spanwise vortex wavelength which will result in uniform vortex size, two types of spanwise disturbances were used: a series of perturbation wires placed prior and normal to the leading edge of the wavy surface, and a jagged pattern in the form of uniform triangles cut at the leading edge. These perturbation wires and jagged pattern induce low-velocity streaks that result in the formation of counter-rotating streamwise vortices that evolve downstream to form the mushroom-like structures on the cross-sectional plane of the flow. The evolution of the most amplified disturbances can be attributed to the formation of these mushroom-like structures. It is also shown that the size of the mushroom-like structures depends on the channel entrance geometry, Reynolds number, and the channel gap.Graphical Abstract: [Figure not available: see fulltext.

  13. Modulation of Tidal Channel Signatures on SAR Images Over Gyeonggi Bay in Relation to Environmental Factors

    Directory of Open Access Journals (Sweden)

    Tae-Sung Kim

    2018-04-01

    Full Text Available In this study, variations of radar backscatter features of the tidal channel in Gyeonggi Bay in the Eastern Yellow Sea were investigated using spaceborne synthetic aperture radar (SAR images. Consistent quasi-linear bright features appeared on the SAR images. Examining the detailed local bathymetry chart, we found that the features were co-located with the major axis of the tidal channel in the region. It was also shown that modulation of the radar backscatter features changed according to the environmental conditions at the time of imaging. For the statistical analysis, the bathymetric features over the tidal channel were extracted by an objective method. In terms of shape, the extracted features had higher variability in width than in length. The analysis of the variation in intensity with the coinciding bathymetric distribution confirmed that the quasi-linear bright features on the SAR images are fundamentally imprinted due to the surface current convergence and divergence caused by the bathymetry-induced tidal current variation. Furthermore, the contribution of environmental factors to the intensity modulation was quantitatively analyzed. A comparison of the variation in normalized radar cross section (NRCS with tidal current showed a positive correlation only with the perpendicular component of tidal current (r= 0.47. This implies that the modulation in intensity of the tidal channel signatures is mainly affected by the interaction with cross-current flow. On the other hand, the modulation of the NRCS over the tidal channel tended to be degraded as wind speed increased (r= −0.65. Considering the environmental circumstances in the study area, it can be inferred that the imaging capability of SAR for the detection of tidal channel signatures mainly relies on wind speed.

  14. Artificial modulation of the gating behavior of a K+ channel in a KvAP-DNA chimera.

    Directory of Open Access Journals (Sweden)

    Andrew Wang

    Full Text Available We present experiments where the gating behavior of a voltage-gated ion channel is modulated by artificial ligand binding. We construct a channel-DNA chimera with the KvAP potassium channel reconstituted in an artificial membrane. The channel is functional and the single channel ion conductivity unperturbed by the presence of the DNA. However, the channel opening probability vs. bias voltage, i.e., the gating, can be shifted considerably by the electrostatic force between the charges on the DNA and the voltage sensing domain of the protein. Different hybridization states of the chimera DNA thus lead to different response curves of the channel.

  15. Use of Ion-Channel Modulating Agents to Study Cyanobacterial Na+ - K+ Fluxes

    Directory of Open Access Journals (Sweden)

    Pomati Francesco

    2004-01-01

    Full Text Available Here we describe an experimental design aimed to investigate changes in total cellular levels of Na+ and K+ ions in cultures of freshwater filamentous cyanobacteria. Ion concentrations were measured in whole cells by flame photometry. Cellular Na+ levels increased exponentially with rising alkalinity, with K+ levels being maximal for optimal growth pH (~8. At standardized pH conditions, the increase in cellular Na+, as induced by NaCl at 10 mM, was coupled by the two sodium channel-modulating agents lidocaine hydrochloride at 1 &mgr;M and veratridine at 100 &mgr;M. Both the channel-blockers amiloride (1 mM and saxitoxin (1 &mgr;M, decreased cell-bound Na+ and K+ levels. Results presented demonstrate the robustness of well-defined channel blockers and channel-activators in the study of cyanobacterial Na+- K+ fluxes.

  16. The module CCM for the simulation of the thermal-hydraulic situation within a coolant channel

    International Nuclear Information System (INIS)

    Hoeld, A.

    2000-01-01

    A coolant channel module (Cc) will be presented which aim is to simulate, in a very general way, the thermal-hydraulic behaviour of single- and two-phase fluids flowing along a heated (or cooled) vertical, inclined or horizontal coolant channel. It is based on a theoretical drift-flux supported 3-equation mixture-fluid model describing the steady state and transient behaviour of characteristic thermal-hydraulic parameters of a single- and two-phase flow within such a channel. The module can be applied as an element within an overall theoretical model for large and complex plant assemblies (PWR and BWR core channels, parallel channels in 3D cores, primary and secondary sides of different steam generators types etc.). The model refers to a general (basic) coolant channel (BC) which can consists of different flow regimes. The BC has thus to be subdivided accordingly into a number of subchannels (SC-s). All of them can belong, however, to only two types of SC-s (single-phase fluid with subcooled water or superheated steam or a two-phase flow regime). For both of them the possibility of variable entrance or outlet positions has to be considered. For discretization purposes the BC (and thus also the SC-s) have to be subdivided into a number of (BC and SC) nodes, discretizing thus the conservation equations for mass, energy and momentum along these nodes by applying a very general spatial procedure, namely a 'modified finite volume method'. A special quadratic polygon approximation method (PAX procedure) helps then to establish a connection between nodal boundary and mean nodal parameters. Considering their constitutive equations (among them an adequate drift-flux correlation package) yields finally a set of non-linear algebraic and non-linear ordinary differential equations for the characteristic parameters of each of these SC nodes (mass flow, pressure drop, coolant temperature and/or void fraction). Based on this theory a code package (CCM) could be established

  17. pH-modulation of chloride channels from the sarcoplasmic reticulum of skeletal muscle.

    Science.gov (United States)

    Kourie, J I

    1999-01-01

    The understanding of the role of cytoplasmic pH in modulating sarcoplasmic reticulum (SR) ion channels involved in Ca2+ regulation is important for the understanding of the function of normal and adversely affected muscles. The dependency of the SR small chloride (SCl) channel from rabbit skeletal muscle on cytoplasmic pH (pHcis) and luminal pH (pHtrans) was investigated using the lipid bilayer-vesicle fusion technique. Low pHcis 6.75-4.28 modifies the operational mode of this multiconductance channel (conductance levels between 5 and 75 pS). At pHcis 7.26-7.37 the channel mode is dominated by the conductance and kinetics of the main conductance state (65-75 pS) whereas at low pHcis 6.75-4.28 the channel mode is dominated by the conductance and kinetics of subconductance states (5-40 pS). Similarly, low pHtrans 4.07, but not pHtrans 6.28, modified the activity of SCl channels. The effects of low pHcis are pronounced at 10(-3) and 10(-4) M [Ca2+]cis but are not apparent at 10(-5) M [Ca2+]cis, where the subconductances of the channel are already prominent. Low pHcis-induced mode shift in the SCl channel activity is due to modification of the channel proteins that cause the uncoupling of the subconductance states. The results in this study suggest that low pHcis can modify the functional properties of the skeletal SR ion channels and hence contribute, at least partly, to the malfunction in the contraction-relaxation mechanism in skeletal muscle under low cytoplasmic pH levels.

  18. DEG/ENaC ion channels involved in sensory transduction are modulated by cold temperature

    Science.gov (United States)

    Askwith, Candice C.; Benson, Christopher J.; Welsh, Michael J.; Snyder, Peter M.

    2001-01-01

    Several DEG/ENaC cation channel subunits are expressed in the tongue and in cutaneous sensory neurons, where they are postulated to function as receptors for salt and sour taste and for touch. Because these tissues are exposed to large temperature variations, we examined how temperature affects DEG/ENaC channel function. We found that cold temperature markedly increased the constitutively active Na+ currents generated by epithelial Na+ channels (ENaC). Half-maximal stimulation occurred at 25°C. Cold temperature did not induce current from other DEG/ENaC family members (BNC1, ASIC, and DRASIC). However, when these channels were activated by acid, cold temperature potentiated the currents by slowing the rate of desensitization. Potentiation was abolished by a “Deg” mutation that alters channel gating. Temperature changes in the physiologic range had prominent effects on current in cells heterologously expressing acid-gated DEG/ENaC channels, as well as in dorsal root ganglion sensory neurons. The finding that cold temperature modulates DEG/ENaC channel function may provide a molecular explanation for the widely recognized ability of temperature to modify taste sensation and mechanosensation. PMID:11353858

  19. A study of mini-channel thermal module design for achieving high stability and high capability in electronic cooling

    International Nuclear Information System (INIS)

    Wang, Hsiang-Li; Wu, Huang-Ching; Kong Wang, S.; Hung, Tzu-Chen; Yang, Ruey-Jen

    2013-01-01

    In this study, pressure drop and heat transfer characteristics of multiple-mini-channel thermal modules were investigated quantitatively. The flow channels, which were mounted on one side of a copper test section, were designed in three types: (1) the first module consists of fourteen straight and parallel channels with a rectangular cross section of 1 mm × 3 mm, (2) the second module consists of fourteen gradually widening channels with a U-shaped cross section starting from an inlet section of 0.5 mm × 3 mm and increasing to an outlet section of 1 mm × 3 mm, and (3) the third module is similar to the second module except for the rectangular cross section. Visual observations and the measured boiling curves show that, in the straight channels, some bubbles cannot be flushed out of the channels fast enough, so they tend to flow back and accumulate at the entrance. This results in a rather dry channel condition for CHF (critical heat flux) to occur for the cases with low flow rates. For the widening channel modules, no occurrence of CHF was observed under an even lower operating pressure in an attempt to induce the incipient of CHF. Under a similar temperature rise at the channel exit, the maximum heat removal rate of the widening channels reaches 27 W/cm 2 which is at least twice as high as that of the straight channels. -- Highlights: ► Three mini-channel modules were designed, and experiments were carried out on pressure drop and heat transfer characteristics. ► Comparisons were made between one regular straight-channel module and two widening-channel modules with rectangular and U-shaped cross sections. ► It was found that the widening channels yield a stable two-phase heat transfer mode with no occurrence of CHF due to a better movement of the bubbles and the absence of backflow which causes accumulation of bubbles commonly occur at the entrance of the straight-shaped parallel channels. ► The maximum heat removal rate of the widening channels reaches

  20. A Robust Pre-Filter and Power Loading Design for Time Reversal UWB Systems over Time-Correlated MIMO Channels

    Directory of Open Access Journals (Sweden)

    Sajjad Alizadeh

    2014-04-01

    Full Text Available Conventional Time Reversal (TR technique suffers from performance degradation in time varying Multiple-Input Multiple-Output Ultra-Wideband (MIMO-UWB systems due to outdating Channel State Information (CSI over time progressions. That is, the outdated CSI degrades the TR performance significantly in time varying channels. The correlation property of time correlated channels can improve the TR performance against other traditional TR designs. Based on this property, at first, we propose a robust TR-MIMO-UWB system design for a time-varying channel in which the CSI is updated only at the beginning of each block of data where the CSI is assumed to be known. As the channel varies over time, pre-processor blindly pre-equalizes the channel during the next symbol time by using the correlation property. Then, a novel recursive power allocation strategy is derived over time-correlated time-varying TR-MIMO-UWB channels. We show that the proposed power loading technique, considerably improves the BER performance of TR-MIMO-UWB system in imperfect CSI with robust pre-filter. The proposed algorithms lead to a cost-efficient CSI updating procedure for the TR optimization. Simulation results are provided to confirm the new design performance against traditional method.

  1. Experimental study of cooling BIPV modules by forced convection in the air channel

    International Nuclear Information System (INIS)

    Kaiser, A.S.; Zamora, B.; Mazón, R.; García, J.R.; Vera, F.

    2014-01-01

    Highlights: • An experimental setup for studying the effects of forced convection on cell temperature. • The induced velocity within the forced convection channel significantly affects the PV cooling. • Correlations for the Ross coefficient, module temperature, efficiency, and power output. • Prediction of the thermal behavior of the PV module in BIPV configurations. - Abstract: The efficiency of photovoltaic systems depends mainly on the cell temperature. Frequently, the PV collectors are installed on the top of the building. One cost effective method to regulate the temperature of rooftop integrated photovoltaic panels is to provide an open air channel beneath the panel. The cell temperature of these PV modules is very much influenced by the capability of ventilating this channel. The ventilation may be modified by different factors such as the wind velocity, the air gap size, and the forced convection induced by a fan or by a conventional air conditioning system. This paper describes an experimental setup to study the influence of the air gap size and the forced ventilation on the cell temperature (and consequently on the electrical efficiency of the PV module) of a BIPV configuration, for different values of the incident solar radiation, ambient temperatures, and aspect ratios, as well as for several forced ventilation conditions. Semi empirical correlations for the Ross coefficient, module temperature, electrical efficiency, and power output are proposed, showing a good agreement with respect to experimental measurements. A critical channel aspect ratio close to 0.11 can be considered to minimize overheating of PV devices. For a duct velocity V v = 6 m/s, a power output increase of 19% is observed over the natural ventilation case (V v = 0.5 m/s)

  2. Functional characterization of neurotransmitter activation and modulation in a nematode model ligand-gated ion channel.

    Science.gov (United States)

    Heusser, Stephanie A; Yoluk, Özge; Klement, Göran; Riederer, Erika A; Lindahl, Erik; Howard, Rebecca J

    2016-07-01

    The superfamily of pentameric ligand-gated ion channels includes neurotransmitter receptors that mediate fast synaptic transmission in vertebrates, and are targets for drugs including alcohols, anesthetics, benzodiazepines, and anticonvulsants. However, the mechanisms of ion channel opening, gating, and modulation in these receptors leave many open questions, despite their pharmacological importance. Subtle conformational changes in both the extracellular and transmembrane domains are likely to influence channel opening, but have been difficult to characterize given the limited structural data available for human membrane proteins. Recent crystal structures of a modified Caenorhabditis elegans glutamate-gated chloride channel (GluCl) in multiple states offer an appealing model system for structure-function studies. However, the pharmacology of the crystallographic GluCl construct is not well established. To establish the functional relevance of this system, we used two-electrode voltage-clamp electrophysiology in Xenopus oocytes to characterize activation of crystallographic and native-like GluCl constructs by L-glutamate and ivermectin. We also tested modulation by ethanol and other anesthetic agents, and used site-directed mutagenesis to explore the role of a region of Loop F which was implicated in ligand gating by molecular dynamics simulations. Our findings indicate that the crystallographic construct functionally models concentration-dependent agonism and allosteric modulation of pharmacologically relevant receptors. Specific substitutions at residue Leu174 in loop F altered direct L-glutamate activation, consistent with computational evidence for this region's role in ligand binding. These insights demonstrate conservation of activation and modulation properties in this receptor family, and establish a framework for GluCl as a model system, including new possibilities for drug discovery. In this study, we elucidate the validity of a modified glutamate

  3. Development of Pre-set Counter-rotating Streamwise Vortices in Wavy Channel

    KAUST Repository

    Budiman, A.C.

    2015-10-23

    Development of counter-rotating streamwise vortices in a rectangular channel with one-sided wavy surface has been experimentally quantified using hot-wire anemometry. The wavy surface has fixed amplitude of 3.75 mm. The counter-rotating vortices are pre-set by means of a sawtooth pattern cut at the leading edge of the wavy surface. Variations of the central streamwise velocity Uc with a channel gap H = 35 mm and 50 mm (corresponding to a Reynolds number from 1600 to 4400) change the instability of the flow which can be distinguished from the velocity contours at a certain spanwise plane. The streamwise velocity contours and turbulence intensity for Reynolds number Re = 3100 and H = 35 mm show the disappearance of the mushroom-like vortices prior to turbulence near the second peak of the wavy surface, while for higher Re, this phenomenon occurs earlier. Under certain conditions, for example, for Re = 4400 and H = 50 mm, the splitting of the vortices can also be observed.

  4. Development of Pre-set Counter-rotating Streamwise Vortices in Wavy Channel

    KAUST Repository

    Budiman, A.C.; Mitsudharmadi, Hatsari; Bouremel, Y.; Winoto, S.H.; Low, H.T.

    2015-01-01

    Development of counter-rotating streamwise vortices in a rectangular channel with one-sided wavy surface has been experimentally quantified using hot-wire anemometry. The wavy surface has fixed amplitude of 3.75 mm. The counter-rotating vortices are pre-set by means of a sawtooth pattern cut at the leading edge of the wavy surface. Variations of the central streamwise velocity Uc with a channel gap H = 35 mm and 50 mm (corresponding to a Reynolds number from 1600 to 4400) change the instability of the flow which can be distinguished from the velocity contours at a certain spanwise plane. The streamwise velocity contours and turbulence intensity for Reynolds number Re = 3100 and H = 35 mm show the disappearance of the mushroom-like vortices prior to turbulence near the second peak of the wavy surface, while for higher Re, this phenomenon occurs earlier. Under certain conditions, for example, for Re = 4400 and H = 50 mm, the splitting of the vortices can also be observed.

  5. Development of a novel fast frequency modulation scheme for the JET multi-channel reflectometer

    International Nuclear Information System (INIS)

    Deliyanakis, N.

    1999-10-01

    A novel frequency modulation scheme has been developed for the multi-channel reflectometer used to measure density profiles and density fluctuations on the JET tokamak. This reflectometer normally uses slow frequency sweeping, combined with fixed-frequency operation, to measure the group delay, as well as plasma fluctuations, at 10 different microwave frequencies. The novel scheme uses continuous frequency modulation on a time-scale much faster than that of plasma fluctuations, the main aim being to make the group delay measurement more robust against plasma fluctuations. This paper discusses the theoretical background of the scheme, gives a detailed description of the system, and presents results from plasma measurements. (author)

  6. Adaptive Modulation with Best User Selection over Non-Identical Nakagami Fading Channels

    KAUST Repository

    Rao, Anlei

    2012-09-08

    In this paper, we analyze the performance of adaptive modulation with single-cell multiuser scheduling over independent but not identical distributed (i.n.i.d.) Nakagami fading channels. Closed-form expressions are derived for the average channel capacity, spectral efficiency, and bit-error-rate (BER) for both constant-power variable-rate and variable-power variable-rate uncoded M-ary quadrature amplitude modulation (M-QAM) schemes. We also study the impact of time delay on the average BER of adaptive M-QAM. Selected numerical results show that the multiuser diversity brings a considerably better performance even over i.n.i.d. fading environments.

  7. Analytical evaluation of adaptive-modulation-based opportunistic cognitive radio in nakagami-m fading channels

    KAUST Repository

    Chen, Yunfei; Alouini, Mohamed-Slim; Tang, Liang; Khan, Fahdahmed

    2012-01-01

    The performance of adaptive modulation for cognitive radio with opportunistic access is analyzed by considering the effects of spectrum sensing, primary user (PU) traffic, and time delay for Nakagami- m fading channels. Both the adaptive continuous rate scheme and the adaptive discrete rate scheme are considered. Numerical examples are presented to quantify the effects of spectrum sensing, PU traffic, and time delay for different system parameters. © 1967-2012 IEEE.

  8. Analytical evaluation of adaptive-modulation-based opportunistic cognitive radio in nakagami-m fading channels

    KAUST Repository

    Chen, Yunfei

    2012-09-01

    The performance of adaptive modulation for cognitive radio with opportunistic access is analyzed by considering the effects of spectrum sensing, primary user (PU) traffic, and time delay for Nakagami- m fading channels. Both the adaptive continuous rate scheme and the adaptive discrete rate scheme are considered. Numerical examples are presented to quantify the effects of spectrum sensing, PU traffic, and time delay for different system parameters. © 1967-2012 IEEE.

  9. Ciguatoxins: Cyclic Polyether Modulators of Voltage-gated Iion Channel Function

    Directory of Open Access Journals (Sweden)

    Richard J. Lewis

    2006-04-01

    Full Text Available Ciguatoxins are cyclic polyether toxins, derived from marine dinoflagellates, which are responsible for the symptoms of ciguatera poisoning. Ingestion of tropical and subtropical fin fish contaminated by ciguatoxins results in an illness characterised by neurological, cardiovascular and gastrointestinal disorders. The pharmacology of ciguatoxins is characterised by their ability to cause persistent activation of voltage-gated sodium channels, to increase neuronal excitability and neurotransmitter release, to impair synaptic vesicle recycling, and to cause cell swelling. It is these effects, in combination with an action to block voltage-gated potassium channels at high doses, which are believed to underlie the complex of symptoms associated with ciguatera. This review examines the sources, structures and pharmacology of ciguatoxins. In particular, attention is placed on their cellular modes of actions to modulate voltage-gated ion channels and other Na+-dependent mechanisms in numerous cell types and to current approaches for detection and treatment of ciguatera.

  10. Modulation of low-frequency oscillations in GaAs MESFETs' channel current by sidegating bias

    Institute of Scientific and Technical Information of China (English)

    DING Yong; LU Shengli; ZHAO Fuchuan

    2005-01-01

    Low-frequency oscillations in channel current are usually observed when measuring the GaAs MESFET's output characteristics. This paper studies the oscillations by testing the MESFET's output characteristics under different sidegate bias conditions. It is shown that the low-frequency oscillations of channel current are directly related to the sidegate bias. In other words, the sidegate bias can modulate the oscillations. Whether the sidegate bias varies positively or negatively, there will inevitably be a threshold voltage after which the low-frequency oscillations disappear. The observation is strongly dependent upon the peculiarities of channel-substrate (C-S) junction and impact ionization of traps-EL2 under high field. This conclusion is of particular pertinence to the design of low-noise GaAs IC's.

  11. Ciguatoxins: Cyclic Polyether Modulators of Voltage-gated Iion Channel Function

    Science.gov (United States)

    Nicholson, Graham M.; Lewis, Richard J.

    2006-01-01

    Ciguatoxins are cyclic polyether toxins, derived from marine dinoflagellates, which are responsible for the symptoms of ciguatera poisoning. Ingestion of tropical and subtropical fin fish contaminated by ciguatoxins results in an illness characterised by neurological, cardiovascular and gastrointestinal disorders. The pharmacology of ciguatoxins is characterised by their ability to cause persistent activation of voltage-gated sodium channels, to increase neuronal excitability and neurotransmitter release, to impair synaptic vesicle recycling, and to cause cell swelling. It is these effects, in combination with an action to block voltage-gated potassium channels at high doses, which are believed to underlie the complex of symptoms associated with ciguatera. This review examines the sources, structures and pharmacology of ciguatoxins. In particular, attention is placed on their cellular modes of actions to modulate voltage-gated ion channels and other Na+-dependent mechanisms in numerous cell types and to current approaches for detection and treatment of ciguatera.

  12. Mechanism for modulation of gating of connexin26-containing channels by taurine

    Science.gov (United States)

    Kieken, Fabien; Tao, Liang; Sorgen, Paul L.; Harris, Andrew L.

    2011-01-01

    The mechanisms of action of endogenous modulatory ligands of connexin channels are largely unknown. Previous work showed that protonated aminosulfonates (AS), notably taurine, directly and reversibly inhibit homomeric and heteromeric channels that contain Cx26, a widely distributed connexin, but not homomeric Cx32 channels. The present study investigated the molecular mechanisms of connexin channel modulation by taurine, using hemichannels and junctional channels composed of Cx26 (homomeric) and Cx26/Cx32 (heteromeric). The addition of a 28–amino acid “tag” to the carboxyl-terminal domain (CT) of Cx26 (Cx26T) eliminated taurine sensitivity of homomeric and heteromeric hemichannels in cells and liposomes. Cleavage of all but four residues of the tag (Cx26Tc) resulted in taurine-induced pore narrowing in homomeric hemichannels, and restored taurine inhibition of heteromeric hemichannels (Cx26Tc/Cx32). Taurine actions on junctional channels were fully consistent with those on hemichannels. Taurine-induced inhibition of Cx26/Cx32T and nontagged Cx26 junctional channels was blocked by extracellular HEPES, a blocker of the taurine transporter, confirming that the taurine-sensitive site of Cx26 is cytoplasmic. Nuclear magnetic resonance of peptides corresponding to Cx26 cytoplasmic domains showed that taurine binds to the cytoplasmic loop (CL) and not the CT, and that the CT and CL directly interact. ELISA showed that taurine disrupts a pH-dependent interaction between the CT and the CT-proximal half of the CL. These studies reveal that AS disrupt a pH-driven cytoplasmic interdomain interaction in Cx26-containing channels, causing closure, and that the Cx26CT has a modulatory role in Cx26 function. PMID:21844220

  13. KCNQ1 channel modulation by KCNE proteins via the voltage-sensing domain.

    Science.gov (United States)

    Nakajo, Koichi; Kubo, Yoshihiro

    2015-06-15

    The gating of the KCNQ1 potassium channel is drastically regulated by auxiliary subunit KCNE proteins. KCNE1, for example, slows the activation kinetics of KCNQ1 by two orders of magnitude. Like other voltage-gated ion channels, the opening of KCNQ1 is regulated by the voltage-sensing domain (VSD; S1-S4 segments). Although it has been known that KCNE proteins interact with KCNQ1 via the pore domain, some recent reports suggest that the VSD movement may be altered by KCNE. The altered VSD movement of KCNQ1 by KCNE proteins has been examined by site-directed mutagenesis, the scanning cysteine accessibility method (SCAM), voltage clamp fluorometry (VCF) and gating charge measurements. These accumulated data support the idea that KCNE proteins interact with the VSDs of KCNQ1 and modulate the gating of the KCNQ1 channel. In this review, we will summarize recent findings and current views of the KCNQ1 modulation by KCNE via the VSD. In this context, we discuss our recent findings that KCNE1 may alter physical interactions between the S4 segment (VSD) and the S5 segment (pore domain) of KCNQ1. Based on these findings from ourselves and others, we propose a hypothetical mechanism for how KCNE1 binding alters the VSD movement and the gating of the channel. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

  14. Interplay between inertial and non-Newtonian effects on the flow in weakly modulated channel

    International Nuclear Information System (INIS)

    Abu-Ramadan, E.; Khayat, R.E.

    2002-01-01

    The flow inside a spatially modulated channel is examined for shear-thinning and shear-thickening fluids. The modulation amplitude is assumed to be small. A regular perturbation expansion of the flow field is used, coupled to a variable-step finite-difference scheme, to solve the problem. Since this method is intended to provide a fast and accurate alternative to conventional methods in the limit of small modulation amplitude, establishing the accuracy of the solution is critical. Numerical accuracy and convergence will be assessed, therefore. The influence of the wall geometry, inertia and non-Newtonian effects are investigated systematically. In particular, the influence of the flow and fluid parameters is examined on the conditions for the onset of separation. (author)

  15. Capacity Bounds and High-SNR Capacity of MIMO Intensity-Modulation Optical Channels

    KAUST Repository

    Chaaban, Anas

    2018-02-19

    The capacity of the intensity modulation direct detection multiple-input multiple-output channel is studied. Therein, the nonnegativity constraint of the transmit signal limits the applicability of classical schemes, including precoding. Thus, new ways are required for deriving capacity bounds for this channel. To this end, capacity lower bounds are developed in this paper by deriving the achievable rates of two precodingfree schemes: Channel inversion and QR decomposition. The achievable rate of a DC-offset SVD-based scheme is also derived as a benchmark. Then, capacity upper bounds are derived and compared against the lower bounds. As a result, the capacity at high signal-to-noise ratio (SNR) is characterized for the case where the number of transmit apertures is not larger than the number of receive apertures, and is shown to be achievable by the QR decomposition scheme. This is shown for a channel with average intensity or peak intensity constraints. Under both constraints, the high-SNR capacity is approximated within a small gap. Extensions to a channel with more transmit apertures than receive apertures are discussed, and capacity bounds for this case are derived.

  16. Capacity Bounds and High-SNR Capacity of MIMO Intensity-Modulation Optical Channels

    KAUST Repository

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

    2018-01-01

    The capacity of the intensity modulation direct detection multiple-input multiple-output channel is studied. Therein, the nonnegativity constraint of the transmit signal limits the applicability of classical schemes, including precoding. Thus, new ways are required for deriving capacity bounds for this channel. To this end, capacity lower bounds are developed in this paper by deriving the achievable rates of two precodingfree schemes: Channel inversion and QR decomposition. The achievable rate of a DC-offset SVD-based scheme is also derived as a benchmark. Then, capacity upper bounds are derived and compared against the lower bounds. As a result, the capacity at high signal-to-noise ratio (SNR) is characterized for the case where the number of transmit apertures is not larger than the number of receive apertures, and is shown to be achievable by the QR decomposition scheme. This is shown for a channel with average intensity or peak intensity constraints. Under both constraints, the high-SNR capacity is approximated within a small gap. Extensions to a channel with more transmit apertures than receive apertures are discussed, and capacity bounds for this case are derived.

  17. PReMod: a database of genome-wide mammalian cis-regulatory module predictions.

    Science.gov (United States)

    Ferretti, Vincent; Poitras, Christian; Bergeron, Dominique; Coulombe, Benoit; Robert, François; Blanchette, Mathieu

    2007-01-01

    We describe PReMod, a new database of genome-wide cis-regulatory module (CRM) predictions for both the human and the mouse genomes. The prediction algorithm, described previously in Blanchette et al. (2006) Genome Res., 16, 656-668, exploits the fact that many known CRMs are made of clusters of phylogenetically conserved and repeated transcription factors (TF) binding sites. Contrary to other existing databases, PReMod is not restricted to modules located proximal to genes, but in fact mostly contains distal predicted CRMs (pCRMs). Through its web interface, PReMod allows users to (i) identify pCRMs around a gene of interest; (ii) identify pCRMs that have binding sites for a given TF (or a set of TFs) or (iii) download the entire dataset for local analyses. Queries can also be refined by filtering for specific chromosomal regions, for specific regions relative to genes or for the presence of CpG islands. The output includes information about the binding sites predicted within the selected pCRMs, and a graphical display of their distribution within the pCRMs. It also provides a visual depiction of the chromosomal context of the selected pCRMs in terms of neighboring pCRMs and genes, all of which are linked to the UCSC Genome Browser and the NCBI. PReMod: http://genomequebec.mcgill.ca/PReMod.

  18. Performance analysis of subcarrier intensity modulation using rectangular QAM over Malaga turbulence channels with integer and non-integerβ

    KAUST Repository

    Alheadary, Wael Ghazy; Park, Kihong; Alouini, Mohamed-Slim

    2016-01-01

    In this paper, we derive the performances of optical wireless communication system utilizing adaptive subcarrier intensity modulation over the Malaga turbulent channel. More specifically, analytical closed-form solutions and asymptotic results

  19. cAMP-dependent kinase does not modulate the Slack sodium-activated potassium channel.

    Science.gov (United States)

    Nuwer, Megan O; Picchione, Kelly E; Bhattacharjee, Arin

    2009-09-01

    The Slack gene encodes a Na(+)-activated K(+) channel and is expressed in many different types of neurons. Like the prokaryotic Ca(2+)-gated K(+) channel MthK, Slack contains two 'regulator of K(+) conductance' (RCK) domains within its carboxy terminal, domains likely involved in Na(+) binding and channel gating. It also contains multiple consensus protein kinase C (PKC) and protein kinase A (PKA) phosphorylation sites and although regulated by protein kinase C (PKC) phosphorylation, modulation by PKA has not been determined. To test if PKA directly regulates Slack, nystatin-perforated patch whole-cell currents were recorded from a human embryonic kidney (HEK-293) cell line stably expressing Slack. Bath application of forskolin, an adenylate cyclase activator, caused a rapid and complete inhibition of Slack currents however, the inactive homolog of forskolin, 1,9-dideoxyforskolin caused a similar effect. In contrast, bath application of 8-bromo-cAMP did not affect the amplitude nor the activation kinetics of Slack currents. In excised inside-out patch recordings, direct application of the PKA catalytic subunit to patches did not affect the open probability of Slack channels nor was open probability affected by direct application of protein phosphatase 2B. Preincubation of cells with the protein kinase A inhibitor KT5720 also did not change current density. Finally, mutating the consensus phosphorylation site located between RCK domain 1 and domain 2 from serine to glutamate did not affect current activation kinetics. We conclude that unlike PKC, phosphorylation by PKA does not acutely modulate the function and gating activation kinetics of Slack channels.

  20. Post-translational regulation of P2X receptor channels: modulation by phospholipids

    Directory of Open Access Journals (Sweden)

    Louis-Philippe eBernier

    2013-11-01

    Full Text Available P2X receptor channels mediate fast excitatory signaling by ATP and play major roles in sensory transduction, neuro-immune communication and inflammatory response. P2X receptors constitute a gene family of calcium-permeable ATP-gated cation channels therefore the regulation of P2X signaling is critical for both membrane potential and intracellular calcium homeostasis. Phosphoinositides (PIPn are anionic signaling phospholipids that act as functional regulators of many types of ion channels. Direct PIPn binding was demonstrated for several ligand- or voltage-gated ion channels, however no generic motif emerged to accurately predict lipid-protein binding sites. This review presents what is currently known about the modulation of the different P2X subtypes by phospholipids and about critical determinants underlying their sensitivity to PIPn levels in the plasma membrane.All functional mammalian P2X subtypes tested, with the notable exception of P2X5, have been shown to be positively modulated by PIPn, i.e. homomeric P2X1, P2X2, P2X3, P2X4, and P2X7, as well as heteromeric P2X1/5 and P2X2/3 receptors. Based on various results reported on the aforementioned subtypes including mutagenesis of the prototypical PIPn-sensitive P2X4 and PIPn-insensitive P2X5 receptor subtypes, an increasing amount of functional, biochemical and structural evidence converges on the modulatory role of a short polybasic domain located in the proximal C-terminus of P2X subunits. This linear motif, semi-conserved in the P2X family, seems necessary and sufficient for encoding direct modulation of ATP-gated channels by PIPn. Furthermore, the physiological impact of the regulation of ionotropic purinergic responses by phospholipids on pain pathways was recently revealed in the context of native crosstalks between phospholipase C-linked metabotropic receptors and P2X receptor channels in DRG sensory neurons and microglia.

  1. Modulation of T-type Ca2+ channels by Lavender and Rosemary extracts.

    Directory of Open Access Journals (Sweden)

    Chaymae El Alaoui

    Full Text Available Medicinal plants represent a significant reservoir of unexplored substances for early-stage drug discovery. Of interest, two flowering Mediterranean plants have been used for thousands of years for their beneficial effects on nervous disorders, including anxiety and mood. However, the therapeutic potential of these plants regarding their ability to target ion channels and neuronal excitability remains largely unknown. Towards this goal, we have investigated the ability of Lavender and Rosemary to modulate T-type calcium channels (TTCCs. TTCCs play important roles in neuronal excitability, neuroprotection, sensory processes and sleep. These channels are also involved in epilepsy and pain. Using the whole-cell patch-clamp technique, we have characterized how Lavender and Rosemary extracts, as well as their major active compounds Linalool and Rosmarinic acid, modulate the electrophysiological properties of recombinant TTCCs (CaV3.2 expressed in HEK-293T cells. Both the methanolic and essential oil extracts as well as the active compounds of these plants inhibit Cav3.2 current in a concentration-dependent manner. In addition, these products also induce a negative shift of the steady-state inactivation of CaV3.2 current with no change in the activation properties. Taken together, our findings reveal that TTCCs are a molecular target of the Lavender and Rosemary compounds, suggesting that inhibition of TTCCs could contribute to the anxiolytic and the neuroprotective effects of these plants.

  2. Joint nonbinary low-density parity-check codes and modulation diversity over fading channels

    Science.gov (United States)

    Shi, Zhiping; Li, Tiffany Jing; Zhang, Zhongpei

    2010-09-01

    A joint exploitation of coding and diversity techniques to achieve efficient, reliable wireless transmission is considered. The system comprises a powerful non-binary low-density parity-check (LDPC) code that will be soft-decoded to supply strong error protection, a quadratic amplitude modulator (QAM) that directly takes in the non-binary LDPC symbols and a modulation diversity operator that will provide power- and bandwidth-efficient diversity gain. By relaxing the rate of the modulation diversity rotation matrices to below 1, we show that a better rate allocation can be arranged between the LDPC codes and the modulation diversity, which brings significant performance gain over previous systems. To facilitate the design and evaluation of the relaxed modulation diversity rotation matrices, based on a set of criteria, three practical design methods are given and their point pairwise error rate are analyzed. With EXIT chart, we investigate the convergence between demodulator and decoder.A rate match method is presented based on EXIT analysis. Through analysis and simulations, we show that our strategies are very effective in combating random fading and strong noise on fading channels.

  3. The Role of L-type Calcium Channels in Olfactory Learning and Its Modulation by Norepinephrine

    Directory of Open Access Journals (Sweden)

    Abhinaba Ghosh

    2017-12-01

    Full Text Available L type calcium channels (LTCCs are prevalent in different systems and hold immense importance for maintaining/performing selective functions. In the nervous system, CaV1.2 and CaV1.3 are emerging as critical modulators of neuronal functions. Although the general role of these calcium channels in modulating synaptic plasticity and memory has been explored, their role in olfactory learning is not well understood. In this review article we first discuss the role of LTCCs in olfactory learning especially focusing on early odor preference learning in neonate rodents, presenting evidence that while NMDARs initiate stimulus-specific learning, LTCCs promote protein-synthesis dependent long-term memory (LTM. Norepinephrine (NE release from the locus coeruleus (LC is essential for early olfactory learning, thus noradrenergic modulation of LTCC function and its implication in olfactory learning is discussed here. We then address the differential roles of LTCCs in adult learning and learning in aged animals.

  4. Design and construction of the 8K multi-channel gamma spectrometer module (ADC+MCD)

    International Nuclear Information System (INIS)

    Vu Xuan Cach; Hoang Thi Ngoc Bich; Truong Van Dat; Pham Ngoc Tuan; Dang Lanh; Tuong Thi Thu Huong; Nguyen Xuan Hai

    2007-01-01

    A multichannel pulse-height analyzer system (MCA) consists of an ADC with 8192 channel performance, a histogramming memory, and a visual display of the histogram, implemented on a Personal Computer (PC). The purpose of the analog-to-digital converter (ADC) is to measure the maximum amplitude of an analog pulse, and convert that value into a digital number. This digital output is a proportional representation of the analog amplitude at the ADC input. The digital ADC outputs are stored in a histogram memory, where each bin represents a pulse height interval and the number of events in each bin represents the number of events in that interval. The combination of ADC, histogramming memory and display functions are the minimum to constitute a multichannel analyzer or MCA based on PC. It is designed and fabricated on a single NIM module. The communication between MCA module and PC implements via USB bus. In our application, performance of the USB standard version 1.1 is good enough for purposes. The application program was designed in LabWIEW 8.0 software. This application is the main display and acquisition software for the MCA module. It is compatible with Windows 98SE/XP. The libraries USB driver, with their supporting files, are in the FTD2XX driver DLL Package and D2XX function 7.0 for LabWIEW supporting. These libraries are used to write custom code to control the MCA module. The 8K MCA module has the main following hardware specifications: ADC Successive-approximation type with sliding scale linearization; resolution: 8192 channels; dead time per event: 5 μs, including memory transfer; integral nonlinearity: ±0.025% over the top 98% of the dynamic range; differential nonlinearity: < ±1% over the top 98% of the dynamic range; data memory: 224 counts per channel (16 millions counts); presets; Real Time/Live Time: 1 to 232(s), Multiples of 1 s; ADC LLD and ULD Aajustable from 0 to 100% of full scale via hardware control; input accepts positive unipolar pulses in

  5. Aberrant modulation of a delayed rectifier potassium channel by glutamate in Alzheimer's disease.

    Science.gov (United States)

    Poulopoulou, Cornelia; Markakis, Ioannis; Davaki, Panagiota; Tsaltas, Eleftheria; Rombos, Antonis; Hatzimanolis, Alexandros; Vassilopoulos, Dimitrios

    2010-02-01

    In Alzheimer's disease (AD), potassium channel abnormalities have been reported in both neural and peripheral tissues. Herein, using whole-cell patch-clamp, we demonstrate an aberrant glutamate-dependent modulation of K(V)1.3 channels in T lymphocytes of AD patients. Although intrinsic K(V)1.3 properties in patients were similar to healthy individuals, glutamate (1-1000 microM) failed to yield the hyperpolarizing shift normally observed in K(V)1.3 steady-state inactivation (-4.4+/-2.7 mV in AD vs. -14.3+/-2.5 mV in controls, 10 microM glutamate), resulting in a 4-fold increase of resting channel activity. Specific agonist and antagonist data indicate that this abnormality is due to dysfunction of cognate group II mGluRs. Given that glutamate is present in plasma and that both mGluRs and K(V)1.3 channels regulate T-lymphocyte responsiveness, our finding may account for the presence of immune-associated alterations in AD. Furthermore, if this aberration reflects a corresponding one in neural tissue, it could provide a potential target in AD pathogenesis.

  6. Modulation of rod photoreceptor output by HCN1 channels is essential for regular mesopic cone vision.

    Science.gov (United States)

    Seeliger, Mathias W; Brombas, Arne; Weiler, Reto; Humphries, Peter; Knop, Gabriel; Tanimoto, Naoyuki; Müller, Frank

    2011-11-08

    Retinal photoreceptors permit visual perception over a wide range of lighting conditions. Rods work best in dim, and cones in bright environments, with considerable functional overlap at intermediate (mesopic) light levels. At many sites in the outer and inner retina where rod and cone signals interact, gap junctions, particularly those containing Connexin36, have been identified. However, little is known about the dynamic processes associated with the convergence of rod and cone system signals into ON- and OFF-pathways. Here we show that proper cone vision under mesopic conditions requires rapid adaptational feedback modulation of rod output via hyperpolarization-activated and cyclic nucleotide-gated channels 1. When these channels are absent, sustained rod responses following bright light exposure saturate the retinal network, resulting in a loss of downstream cone signalling. By specific genetic and pharmacological ablation of key signal processing components, regular cone signalling can be restored, thereby identifying the sites involved in functional rod-cone interactions.

  7. Molecular pathophysiology and pharmacology of the voltage-sensing module of neuronal ion channels.

    Science.gov (United States)

    Miceli, Francesco; Soldovieri, Maria Virginia; Ambrosino, Paolo; De Maria, Michela; Manocchio, Laura; Medoro, Alessandro; Taglialatela, Maurizio

    2015-01-01

    Voltage-gated ion channels (VGICs) are membrane proteins that switch from a closed to open state in response to changes in membrane potential, thus enabling ion fluxes across the cell membranes. The mechanism that regulate the structural rearrangements occurring in VGICs in response to changes in membrane potential still remains one of the most challenging topic of modern biophysics. Na(+), Ca(2+) and K(+) voltage-gated channels are structurally formed by the assembly of four similar domains, each comprising six transmembrane segments. Each domain can be divided into two main regions: the Pore Module (PM) and the Voltage-Sensing Module (VSM). The PM (helices S5 and S6 and intervening linker) is responsible for gate opening and ion selectivity; by contrast, the VSM, comprising the first four transmembrane helices (S1-S4), undergoes the first conformational changes in response to membrane voltage variations. In particular, the S4 segment of each domain, which contains several positively charged residues interspersed with hydrophobic amino acids, is located within the membrane electric field and plays an essential role in voltage sensing. In neurons, specific gating properties of each channel subtype underlie a variety of biological events, ranging from the generation and propagation of electrical impulses, to the secretion of neurotransmitters and to the regulation of gene expression. Given the important functional role played by the VSM in neuronal VGICs, it is not surprising that various VSM mutations affecting the gating process of these channels are responsible for human diseases, and that compounds acting on the VSM have emerged as important investigational tools with great therapeutic potential. In the present review we will briefly describe the most recent discoveries concerning how the VSM exerts its function, how genetically inherited diseases caused by mutations occurring in the VSM affects gating in VGICs, and how several classes of drugs and toxins

  8. Do TRPC channels support working memory? Comparing modulations of TRPC channels and working memory through G-protein coupled receptors and neuromodulators.

    Science.gov (United States)

    Reboreda, Antonio; Theissen, Frederik M; Valero-Aracama, Maria J; Arboit, Alberto; Corbu, Mihaela A; Yoshida, Motoharu

    2018-03-01

    Working memory is a crucial ability we use in daily life. However, the cellular mechanisms supporting working memory still remain largely unclear. A key component of working memory is persistent neural firing which is believed to serve short-term (hundreds of milliseconds up to tens of seconds) maintenance of necessary information. In this review, we will focus on the role of transient receptor potential canonical (TRPC) channels as a mechanism underlying persistent firing. Many years of in vitro work have been suggesting a crucial role of TRPC channels in working memory and temporal association tasks. If TRPC channels are indeed a central mechanism for working memory, manipulations which impair or facilitate working memory should have a similar effect on TRPC channel modulation. However, modulations of working memory and TRPC channels were never systematically compared, and it remains unanswered whether TRPC channels indeed contribute to working memory in vivo or not. In this article, we review the effects of G-protein coupled receptors (GPCR) and neuromodulators, including acetylcholine, noradrenalin, serotonin and dopamine, on working memory and TRPC channels. Based on comparisons, we argue that GPCR and downstream signaling pathways that activate TRPC, generally support working memory, while those that suppress TRPC channels impair it. However, depending on the channel types, areas, and systems tested, this is not the case in all studies. Further work to clarify involvement of specific TRPC channels in working memory tasks and how they are affected by neuromodulators is still necessary in the future. Copyright © 2018 Elsevier B.V. All rights reserved.

  9. The Sensorless Pore Module of Voltage-gated K+ Channel Family 7 Embodies the Target Site for the Anticonvulsant Retigabine.

    Science.gov (United States)

    Syeda, Ruhma; Santos, Jose S; Montal, Mauricio

    2016-02-05

    KCNQ (voltage-gated K(+) channel family 7 (Kv7)) channels control cellular excitability and underlie the K(+) current sensitive to muscarinic receptor signaling (the M current) in sympathetic neurons. Here we show that the novel anti-epileptic drug retigabine (RTG) modulates channel function of pore-only modules (PMs) of the human Kv7.2 and Kv7.3 homomeric channels and of Kv7.2/3 heteromeric channels by prolonging the residence time in the open state. In addition, the Kv7 channel PMs are shown to recapitulate the single-channel permeation and pharmacological specificity characteristics of the corresponding full-length proteins in their native cellular context. A mutation (W265L) in the reconstituted Kv7.3 PM renders the channel insensitive to RTG and favors the conductive conformation of the PM, in agreement to what is observed when the Kv7.3 mutant is heterologously expressed. On the basis of the new findings and homology models of the closed and open conformations of the Kv7.3 PM, we propose a structural mechanism for the gating of the Kv7.3 PM and for the site of action of RTG as a Kv7.2/Kv7.3 K(+) current activator. The results validate the modular design of human Kv channels and highlight the PM as a high-fidelity target for drug screening of Kv channels. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  10. Design, modeling and performance analysis of dual channel semitransparent photovoltaic thermal hybrid module in the cold environment

    International Nuclear Information System (INIS)

    Singh, Sonveer; Agrawal, Sanjay; Avasthi, D.V.

    2016-01-01

    Highlights: • Thermal modeling of novel dual channel semitransparent PVT hybrid module. • Exergy and carbon credit analysis has been performed. • Annual performance has been evaluated for Srinagar (India). • There are improvements in results for case-I as compared to case-II. - Abstract: In this work, thermal modeling and performance analysis of the dual channel semitransparent photovoltaic thermal (DCSPVT) module has been carried out. For extracting heat associated with the lower and upper surface of the solar cell, two channels have been proposed; (i) one is above the solar cell called upper channel and (ii) second is below the solar cell called lower channel. Firstly, thermal modeling of DCSPVT module has been developed. After that, performance analysis of the above system has been carried out for Srinagar, Indian climatic condition. Performance in terms of electrical gain (EG), thermal gain (TG), overall exergy gain (OEG), overall thermal gain (OTG), electrical efficiency (EE) and overall exergy efficiency (OEE) of the DCSPVT module (case-I) have been compared with single channel semitransparent photovoltaic thermal (SCSPVT) hybrid module (case-II). The average improvement in EG, TG, OEG, OTG of the case-I have been observed by 71.51%, 34.57%, 5.78% and 35.41% respectively as compared to case-II.

  11. PRRT2 controls neuronal excitability by negatively modulating Na+ channel 1.2/1.6 activity.

    Science.gov (United States)

    Fruscione, Floriana; Valente, Pierluigi; Sterlini, Bruno; Romei, Alessandra; Baldassari, Simona; Fadda, Manuela; Prestigio, Cosimo; Giansante, Giorgia; Sartorelli, Jacopo; Rossi, Pia; Rubio, Alicia; Gambardella, Antonio; Nieus, Thierry; Broccoli, Vania; Fassio, Anna; Baldelli, Pietro; Corradi, Anna; Zara, Federico; Benfenati, Fabio

    2018-04-01

    -dependent Na+ channels in homozygous PRRT2 knockout human and mouse neurons and that, in addition to the reported synaptic functions, PRRT2 is an important negative modulator of Nav1.2 and Nav1.6 channels. Given the predominant paroxysmal character of PRRT2-linked diseases, the disturbance in cellular excitability by lack of negative modulation of Na+ channels appears as the key pathogenetic mechanism.

  12. PRRT2 controls neuronal excitability by negatively modulating Na+ channel 1.2/1.6 activity

    Science.gov (United States)

    Fruscione, Floriana; Valente, Pierluigi; Sterlini, Bruno; Romei, Alessandra; Baldassari, Simona; Fadda, Manuela; Prestigio, Cosimo; Giansante, Giorgia; Sartorelli, Jacopo; Rossi, Pia; Rubio, Alicia; Gambardella, Antonio; Nieus, Thierry; Broccoli, Vania; Fassio, Anna; Baldelli, Pietro; Corradi, Anna; Zara, Federico

    2018-01-01

    voltage-dependent Na+ channels in homozygous PRRT2 knockout human and mouse neurons and that, in addition to the reported synaptic functions, PRRT2 is an important negative modulator of Nav1.2 and Nav1.6 channels. Given the predominant paroxysmal character of PRRT2-linked diseases, the disturbance in cellular excitability by lack of negative modulation of Na+ channels appears as the key pathogenetic mechanism. PMID:29554219

  13. Calcium channels in the brain as targets for the calcium-channel modulators used in the treatment of neurological disorders

    NARCIS (Netherlands)

    Peters, Thies; WILFFERT, B; VANHOUTTE, PM; VANZWIETEN, PA

    1991-01-01

    Recent investigations of calcium channels in brain cells by voltage-clamp techniques have revealed that, in spite of electrophysiological similarities, the pharmacological properties of these channels differ considerably from channels in peripheral tissues, e.g., heart and smooth muscle. Therefore,

  14. Cholesterol modulates the cellular localization of Orai1 channels and its disposition among membrane domains.

    Science.gov (United States)

    Bohórquez-Hernández, A; Gratton, Enrico; Pacheco, Jonathan; Asanov, Alexander; Vaca, Luis

    2017-12-01

    Store Operated Calcium Entry (SOCE) is one of the most important mechanisms for calcium mobilization in to the cell. Two main proteins sustain SOCE: STIM1 that acts as the calcium sensor in the endoplasmic reticulum (ER) and Orai1 responsible for calcium influx upon depletion of ER. There are many studies indicating that SOCE is modulated by the cholesterol content of the plasma membrane (PM). However, a myriad of questions remain unanswered concerning the precise molecular mechanism by which cholesterol modulates SOCE. In the present study we found that reducing PM cholesterol results in the internalization of Orai1 channels, which can be prevented by overexpressing caveolin 1 (Cav1). Furthermore, Cav1 and Orai1 associate upon SOCE activation as revealed by FRET and coimmunoprecipitation assays. The effects of reducing cholesterol were not limited to an increased rate of Orai1 internalization, but also, affects the lateral movement of Orai1, inducing movement in a linear pattern (unobstructed diffusion) opposite to basal cholesterol conditions were most of Orai1 channels moves in a confined space, as assessed by Fluorescence Correlation Spectroscopy, Cav1 overexpression inhibited these alterations maintaining Orai1 into a confined and partially confined movement. These results not only highlight the complex effect of cholesterol regulation on SOCE, but also indicate a direct regulatory effect on Orai1 localization and compartmentalization by this lipid. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Galvanically Decoupled Current Source Modules for Multi-Channel Bioimpedance Measurement Systems

    Directory of Open Access Journals (Sweden)

    Roman Kusche

    2017-10-01

    Full Text Available Bioimpedance measurements have become a useful technique in the past several years in biomedical engineering. Especially, multi-channel measurements facilitate new imaging and patient monitoring techniques. While most instrumentation research has focused on signal acquisition and signal processing, this work proposes the design of an excitation current source module that can be easily implemented in existing or upcoming bioimpedance measurement systems. It is galvanically isolated to enable simultaneous multi-channel bioimpedance measurements with a very low channel-coupling. The system is based on a microcontroller in combination with a voltage-controlled current source circuit. It generates selectable sinusoidal excitation signals between 0.12 and 1.5 mA in a frequency range from 12 to 250 kHz, whereas the voltage compliance range is ±3.2 V. The coupling factor between two current sources, experimentally galvanically connected with each other, is measured to be less than −48 dB over the entire intended frequency range. Finally, suggestions for developments in the future are made.

  16. 12-lipoxygenase regulates hippocampal long-term potentiation by modulating L-type Ca2+ channels

    Science.gov (United States)

    DeCostanzo, Anthony J.; Voloshyna, Iryna; Rosen, Zev B.; Feinmark, Steven J.; Siegelbaum, Steven A.

    2010-01-01

    Although long-term potentiation (LTP) has been intensely studied, there is disagreement as to which molecules mediate and modulate LTP. This is partly due to the presence of mechanistically distinct forms of LTP that are induced by different patterns of stimulation and that depend on distinct Ca2+ sources. Here we report a novel role for the arachidonic acid-metabolizing enzyme 12-lipoxygenase (12-LO) in LTP at CA3-CA1 hippocampal synapses that is dependent on the pattern of tetanic stimulation. We find that 12-LO activity is required for the induction of LTP in response to a theta-burst stimulation (TBS) protocol, which depends on Ca2+ influx through both NMDA receptors and L-type voltage-gated Ca2+ channels. In contrast, LTP induced by 100 Hz tetanic stimulation, which requires Ca2+ influx through NMDA receptors but not L-type channels, does not require 12-LO. We find that 12-LO regulates LTP by enhancing postsynaptic somatodendritic Ca2+ influx through L-type channels during theta burst stimulation, an action exerted via 12(S)-HPETE, a downstream metabolite of 12-LO. These results help define the role of a long-disputed signaling enzyme in LTP. PMID:20130191

  17. Efficiency maximization and performance evaluation of hybrid dual channel semitransparent photovoltaic thermal module using fuzzyfied genetic algorithm

    International Nuclear Information System (INIS)

    Singh, Sonveer; Agrawal, Sanjay

    2016-01-01

    Highlights: • Thermal modeling of novel dual channel semitransparent photovoltaic thermal hybrid module. • Efficiency maximization and performance evaluation of dual channel photovoltaic thermal module. • Annual performance has been evaluated for Srinagar, Jodhpur, Bangalore and New Delhi (India). • There are improvements in results for optimized system as compared to un-optimized system. - Abstract: The work has been carried out in two steps; firstly the parameters of hybrid dual channel semitransparent photovoltaic thermal module has been optimized using a fuzzyfied genetic algorithm. During the course of optimization, overall exergy efficiency is considered as an objective function and different design parameters of the proposed module have been optimized. Fuzzy controller is used to improve the performance of genetic algorithms and the approach is called as a fuzzyfied genetic algorithm. In the second step, the performance of the module has been analyzed for four cities of India such as Srinagar, Bangalore, Jodhpur and New Delhi. The performance of the module has been evaluated for daytime 08:00 AM to 05:00 PM and annually from January to December. It is to be noted that, an average improvement occurs in electrical efficiency of the optimized module, simultaneously there is also a reduction in solar cell temperature as compared to un-optimized module.

  18. A TRPV channel modulates C. elegans neurosecretion, larval starvation survival, and adult lifespan.

    Directory of Open Access Journals (Sweden)

    Brian H Lee

    2008-10-01

    Full Text Available For most organisms, food is only intermittently available; therefore, molecular mechanisms that couple sensation of nutrient availability to growth and development are critical for survival. These mechanisms, however, remain poorly defined. In the absence of nutrients, newly hatched first larval (L1 stage Caenorhabditis elegans halt development and survive in this state for several weeks. We isolated mutations in unc-31, encoding a calcium-activated regulator of neural dense-core vesicle release, which conferred enhanced starvation survival. This extended survival was reminiscent of that seen in daf-2 insulin-signaling deficient mutants and was ultimately dependent on daf-16, which encodes a FOXO transcription factor whose activity is inhibited by insulin signaling. While insulin signaling modulates metabolism, adult lifespan, and dauer formation, insulin-independent mechanisms that also regulate these processes did not promote starvation survival, indicating that regulation of starvation survival is a distinct program. Cell-specific rescue experiments identified a small subset of primary sensory neurons where unc-31 reconstitution modulated starvation survival, suggesting that these neurons mediate perception of food availability. We found that OCR-2, a transient receptor potential vanilloid (TRPV channel that localizes to the cilia of this subset of neurons, regulates peptide-hormone secretion and L1 starvation survival. Moreover, inactivation of ocr-2 caused a significant extension in adult lifespan. These findings indicate that TRPV channels, which mediate sensation of diverse noxious, thermal, osmotic, and mechanical stimuli, couple nutrient availability to larval starvation survival and adult lifespan through modulation of neural dense-core vesicle secretion.

  19. Hydrogen sulfide: role in ion channel and transporter modulation in the eye

    Directory of Open Access Journals (Sweden)

    Ya Fatou eNjie-Mbye

    2012-07-01

    Full Text Available Hydrogen sulfide (H2S, a colorless gas with a characteristic smell of rotten eggs, has been portrayed for decades as a toxic environmental pollutant. Since evidence of its basal production in mammalian tissues a decade ago, H2S has attracted substantial interest as a potential inorganic gaseous mediator with biological importance in cellular functions. Current research suggests that, next to its counterparts nitric oxide and carbon monoxide, H2S is an important multifunctional signaling molecule with pivotal regulatory roles in various physiological and pathophysiological processes as diverse as learning and memory, modulation of synaptic activities, cell survival, inflammation and maintenance of vascular tone in the central nervous and cardiovascular systems. In contrast, there are few reports of a regulatory role of H2S in the eye. Accumulating reports on the pharmacological role of H2S in ocular tissues indicate the existence of a functional trans-sulfuration pathway and a potential physiological role for H2S as a gaseous neuromodulator in the eye. Thus, understanding the role of H2S in vision-related processes is imperative to our expanding knowledge of this molecule as a gaseous mediator in ocular tissues. This review aims to provide a comprehensive and current understanding of the potential role of H2S as a signaling molecule in the eye. This objective is achieved by discussing the involvement of H2S in the regulation of (1 ion channels such as calcium (L-type, T-type and intracellular stores, potassium (KATP and small conductance channels and chloride channels, (2 glutamate transporters such as EAAT1/GLAST and the L-cystine/glutamate antiporter. The role of H2S as an important mediator in cellular functions and physiological processes that are triggered by its interaction with ion channels/transporters in the eye will also be discussed.

  20. Modulation of voltage-gated channel currents by harmaline and harmane.

    Science.gov (United States)

    Splettstoesser, Frank; Bonnet, Udo; Wiemann, Martin; Bingmann, Dieter; Büsselberg, Dietrich

    2005-01-01

    Harmala alkaloids are endogenous substances, which are involved in neurodegenerative disorders such as M. Parkinson, but some of them also have neuroprotective effects in the nervous system. While several sites of action at the cellular level (e.g. benzodiazepine receptors, 5-HT and GABA(A) receptors) have been identified, there is no report on how harmala alkaloids interact with voltage-gated membrane channels. The aim of this study was to investigate the effects of harmaline and harmane on voltage-activated calcium- (I(Ca(V))), sodium- (I(Na(V))) and potassium (I(K(V)))-channel currents, using the whole-cell patch-clamp method with cultured dorsal root ganglion neurones of 3-week-old rats. Currents were elicited by voltage steps from the holding potential to different command potentials. Harmaline and harmane reduced I(Ca(V)), I(Na(V)) and I(K(V)) concentration-dependent (10-500 microM) over the voltage range tested. I(Ca(V)) was reduced with an IC(50) of 100.6 microM for harmaline and by a significantly lower concentration of 75.8 microM (P<0.001, t-test) for harmane. The Hill coefficient was close to 1. Threshold concentration was around 10 microM for both substances. The steady state of inhibition of I(Ca(V)) by harmaline or harmane was reached within several minutes. The action was not use-dependent and at least partly reversible. It was mainly due to a reduction in the sustained calcium channel current (I(Ca(L+N))), while the transient voltage-gated calcium channel current (I(Ca(T))) was only partially affected. We conclude that harmaline and harmane are modulators of I(Ca(V)) in vitro. This might be related to their neuroprotective effects.

  1. An application of the MEMbrain training module: Pre-hospital rescue operation

    DEFF Research Database (Denmark)

    Andersen, V.

    1998-01-01

    A system for training in pre-hospital emergency management is being developed and the first version of a prototype has been completed. The training system fulfils the demands from the domain of hospital emergency planning centres and medical attendants concerning increased efficiency of rescue...... efforts. This includes enhanced first aid on site and improved overall co-ordination amongst the organisations involved in coping with emergency situations. The training system is based on the Multi-User System for Training Emergency Response (MUSTER) concept which is used for the training module...

  2. Progress on the RF Coupling Coil Module Design for the MICE Channel

    International Nuclear Information System (INIS)

    Li, D.; Green, M.A.; Virostek, S.P.; Zisman, M.S.; Lau, W.; White, A.E.; Yang, S.Q.

    2005-01-01

    We describe the progress on the design of the RF coupling coil (RFCC) module for the international Muon Ionization Cooling Experiment (MICE) at Rutherford Appleton Laboratory (RAL) in the UK. The MICE cooling channel design consists of one SFOFO cell that is similar to that of the US Study-II of a neutrino factory. The MICE RFCC module comprises a superconducting solenoid, mounted around four normal conducting 201.25-MHz RF cavities. Each cavity has a pair of thin curved beryllium windows to close the conventional open beam irises, which allows for independent control of the phase in each cavity and for the RF power to be fed separately. The coil package that surrounds the RF cavities is mounted on a vacuum vessel. The RF vacuum is shared between the cavities and the vacuum vessel around the cavities such that there is no differential pressure on the thin beryllium windows. This paper discusses the design progress of the RFCC module and the fabrication progress of a prototype 201.25-MHz cavity

  3. A 201 MHz RF cavity design with non-stressed pre-curved Be windows for muon cooling channels

    International Nuclear Information System (INIS)

    Li, Derun; Ladran, A.; Staples, J.; Virostek, S.; Zisman, M.; Lau, W.; Yang, S.; Rimmer, R.A.

    2003-01-01

    We present a 201-MHz RF cavity design for muon cooling channels with non-stressed and pre-curved Be foils to terminate the beam apertures. The Be foils are necessary to improve the cavity shunt impedance with large beam apertures needed for accommodating large transverse size muon beams. Be is a low-Z material with good electrical and thermal properties. It presents an almost transparent window to muon beams, but terminates the RF cavity electro-magnetically. Previous designs use pre-stressed flat Be foils in order to keep cavity from detuning resulted from RF heating on the window surface. Be foils are expensive, and it is difficult to make them under desired tension. An alternative design is to use pre-curved and non-stressed Be foils where the buckling direction is known, and frequency shifts can be properly predicted. We will present mechanical simulations on the Be foils in this paper

  4. Nano hydroxyapatite-blasted titanium surface affects pre-osteoblast morphology by modulating critical intracellular pathways.

    Science.gov (United States)

    Bezerra, Fábio; Ferreira, Marcel R; Fontes, Giselle N; da Costa Fernandes, Célio Jr; Andia, Denise C; Cruz, Nilson C; da Silva, Rodrigo A; Zambuzzi, Willian F

    2017-08-01

    Although, intracellular signaling pathways are proposed to predict the quality of cell-surface relationship, this study addressed pre-osteoblast behavior in response to nano hydroxyapatite (HA)-blasted titanium (Ti) surface by exploring critical intracellular pathways and pre-osteoblast morphological change. Physicochemical properties were evaluated by atomic force microscopy (AFM) and wettability considering water contact angle of three differently texturized Ti surfaces: Machined (Mac), Dual acid-etching (DAE), and nano hydroxyapatite-blasted (nHA). The results revealed critical differences in surface topography, impacting the water contact angle and later the osteoblast performance. In order to evaluate the effect of those topographical characteristics on biological responses, we have seeded pre-osteoblast cells on the Ti discs for up to 4 h and subjected the cultures to biological analysis. First, we have observed pre-osteoblasts morphological changes resulting from the interaction with the Ti texturized surfaces whereas the cells cultured on nHA presented a more advanced spreading process when compared with the cells cultured on the other surfaces. These results argued us for analyzing the molecular machinery and thus, we have shown that nHA promoted a lower Bax/Bcl2 ratio, suggesting an interesting anti-apoptotic effect, maybe explained by the fact that HA is a natural element present in bone composition. Thereafter, we investigated the potential effect of those surfaces on promoting pre-osteoblast adhesion and survival signaling by performing crystal violet and immunoblotting approaches, respectively. Our results showed that nHA promoted a higher pre-osteoblast adhesion supported by up-modulating FAK and Src activations, both signaling transducers involved during eukaryotic cell adhesion. Also, we have shown Ras-Erk stimulation by the all evaluated surfaces. Finally, we showed that all Ti-texturing surfaces were able to promote osteoblast differentiation

  5. Development of a multi-channel front-end electronics module based on ASIC for silicon strip array detectors

    International Nuclear Information System (INIS)

    Zhao Xingwen; Yan Duo; Su Hong; Qian Yi; Kong Jie; Zhang Xueheng; Li Zhankui; Li Haixia

    2014-01-01

    The silicon strip array detector is one of external target facility subsystems in the Cooling Storage Ring on the Heavy Ion Research Facility at Lanzhou (HIRFL-CSR). Using the ASICs, the front-end electronics module has been developed for the silicon strip array detectors and can implement measurement of energy of 96 channels. The performance of the front-end electronics module has been tested. The energy linearity of the front-end electronics module is better than 0.3% for the dynamic range of 0.1∼0.7 V. The energy resolution is better than 0.45%. The maximum channel crosstalk is better than 10%. The channel consistency is better than 1.3%. After continuously working for 24 h at room temperature, the maximum drift of the zero-peak is 1.48 mV. (authors)

  6. Seeking Structural Specificity: Direct Modulation of Pentameric Ligand-Gated Ion Channels by Alcohols and General Anesthetics

    Science.gov (United States)

    Trudell, James R.; Harris, R. Adron

    2014-01-01

    Alcohols and other anesthetic agents dramatically alter neurologic function in a wide range of organisms, yet their molecular sites of action remain poorly characterized. Pentameric ligand-gated ion channels, long implicated in important direct effects of alcohol and anesthetic binding, have recently been illuminated in renewed detail thanks to the determination of atomic-resolution structures of several family members from lower organisms. These structures provide valuable models for understanding and developing anesthetic agents and for allosteric modulation in general. This review surveys progress in this field from function to structure and back again, outlining early evidence for relevant modulation of pentameric ligand-gated ion channels and the development of early structural models for ion channel function and modulation. We highlight insights and challenges provided by recent crystal structures and resulting simulations, as well as opportunities for translation of these newly detailed models back to behavior and therapy. PMID:24515646

  7. Negative modulation of NMDA receptor channel function by DREAM/calsenilin/KChIP3 provides neuroprotection?

    Science.gov (United States)

    Wang, KeWei; Wang, Yun

    2012-01-01

    N-methyl-D-aspartate receptors (NMDARs) are glutamate-gated ion channels highly permeable to calcium and essential to excitatory neurotransmission. The NMDARs have attracted much attention because of their role in synaptic plasticity and excitotoxicity. Evidence has recently accumulated that NMDARs are negatively regulated by intracellular calcium binding proteins. The calcium-dependent suppression of NMDAR function serves as a feedback mechanism capable of regulating subsequent Ca2+ entry into the postsynaptic cell, and may offer an alternative approach to treating NMDAR-mediated excitotoxic injury. This short review summarizes the recent progress made in understanding the negative modulation of NMDAR function by DREAM/calsenilin/KChIP3, a neuronal calcium sensor (NCS) protein. PMID:22518099

  8. H.264 Layered Coded Video over Wireless Networks: Channel Coding and Modulation Constraints

    Directory of Open Access Journals (Sweden)

    Ghandi MM

    2006-01-01

    Full Text Available This paper considers the prioritised transmission of H.264 layered coded video over wireless channels. For appropriate protection of video data, methods such as prioritised forward error correction coding (FEC or hierarchical quadrature amplitude modulation (HQAM can be employed, but each imposes system constraints. FEC provides good protection but at the price of a high overhead and complexity. HQAM is less complex and does not introduce any overhead, but permits only fixed data ratios between the priority layers. Such constraints are analysed and practical solutions are proposed for layered transmission of data-partitioned and SNR-scalable coded video where combinations of HQAM and FEC are used to exploit the advantages of both coding methods. Simulation results show that the flexibility of SNR scalability and absence of picture drift imply that SNR scalability as modelled is superior to data partitioning in such applications.

  9. Molecular pharmacology of cell receptors for cardiac glycosides, opiates, ACTH and ion channel modulators

    Energy Technology Data Exchange (ETDEWEB)

    Hnatowich, M R

    1986-01-01

    The influence of light and oxygen on molecular interactions between the artificial food dye, erythrosine (ERY), and (/sup 3/H)ouabain ((/sup 3/H)OUA) binding sites on (Na/sup +/ + K/sup +/)-ATPase in rat brain and guinea pig heart was investigated. Putative endogenous digitalis-like factors (DLF's) were studied in four in vitro assays for cardiac glycosides. (/sup 3/H)Etorphine binding was characterized in rat brain homogenates, depleted of opioids, from animals acutely and chronically treated with morphine and naloxone, and either unstressed or cold-restraint-stressed. Binding sites for the ion channel modulators (/sup 3/H)verapamil ((/sup 3/H)VER) and (/sup 3/H) phencyclidine ((/sup 3/H)PCP) were characterized in rat brain.

  10. On the possibility of a quantum bremsstrahlung induced self-modulation of a relativistic beam channeling in crystals

    International Nuclear Information System (INIS)

    Vysotskij, V.I.; Vorontsov, V.I.; Kuz'min, R.N.

    1987-01-01

    Physical predictions and quantitative estimations of a new physical effect - the phenomenon of quantum bremsstrahlung induced selfmodulation of a fast beam channeling in the crystals are considered and carried out. The occurrence of induced self-modulation results from nonstationary interference of proper waves of a channeled particle in the range of mutual coherence and with account of difference of selective bremsstrahlung losses of these waves. The modulation frequency for superrelativistic particles is shown to lie within the range from soft X-ray to hard gamma range. It proceeds from the estimations that modulation at these frequencies is preserved within the limits of macroscopically large ranges after the crystal attaining several meters. The maximum frequency of modulation for nonrelativistic heavy particles (protons) corresponds to the optical range

  11. Modulation of thalamocortical oscillations by TRIP8b, an auxiliary subunit for HCN channels.

    Science.gov (United States)

    Zobeiri, Mehrnoush; Chaudhary, Rahul; Datunashvili, Maia; Heuermann, Robert J; Lüttjohann, Annika; Narayanan, Venu; Balfanz, Sabine; Meuth, Patrick; Chetkovich, Dane M; Pape, Hans-Christian; Baumann, Arnd; van Luijtelaar, Gilles; Budde, Thomas

    2018-04-01

    Hyperpolarization-activated cyclic nucleotide-gated cation (HCN) channels have important functions in controlling neuronal excitability and generating rhythmic oscillatory activity. The role of tetratricopeptide repeat-containing Rab8b-interacting protein (TRIP8b) in regulation of hyperpolarization-activated inward current, I h , in the thalamocortical system and its functional relevance for the physiological thalamocortical oscillations were investigated. A significant decrease in I h current density, in both thalamocortical relay (TC) and cortical pyramidal neurons was found in TRIP8b-deficient mice (TRIP8b -/- ). In addition basal cAMP levels in the brain were found to be decreased while the availability of the fast transient A-type K + current, I A , in TC neurons was increased. These changes were associated with alterations in intrinsic properties and firing patterns of TC neurons, as well as intrathalamic and thalamocortical network oscillations, revealing a significant increase in slow oscillations in the delta frequency range (0.5-4 Hz) during episodes of active-wakefulness. In addition, absence of TRIP8b suppresses the normal desynchronization response of the EEG during the switch from slow-wave sleep to wakefulness. It is concluded that TRIP8b is necessary for the modulation of physiological thalamocortical oscillations due to its direct effect on HCN channel expression in thalamus and cortex and that mechanisms related to reduced cAMP signaling may contribute to the present findings.

  12. PRE-ACTIVITY MODULATION OF LOWER EXTREMITY MUSCLES WITHIN DIFFERENT TYPES AND HEIGHTS OF DEEP JUMP

    Directory of Open Access Journals (Sweden)

    Vladimir Mrdakovic

    2008-06-01

    Full Text Available The purpose of this study was to determine modulation of pre- activity related to different types and heights of deep jump. Sixteen male soccer players without experience in deep jumps training (the national competition; 15.0 ± 0.5yrs; weight 61.9 ± 6.1kg; height 1.77 ± 0.07m, who participated in the study, performed three types of deep jump (bounce landing, counter landing, and bounce drop jump from three different heights (40cm, 60cm, and 80cm. Surface EMG device (1000Hz was used to estimate muscle activity (maximal amplitude of EMG - AmaxEMG; integral EMG signal - iEMG of five muscles (mm.gastrocnemii, m.soleus, m.tibialis anterior, m.vastus lateralis within 150ms before touchdown. All the muscles, except m. gastrocnemius medialis, showed systematic increase in pre-activity when platform height was raised. For most of the lower extremity muscles, the most significant differences were between values of pre-activity obtained for 40 cm and 80 cm platforms. While the amount of muscle pre-activity in deep jumps from the heights above and beneath the optimal one did not differ significantly from that generated in deep jumps from the optimal drop height of 60 cm, the patterns of muscle pre-activity obtained for the heights above the optimal one did differ from those obtained for the optimal drop height. That suggests that deep jumps from the heights above the optimal one do not seem to be an adequate exercise for adjusting muscle activity for the impact. Muscle pre-activity in bounce drop jumps differed significantly from that in counter landing and bounce landing respectively, which should indicate that a higher amount of pre-activity generated during bounce drop jumps was used for performing take-offs. As this study included the subjects who were not familiar with deep jumps training, the prospective studies should reveal the results of athletes with previous experience

  13. Modulation of ASIC channels in rat cerebellar purkinje neurons by ischaemia-related signals

    Science.gov (United States)

    Allen, Nicola J; Attwell, David

    2002-01-01

    Acid-sensing ion channels (ASICs), activated by a decrease of extracellular pH, are found in neurons throughout the nervous system. They have an amino acid sequence similar to that of ion channels activated by membrane stretch, and have been implicated in touch sensation. Here we characterize the pH-dependent activation of ASICs in cerebellar Purkinje cells and investigate how they are modulated by factors released in ischaemia. Lowering the external pH from 7.4 activated an inward current at −66 mV, carried largely by Na+ ions, which was half-maximal for a step to pH 6.4 and was blocked by amiloride and gadolinium. The H+-gated current desensitized within a few seconds, but approximately 30% of cells showed a sustained inward current (11% of the peak current) in response to the maintained presence of pH 6 solution. The peak H+-evoked current was potentiated by membrane stretch (which occurs in ischaemia when [K+]o rises) and by arachidonic acid (which is released when [Ca2+]i rises in ischaemia). Arachidonic acid increased to 77% the fraction of cells showing a sustained current evoked by acid pH. The ASIC currents were also potentiated by lactate (which is released when metabolism becomes anaerobic in ischaemia) and by FMRFamide (which may mimic the action of related mammalian RFamide transmitters). These data reinforce suggestions of a mechanosensory aspect to ASIC channel function, and show that the activation of ASICs reflects the integration of multiple signals which are present during ischaemia. PMID:12205186

  14. Pre-attentive modulation of brain responses to tones in coloured-hearing synesthetes

    Directory of Open Access Journals (Sweden)

    Jäncke Lutz

    2012-12-01

    Full Text Available Abstract Background Coloured-hearing (CH synesthesia is a perceptual phenomenon in which an acoustic stimulus (the inducer initiates a concurrent colour perception (the concurrent. Individuals with CH synesthesia "see" colours when hearing tones, words, or music; this specific phenomenon suggesting a close relationship between auditory and visual representations. To date, it is still unknown whether the perception of colours is associated with a modulation of brain functions in the inducing brain area, namely in the auditory-related cortex and associated brain areas. In addition, there is an on-going debate as to whether attention to the inducer is necessarily required for eliciting a visual concurrent, or whether the latter can emerge in a pre-attentive fashion. Results By using the EEG technique in the context of a pre-attentive mismatch negativity (MMN paradigm, we show that the binding of tones and colours in CH synesthetes is associated with increased MMN amplitudes in response to deviant tones supposed to induce novel concurrent colour perceptions. Most notably, the increased MMN amplitudes we revealed in the CH synesthetes were associated with stronger intracerebral current densities originating from the auditory cortex, parietal cortex, and ventral visual areas. Conclusions The automatic binding of tones and colours in CH synesthetes is accompanied by an early pre-attentive process recruiting the auditory cortex, inferior and superior parietal lobules, as well as ventral occipital areas.

  15. LDPC-coded MIMO optical communication over the atmospheric turbulence channel using Q-ary pulse-position modulation.

    Science.gov (United States)

    Djordjevic, Ivan B

    2007-08-06

    We describe a coded power-efficient transmission scheme based on repetition MIMO principle suitable for communication over the atmospheric turbulence channel, and determine its channel capacity. The proposed scheme employs the Q-ary pulse-position modulation. We further study how to approach the channel capacity limits using low-density parity-check (LDPC) codes. Component LDPC codes are designed using the concept of pairwise-balanced designs. Contrary to the several recent publications, bit-error rates and channel capacities are reported assuming non-ideal photodetection. The atmospheric turbulence channel is modeled using the Gamma-Gamma distribution function due to Al-Habash et al. Excellent bit-error rate performance improvement, over uncoded case, is found.

  16. Oxygen-Sensitive K+ Channels Modulate Human Chorionic Gonadotropin Secretion from Human Placental Trophoblast

    Science.gov (United States)

    Díaz, Paula; Sibley, Colin P.; Greenwood, Susan L.

    2016-01-01

    Human chorionic gonadotropin (hCG) is a key autocrine/paracrine regulator of placental syncytiotrophoblast, the transport epithelium of the human placenta. Syncytiotrophoblast hCG secretion is modulated by the partial pressure of oxygen (pO2), reactive oxygen species (ROS) and potassium (K+) channels. Here we test the hypothesis that K+ channels mediate the effects of pO2 and ROS on hCG secretion. Placental villous explants from normal term pregnancies were cultured for 6 days at 6% (normoxia), 21% (hyperoxia) or 1% (hypoxia) pO2. On days 3–5, explants were treated with 5mM 4-aminopyridine (4-AP) or tetraethylammonium (TEA), blockers of pO2-sensitive voltage-gated K+ (KV) channels, or ROS (10–1000μM H2O2). hCG secretion and lactate dehydrogenase (LDH) release, a marker of necrosis, were determined daily. At day 6, hCG and LDH were measured in tissue lysate and 86Rb (K+) efflux assessed to estimate syncytiotrophoblast K+ permeability. hCG secretion and 86Rb efflux were significantly greater in explants maintained in 21% pO2 than normoxia. 4-AP/TEA inhibited hCG secretion to a greater extent at 21% than 6% and 1% pO2, and reduced 86Rb efflux at 21% but not 6% pO2. LDH release and tissue LDH/hCG were similar in 6%, 21% and 1% pO2 and unaffected by 4-AP/TEA. H2O2 stimulated 86Rb efflux and hCG secretion at normoxia but decreased 86Rb efflux, without affecting hCG secretion, at 21% pO2. 4-AP/TEA-sensitive K+ channels participate in pO2-sensitive hCG secretion from syncytiotrophoblast. ROS effects on both hCG secretion and 86Rb efflux are pO2-dependent but causal links between the two remain to be established. PMID:26863525

  17. Optical modulation of neurotransmission using calcium photocurrents through the ion channel LiGluR

    Directory of Open Access Journals (Sweden)

    Mercè eIzquierdo-Serra

    2013-03-01

    Full Text Available A wide range of light-activated molecules (photoswitches and phototriggers have been used to the study of computational properties of an isolated neuron by acting pre and postsynaptically. However, new tools are being pursued to elicit a presynaptic calcium influx that triggers the release of neurotransmitters, most of them based in calcium-permeable Channelrhodopsin-2 mutants. Here we describe a method to control exocytosis of synaptic vesicles through the use of a light-gated glutamate receptor (LiGluR, which has recently been demonstrated that supports secretion by means of calcium influx in chromaffin cells. Expression of LiGluR in hippocampal neurons enables reversible control of neurotransmission with light, and allows modulating the firing rate of the postsynaptic neuron with the wavelength of illumination. This method may be useful for the determination of the complex transfer function of individual synapses.

  18. Effects of Carrier Frequency Offset, Timing Offset, and Channel Spread Factor on the Performance of Hexagonal Multicarrier Modulation Systems

    Directory of Open Access Journals (Sweden)

    Kui Xu

    2009-01-01

    Full Text Available Hexagonal multicarrier modulation (HMM system is the technique of choice to overcome the impact of time-frequency dispersive transmission channel. This paper examines the effects of insufficient synchronization (carrier frequency offset, timing offset on the amplitude and phase of the demodulated symbol by using a projection receiver in hexagonal multicarrier modulation systems. Furthermore, effects of CFO, TO, and channel spread factor on the performance of signal-to-interference-plus-noise ratio (SINR in hexagonal multicarrier modulation systems are further discussed. The exact SINR expression versus insufficient synchronization and channel spread factor is derived. Theoretical analysis shows that similar degradation on symbol amplitude and phase caused by insufficient synchronization is incurred as in traditional cyclic prefix orthogonal frequency-division multiplexing (CP-OFDM transmission. Our theoretical analysis is confirmed by numerical simulations in a doubly dispersive (DD channel with exponential delay power profile and U-shape Doppler power spectrum, showing that HMM systems outperform traditional CP-OFDM systems with respect to SINR against ISI/ICI caused by insufficient synchronization and doubly dispersive channel.

  19. Analysis of thermal issues associated with the pre-amplifier modules in the National Ignition Facility

    International Nuclear Information System (INIS)

    Lam, K.L.

    1998-01-01

    The design of the National Ignition Facility (NIF) calls for a desired temperature field of 20.00 ± 0.28 C throughout the facility. This design requirement is needed to prevent degradation of the operating performance and net yield of the NIF by heat loads generated within the facility. In particular, the potential interference of waste heat from the lighting fixtures and equipment such as the electronics racks, and pre-amplifier modules (PAMs), and its impact on the operational performance of the laser beam transport tubes and optical alignment components must be evaluated. This report describes the thermal analyses associated with the PAMs. Evaluation of thermal issues for the other equipment is discussed elsewhere

  20. Modulation of respiratory frequency by peptidergic input to rhythmogenic neurons in the preBötzinger complex

    DEFF Research Database (Denmark)

    Gray, P A; Rekling, J C; Bocchiaro, C M

    1999-01-01

    Neurokinin-1 receptor (NK1R) and mu-opioid receptor (muOR) agonists affected respiratory rhythm when injected directly into the preBötzinger Complex (preBötC), the hypothesized site for respiratory rhythmogenesis in mammals. These effects were mediated by actions on preBötC rhythmogenic neurons....... The distribution of NK1R+ neurons anatomically defined the preBötC. Type 1 neurons in the preBötC, which have rhythmogenic properties, expressed both NK1Rs and muORs, whereas type 2 neurons expressed only NK1Rs. These findings suggest that the preBötC is a definable anatomic structure with unique physiological...... function and that a subpopulation of neurons expressing both NK1Rs and muORs generate respiratory rhythm and modulate respiratory frequency....

  1. Social Pre-treatment Modulates Attention Allocation to Transient and Stable Object Properties

    Directory of Open Access Journals (Sweden)

    Katalin Oláh

    2016-10-01

    Full Text Available Increasing evidence suggests that ostensive-communicative signals in social learning situations enable observers to focus their attention on the intrinsic features of an object (e.g. color at the expense of ignoring transient object properties (e.g. location. Here we investigated whether off-line social cues, presented as social primes, have the same power to modulate attention allocation to stable and transient object properties as on-line ostensive-communicative cues. The first part of the experiment consisted of a pre-treatment phase, where adult male participants either received intensive social stimulation or were asked to perform non-social actions. Then, they participated in a change detection test, where they watched pairs of pictures depicting an array of five objects. On the second picture, a change occurred compared to the first picture. One object changed either its location (moving forward or backward or was replaced by another object, and participants were required to indicate where the change had happened. We found that participants detected the change more successfully if it had happened in the location of the object; however, this difference was reduced following a socially intense pre-treatment phase. The results are discussed in relation to the claims of the natural pedagogy theory.

  2. Excitatory Modulation of the preBötzinger Complex Inspiratory Rhythm Generating Network by Endogenous Hydrogen Sulfide

    Directory of Open Access Journals (Sweden)

    Glauber S. F. da Silva

    2017-06-01

    Full Text Available Hydrogen Sulfide (H2S is one of three gasotransmitters that modulate excitability in the CNS. Global application of H2S donors or inhibitors of H2S synthesis to the respiratory network has suggested that inspiratory rhythm is modulated by exogenous and endogenous H2S. However, effects have been variable, which may reflect that the RTN/pFRG (retrotrapezoid nucleus, parafacial respiratory group and the preBötzinger Complex (preBötC, critical for inspiratory rhythm generation are differentially modulated by exogenous H2S. Importantly, site-specific modulation of respiratory nuclei by H2S means that targeted, rather than global, manipulation of respiratory nuclei is required to understand the role of H2S signaling in respiratory control. Thus, our aim was to test whether endogenous H2S, which is produced by cystathionine-β-synthase (CBS in the CNS, acts specifically within the preBötC to modulate inspiratory activity under basal (in vitro/in vivo and hypoxic conditions (in vivo. Inhibition of endogenous H2S production by bath application of the CBS inhibitor, aminooxyacetic acid (AOAA, 0.1–1.0 mM to rhythmic brainstem spinal cord (BSSC and medullary slice preparations from newborn rats, or local application of AOAA into the preBötC (slices only caused a dose-dependent decrease in burst frequency. Unilateral injection of AOAA into the preBötC of anesthetized, paralyzed adult rats decreased basal inspiratory burst frequency, amplitude and ventilatory output. AOAA in vivo did not affect the initial hypoxia-induced (10% O2, 5 min increase in ventilatory output, but enhanced the secondary hypoxic respiratory depression. These data suggest that the preBötC inspiratory network receives tonic excitatory modulation from the CBS-H2S system, and that endogenous H2S attenuates the secondary hypoxic respiratory depression.

  3. Sensitivity Analysis of Multicarrier Digital Pre-distortion/ Equalization Techniques for Non-linear Satellite Channels

    OpenAIRE

    Piazza, Roberto; Shankar, Bhavani; Zenteno, Efrain; Ronnow, Daniel; Liolis, Kostantinos; Zimmer, Frank; Grasslin, Michael; Berheide, Tobias; Cioni, Stefano

    2013-01-01

    On-board joint power amplification of multiple-carrier DVB-S2 signals using a single High-Power Amplifier (HPA) is an emerging configuration that aims to reduce flight hardware and weight. However, effects specific to such a scenario degrade power and spectral efficiencies with increased Adjacent Channel Interference caused by non-linear characteristic of the HPA and power efficiency loss due to the increased Peak to Average Power Ratio (PAPR). The paper studies signal processing techniques ...

  4. Modulation of epithelial sodium channel (ENaC expression in mouse lung infected with Pseudomonas aeruginosa

    Directory of Open Access Journals (Sweden)

    Radzioch Danuta

    2005-01-01

    Full Text Available Abstract Background The intratracheal instillation of Pseudomonas aeruginosa entrapped in agar beads in the mouse lung leads to chronic lung infection in susceptible mouse strains. As the infection generates a strong inflammatory response with some lung edema, we tested if it could modulate the expression of genes involved in lung liquid clearance, such as the α, β and γ subunits of the epithelial sodium channel (ENaC and the catalytic subunit of Na+-K+-ATPase. Methods Pseudomonas aeruginosa entrapped in agar beads were instilled in the lung of resistant (BalB/c and susceptible (DBA/2, C57BL/6 and A/J mouse strains. The mRNA expression of ENaC and Na+-K+-ATPase subunits was tested in the lung by Northern blot following a 3 hours to 14 days infection. Results The infection of the different mouse strains evoked regulation of α and β ENaC mRNA. Following Pseudomonas instillation, the expression of αENaC mRNA decreased to a median of 43% on days 3 and 7 after infection and was still decreased to a median of 45% 14 days after infection (p 1Na+-K+-ATPase mRNA, the catalytic subunit of the sodium pump, was recorded. The distinctive expression profiles of the three subunits were not different, between the susceptible and resistant mouse strains. Conclusions These results show that Pseudomonas infection, by modulating ENaC subunit expression, could influence edema formation and clearance in infected lungs.

  5. Multi-channel logical circuit module used for high-speed, low amplitude signals processing and QDC gate signals generation

    International Nuclear Information System (INIS)

    Su Hong; Li Xiaogang; Zhu Haidong; Ma Xiaoli; Yin Weiwei; Li Zhuyu; Jin Genming; Wu Heyu

    2001-01-01

    A new kind of logical circuit will be introduced in brief. There are 16 independent channels in the module. The module receives low amplitude signals(≥40 mV), and processes them to amplify, shape, delay, sum and etc. After the processing each channel produces 2 pairs of ECL logical signal to feed the gate of QDC as the gate signal of QDC. The module consists of high-speed preamplifier unit, high-speed discriminate unit, delaying and shaping unit, summing unit and trigger display unit. The module is developed for 64 CH. 12 BIT Multi-event QDC. The impedance of QDC is 110 Ω. Each gate signal of QDC requires a pair of differential ECL level, Min. Gate width 30 ns and Max. Gate width 1 μs. It has showed that the outputs of logical circuit module satisfy the QDC requirements in experiment. The module can be used on data acquisition system to acquire thousands of data at high-speed ,high-density and multi-parameter, in heavy particle nuclear physics experiment. It also can be used to discriminate multi-coincidence events

  6. Progress in the structural understanding of voltage-gated calcium channel (CaV) function and modulation.

    Science.gov (United States)

    Minor, Daniel L; Findeisen, Felix

    2010-01-01

    Voltage-gated calcium channels (CaVs) are large, transmembrane multiprotein complexes that couple membrane depolarization to cellular calcium entry. These channels are central to cardiac action potential propagation, neurotransmitter and hormone release, muscle contraction, and calcium-dependent gene transcription. Over the past six years, the advent of high-resolution structural studies of CaV components from different isoforms and CaV modulators has begun to reveal the architecture that underlies the exceptionally rich feedback modulation that controls CaV action. These descriptions of CaV molecular anatomy have provided new, structure-based insights into the mechanisms by which particular channel elements affect voltage-dependent inactivation (VDI), calcium‑dependent inactivation (CDI), and calcium‑dependent facilitation (CDF). The initial successes have been achieved through structural studies of soluble channel domains and modulator proteins and have proven most powerful when paired with biochemical and functional studies that validate ideas inspired by the structures. Here, we review the progress in this growing area and highlight some key open challenges for future efforts.

  7. Two pore channel 2 differentially modulates neural differentiation of mouse embryonic stem cells.

    Directory of Open Access Journals (Sweden)

    Zhe-Hao Zhang

    Full Text Available Nicotinic acid adenine dinucleotide phosphate (NAADP is an endogenous Ca(2+ mobilizing nucleotide presented in various species. NAADP mobilizes Ca(2+ from acidic organelles through two pore channel 2 (TPC2 in many cell types and it has been previously shown that NAADP can potently induce neuronal differentiation in PC12 cells. Here we examined the role of TPC2 signaling in the neural differentiation of mouse embryonic stem (ES cells. We found that the expression of TPC2 was markedly decreased during the initial ES cell entry into neural progenitors, and the levels of TPC2 gradually rebounded during the late stages of neurogenesis. Correspondingly, TPC2 knockdown accelerated mouse ES cell differentiation into neural progenitors but inhibited these neural progenitors from committing to neurons. Overexpression of TPC2, on the other hand, inhibited mouse ES cell from entering the early neural lineage. Interestingly, TPC2 knockdown had no effect on the differentiation of astrocytes and oligodendrocytes of mouse ES cells. Taken together, our data indicate that TPC2 signaling plays a temporal and differential role in modulating the neural lineage entry of mouse ES cells, in that TPC2 signaling inhibits ES cell entry to early neural progenitors, but is required for late neuronal differentiation.

  8. On the Capacity Region of the Intensity-Modulation Direct-Detection Optical Broadcast Channel

    KAUST Repository

    Chaaban, Anas

    2015-08-11

    The capacity of the intensity-modulation direct-detection free-space optical broadcast channel (OBC) is investigated. The Gaussian model with input-independent Gaussian noise is used, with both average and peak intensity constraints. An outer bound on the capacity region is derived by adapting Bergmans\\' approach to the OBC. Inner bounds are derived by using superposition coding with either truncated-Gaussian distributions or discrete distributions. While the discrete input distribution achieves higher rates than the truncated-Gaussian distribution, the latter allows expressing the achievable rate region in a closed form. At high signal-to-noise ratio (SNR), it is shown that the truncated-Gaussian distribution is nearly optimal. It achieves the symmetric-capacity within a constant gap (independent of SNR), which approaches half a bit as the number of users grows large. It also achieves the capacity region within a constant gap, which depends on the number of users. At low SNR, it is shown that on-off keying with time-division multiple-access (TDMA) is optimal, as it achieves any point on the boundary of the developed outer bound. This is interesting in practice since both OOK and TDMA have low complexity. At moderate SNR (typically [0,8] dB), a discrete distribution with a small alphabet size achieves a fairly good performance in terms of symmetric rate.

  9. On the Capacity of the Intensity-Modulation Direct-Detection Optical Broadcast Channel

    KAUST Repository

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

    2016-01-01

    The capacity of the intensity-modulation directdetection optical broadcast channel (OBC) is investigated, under both average and peak intensity constraints. An outer bound on the capacity region is derived by adapting Bergmans’ approach to the OBC. Inner bounds are derived by using superposition coding with either truncated-Gaussian (TG) distributions or discrete distributions. While the discrete distribution achieves higher rates, the TG distribution leads to a simpler representation of the achievable rate region. At high signal-to-noise ratio (SNR), it is shown that the TG distribution is nearly optimal. It achieves the symmetric-capacity within a constant gap (independent of SNR), which approaches half a bit as the number of users grows. It also achieves the capacity region within a constant gap. At low SNR, it is shown that on-off keying (OOK) with time-division multipleaccess (TDMA) is optimal. This is interesting in practice since both OOK and TDMA have low complexity. At moderate SNR (typically [0,8] dB), a discrete distribution with a small alphabet size achieves fairly good performance.

  10. Modulation of the epithelial sodium channel (ENaC by bacterial metalloproteases and protease inhibitors.

    Directory of Open Access Journals (Sweden)

    Michael B Butterworth

    Full Text Available The serralysin family of metalloproteases is associated with the virulence of multiple gram-negative human pathogens, including Pseudomonas aeruginosa and Serratia marcescens. The serralysin proteases share highly conserved catalytic domains and show evolutionary similarity to the mammalian matrix metalloproteases. Our previous studies demonstrated that alkaline protease (AP from Pseudomonas aeruginosa is capable of activating the epithelial sodium channel (ENaC, leading to an increase in sodium absorption in airway epithelia. The serralysin proteases are often co-expressed with endogenous, intracellular or periplasmic inhibitors, which putatively protect the bacterium from unwanted or unregulated protease activities. To evaluate the potential use of these small protein inhibitors in regulating the serralysin induced activation of ENaC, proteases from Pseudomonas aeruginosa and Serratia marcescens were purified for characterization along with a high affinity inhibitor from Pseudomonas. Both proteases showed activity against in vitro substrates and could be blocked by near stoichiometric concentrations of the inhibitor. In addition, both proteases were capable of activating ENaC when added to the apical surfaces of multiple epithelial cells with similar slow activation kinetics. The high-affinity periplasmic inhibitor from Pseudomonas effectively blocked this activation. These data suggest that multiple metalloproteases are capable of activating ENaC. Further, the endogenous, periplasmic bacterial inhibitors may be useful for modulating the downstream effects of the serralysin virulence factors under physiological conditions.

  11. On the Capacity of the Intensity-Modulation Direct-Detection Optical Broadcast Channel

    KAUST Repository

    Chaaban, Anas

    2016-01-12

    The capacity of the intensity-modulation directdetection optical broadcast channel (OBC) is investigated, under both average and peak intensity constraints. An outer bound on the capacity region is derived by adapting Bergmans’ approach to the OBC. Inner bounds are derived by using superposition coding with either truncated-Gaussian (TG) distributions or discrete distributions. While the discrete distribution achieves higher rates, the TG distribution leads to a simpler representation of the achievable rate region. At high signal-to-noise ratio (SNR), it is shown that the TG distribution is nearly optimal. It achieves the symmetric-capacity within a constant gap (independent of SNR), which approaches half a bit as the number of users grows. It also achieves the capacity region within a constant gap. At low SNR, it is shown that on-off keying (OOK) with time-division multipleaccess (TDMA) is optimal. This is interesting in practice since both OOK and TDMA have low complexity. At moderate SNR (typically [0,8] dB), a discrete distribution with a small alphabet size achieves fairly good performance.

  12. Intron retention in mRNA encoding ancillary subunit of insect voltage-gated sodium channel modulates channel expression, gating regulation and drug sensitivity.

    Directory of Open Access Journals (Sweden)

    Céline M Bourdin

    Full Text Available Insect voltage-gated sodium (Nav channels are formed by a well-known pore-forming α-subunit encoded by para-like gene and ancillary subunits related to TipE from the mutation "temperature-induced-paralysis locus E." The role of these ancillary subunits in the modulation of biophysical and pharmacological properties of Na(+ currents are not enough documented. The unique neuronal ancillary subunit TipE-homologous protein 1 of Drosophila melanogaster (DmTEH1 strongly enhances the expression of insect Nav channels when heterologously expressed in Xenopus oocytes. Here we report the cloning and functional expression of two neuronal DmTEH1-homologs of the cockroach, Periplaneta americana, PaTEH1A and PaTEH1B, encoded by a single bicistronic gene. In PaTEH1B, the second exon encoding the last 11-amino-acid residues of PaTEH1A is shifted to 3'UTR by the retention of a 96-bp intron-containing coding-message, thus generating a new C-terminal end. We investigated the gating and pharmacological properties of the Drosophila Nav channel variant (DmNav1-1 co-expressed with DmTEH1, PaTEH1A, PaTEH1B or a truncated mutant PaTEH1Δ(270-280 in Xenopus oocytes. PaTEH1B caused a 2.2-fold current density decrease, concomitant with an equivalent α-subunit incorporation decrease in the plasma membrane, compared to PaTEH1A and PaTEH1Δ(270-280. PaTEH1B positively shifted the voltage-dependences of activation and slow inactivation of DmNav1-1 channels to more positive potentials compared to PaTEH1A, suggesting that the C-terminal end of both proteins may influence the function of the voltage-sensor and the pore of Nav channel. Interestingly, our findings showed that the sensitivity of DmNav1-1 channels to lidocaine and to the pyrazoline-type insecticide metabolite DCJW depends on associated TEH1-like subunits. In conclusion, our work demonstrates for the first time that density, gating and pharmacological properties of Nav channels expressed in Xenopus oocytes can be

  13. Pre-clinical evaluation of an inverse planning module for segmental MLC based IMRT delivery

    International Nuclear Information System (INIS)

    Georg, Dietmar; Kroupa, Bernhard

    2002-01-01

    Phantom tests are performed for pre-clinical evaluation of a commercial inverse planning system (HELAX TMS, V 6.0) for segmented multileaf collimator (MLC) intensity modulated radiotherapy (IMRT) delivery. The optimization module has available two optimization algorithms: the target primary feasibility and the weighted feasibility algorithm, only the latter allows the user to specify weights for structures. In the first series, single beam tests are performed to evaluate the outcome of inverse planning in terms of plausibility for the following situations: oblique incidence, presence of inhomogeneities, multiple targets at different depths and multiple targets with different desired doses. Additionally, for these tests a manual plan is made for comparison. In the absence of organs at risk, both the optimization algorithms are found to assign the highest priority to low dose constraints for targets. In the second series, tests resembling clinical relevant configurations (simultaneous boost and concave target with critical organ) are performed with multiple beam arrangements in order to determine the impact of the system's configuration on inverse planning. It is found that the definition of certain segment number and segment size limitations does not largely compromise treatment plans when using multiple beams. On the other hand, these limitations are important for delivery efficiency and dosimetry. For the number of iterations and voxels per volume of interest, standard values in the system's configuration are considered to be sufficient. Additionally, it is demonstrated that precautions must be taken to precisely define treatment goals when using computerized treatment optimization. Similar phantom tests could be used for a direct dosimetric verification of all steps from inverse treatment planning to IMRT delivery. (note)

  14. A 32-channel photon counting module with embedded auto/cross-correlators for real-time parallel fluorescence correlation spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Gong, S.; Labanca, I.; Rech, I.; Ghioni, M. [Dipartimento di Elettronica, Informazione e Bioingegneria, Politecnico di Milano, Piazza Leonardo da Vinci 32, 20133 Milano (Italy)

    2014-10-15

    Fluorescence correlation spectroscopy (FCS) is a well-established technique to study binding interactions or the diffusion of fluorescently labeled biomolecules in vitro and in vivo. Fast FCS experiments require parallel data acquisition and analysis which can be achieved by exploiting a multi-channel Single Photon Avalanche Diode (SPAD) array and a corresponding multi-input correlator. This paper reports a 32-channel FPGA based correlator able to perform 32 auto/cross-correlations simultaneously over a lag-time ranging from 10 ns up to 150 ms. The correlator is included in a 32 × 1 SPAD array module, providing a compact and flexible instrument for high throughput FCS experiments. However, some inherent features of SPAD arrays, namely afterpulsing and optical crosstalk effects, may introduce distortions in the measurement of auto- and cross-correlation functions. We investigated these limitations to assess their impact on the module and evaluate possible workarounds.

  15. Tunable Channel Drop Filter in a Two-Dimensional Photonic Crystal Modulated by a Nematic Liquid Crystal

    Directory of Open Access Journals (Sweden)

    2006-01-01

    Full Text Available Photonic crystals (PCs have many potential applications because of their ability to control light-wave propagation and because PC-based waveguides may be integrated into optical circuits. We propose a novel tunable PC channel drop filter based on nematic liquid crystals and investigate its properties numerically by using the finite-difference time-domain (FDTD method. The refractive indices of liquid crystals can be actively modulated after infiltrating nematic liquid crystals into the microcavity in PC waveguides with square lattices. Then we can control light propagation in a PC waveguide. We analyze the Q -factors and resonance frequencies of a tunable PC channel drop filter by considering various indices modulation of liquid crystals. The novel component can be used as wavelength division multiplexing in photonic integrated circuits.

  16. A 32-channel photon counting module with embedded auto/cross-correlators for real-time parallel fluorescence correlation spectroscopy

    International Nuclear Information System (INIS)

    Gong, S.; Labanca, I.; Rech, I.; Ghioni, M.

    2014-01-01

    Fluorescence correlation spectroscopy (FCS) is a well-established technique to study binding interactions or the diffusion of fluorescently labeled biomolecules in vitro and in vivo. Fast FCS experiments require parallel data acquisition and analysis which can be achieved by exploiting a multi-channel Single Photon Avalanche Diode (SPAD) array and a corresponding multi-input correlator. This paper reports a 32-channel FPGA based correlator able to perform 32 auto/cross-correlations simultaneously over a lag-time ranging from 10 ns up to 150 ms. The correlator is included in a 32 × 1 SPAD array module, providing a compact and flexible instrument for high throughput FCS experiments. However, some inherent features of SPAD arrays, namely afterpulsing and optical crosstalk effects, may introduce distortions in the measurement of auto- and cross-correlation functions. We investigated these limitations to assess their impact on the module and evaluate possible workarounds

  17. A New Negative Allosteric Modulator AP14145 for the Study of Small Conductance Calcium-Activated Potassium Channels

    DEFF Research Database (Denmark)

    Simo Vicens, Rafel; Kirchhoff, Jeppe Egedal; Dolce, Bernardo

    2017-01-01

    ) prolongation in anaesthetised rats and a beam walk test was performed in mice to determine acute CNS related effects of the drug. Key results: AP14145 was found to be an equipotent negative allosteric modulator of KCa2.2 and KCa2.3 channels (IC50 = 1.1 ± 0.3 μM L-1). The presence of AP14145 (10 μM L-1...

  18. Stochastic nanoroughness modulates neuron-astrocyte interactions and function via mechanosensing cation channels.

    Science.gov (United States)

    Blumenthal, Nils R; Hermanson, Ola; Heimrich, Bernd; Shastri, V Prasad

    2014-11-11

    Extracellular soluble signals are known to play a critical role in maintaining neuronal function and homeostasis in the CNS. However, the CNS is also composed of extracellular matrix macromolecules and glia support cells, and the contribution of the physical attributes of these components in maintenance and regulation of neuronal function is not well understood. Because these components possess well-defined topography, we theorize a role for topography in neuronal development and we demonstrate that survival and function of hippocampal neurons and differentiation of telencephalic neural stem cells is modulated by nanoroughness. At roughnesses corresponding to that of healthy astrocytes, hippocampal neurons dissociated and survived independent from astrocytes and showed superior functional traits (increased polarity and calcium flux). Furthermore, telencephalic neural stem cells differentiated into neurons even under exogenous signals that favor astrocytic differentiation. The decoupling of neurons from astrocytes seemed to be triggered by changes to astrocyte apical-surface topography in response to nanoroughness. Blocking signaling through mechanosensing cation channels using GsMTx4 negated the ability of neurons to sense the nanoroughness and promoted decoupling of neurons from astrocytes, thus providing direct evidence for the role of nanotopography in neuron-astrocyte interactions. We extrapolate the role of topography to neurodegenerative conditions and show that regions of amyloid plaque buildup in brain tissue of Alzheimer's patients are accompanied by detrimental changes in tissue roughness. These findings suggest a role for astrocyte and ECM-induced topographical changes in neuronal pathologies and provide new insights for developing therapeutic targets and engineering of neural biomaterials.

  19. Domain-domain interactions determine the gating, permeation, pharmacology, and subunit modulation of the IKs ion channel.

    Science.gov (United States)

    Zaydman, Mark A; Kasimova, Marina A; McFarland, Kelli; Beller, Zachary; Hou, Panpan; Kinser, Holly E; Liang, Hongwu; Zhang, Guohui; Shi, Jingyi; Tarek, Mounir; Cui, Jianmin

    2014-12-23

    Voltage-gated ion channels generate electrical currents that control muscle contraction, encode neuronal information, and trigger hormonal release. Tissue-specific expression of accessory (β) subunits causes these channels to generate currents with distinct properties. In the heart, KCNQ1 voltage-gated potassium channels coassemble with KCNE1 β-subunits to generate the IKs current (Barhanin et al., 1996; Sanguinetti et al., 1996), an important current for maintenance of stable heart rhythms. KCNE1 significantly modulates the gating, permeation, and pharmacology of KCNQ1 (Wrobel et al., 2012; Sun et al., 2012; Abbott, 2014). These changes are essential for the physiological role of IKs (Silva and Rudy, 2005); however, after 18 years of study, no coherent mechanism explaining how KCNE1 affects KCNQ1 has emerged. Here we provide evidence of such a mechanism, whereby, KCNE1 alters the state-dependent interactions that functionally couple the voltage-sensing domains (VSDs) to the pore.

  20. A Common Structural Component for β-Subunit Mediated Modulation of Slow Inactivation in Different KV Channels

    Directory of Open Access Journals (Sweden)

    Nathalie Strutz-Seebohm

    2013-06-01

    Full Text Available Background/Aims: Potassium channels are tetrameric proteins providing potassium selective passage through lipid embedded proteinaceous pores with highest fidelity. The selectivity results from binding to discrete potassium binding sites and stabilization of a hydrated potassium ion in a central internal cavity. The four potassium binding sites, generated by the conserved TTxGYGD signature sequence are formed by the backbone carbonyls of the amino acids TXGYG. Residues KV1.5-Val481, KV4.3-Leu368 and KV7.1- Ile 313 represent the amino acids in the X position of the respective channels. Methods: Here, we study the impact of these residues on ion selectivity, permeation and inactivation kinetics as well as the modulation by β-subunits using site-specific mutagenesis, electrophysiological analyses and molecular dynamics simulations. Results: We identify this position as key in modulation of slow inactivation by structurally dissimilar β-subunits in different KV channels. Conclusion: We propose a model in which structural changes accompanying activation and β-subunit modulation allosterically constrain the backbone carbonyl oxygen atoms via the side chain of the respective X-residue in the signature sequence to reduce conductance during slow inactivation.

  1. Modulation of mdm2 pre-mRNA splicing by 9-aminoacridine-PNA (peptide nucleic acid) conjugates targeting intron-exon junctions

    DEFF Research Database (Denmark)

    Shiraishi, Takehiko; Eysturskard, Jonhard; Nielsen, Peter E

    2010-01-01

    ABSTRACT: BACKGROUND: Modulation of pre-mRNA splicing by antisense molecules is a promising mechanism of action for gene therapeutic drugs. In this study, we have examined the potential of peptide nucleic acid (PNA) 9-aminoacridine conjugates to modulate the pre-mRNA splicing of the mdm2 human ca...

  2. Amino-termini isoforms of the Slack K+ channel, regulated by alternative promoters, differentially modulate rhythmic firing and adaptation.

    Science.gov (United States)

    Brown, Maile R; Kronengold, Jack; Gazula, Valeswara-Rao; Spilianakis, Charalampos G; Flavell, Richard A; von Hehn, Christian A A; Bhattacharjee, Arin; Kaczmarek, Leonard K

    2008-11-01

    The rates of activation and unitary properties of Na+-activated K+ (K(Na)) currents have been found to vary substantially in different types of neurones. One class of K(Na) channels is encoded by the Slack gene. We have now determined that alternative RNA splicing gives rise to at least five different transcripts for Slack, which produce Slack channels that differ in their predicted cytoplasmic amino-termini and in their kinetic properties. Two of these, termed Slack-A channels, contain an amino-terminus domain closely resembling that of another class of K(Na) channels encoded by the Slick gene. Neuronal expression of Slack-A channels and of the previously described Slack isoform, now called Slack-B, are driven by independent promoters. Slack-A mRNAs were enriched in the brainstem and olfactory bulb and detected at significant levels in four different brain regions. When expressed in CHO cells, Slack-A channels activate rapidly upon depolarization and, in single channel recordings in Xenopus oocytes, are characterized by multiple subconductance states with only brief transient openings to the fully open state. In contrast, Slack-B channels activate slowly over hundreds of milliseconds, with openings to the fully open state that are approximately 6-fold longer than those for Slack-A channels. In numerical simulations, neurones in which outward currents are dominated by a Slack-A-like conductance adapt very rapidly to repeated or maintained stimulation over a wide range of stimulus strengths. In contrast, Slack-B currents promote rhythmic firing during maintained stimulation, and allow adaptation rate to vary with stimulus strength. Using an antibody that recognizes all amino-termini isoforms of Slack, Slack immunoreactivity is present at locations that have no Slack-B-specific staining, including olfactory bulb glomeruli and the dendrites of hippocampal neurones, suggesting that Slack channels with alternate amino-termini such as Slack-A channels are present at

  3. A CAMAC 32-channel pile-up detection and rejection module

    International Nuclear Information System (INIS)

    Wikne, J.C.

    1992-08-01

    A specially developed CAMAC module for detection and rejection of analog pile-up in multiparameter, nuclear spectroscopy experiments is described. The present report is a complete technical manual for the module. 23 refs., 6 figs

  4. Cross-layer designed adaptive modulation algorithm with packet combining and truncated ARQ over MIMO Nakagami fading channels

    KAUST Repository

    Aniba, Ghassane

    2011-04-01

    This paper presents an optimal adaptive modulation (AM) algorithm designed using a cross-layer approach which combines truncated automatic repeat request (ARQ) protocol and packet combining. Transmissions are performed over multiple-input multiple-output (MIMO) Nakagami fading channels, and retransmitted packets are not necessarily modulated using the same modulation format as in the initial transmission. Compared to traditional approach, cross-layer design based on the coupling across the physical and link layers, has proven to yield better performance in wireless communications. However, there is a lack for the performance analysis and evaluation of such design when the ARQ protocol is used in conjunction with packet combining. Indeed, previous works addressed the link layer performance of AM with truncated ARQ but without packet combining. In addition, previously proposed AM algorithms are not optimal and can provide poor performance when packet combining is implemented. Herein, we first show that the packet loss rate (PLR) resulting from the combining of packets modulated with different constellations can be well approximated by an exponential function. This model is then used in the design of an optimal AM algorithm for systems employing packet combining, truncated ARQ and MIMO antenna configurations, considering transmission over Nakagami fading channels. Numerical results are provided for operation with or without packet combining, and show the enhanced performance and efficiency of the proposed algorithm in comparison with existing ones. © 2011 IEEE.

  5. Modulation of firing and synaptic transmission of serotonergic neurons by intrinsic G protein-coupled receptors and ion channels

    Directory of Open Access Journals (Sweden)

    Takashi eMaejima

    2013-05-01

    Full Text Available Serotonergic neurons project to virtually all regions of the CNS and are consequently involved in many critical physiological functions such as mood, sexual behavior, feeding, sleep/wake cycle, memory, cognition, blood pressure regulation, breathing and reproductive success. Therefore serotonin release and serotonergic neuronal activity have to be precisely controlled and modulated by interacting brain circuits to adapt to specific emotional and environmental states. We will review the current knowledge about G protein-coupled receptors and ion channels involved in the regulation of serotonergic system, how their regulation is modulating the intrinsic activity of serotonergic neurons and its transmitter release and will discuss the latest methods for controlling the modulation of serotonin release and intracellular signaling in serotonergic neurons in vitro and in vivo.

  6. Performances of Hybrid Amplitude Shape Modulation for UWB Communications Systems over AWGN Channel in a Single and Multi-User Environment

    Directory of Open Access Journals (Sweden)

    M. Herceg

    2009-09-01

    Full Text Available This paper analyzes the performance of the hybrid Amplitude Shape Modulation (h-ASM scheme for the time-hopping ultra-wideband (TH-UWB communication systems in the single and multi-user environment. h-ASM is the combination of Pulse Amplitude Modulation (PAM and Pulse Shape Modulation (PSM based on modified Hermite pulses (MHP. This scheme is suitable for high rate data transmission applications because b = log2(MN bits can be mapped with one waveform. The channel capacity and error probability over AWGN channel are derived and compared with other modulation schemes.

  7. Modulation of nucleotide sensitivity of ATP-sensitive potassium channels by phosphatidylinositol-4-phosphate 5-kinase.

    Science.gov (United States)

    Shyng, S L; Barbieri, A; Gumusboga, A; Cukras, C; Pike, L; Davis, J N; Stahl, P D; Nichols, C G

    2000-01-18

    ATP-sensitive potassium channels (K(ATP) channels) regulate cell excitability in response to metabolic changes. K(ATP) channels are formed as a complex of a sulfonylurea receptor (SURx), a member of the ATP-binding cassette protein family, and an inward rectifier K(+) channel subunit (Kir6.x). Membrane phospholipids, in particular phosphatidylinositol (PI) 4,5-bisphosphate (PIP(2)), activate K(ATP) channels and antagonize ATP inhibition of K(ATP) channels when applied to inside-out membrane patches. To examine the physiological relevance of this regulatory mechanism, we manipulated membrane PIP(2) levels by expressing either the wild-type or an inactive form of PI-4-phosphate 5-kinase (PIP5K) in COSm6 cells and examined the ATP sensitivity of coexpressed K(ATP) channels. Channels from cells expressing the wild-type PIP5K have a 6-fold lower ATP sensitivity (K(1/2), the half maximal inhibitory concentration, approximately 60 microM) than the sensitivities from control cells (K(1/2) approximately 10 microM). An inactive form of the PIP5K had little effect on the K(1/2) of wild-type channels but increased the ATP-sensitivity of a mutant K(ATP) channel that has an intrinsically lower ATP sensitivity (from K(1/2) approximately 450 microM to K(1/2) approximately 100 microM), suggesting a decrease in membrane PIP(2) levels as a consequence of a dominant-negative effect of the inactive PIP5K. These results show that PIP5K activity, which regulates PIP(2) and PI-3,4,5-P(3) levels, is a significant determinant of the physiological nucleotide sensitivity of K(ATP) channels.

  8. Acoustic calibration for the KM3NeT pre-production module

    Energy Technology Data Exchange (ETDEWEB)

    Enzenhöfer, A., E-mail: alexander.enzenhoefer@physik.uni-erlangen.de [Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen Centre for Astroparticle Physics, Erwin-Rommel-Str. 1, D-91058 Erlangen (Germany)

    2013-10-11

    The proposed large scale Cherenkov neutrino telescope KM3NeT will carry photo-sensors on flexible structures, the detection units. The Mediterranean Sea, where KM3NeT will be installed, constitutes a highly dynamic environment in which the detection units are constantly in motion. Thus it is necessary to monitor the exact sensor positions continuously to achieve the desired resolution for the neutrino telescope. A common way to perform this monitoring is the use of acoustic positioning systems with emitters and receivers based on the piezoelectric effect. The acoustic receivers are attached to detection units whereas the emitters are located at known positions on the sea floor. There are complete commercial systems for this application with sufficient precision. But these systems are limited in the use of their data and inefficient as they were designed to perform only this single task. Several working groups in the KM3NeT consortium are cooperating to custom-design a positioning system for the specific requirements of KM3NeT. Most of the studied solutions hold the possibility to extend the application area from positioning to additional tasks like acoustic particle detection or monitoring of the deep-sea acoustic environment. The KM3NeT Pre-Production Module (PPM) is a test system to verify the correct operation and interoperability of the major involved hardware and software components developed for KM3NeT. In the context of the PPM, alternative designs of acoustic sensors including small piezoelectric elements equipped with preamplifiers inside the same housing as the optical sensors will be tested. These will be described in this article.

  9. Numerical investigation of the thermal and electrical performances for combined solar photovoltaic/thermal (PV/T) modules based on internally extruded fin flow channel

    Science.gov (United States)

    Deng, Y. C.; Li, Q. P.; Wang, G. J.

    2017-11-01

    A solar photovoltaic/thermal (PV/T) module based on internally extruded fin flow channel was investigated numerically in this paper. First of all, the structures of the thin plate heat exchanger and the PV/T module were presented. Then, a numerical model of the PV/T module considering solar irradiation, fluid flow and heat transfer was developed to analyze the performance of the module. Finally, the steady electrical and thermal efficiencies of the PV/T module at different inlet water temperatures and mass flow rates were achieved. These numerical results supply theory basis for practical application of the PV/T module.

  10. Modulation of KCNQ4 channel activity by changes in cell volume

    DEFF Research Database (Denmark)

    Hougaard, Charlotte; Klaerke, Dan A; Hoffmann, Else K

    2004-01-01

    KCNQ4 channels expressed in HEK 293 cells are sensitive to cell volume changes, being activated by swelling and inhibited by shrinkage, respectively. The KCNQ4 channels contribute significantly to the regulatory volume decrease (RVD) process following cell swelling. Under isoosmotic conditions...

  11. Channel catfish (Ictalurus punctatus) leukocytes express estrogen receptor isoforms ERα and ERβ2 and are functionally modulated by estrogens.

    Science.gov (United States)

    Iwanowicz, Luke R; Stafford, James L; Patiño, Reynaldo; Bengten, Eva; Miller, Norman W; Blazer, Vicki S

    2014-09-01

    Estrogens are recognized as modulators of immune responses in mammals and teleosts. While it is known that the effects of estrogens are mediated via leukocyte-specific estrogen receptors (ERs) in humans and mice, leucocyte-specific estrogen receptor expression and the effects of estrogens on this cell population is less explored and poorly understood in teleosts. Here in, we verify that channel catfish (Ictalurus punctaus) leukocytes express ERα and ERβ2. Transcripts of these isoforms were detected in tissue-associated leukocyte populations by PCR, but ERβ2 was rarely detected in PBLs. Expression of these receptors was temporally regulated in PBLs following polyclonal activation by concanavalin A, lipopolysaccharide or alloantigen based on evaluation by quantitative and end-point PCR. Examination of long-term leukocyte cell lines demonstrated that these receptors are differentially expressed depending on leukocyte lineage and phenotype. Expression of ERs was also temporally dynamic in some leukocyte lineages and may reflect stage of cell maturity. Estrogens affect the responsiveness of channel catfish peripheral blood leukocytes (PBLs) to mitogens in vitro. Similarly, bactericidal activity and phorbol 12-myristate 13-acetate induced respiratory burst was modulated by 17β-estradiol. These actions were blocked by the pure ER antagonist ICI 182780 indicating that response is, in part, mediated via ERα. In summary, estrogen receptors are expressed in channel catfish leukocytes and participate in the regulation of the immune response. This is the first time leukocyte lineage expression has been reported in teleost cell lines. Published by Elsevier Ltd.

  12. Enhanced pre-synaptic glutamate release in deep-dorsal horn contributes to calcium channel alpha-2-delta-1 protein-mediated spinal sensitization and behavioral hypersensitivity

    Directory of Open Access Journals (Sweden)

    Dickenson Anthony H

    2009-02-01

    Full Text Available Abstract Nerve injury-induced expression of the spinal calcium channel alpha-2-delta-1 subunit (Cavα2δ1 has been shown to mediate behavioral hypersensitivity through a yet identified mechanism. We examined if this neuroplasticity modulates behavioral hypersensitivity by regulating spinal glutamatergic neurotransmission in injury-free transgenic mice overexpressing the Cavα2δ1 proteins in neuronal tissues. The transgenic mice exhibited hypersensitivity to mechanical stimulation (allodynia similar to the spinal nerve ligation injury model. Intrathecally delivered antagonists for N-methyl-D-aspartate (NMDA and α-amino-3-hydroxyl-5-methylisoxazole-4-propionic acid (AMPA/kainate receptors, but not for the metabotropic glutamate receptors, caused a dose-dependent allodynia reversal in the transgenic mice without changing the behavioral sensitivity in wild-type mice. This suggests that elevated spinal Cavα2δ1 mediates allodynia through a pathway involving activation of selective glutamate receptors. To determine if this is mediated by enhanced spinal neuronal excitability or pre-synaptic glutamate release in deep-dorsal horn, we examined wide-dynamic-range (WDR neuron excitability with extracellular recording and glutamate-mediated excitatory postsynaptic currents with whole-cell patch recording in deep-dorsal horn of the Cavα2δ1 transgenic mice. Our data indicated that overexpression of Cavα2δ1 in neuronal tissues led to increased frequency, but not amplitude, of miniature excitatory post synaptic currents mediated mainly by AMPA/kainate receptors at physiological membrane potentials, and also by NMDA receptors upon depolarization, without changing the excitability of WDR neurons to high intensity stimulation. Together, these findings support a mechanism of Cavα2δ1-mediated spinal sensitization in which elevated Cavα2δ1 causes increased pre-synaptic glutamate release that leads to reduced excitation thresholds of post-synaptic dorsal

  13. Enhanced pre-synaptic glutamate release in deep-dorsal horn contributes to calcium channel alpha-2-delta-1 protein-mediated spinal sensitization and behavioral hypersensitivity

    Science.gov (United States)

    Nguyen, David; Deng, Ping; Matthews, Elizabeth A; Kim, Doo-Sik; Feng, Guoping; Dickenson, Anthony H; Xu, Zao C; Luo, Z David

    2009-01-01

    Nerve injury-induced expression of the spinal calcium channel alpha-2-delta-1 subunit (Cavα2δ1) has been shown to mediate behavioral hypersensitivity through a yet identified mechanism. We examined if this neuroplasticity modulates behavioral hypersensitivity by regulating spinal glutamatergic neurotransmission in injury-free transgenic mice overexpressing the Cavα2δ1 proteins in neuronal tissues. The transgenic mice exhibited hypersensitivity to mechanical stimulation (allodynia) similar to the spinal nerve ligation injury model. Intrathecally delivered antagonists for N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxyl-5-methylisoxazole-4-propionic acid (AMPA)/kainate receptors, but not for the metabotropic glutamate receptors, caused a dose-dependent allodynia reversal in the transgenic mice without changing the behavioral sensitivity in wild-type mice. This suggests that elevated spinal Cavα2δ1 mediates allodynia through a pathway involving activation of selective glutamate receptors. To determine if this is mediated by enhanced spinal neuronal excitability or pre-synaptic glutamate release in deep-dorsal horn, we examined wide-dynamic-range (WDR) neuron excitability with extracellular recording and glutamate-mediated excitatory postsynaptic currents with whole-cell patch recording in deep-dorsal horn of the Cavα2δ1 transgenic mice. Our data indicated that overexpression of Cavα2δ1 in neuronal tissues led to increased frequency, but not amplitude, of miniature excitatory post synaptic currents mediated mainly by AMPA/kainate receptors at physiological membrane potentials, and also by NMDA receptors upon depolarization, without changing the excitability of WDR neurons to high intensity stimulation. Together, these findings support a mechanism of Cavα2δ1-mediated spinal sensitization in which elevated Cavα2δ1 causes increased pre-synaptic glutamate release that leads to reduced excitation thresholds of post-synaptic dorsal horn neurons to innocuous

  14. Functional K(ATP) channels in the rat retinal microvasculature: topographical distribution, redox regulation, spermine modulation and diabetic alteration.

    Science.gov (United States)

    Ishizaki, Eisuke; Fukumoto, Masanori; Puro, Donald G

    2009-05-15

    The essential task of the circulatory system is to match blood flow to local metabolic demand. However, much remains to be learned about this process. To better understand how local perfusion is regulated, we focused on the functional organization of the retinal microvasculature, which is particularly well adapted for the local control of perfusion. Here, we assessed the distribution and regulation of functional K(ATP) channels whose activation mediates the hyperpolarization induced by adenosine. Using microvascular complexes freshly isolated from the rat retina, we found a topographical heterogeneity in the distribution of functional K(ATP) channels; capillaries generate most of the K(ATP) current. The initiation of K(ATP)-induced responses in the capillaries supports the concept that the regulation of retinal perfusion is highly decentralized. Additional study revealed that microvascular K(ATP) channels are redox sensitive, with oxidants increasing their activity. Furthermore, the oxidant-mediated activation of these channels is driven by the polyamine spermine, whose catabolism produces oxidants. In addition, our observation that spermine-dependent oxidation occurs predominately in the capillaries accounts for why they generate most of the K(ATP) current detected in retinal microvascular complexes. Here, we also analysed retinal microvessels of streptozotocin-injected rats. We found that soon after the onset of diabetes, an increase in spermine-dependent oxidation at proximal microvascular sites boosts their K(ATP) current and thereby virtually eliminates the topographical heterogeneity of functional K(ATP) channels. We conclude that spermine-dependent oxidation is a previously unrecognized mechanism by which this polyamine modulates ion channels; in addition to a physiological role, spermine-dependent oxidation may also contribute to microvascular dysfunction in the diabetic retina.

  15. Bidirectional shifts of TRPM8 channel gating by temperature and chemical agents modulate the cold sensitivity of mammalian thermoreceptors.

    Science.gov (United States)

    Mälkiä, Annika; Madrid, Rodolfo; Meseguer, Victor; de la Peña, Elvira; Valero, María; Belmonte, Carlos; Viana, Félix

    2007-05-15

    TRPM8, a member of the melastatin subfamily of transient receptor potential (TRP) cation channels, is activated by voltage, low temperatures and cooling compounds. These properties and its restricted expression to small sensory neurons have made it the ion channel with the most advocated role in cold transduction. Recent work suggests that activation of TRPM8 by cold and menthol takes place through shifts in its voltage-activation curve, which cause the channel to open at physiological membrane potentials. By contrast, little is known about the actions of inhibitors on the function of TRPM8. We investigated the chemical and thermal modulation of TRPM8 in transfected HEK293 cells and in cold-sensitive primary sensory neurons. We show that cold-evoked TRPM8 responses are effectively suppressed by inhibitor compounds SKF96365, 4-(3-chloro-pyridin-2-yl)-piperazine-1-carboxylic acid (4-tert-butyl-phenyl)-amide (BCTC) and 1,10-phenanthroline. These antagonists exert their effect by shifting the voltage dependence of TRPM8 activation towards more positive potentials. An opposite shift towards more negative potentials is achieved by the agonist menthol. Functionally, the bidirectional shift in channel gating translates into a change in the apparent temperature threshold of TRPM8-expressing cells. Accordingly, in the presence of the antagonist compounds, the apparent response-threshold temperature of TRPM8 is displaced towards colder temperatures, whereas menthol sensitizes the response, shifting the threshold in the opposite direction. Co-application of agonists and antagonists produces predictable cancellation of these effects, suggesting the convergence on a common molecular process. The potential for half maximal activation of TRPM8 activation by cold was approximately 140 mV more negative in native channels compared to recombinant channels, with a much higher open probability at negative membrane potentials in the former. In functional terms, this difference translates

  16. Hypoosmotic cell swelling as a novel mechanism for modulation of cloned HCN2 channels

    DEFF Research Database (Denmark)

    Calloe, Kirstine; Elmedyb, Pernille; Olesen, Søren-Peter

    2005-01-01

    This work demonstrates cell swelling as a new regulatory mechanism for the cloned hyperpolarization-activated, cyclic nucleotide-gated channel 2 (HCN2). HCN2 channels were coexpressed with aquaporin1 in Xenopus laevis oocytes and currents were monitored using a two-electrode voltage-clamp. HCN2...... channels were activated by hyperpolarization to -100 mV and the currents were measured before and during hypoosmotic cell swelling. Cell swelling increased HCN2 currents by 30% without changing the kinetics of the currents. Injection of 50 nl intracellular solution resulted in a current increase of 20......%, indicating that an increase in cell volume also under isoosmotic conditions may lead to activation of HCN2. In the absence of aquaporin1 only negligible changes in oocyte cell volume occur during exposure to hypoosmotic media and no significant change in HCN2 channel activity was observed during perfusion...

  17. An inhibitor of K+ channels modulates human endometrial tumor-initiating cells

    Directory of Open Access Journals (Sweden)

    Leslie Kimberly K

    2011-08-01

    Full Text Available Abstract Background Many potassium ion (K+ channels function as oncogenes to sustain growth of solid tumors, but their role in cancer progression is not well understood. Emerging evidence suggests that the early progenitor cancer cell subpopulation, termed tumor initiating cells (TIC, are critical to cancer progression. Results A non-selective antagonist of multiple types of K+ channels, tetraethylammonium (TEA, was found to suppress colony formation in endometrial cancer cells via inhibition of putative TIC. The data also indicated that withdrawal of TEA results in a significant enhancement of tumorigenesis. When the TIC-enriched subpopulation was isolated from the endometrial cancer cells, TEA was also found to inhibit growth in vitro. Conclusions These studies suggest that the activity of potassium channels significantly contributes to the progression of endometrial tumors, and the antagonists of potassium channels are candidate anti-cancer drugs to specifically target tumor initiating cells in endometrial cancer therapy.

  18. High SNR BER comparison of coherent and differentially coherent modulation schemes in lognormal fading channels

    KAUST Repository

    Song, Xuegui; Cheng, Julian; Alouini, Mohamed-Slim

    2014-01-01

    Using an auxiliary random variable technique, we prove that binary differential phase-shift keying and binary phase-shift keying have the same asymptotic bit-error rate performance in lognormal fading channels. We also show that differential quaternary phase-shift keying is exactly 2.32 dB worse than quaternary phase-shift keying over the lognormal fading channels in high signal-to-noise ratio regimes.

  19. High SNR BER comparison of coherent and differentially coherent modulation schemes in lognormal fading channels

    KAUST Repository

    Song, Xuegui

    2014-09-01

    Using an auxiliary random variable technique, we prove that binary differential phase-shift keying and binary phase-shift keying have the same asymptotic bit-error rate performance in lognormal fading channels. We also show that differential quaternary phase-shift keying is exactly 2.32 dB worse than quaternary phase-shift keying over the lognormal fading channels in high signal-to-noise ratio regimes.

  20. Anoctamin Calcium-Activated Chloride Channels May Modulate Inhibitory Transmission in the Cerebellar Cortex.

    Directory of Open Access Journals (Sweden)

    Weiping Zhang

    Full Text Available Calcium-activated chloride channels of the anoctamin (alias TMEM16 protein family fulfill critical functions in epithelial fluid transport, smooth muscle contraction and sensory signal processing. Little is known, however, about their contribution to information processing in the central nervous system. Here we examined the recent finding that a calcium-dependent chloride conductance impacts on GABAergic synaptic inhibition in Purkinje cells of the cerebellum. We asked whether anoctamin channels may underlie this chloride conductance. We identified two anoctamin channel proteins, ANO1 and ANO2, in the cerebellar cortex. ANO1 was expressed in inhibitory interneurons of the molecular layer and the granule cell layer. Both channels were expressed in Purkinje cells but, while ANO1 appeared to be retained in the cell body, ANO2 was targeted to the dendritic tree. Functional studies confirmed that ANO2 was involved in a calcium-dependent mode of ionic plasticity that reduces the efficacy of GABAergic synapses. ANO2 channels attenuated GABAergic transmission by increasing the postsynaptic chloride concentration, hence reducing the driving force for chloride influx. Our data suggest that ANO2 channels are involved in a Ca2+-dependent regulation of synaptic weight in GABAergic inhibition. Thus, in balance with the chloride extrusion mechanism via the co-transporter KCC2, ANO2 appears to regulate ionic plasticity in the cerebellum.

  1. Performance analysis of subcarrier intensity modulation using rectangular QAM over Malaga turbulence channels with integer and non-integerβ

    KAUST Repository

    Alheadary, Wael G.

    2016-10-13

    In this paper, we derive the performances of optical wireless communication system utilizing adaptive subcarrier intensity modulation over the Malaga turbulent channel. More specifically, analytical closed-form solutions and asymptotic results are derived for average bit error rate, achievable spectral efficiency, outage probability, and ergodic capacity by utilizing series expansion identity of modified Bessel function. Our asymptotic and analytical results based on series solutions with finite numbers highly matched to the numerical results. By exploiting the inherent nature of fading channel, the proposed adaptive scheme enhances the spectral efficiency without additional transmit power while satisfying the required bit error rate criterion. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  2. A chimeric prokaryotic-eukaryotic pentameric ligand gated ion channel reveals interactions between the extracellular and transmembrane domains shape neurosteroid modulation.

    Science.gov (United States)

    Ghosh, Borna; Tsao, Tzu-Wei; Czajkowski, Cynthia

    2017-10-01

    Pentameric ligand-gated ion channels (pLGICs) are the targets of several clinical and endogenous allosteric modulators including anesthetics and neurosteroids. Molecular mechanisms underlying allosteric drug modulation are poorly understood. Here, we constructed a chimeric pLGIC by fusing the extracellular domain (ECD) of the proton-activated, cation-selective bacterial channel GLIC to the transmembrane domain (TMD) of the human ρ1 chloride-selective GABA A R, and tested the hypothesis that drug actions are regulated locally in the domain that houses its binding site. The chimeric channels were proton-gated and chloride-selective demonstrating the GLIC ECD was functionally coupled to the GABAρ TMD. Channels were blocked by picrotoxin and inhibited by pentobarbital, etomidate and propofol. The point mutation, ρ TMD W328M, conferred positive modulation and direct gating by pentobarbital. The data suggest that the structural machinery mediating general anesthetic modulation resides in the TMD. Proton-activation and neurosteroid modulation of the GLIC-ρ chimeric channels, however, did not simply mimic their respective actions on GLIC and GABAρ revealing that across domain interactions between the ECD and TMD play important roles in determining their actions. Proton-induced current responses were biphasic suggesting that the chimeric channels contain an additional proton sensor. Neurosteroid modulation of the GLIC-ρ chimeric channels by the stereoisomers, 5α-THDOC and 5β-THDOC, were swapped compared to their actions on GABAρ indicating that positive versus negative neurosteroid modulation is not encoded solely in the TMD nor by neurosteroid isomer structure but is dependent on specific interdomain connections between the ECD and TMD. Our data reveal a new mechanism for shaping neurosteroid modulation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Antibodies to the CFTR modulate the turgor pressure of guard cell protoplasts via slow anion channels.

    Science.gov (United States)

    Leonhardt, N; Bazin, I; Richaud, P; Marin, E; Vavasseur, A; Forestier, C

    2001-04-06

    The plasma membrane guard cell slow anion channel is a key element at the basis of water loss control in plants allowing prolonged osmolite efflux necessary for stomatal closure. This channel has been extensively studied by electrophysiological approaches but its molecular identification is still lacking. Recently, we described that this channel was sharing some similarities with the mammalian ATP-binding cassette protein, cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel [Leonhardt, N. et al. (1999) Plant Cell 11, 1141-1151]. Here, using the patch-clamp technique and a bioassay, consisting in the observation of the change in guard cell protoplasts volume, we demonstrated that a functional antibody raised against the mammalian CFTR prevented ABA-induced guard cell protoplasts shrinking and partially inhibited the slow anion current. Moreover, this antibody immunoprecipitated a polypeptide from guard cell protein extracts and immunolabeled stomata in Vicia faba leaf sections. These results indicate that the guard cell slow anion channel is, or is closely controlled by a polypeptide, exhibiting one epitope shared with the mammalian CFTR.

  4. Design And Construction Of The 8K Multi-Channel GAMMA Spectrometer Module (AMPLIFIER+ADC+MCD)

    International Nuclear Information System (INIS)

    Truong Van Dat; Hoang Thi Ngoc Bich; Pham Ngoc Tuan; Dang Lanh; Tuong Thi Thu Huong; Vu Xuan Cach

    2007-01-01

    A multichannel pulse-height analyzer system (MCA) consists of an spectroscopy Amplifier, ADC with 8192 channel performance, a histogramming memory, and a visual display of the histogram implemented on a Personal Computer (PC). The purpose of the analog-to-digital converter (ADC) is to measure the maximum amplitude of an analog pulse, and convert that value into a digital number. This digital output is a proportional representation of the analog amplitude at the ADC input. The digital ADC outputs are stored in a histogram memory, where each bin represents a pulse height interval and the number of events in each bin represents the number of events in that interval. The combination of ADC, histogramming memory and display functions are the minimum to constitute a multichannel analyzer or MCA based on PC. It is designed and fabricated on a single NIM module. The communication between MCA module and PC implements via USB bus. In our application, performance of the USB standard version 1.1 is good enough for purposes. The application program was designed in LabWIEW 8.0 software. This application is the main display and acquisition software for the MCA module. It is compatible with Windows 98SE/XP. The libraries USB driver, with their supporting files, are in the FTD2XX driver DLL Package and D2XX function 7.0 for LabWIEW supporting. These libraries are used to write custom code to control the MCA module. (author)

  5. Fertilizing ROSES through the STEM: Interdisciplinary Modules as Pre-service Research Experiences for Secondary STEM Educators (IMPRESS-Ed)

    Science.gov (United States)

    Kavic, Michael; Wiita, P. J.; Benoit, M.; Magee, N.

    2013-01-01

    IMPRESS-Ed is a program designed to provide authentic summer research experiences in the space, earth, and atmospheric sciences for pre-service K-12 educators at Long Island University (LIU) and The College of New Jersey (TCNJ). In 2011 and 2012, the program involved five students and took place over eight weeks with recruitment occurring during the preceding academic year. The program was divided into two modules: A common core module and an individual mentored research experience. The common module consisted of three units focusing on data-driven pedagogical approaches in astrophysics, tectonophysics, and atmospheric science, respectively. The common module also featured training sessions in observational astronomy, and use of a 3D geowall and state of the art planetarium. Participants in the program are also offered the opportunity to utilize the available TCNJ facilities with their future students. The individual mentored research module matched student interests with potential projects. All five students demonstrated strong gains in earth and space science literacy compared to a baseline measurement. Each student also reported gaining confidence to incorporate data and research-driven instruction in the space and earth sciences into the K-12 STEM classroom setting. All five research projects were also quite successful: several of the students plan to continue research during the academic year and two students are presenting research findings as first authors here at AAS. Other research results are likely to be presented at this year's American Geophysical Union meeting.

  6. Time spent studying on a pre-registration nursing programme module: an exploratory study and implications for regulation.

    Science.gov (United States)

    Snelling, Paul C; Lipscomb, Martin; Lockyer, Lesley; Yates, Sue; Young, Pat

    2010-11-01

    European Union (EU) regulations require that university programmes are of specified duration. Additional EU regulations apply specifically to university based nurse education, enacted in the UK by the Nursing and Midwifery Council (NMC). However, little is known about how much time student nurses spend on their studies. In this exploratory study, students undertaking a single module in the pre-registration diploma programme at an English university were asked to keep a log of learning activity for the duration of the module. Twenty-six students completed the log. These students achieved higher grades and attended more lectures than the average for the module. The mean study time was 128.4 h against a regulatory assumption that the module should take 200 h. More than half of the 26 students undertook paid work during the module run, though this work was not associated with poorer performance. Problems in regulation for course duration are discussed and it is suggested that undertaking a 4600 h course in 3 years is problematic. More research is required so that patterns of study can be better understood and student centred programmes meeting regulatory requirements developed. Copyright © 2010 Elsevier Ltd. All rights reserved.

  7. Channel control ASIC for the CMS hadron calorimeter front end readout module

    International Nuclear Information System (INIS)

    Ray Yarema et al.

    2002-01-01

    The Channel Control ASIC (CCA) is used along with a custom Charge Integrator and Encoder (QIE) ASIC to digitize signals from the hybrid photo diodes (HPDs) and photomultiplier tubes (PMTs) in the CMS hadron calorimeter. The CCA sits between the QIE and the data acquisition system. All digital signals to and from the QIE pass through the CCA chip. One CCA chip interfaces with two QIE channels. The CCA provides individually delayed clocks to each of the QIE chips in addition to various control signals. The QIE sends digitized PMT or HPD signals and time slice information to the CCA, which sends the data to the data acquisition system through an optical link

  8. History-based Adaptive Modulation for a Downlink Multicast Channel in OFDMA systems

    DEFF Research Database (Denmark)

    Wang, Haibo; Schwefel, Hans-Peter; Toftegaard, Thomas Skjødeberg

    2008-01-01

    In this paper we investigated the adaptive modulation strategies for Multicast service in orthogonal frequency division multiple access systems. We defined a Reward function as the performance optimization target and developed adaptive modulation strategies to maximize this Reward function....... The proposed optimization algorithm varied the instantaneous BER constraint of each mobile Multicast receiver according to its individual cumulated BER, which resulted in a significant Reward gain....

  9. A New Negative Allosteric Modulator AP14145 for the Study of Small Conductance Calcium-Activated Potassium Channels

    DEFF Research Database (Denmark)

    Simo Vicens, Rafel; Kirchhoff, Jeppe Egedal; Dolce, Bernardo

    2017-01-01

    ) prolongation in anaesthetised rats and a beam walk test was performed in mice to determine acute CNS related effects of the drug. Key results: AP14145 was found to be an equipotent negative allosteric modulator of KCa2.2 and KCa2.3 channels (IC50 = 1.1 ± 0.3 μM L-1). The presence of AP14145 (10 μM L-1......) increased the EC50 of Ca2+ on KCa2.3 from 0.36 ± 0.02 μM L-1 to 1.2 ± 0.1 μM L-1. The inhibitory effect strongly depended on two amino acids, S508 and A533. AP14145 concentration-dependently prolonged AERP in rats. Moreover, AP14145 (10 mg kg-1) did not trigger any apparent CNS effects in mice. Conclusion...... and implications: AP14145 is a negative allosteric modulator of KCa2.2 and KCa2.3 that shifts the calcium dependence of channel activation, an effect strongly dependent on two identified amino acids. AP14145 prolongs AERP in rats and does not trigger any acute CNS effects in mice. The understanding of how KCa2...

  10. Choline Modulation of the Aβ P1-40 Channel Reconstituted into a Model Lipid Membrane

    Directory of Open Access Journals (Sweden)

    Daniela Meleleo

    2010-01-01

    Full Text Available Nicotinic acetylcholine receptors (AChRs, implicated in memory and learning, in subjects affected by Alzheimer's disease result altered. Stimulation of α7-nAChRs inhibits amyloid plaques and increases ACh release. β-amyloid peptide (AβP forms ion channels in the cell and model phospholipid membranes that are retained responsible in Alzheimer disease. We tested if choline, precursor of ACh, could affect the AβP1-40 channels in oxidized cholesterol (OxCh and in palmitoyl-oleoyl-phosphatidylcholine (POPC:Ch lipid bilayers. Choline concentrations of 5 × 10−11 M–1.5 × 10−8 M added to the cis- or trans-side of membrane quickly increased AβP1-40 ion channel frequency (events/min and ion conductance in OxCh membranes, but not in POPC:Ch membranes. Circular Dichroism (CD spectroscopy shows that after 24 and 48 hours of incubation with AβP1-40, choline stabilizes the random coil conformation of the peptide, making it less prone to fibrillate. These actions seem to be specific in that ACh is ineffective either in solution or on AβP1-40 channel incorporated into PLMs.

  11. On probabilistic shaping of Quadrature Amplitude Modulation for the nonlinear fiber channel

    NARCIS (Netherlands)

    Fehenberger, T.; Alvarado, A.; Böcherer, G.; Hanik, N.

    2016-01-01

    Different aspects of probabilistic shaping for a multispan optical communication system are studied. First, a numerical analysis of the additive white Gaussian noise (AWGN) channel investigates the effect of using a small number of input probability mass functions (PMFs) for a range of

  12. Modulation of thalamocortical oscillations by TRIP8b, an auxiliary subunit for HCN channels

    NARCIS (Netherlands)

    Zobeiri, M.; Chaudhary, R.; Datunashvili, M.; Heuermann, R.J.; Lüttjohann, A.; Narayanan, V.; Balfanz, S.; Meuth, P.; Chetkovich, D.M.; Pape, H.C.; Baumann, A.; Luijtelaar, E.L.J.M. van; Budde, T.

    2018-01-01

    Hyperpolarization-activated cyclic nucleotide-gated cation (HCN) channels have important functions in controlling neuronal excitability and generating rhythmic oscillatory activity. The role of tetratricopeptide repeat-containing Rab8b-interacting protein (TRIP8b) in regulation of

  13. High-speed multiple-channel analog to digital data-acquisition module for microprocessor systems

    International Nuclear Information System (INIS)

    Ethridge, C.D.

    1977-01-01

    Intelligent data acquisition and instrumentation systems established by the incorporation of microprocessor technology require high-speed analog to digital conversion of multiple-channel input signals. Sophisticated data systems or subsystems are enabled by the microprocessor software flexibility to establish adaptive input data procedures. These adaptive procedures are enhanced by versatile interface circuitry which is software controlled

  14. Semi-local scaling and turbulence modulation in variable property turbulent channel flows

    NARCIS (Netherlands)

    Patel, A.; Peeters, J.W.R.; Boersma, B.J.; Pecnik, R.

    2015-01-01

    We theoretically and numerically investigate the effect of temperature dependent density and viscosity on turbulence in channel flows. First, a mathematical framework is developed to support the validity of the semi-local scaling as proposed based on heuristic arguments by Huang, Coleman, and

  15. Rab4GTPase modulates CFTR function by impairing channel expression at plasma membrane

    International Nuclear Information System (INIS)

    Saxena, Sunil K.; Kaur, Simarna; George, Constantine

    2006-01-01

    Cystic fibrosis (CF), an autosomal recessive disorder, is caused by the disruption of biosynthesis or the function of a membrane cAMP-activated chloride channel, CFTR. CFTR regulatory mechanisms include recruitment of channel proteins to the cell surface from intracellular pools and by protein-protein interactions. Rab proteins are small GTPases involved in regulated trafficking controlling vesicle docking and fusion. Rab4 controls recycling events from endosome to the plasma membrane, fusion, and degradation. The colorectal cell line HT-29 natively expresses CFTR and responds to cAMP stimulation with an increase in CFTR-mediated currents. Rab4 over-expression in HT-29 cells inhibits both basal and cAMP-stimulated CFTR-mediated currents. GTPase-deficient Rab4Q67L and GDP locked Rab4S22N both inhibit channel activity, which appears characteristically different. Active status of Rab4 was confirmed by GTP overlay assay, while its expression was verified by Western blotting. The pull-down and immunoprecipitation experiments suggest that Rab4 physically interacts with CFTR through protein-protein interaction. Biotinylation with cell impermeant NHS-Sulfo-SS-Biotin implies that Rab4 impairs CFTR expression at cell surface. The enhanced cytosolic CFTR indicates that Rab4 expression restrains CFTR appearance at the cell membrane. The study suggests that Rab4 regulates the channel through multiple mechanisms that include protein-protein interaction, GTP/GDP exchange, and channel protein trafficking. We propose that Rab4 is a dynamic molecule with a significant role in CFTR function

  16. Carrier frequency offset estimation for an acoustic-electric channel using 16 QAM modulation

    Science.gov (United States)

    Cunningham, Michael T.; Anderson, Leonard A.; Wilt, Kyle R.; Chakraborty, Soumya; Saulnier, Gary J.; Scarton, Henry A.

    2016-05-01

    Acoustic-electric channels can be used to send data through metallic barriers, enabling communications where electromagnetic signals are ineffective. This paper considers an acoustic-electric channel that is formed by mounting piezoelectric transducers on metallic barriers that are separated by a thin water layer. The transducers are coupled to the barriers using epoxy and the barriers are positioned to axially-align the PZTs, maximizing energy transfer efficiency. The electrical signals are converted by the transmitting transducers into acoustic waves, which propagate through the elastic walls and water medium to the receiving transducers. The reverberation of the acoustic signals in these channels can produce multipath distortion with a significant delay spread that introduces inter-symbol interference (ISI) into the received signal. While the multipath effects can be severe, the channel does not change rapidly which makes equalization easier. Here we implement a 16-QAM system on this channel, including a method for obtaining accurate carrier frequency offset (CFO) estimates in the presence of the quasi-static multipath propagation. A raised-power approach is considered but found to suffer from excessive data noise resulting from the ISI. An alternative approach that utilizes a pilot tone burst at the start of a data packet is used for CFO estimation and found to be effective. The autocorrelation method is used to estimate the frequency of the received burst. A real-time prototype of the 16 QAM system that uses a Texas Instruments MSP430 microcontroller-based transmitter and a personal computer-based receiver is presented along with performance results.

  17. Design of multiplier-less sharp non-uniform cosine modulated filter banks for efficient channelizers in software defined radio

    Directory of Open Access Journals (Sweden)

    Shaeen Kalathil

    2016-03-01

    Full Text Available Forthcoming software defined radios require filter banks which satisfy stringent specifications efficiently with low implementation complexity. Cosine modulated filter banks (CMFB have simple and efficient design procedure. The different wireless standards have different channel spacing or bandwidths and hence demand non-uniform decomposition of subbands. The non-uniform CMFB can be obtained from a uniform CMFB in a simple and efficient approach by merging the adjacent channels of the uniform CMFB. Very narrow transition width filters with low complexity can be achieved using frequency response masking (FRM filter as prototype filter. The complexity is further reduced by the multiplier-less realization of filter banks in which the least number of signed power of two (SPT terms is achieved by representing the filter coefficients using canonic signed digit (CSD representation and then optimizing using suitable modified meta-heuristic algorithms. Hybrid meta-heuristic algorithms are used in this paper. A hybrid algorithm combines the qualities of two meta-heuristic algorithms and results in improved performances with low implementation complexity. Highly frequency selective filter banks characterized by small passband ripple, narrow transition width and high stopband attenuation with non-uniform decomposition of subbands can be designed with least the implementation complexity, using this approach. A digital channelizer can be designed for SDR implementations, using the proposed approach. In this paper, the non-uniform CMFB is designed for various existing wireless standards.

  18. Domain–domain interactions determine the gating, permeation, pharmacology, and subunit modulation of the IKs ion channel

    Science.gov (United States)

    Zaydman, Mark A; Kasimova, Marina A; McFarland, Kelli; Beller, Zachary; Hou, Panpan; Kinser, Holly E; Liang, Hongwu; Zhang, Guohui; Shi, Jingyi; Tarek, Mounir; Cui, Jianmin

    2014-01-01

    Voltage-gated ion channels generate electrical currents that control muscle contraction, encode neuronal information, and trigger hormonal release. Tissue-specific expression of accessory (β) subunits causes these channels to generate currents with distinct properties. In the heart, KCNQ1 voltage-gated potassium channels coassemble with KCNE1 β-subunits to generate the IKs current (Barhanin et al., 1996; Sanguinetti et al., 1996), an important current for maintenance of stable heart rhythms. KCNE1 significantly modulates the gating, permeation, and pharmacology of KCNQ1 (Wrobel et al., 2012; Sun et al., 2012; Abbott, 2014). These changes are essential for the physiological role of IKs (Silva and Rudy, 2005); however, after 18 years of study, no coherent mechanism explaining how KCNE1 affects KCNQ1 has emerged. Here we provide evidence of such a mechanism, whereby, KCNE1 alters the state-dependent interactions that functionally couple the voltage-sensing domains (VSDs) to the pore. DOI: http://dx.doi.org/10.7554/eLife.03606.001 PMID:25535795

  19. Modulation of Acid-sensing Ion Channel 1a by Intracellular pH and Its Role in Ischemic Stroke.

    Science.gov (United States)

    Li, Ming-Hua; Leng, Tian-Dong; Feng, Xue-Chao; Yang, Tao; Simon, Roger P; Xiong, Zhi-Gang

    2016-08-26

    An important contributor to brain ischemia is known to be extracellular acidosis, which activates acid-sensing ion channels (ASICs), a family of proton-gated sodium channels. Lines of evidence suggest that targeting ASICs may lead to novel therapeutic strategies for stroke. Investigations of the role of ASICs in ischemic brain injury have naturally focused on the role of extracellular pH in ASIC activation. By contrast, intracellular pH (pHi) has received little attention. This is a significant gap in our understanding because the ASIC response to extracellular pH is modulated by pHi, and activation of ASICs by extracellular protons is paradoxically enhanced by intracellular alkalosis. Our previous studies show that acidosis-induced cell injury in in vitro models is attenuated by intracellular acidification. However, whether pHi affects ischemic brain injury in vivo is completely unknown. Furthermore, whereas ASICs in native neurons are composed of different subunits characterized by distinct electrophysiological/pharmacological properties, the subunit-dependent modulation of ASIC activity by pHi has not been investigated. Using a combination of in vitro and in vivo ischemic brain injury models, electrophysiological, biochemical, and molecular biological approaches, we show that the intracellular alkalizing agent quinine potentiates, whereas the intracellular acidifying agent propionate inhibits, oxygen-glucose deprivation-induced cell injury in vitro and brain ischemia-induced infarct volume in vivo Moreover, we find that the potentiation of ASICs by quinine depends on the presence of the ASIC1a, ASIC2a subunits, but not ASIC1b, ASIC3 subunits. Furthermore, we have determined the amino acids in ASIC1a that are involved in the modulation of ASICs by pHi. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  20. Characterisation of the effect of ion channel modulators on I1-imidazoline binding sites in bovine adrenal medulla

    International Nuclear Information System (INIS)

    Musgrave, I.F.; Kotsopoulos, D.; Hughes, R.A.

    1998-01-01

    Full text: The structure of I 1 -imidazoline binding sites is still unknown and we have proposed that they represent ion channels (i). In these experiments we characterised the effects of the known ion channel modulators methyltriphenylphosphonium (MTPP), 4-aminopyridine (4-AP) and tetraethyl ammonium (TEA) on [ 3 H] clonidine binding in bovine adrenal medullary membranes as these membranes have a relatively well defined I 1 -imidazoline binding site (Molderings et al, 1993). Membranes from bovine adrenal medulla's were prepared by a minor modification of the method of Rapier et al. [ 3 H] Clonidine binding was performed by the method of Ernsberger et al (3), with [ 3 H] clonidine (62 Ci/mmol) used at a final concentration of 5 nM. [ 3 H] Clonidine binding was displaced from bovine adrenal medullary membranes by adrenergic drugs with the order of potency being oxymetazoline > clonidine > moxonidine = idazoxan >> yonimbine. This order of potency is consistent with previous studies of I 1 -imidazoline binding sites (4). Non-linear curve fitting to this data was consistent with a single site model. Both TEA and 4-AP displaced [ H] clonidine with similar potency to its effect on ion channels, TEA having a EC>> of 54 ± 0.3 μM (n=3). The displacement of [ 3 H] clonidine produced by both TEA and 4-AP also fitted to a single site model. Displacement of [ 3 H] clonidine by MTPP fitted a two site model (p 1 -imidazoline binding sites defined with [ 3 H] clonidine may represent ion channels. We have used this data to perform molecular modelling and have determined a common conformation of I 1 -prefering ligands which will aid in the development of I 1 -selective ligands in the future. Copyright (1998) Australian Neuroscience Society

  1. Drosophila QVR/SSS modulates the activation and C-type inactivation kinetics of Shaker K+ channels

    Science.gov (United States)

    Dean, Terry; Xu, Rong; Joiner, William; Sehgal, Amita; Hoshi, Toshinori

    2011-01-01

    The quiver/sleepless (qvr/sss) gene encodes a small, glycosylphosphatidylinositol-anchored protein that plays a critical role in the regulation of sleep in Drosophila. Loss-of-function mutations in qvr/sss severely suppress sleep and effect multiple changes in in situ Shaker K+ currents, including decreased magnitude, slower time-to-peak, and cumulative inactivation. Recently, we demonstrated that SLEEPLESS (SSS) protein modulates Shaker channel activity, possibly through a direct interaction at the plasma membrane. We show here that SSS accelerates the activation of heterologously expressed Shaker channels with no effect on deactivation or fast N-type inactivation. Furthermore, this SSS-induced acceleration is sensitive to the pharmacological disruption of lipid rafts and sufficiently accounts for the slower time-to-peak of in situ Shaker currents seen in qvr/sss mutants. We also find that SSS decreases the rate of C-type inactivation of heterologously expressed Shaker channels, providing a potential mechanism for the cumulative inactivation phenotype induced by qvr/sss loss of function mutations. Kinetic modeling based on the in vitro results suggests that the SSS-dependent regulation of channel kinetics accounts for nearly 40% of the decrease in Shaker current magnitude in flies lacking SSS. Sleep duration in qvr/sss null mutants is restored to normal by a qvr/sss transgene that fully rescues the Shaker kinetic phenotypes but only partially rescues the decrease in current magnitude. Together, these results suggest that the role of SSS in the regulation of sleep in Drosophila correlates more strongly with the effects of SSS on Shaker kinetics than current magnitude. PMID:21813698

  2. Drosophila QVR/SSS modulates the activation and C-type inactivation kinetics of Shaker K(+) channels.

    Science.gov (United States)

    Dean, Terry; Xu, Rong; Joiner, William; Sehgal, Amita; Hoshi, Toshinori

    2011-08-03

    The quiver/sleepless (qvr/sss) gene encodes a small, glycosylphosphatidylinositol-anchored protein that plays a critical role in the regulation of sleep in Drosophila. Loss-of-function mutations in qvr/sss severely suppress sleep and effect multiple changes in in situ Shaker K(+) currents, including decreased magnitude, slower time-to-peak, and cumulative inactivation. Recently, we demonstrated that SLEEPLESS (SSS) protein modulates Shaker channel activity, possibly through a direct interaction at the plasma membrane. We show here that SSS accelerates the activation of heterologously expressed Shaker channels with no effect on deactivation or fast N-type inactivation. Furthermore, this SSS-induced acceleration is sensitive to the pharmacological disruption of lipid rafts and sufficiently accounts for the slower time-to-peak of in situ Shaker currents seen in qvr/sss mutants. We also find that SSS decreases the rate of C-type inactivation of heterologously expressed Shaker channels, providing a potential mechanism for the cumulative inactivation phenotype induced by qvr/sss loss-of-function mutations. Kinetic modeling based on the in vitro results suggests that the SSS-dependent regulation of channel kinetics accounts for nearly 40% of the decrease in Shaker current magnitude in flies lacking SSS. Sleep duration in qvr/sss-null mutants is restored to normal by a qvr/sss transgene that fully rescues the Shaker kinetic phenotypes but only partially rescues the decrease in current magnitude. Together, these results suggest that the role of SSS in the regulation of sleep in Drosophila correlates more strongly with the effects of SSS on Shaker kinetics than current magnitude.

  3. Molecular mechanisms of Cys-loop ion channel receptor modulation by ivermectin

    DEFF Research Database (Denmark)

    Lynagh, Timothy; Lynch, Joseph W.

    2012-01-01

    Ivermectin is an anthelmintic drug that works by inhibiting neuronal activity and muscular contractility in arthropods and nematodes. It works by activating glutamate-gated chloride channels (GluClRs) at nanomolar concentrations. These receptors, found exclusively in invertebrates, belong to the ...... to the neurotransmitter binding site, thus suggesting a mechanism by which ivermectin potentiates neurotransmitter-gated currents. Together, this information provides new insights into the mechanisms of action of this important drug.......) to its site. Several lines of evidence suggest that ivermectin opens the channel pore via a structural change distinct from that induced by the neurotransmitter agonist. Conformational changes occurring at locations distant from the pore can be probed using voltage-clamp fluorometry (VCF), a technique...

  4. Modulation of the epithelial Ca2+ channel ECaC by extracellular pH.

    NARCIS (Netherlands)

    Vennekens, R.; Prenen, J.; Hoenderop, J.G.J.; Bindels, R.J.M.; Droogmans, G.; Nilius, B.

    2001-01-01

    We investigated the effect of extracellular pH on whole-cell currents through the epithelial Ca2+ channel, ECaC, expressed in HEK 293 cells. Both mono- and divalent current densities were significantly smaller at pH 6.0 than at pH 7.4. At pH 8.5 they were slightly larger. Lowering extracellular pH

  5. Characterization of potassium channel modulators with QPatch automated patch-clamp technology: system characteristics and performance

    DEFF Research Database (Denmark)

    Kutchinsky, Jonatan; Friis, Søren; Asmild, Margit

    2003-01-01

    Planar silicon chips with 1-2-microm etched holes (average resistance: 2.04 +/- 0.02 MOmega in physiological buffer, n = 274) have been developed for patch-clamp recordings of whole-cell currents from cells in suspension. An automated 16-channel parallel screening system, QPatch 16, has been deve......-response relationship characterizations of verapamil and rBeKm-1 blockage of hERG currents provided IC(50) values similar to values reported in the literature....

  6. Modulation of voltage-gated channel currents by harmaline and harmane

    OpenAIRE

    Splettstoesser, Frank; Bonnet, Udo; Wiemann, Martin; Bingmann, Dieter; Büsselberg, Dietrich

    2004-01-01

    Harmala alkaloids are endogenous substances, which are involved in neurodegenerative disorders such as M. Parkinson, but some of them also have neuroprotective effects in the nervous system.While several sites of action at the cellular level (e.g. benzodiazepine receptors, 5-HT and GABAA receptors) have been identified, there is no report on how harmala alkaloids interact with voltage-gated membrane channels.The aim of this study was to investigate the effects of harmaline and harmane on volt...

  7. Clinical Application of Colour Modulation of Gamma Energy and Depth by Dual-Channel Scanning

    Energy Technology Data Exchange (ETDEWEB)

    Kaplan, E.; Ben-Porath, M. [Veterans Administration Hospital, Hines, IL (United States)

    1969-01-15

    A dual-channel scanning system has been described permitting the simultaneous imaging in individual color of the distribution of two gamma-emitting radioisotopes. In those cases where two organs are adjacent and concentrate the same isotope, they may be displayed in separate color if one of the organs concentrates another gamma-emitting isotope with a different energy. This is accomplished by individual color readout of this isotope and the display of the subtraction of this isotope from the common isotope in another color. By using two facing scintillation probes on either side of the individual being scanned, two overlapping organs at different depths concentrating the same isotope can be color differentiated by a dual-channel playout of each probe. The principal application of these dual-channel scanning methods to date has been the simultaneous display of the liver and pancreas in individual colors using {sup 198}Au and {sup 75}selenomethionine. Characteristic scans have been obtained which differentiate a number of disease states from the normal pancreas and liver. The pancreatic and liver diseases studied and characterized are carcinoma of the pancreas, pancreatic insufficiency, acute recurrent pancreatitis, pancreatic pseudocyst and Laennec's cirrhosis, hepatoma and metastatic malignancy in the liver. The uptake of {sup 75}selenomethionine in malignant lesions in many instances produces positive scans of these tumors in contrasting color to the liver. Depth discrimination in color with the two-probe system has permitted the lateralization of intracranial lesions, the color of the display being proportional to the depth of the lesion. The discrimination of depth and gamma-ray energy by dual-channel color scanning and its general application in visualizing other organs has been accomplished. (author)

  8. Efficient and Robust Detection of GFSK Signals under Dispersive Channel, Modulation Index, and Carrier Frequency Offset Conditions

    Directory of Open Access Journals (Sweden)

    Stephan Weiss

    2005-09-01

    Full Text Available Gaussian frequency shift keying is the modulation scheme specified for Bluetooth. Signal adversities typical in Bluetooth networks include AWGN, multipath propagation, carrier frequency, and modulation index offsets. In our effort to realise a robust but efficient Bluetooth receiver, we adopt a high-performance matched-filter-based detector, which is near optimal in AWGN, but requires a prohibitively costly filter bank for processing of K bits worth of the received signal. However, through filtering over a single bit period and performing phase propagation of intermediate results over successive single-bit stages, we eliminate redundancy involved in providing the matched filter outputs and reduce its complexity by up to 90% (for K=9. The constant modulus signal characteristic and the potential for carrier frequency offsets make the constant modulus algorithm (CMA suitable for channel equalisation, and we demonstrate its effectiveness in this paper. We also introduce a stochastic gradient-based algorithm for carrier frequency offset correction, and show that the relative rotation between successive intermediate filter outputs enables us to detect and correct offsets in modulation index.

  9. Improving soft FEC performance for higher-order modulations via optimized bit channel mappings.

    Science.gov (United States)

    Häger, Christian; Amat, Alexandre Graell I; Brännström, Fredrik; Alvarado, Alex; Agrell, Erik

    2014-06-16

    Soft forward error correction with higher-order modulations is often implemented in practice via the pragmatic bit-interleaved coded modulation paradigm, where a single binary code is mapped to a nonbinary modulation. In this paper, we study the optimization of the mapping of the coded bits to the modulation bits for a polarization-multiplexed fiber-optical system without optical inline dispersion compensation. Our focus is on protograph-based low-density parity-check (LDPC) codes which allow for an efficient hardware implementation, suitable for high-speed optical communications. The optimization is applied to the AR4JA protograph family, and further extended to protograph-based spatially coupled LDPC codes assuming a windowed decoder. Full field simulations via the split-step Fourier method are used to verify the analysis. The results show performance gains of up to 0.25 dB, which translate into a possible extension of the transmission reach by roughly up to 8%, without significantly increasing the system complexity.

  10. Adaptive Modulation with Best User Selection over Non-Identical Nakagami Fading Channels

    KAUST Repository

    Rao, Anlei; Alouini, Mohamed-Slim

    2012-01-01

    capacity, spectral efficiency, and bit-error-rate (BER) for both constant-power variable-rate and variable-power variable-rate uncoded M-ary quadrature amplitude modulation (M-QAM) schemes. We also study the impact of time delay on the average BER

  11. Exogenous γ-aminobutyric acid (GABA) affects pollen tube growth via modulating putative Ca2+-permeable membrane channels and is coupled to negative regulation on glutamate decarboxylase

    Science.gov (United States)

    Yu, Guang-Hui; Zou, Jie; Feng, Jing; Peng, Xiong-Bo; Wu, Ju-You; Wu, Ying-Liang; Palanivelu, Ravishankar; Sun, Meng-Xiang

    2014-01-01

    γ-Aminobutyric acid (GABA) is implicated in pollen tube growth, but the molecular and cellular mechanisms that it mediates are largely unknown. Here, it is shown that exogenous GABA modulates putative Ca2+-permeable channels on the plasma membranes of tobacco pollen grains and pollen tubes. Whole-cell voltage-clamp experiments and non-invasive micromeasurement technology (NMT) revealed that the influx of Ca2+ increases in pollen tubes in response to exogenous GABA. It is also demonstrated that glutamate decarboxylase (GAD), the rate-limiting enzyme of GABA biosynthesis, is involved in feedback controls of Ca2+-permeable channels to fluctuate intracellular GABA levels and thus modulate pollen tube growth. The findings suggest that GAD activity linked with Ca2+-permeable channels relays an extracellular GABA signal and integrates multiple signal pathways to modulate tobacco pollen tube growth. Thus, the data explain how GABA mediates the communication between the style and the growing pollen tubes. PMID:24799560

  12. Hormonal modulation of breast cancer gene expression: implications for intrinsic subtyping in pre-menopausal women

    Directory of Open Access Journals (Sweden)

    Sarah M Bernhardt

    2016-11-01

    Full Text Available Clinics are increasingly adopting gene expression profiling to diagnose breast cancer subtype, providing an intrinsic, molecular portrait of the tumour. For example, the PAM50-based Prosigna test quantifies expression of 50 key genes to classify breast cancer subtype, and this method of classification has been demonstrated to be superior over traditional immunohistochemical methods that detect proteins, to predict risk of disease recurrence. However, these tests were largely developed and validated using breast cancer samples from post-menopausal women. Thus, the accuracy of such tests has not been explored in the context of the hormonal fluctuations in estrogen and progesterone that occur during the menstrual cycle in pre-menopausal women. Concordance between traditional methods of subtyping and the new tests in pre-menopausal women is likely to depend on the stage of the menstrual cycle at which the tissue sample is taken, and the relative effect of hormones on expression of genes versus proteins. The lack of knowledge around the effect of fluctuating estrogen and progesterone on gene expression in breast cancer patients raises serious concerns for intrinsic subtyping in pre-menopausal women, which comprise about 25% of breast cancer diagnoses. Further research on the impact of the menstrual cycle on intrinsic breast cancer profiling is required if pre-menopausal women are to benefit from the new technology of intrinsic subtyping.

  13. Evaluation of a Pre-Service Training Module in Microcomputer Applications for the Teaching of Reading.

    Science.gov (United States)

    Balajthy, Ernest

    1988-01-01

    Discussion of the need for increased teacher training in computer applications in education focuses on the evaluation of a training module developed to train preservice teachers in computer applications for reading courses. Student ratings of the importance of computers, self-perception of knowledge of computers, and attitudes toward computers are…

  14. Ecuadorian Quecha Basic Course. Part II: Introduction and Pre-Class Modules.

    Science.gov (United States)

    Ott, Clarence Eric; And Others

    The second of a two-volume series on Ecuadorian Quechua, this text contains 15 units of preclass instructional material designed for individualized study with the use of accompanying tapes. Each unit of the course has a homework section, called a module, to be completed before classwork may be started. Cartoon figures illustrate the instructional…

  15. Modulation of Connexin-36 Gap Junction Channels by Intracellular pH and Magnesium Ions.

    Science.gov (United States)

    Rimkute, Lina; Kraujalis, Tadas; Snipas, Mindaugas; Palacios-Prado, Nicolas; Jotautis, Vaidas; Skeberdis, Vytenis A; Bukauskas, Feliksas F

    2018-01-01

    Connexin-36 (Cx36) protein forms gap junction (GJ) channels in pancreatic beta cells and is also the main Cx isoform forming electrical synapses in the adult mammalian brain. Cx36 GJs can be regulated by intracellular pH (pH i ) and cytosolic magnesium ion concentration ([Mg 2+ ] i ), which can vary significantly under various physiological and pathological conditions. However, the combined effect and relationship of these two factors over Cx36-dependent coupling have not been previously studied in detail. Our experimental results in HeLa cells expressing Cx36 show that changes in both pH i and [Mg 2+ ] i affect junctional conductance (g j ) in an interdependent manner; in other words, intracellular acidification cause increase or decay in g j depending on whether [Mg 2+ ] i is high or low, respectively, and intracellular alkalization cause reduction in g j independently of [Mg 2+ ] i . Our experimental and modelling data support the hypothesis that Cx36 GJ channels contain two separate gating mechanisms, and both are differentially sensitive to changes in pH i and [Mg 2+ ] i . Using recombinant Cx36 we found that two glutamate residues in the N-terminus could be partly responsible for the observed interrelated effect of pH i and [Mg 2+ ] i . Mutation of glutamate at position 8 attenuated the stimulatory effect of intracellular acidification at high [Mg 2+ ] i , while mutation at position 12 and double mutation at both positions reversed stimulatory effect to inhibition. Moreover, Cx36 * E8Q lost the initial increase of g j at low [Mg 2+ ] i and double mutation lost the sensitivity to high [Mg 2+ ] i . These results suggest that E8 and E12 are involved in regulation of Cx36 GJ channels by Mg 2+ and H + ions.

  16. Ergodic channel capacity of spatial correlated multiple-input multiple-output free space optical links using multipulse pulse-position modulation

    Science.gov (United States)

    Wang, Huiqin; Wang, Xue; Cao, Minghua

    2017-02-01

    The spatial correlation extensively exists in the multiple-input multiple-output (MIMO) free space optical (FSO) communication systems due to the channel fading and the antenna space limitation. Wilkinson's method was utilized to investigate the impact of spatial correlation on the MIMO FSO communication system employing multipulse pulse-position modulation. Simulation results show that the existence of spatial correlation reduces the ergodic channel capacity, and the reception diversity is more competent to resist this kind of performance degradation.

  17. Mutagenesis in mammalian cells can be modulated by radiation-induced voltage-dependent potassium channels

    International Nuclear Information System (INIS)

    Saad, A.H.; Zhou, L.Y.; Lambe, E.K.; Hahn, G.M.

    1994-01-01

    In mammalian cells, little is known about the initial events whose ultimate consequence is mutagenesis or DNA repair. The role the plasma membrane may play as an initiator of such a pathway is not understood. We show, for the first time, that membrane voltage-dependent potassium (K + ) currents, activated by ionizing radiation play a significant role in radiation mutagenesis. Specifically, we show that the frequency of mutation at the HGPRT locus is increased as expected to 37.6±4.0 mutations per 100,000 survivors by 800 cGy of ionizing radiation from a spontaneous frequency of 1.5±1.5. This increase, however, is abolished if either K + channel blocker, CsCl or BaCl 2 , is present for 2h following irradiation of the cells. RbCl, chemically similar to CsCl but known not to block K + channels, is ineffective in reducing the mutation frequency. Treatment of cells with CsCl or BaCl 2 had no effect on radiation-induced cell killing

  18. Involvement of TRPV1 channels in the periaqueductal grey on the modulation of innate fear responses.

    Science.gov (United States)

    Aguiar, Daniele C; Almeida-Santos, Ana F; Moreira, Fabricio A; Guimarães, Francisco S

    2015-04-01

    The transient receptor potential vanilloid type-1 channel (TRPV1) is expressed in the midbrain periaqueductal grey (PAG), a region of the brain related to aversive responses. TRPV1 antagonism in the dorsolateral PAG (dlPAG) induces anxiolytic-like effects in models based on conflict situations. No study, however, has investigated whether these receptors could contribute to fear responses to proximal threat. Thus, we tested the hypothesis that TRPV1 in the PAG could mediate fear response in rats exposed to a predator. We verified whether exposure to a live cat (a natural predator) would activate TRPV1-expressing neurons in the PAG. Double-staining immunohistochemistry was used as a technique to detect c-Fos, a marker of neuronal activation, and TRPV1 expression. We also investigated whether intra-dlPAG injections of the TRPV1 antagonist, capsazepine (CPZ), would attenuate the behavioural consequences of predator exposure. Exposure to a cat increased c-Fos expression in TRPV1-positive neurons, mainly in the dorsal columns of the PAG, suggesting that TRPV1-expressing neurons are activated by threatening stimuli. Accordingly, local injection of CPZ inhibited the fear responses. These data support the hypothesis that TRPV1 channels mediate fear reactions in the dlPAG. This may have an implication for the development of TRPV1-antagonists as potential drugs for the treatment of certain psychiatric disorders.

  19. Dietary Factors Modulate Colonic Tumorigenesis Through the Interaction of Gut Microbiota and Host Chloride Channels.

    Science.gov (United States)

    Zhang, Yong; Kang, Chao; Wang, Xiao-Lan; Zhou, Min; Chen, Meng-Ting; Zhu, Xiao-Hui; Liu, Kai; Wang, Bin; Zhang, Qian-Yong; Zhu, Jun-Dong; Mi, Man-Tian

    2018-03-01

    In recent decades, the association among diet, gut microbiota, and the risk of colorectal cancer (CRC) has been established. Gut microbiota and associated metabolites, such as bile acids and butyrate, are now known to play a key role in CRC development. The aim of this study is to identify that the progression to CRC is influenced by cholic acid, sodium butyrate, a high-fat diet, or different dose of dihydromyricetin (DMY) interacted with gut microbiota. An AOM/DSS (azoxymethan/dextran sodium sulfate) model is established to study the gut microbiota compsition before and after tumor formation during colitis-induced tumorigenesis. All above dietary factors profoundly influence the composition of gut microbiota and host colonic tumorigenesis. In addition, mice with DMY-modified initial microbiota display different degrees of chemically induced tumorigenesis. Mechanism analysis reveals that gut microbiota-associated chloride channels participated in colon tumorigenesis. Gut microbiota changes occur in the hyperproliferative stage before tumor formation. Gut microbiota and host chloride channels, both of which are regulated by dietary factors, are associated with CRC development. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Direct evidence that scorpion α-toxins (site-3 modulate sodium channel inactivation by hindrance of voltage-sensor movements.

    Directory of Open Access Journals (Sweden)

    Zhongming Ma

    Full Text Available The position of the voltage-sensing transmembrane segment, S4, in voltage-gated ion channels as a function of voltage remains incompletely elucidated. Site-3 toxins bind primarily to the extracellular loops connecting transmembrane helical segments S1-S2 and S3-S4 in Domain 4 (D4 and S5-S6 in Domain 1 (D1 and slow fast-inactivation of voltage-gated sodium channels. As S4 of the human skeletal muscle voltage-gated sodium channel, hNav1.4, moves in response to depolarization from the resting to the inactivated state, two D4S4 reporters (R2C and R3C, Arg1451Cys and Arg1454Cys, respectively move from internal to external positions as deduced by reactivity to internally or externally applied sulfhydryl group reagents, methane thiosulfonates (MTS. The changes in reporter reactivity, when cycling rapidly between hyperpolarized and depolarized voltages, enabled determination of the positions of the D4 voltage-sensor and of its rate of movement. Scorpion α-toxin binding impedes D4S4 segment movement during inactivation since the modification rates of R3C in hNav1.4 with methanethiosulfonate (CH3SO2SCH2CH2R, where R = -N(CH33 (+ trimethylammonium, MTSET and benzophenone-4-carboxamidocysteine methanethiosulfonate (BPMTS were slowed ~10-fold in toxin-modified channels. Based upon the different size, hydrophobicity and charge of the two reagents it is unlikely that the change in reactivity is due to direct or indirect blockage of access of this site to reagent in the presence of toxin (Tx, but rather is the result of inability of this segment to move outward to the normal extent and at the normal rate in the toxin-modified channel. Measurements of availability of R3C to internally applied reagent show decreased access (slower rates of thiol reaction providing further evidence for encumbered D4S4 movement in the presence of toxins consistent with the assignment of at least part of the toxin binding site to the region of D4S4 region of the voltage

  1. FMECA about pre-treatment system for purge gas of test blanket module in ITER

    International Nuclear Information System (INIS)

    Fu Wanfa; Luo Deli; Tang Tao

    2012-01-01

    The pre-treatment system for purge gas of TBM will be installed in Port Cell for installing TBM in ITER, the function of which includes filtering purge gas, removing HTO, cooling, and adjusting flow rate, etc. The purge gas treated will be conveyed into TES (Tritium Extraction System). The technological process and system components in pre-treatment system were introduced. Tritium releasing risk was regarded as failure criterion; failure mode, effects and criticality analysis (FMECA) were carried out and several weaknesses or failure mode in the system were found. Besides, risk priority number (RPN) and failure mode criticality were calculated. Finally, some design improvement measures and usage compensation measures were given. At last, four important potential failure modes were found out. The analysis will provide the design basis for reducing risk of excessive tritium releasing, which is also a useful assist for safety analysis about other tritium system. (authors)

  2. Electron spin-echo envelope modulation (ESEEM) reveals water and phosphate interactions with the KcsA potassium channel.

    Science.gov (United States)

    Cieslak, John A; Focia, Pamela J; Gross, Adrian

    2010-02-23

    Electron spin-echo envelope modulation (ESEEM) spectroscopy is a well-established technique for the study of naturally occurring paramagnetic metal centers. The technique has been used to study copper complexes, hemes, enzyme mechanisms, micellar water content, and water permeation profiles in membranes, among other applications. In the present study, we combine ESEEM spectroscopy with site-directed spin labeling (SDSL) and X-ray crystallography in order to evaluate the technique's potential as a structural tool to describe the native environment of membrane proteins. Using the KcsA potassium channel as a model system, we demonstrate that deuterium ESEEM can detect water permeation along the lipid-exposed surface of the KcsA outer helix. We further demonstrate that (31)P ESEEM is able to identify channel residues that interact with the phosphate headgroup of the lipid bilayer. In combination with X-ray crystallography, the (31)P data may be used to define the phosphate interaction surface of the protein. The results presented here establish ESEEM as a highly informative technique for SDSL studies of membrane proteins.

  3. Brain-derived neurotrophic factor modulation of Kv1.3 channel is disregulated by adaptor proteins Grb10 and nShc

    Directory of Open Access Journals (Sweden)

    Marks David R

    2009-01-01

    Full Text Available Abstract Background Neurotrophins are important regulators of growth and regeneration, and acutely, they can modulate the activity of voltage-gated ion channels. Previously we have shown that acute brain-derived neurotrophic factor (BDNF activation of neurotrophin receptor tyrosine kinase B (TrkB suppresses the Shaker voltage-gated potassium channel (Kv1.3 via phosphorylation of multiple tyrosine residues in the N and C terminal aspects of the channel protein. It is not known how adaptor proteins, which lack catalytic activity, but interact with members of the neurotrophic signaling pathway, might scaffold with ion channels or modulate channel activity. Results We report the co-localization of two adaptor proteins, neuronal Src homology and collagen (nShc and growth factor receptor-binding protein 10 (Grb10, with Kv1.3 channel as demonstrated through immunocytochemical approaches in the olfactory bulb (OB neural lamina. To further explore the specificity and functional ramification of adaptor/channel co-localization, we performed immunoprecipitation and Western analysis of channel, kinase, and adaptor transfected human embryonic kidney 293 cells (HEK 293. nShc formed a direct protein-protein interaction with Kv1.3 that was independent of BDNF-induced phosphorylation of Kv1.3, whereas Grb10 did not complex with Kv1.3 in HEK 293 cells. Both adaptors, however, co-immunoprecipitated with Kv1.3 in native OB. Grb10 was interestingly able to decrease the total expression of Kv1.3, particularly at the membrane surface, and subsequently eliminated the BDNF-induced phosphorylation of Kv1.3. To examine the possibility that the Src homology 2 (SH2 domains of Grb10 were directly binding to basally phosphorylated tyrosines in Kv1.3, we utilized point mutations to substitute multiple tyrosine residues with phenylalanine. Removal of the tyrosines 111–113 and 449 prevented Grb10 from decreasing Kv1.3 expression. In the absence of either adaptor protein

  4. Subtype-specific Modulation of Acid-sensing Ion Channel (ASIC) Function by 2-Guanidine-4-methylquinazoline*

    Science.gov (United States)

    Alijevic, Omar; Kellenberger, Stephan

    2012-01-01

    Acid-sensing ion channels (ASICs) are neuronal Na+-selective channels that are transiently activated by extracellular acidification. ASICs are involved in fear and anxiety, learning, neurodegeneration after ischemic stroke, and pain sensation. The small molecule 2-guanidine-4-methylquinazoline (GMQ) was recently shown to open ASIC3 at physiological pH. We have investigated the mechanisms underlying this effect and the possibility that GMQ may alter the function of other ASICs besides ASIC3. GMQ shifts the pH dependence of activation to more acidic pH in ASIC1a and ASIC1b, whereas in ASIC3 this shift goes in the opposite direction and is accompanied by a decrease in its steepness. GMQ also induces an acidic shift of the pH dependence of inactivation of ASIC1a, -1b, -2a, and -3. As a consequence, the activation and inactivation curves of ASIC3 but not other ASICs overlap in the presence of GMQ at pH 7.4, thereby creating a window current. At concentrations >1 mm, GMQ decreases maximal peak currents by reducing the unitary current amplitude. Mutation of residue Glu-79 in the palm domain of ASIC3, previously shown to be critical for channel opening by GMQ, disrupted the GMQ effects on inactivation but not activation. This suggests that this residue is involved in the consequences of GMQ binding rather than in the binding interaction itself. This study describes the mechanisms underlying the effects of a novel class of ligands that modulate the function of all ASICs as well as activate ASIC3 at physiological pH. PMID:22948146

  5. Subtype-specific modulation of acid-sensing ion channel (ASIC) function by 2-guanidine-4-methylquinazoline.

    Science.gov (United States)

    Alijevic, Omar; Kellenberger, Stephan

    2012-10-19

    Acid-sensing ion channels (ASICs) are neuronal Na(+)-selective channels that are transiently activated by extracellular acidification. ASICs are involved in fear and anxiety, learning, neurodegeneration after ischemic stroke, and pain sensation. The small molecule 2-guanidine-4-methylquinazoline (GMQ) was recently shown to open ASIC3 at physiological pH. We have investigated the mechanisms underlying this effect and the possibility that GMQ may alter the function of other ASICs besides ASIC3. GMQ shifts the pH dependence of activation to more acidic pH in ASIC1a and ASIC1b, whereas in ASIC3 this shift goes in the opposite direction and is accompanied by a decrease in its steepness. GMQ also induces an acidic shift of the pH dependence of inactivation of ASIC1a, -1b, -2a, and -3. As a consequence, the activation and inactivation curves of ASIC3 but not other ASICs overlap in the presence of GMQ at pH 7.4, thereby creating a window current. At concentrations >1 mM, GMQ decreases maximal peak currents by reducing the unitary current amplitude. Mutation of residue Glu-79 in the palm domain of ASIC3, previously shown to be critical for channel opening by GMQ, disrupted the GMQ effects on inactivation but not activation. This suggests that this residue is involved in the consequences of GMQ binding rather than in the binding interaction itself. This study describes the mechanisms underlying the effects of a novel class of ligands that modulate the function of all ASICs as well as activate ASIC3 at physiological pH.

  6. Control units for the system of unified modules for multi-channel analysis (SUMMA)

    International Nuclear Information System (INIS)

    Bushnin, Yu.B.; Denisenko, A.A.; Dunajtsev, A.F.

    1975-01-01

    The control units of the ''SUMMA'' system unified modules for multichannel analysis are described; the system is used in the experimental physics installations of the Institute of High-Energy Physics for operation on-line with an electronic computer (e.c.). The units allow control of several crates of electronic equipment (up to seven) according to a program from the internal program units or from the e.c. to be assured. The organization of the control is similar to the organization of the CAMAC electronic system. Examples of communication between the system and an NR2100 electronic computer are presented

  7. Heparin/heparan sulfates bind to and modulate neuronal L-type (Cav1.2) voltage-dependent Ca2+ channels

    DEFF Research Database (Denmark)

    Garau, Gianpiero; Magotti, Paola; Heine, Martin

    2015-01-01

    Our previous studies revealed that L-type voltage-dependent Ca2+ channels (Cav1.2 L-VDCCs) are modulated by the neural extracellular matrix backbone, polyanionic glycan hyaluronic acid. Here we used isothermal titration calorimetry and screened a set of peptides derived from the extracellular......M), integrating their enthalpic and entropic binding contributions. Interaction between heparin and recombinant as well as native full-length neuronal Cav1.2α1 channels was confirmed using the heparin–agarose pull down assay. Whole cell patch clamp recordings in HEK293 cells transfected with neuronal Cav1.......2 channels revealed that enzymatic digestion of highly sulfated heparan sulfates with heparinase 1 affects neither voltage-dependence of channel activation nor the level of steady state inactivation, but did speed up channel inactivation. Treatment of hippocampal cultures with heparinase 1 reduced the firing...

  8. Calcium Channel Genes Associated with Bipolar Disorder Modulate Lithium's Amplification of Circadian Rhythms

    Science.gov (United States)

    McCarthy, Michael J.; LeRoux, Melissa; Wei, Heather; Beesley, Stephen; Kelsoe, John R.; Welsh, David K.

    2015-01-01

    Bipolar disorder (BD) is associated with mood episodes and low amplitude circadian rhythms. Previously, we demonstrated that fibroblasts grown from BD patients show weaker amplification of circadian rhythms by lithium compared to control cells. Since calcium signals impact upon the circadian clock, and L-type calcium channels (LTCC) have emerged as genetic risk factors for BD, we examined whether loss of function in LTCCs accounts for the attenuated response to lithium in BD cells. We used fluorescent dyes to measure Ca2+ changes in BD and control fibroblasts after lithium treatment, and bioluminescent reporters to measure Per2∷luc rhythms in fibroblasts from BD patients, human controls, and mice while pharmacologically or genetically manipulating calcium channels. Longitudinal expression of LTCC genes (CACNA1C, CACNA1D and CACNB3) was then measured over 12-24 hr in BD and control cells. Our results indicate that independently of LTCCs, lithium stimulated intracellular Ca2+ less effectively in BD vs. control fibroblasts. In longitudinal studies, pharmacological inhibition of LTCCs or knockdown of CACNA1A, CACNA1C, CACNA1D and CACNB3 altered circadian rhythm amplitude. Diltiazem and knockdown of CACNA1C or CACNA1D eliminated lithium's ability to amplify rhythms. Knockdown of CACNA1A or CACNB3 altered baseline rhythms, but did not affect rhythm amplification by lithium. In human fibroblasts, CACNA1C genotype predicted the amplitude response to lithium, and the expression profiles of CACNA1C, CACNA1D and CACNB3 were altered in BD vs. controls. We conclude that in cells from BD patients, calcium signaling is abnormal, and that LTCCs underlie the failure of lithium to amplify circadian rhythms. PMID:26476274

  9. Microstructural and crystallographic characteristics of modulated martensite, non-modulated martensite, and pre-martensitic tweed austenite in Ni-Mn-Ga alloys

    International Nuclear Information System (INIS)

    Zhou, Le; Schneider, Matthew M.; Giri, Anit; Cho, Kyu; Sohn, Yongho

    2017-01-01

    A combinatorial approach using diffusion couples and TEM analyses was carried out to investigate the composition-dependent martensitic transformation in NiMnGa alloys. The compositions cover a large portion of the off-stoichiometric Ni 2 MnGa compositions and some Mn-rich compositions. Crystallographic variations of the martensitic phase, including non-modulated (NM) martensite, modulated (5M or 7M) martensite, and austenitic phase were identified in the diffusion couples and investigated with respect to their microstructure and crystallography. The 5M and 7M martensitic structures were only found near the interphase boundary between austenite and martensite, while the NM martensitic structures were found mostly away from the interphase boundary. The tetragonality ratio (c/a) for NM martensite generally increases with e/a ratio, but was also dependent on the composition. The habit plane and martensitic microstructure that consists of twinned variants with differing orientations were documented using electron diffraction. The pre-martensitic state was observed in the austenitic phase that was located near the interphase boundary between austenite and martensite, with distinctive tweed microstructure and a strain field originating from the local lattice distortions. The combinatorial approach proves to be efficient and systematic in studying the composition-dependent martensitic transformation in NiMnGa alloys and can be potentially applied to other shape memory alloys.

  10. Porphyromonas gingivalis Differentially Modulates Cell Death Profile in Ox-LDL and TNF-α Pre-Treated Endothelial Cells.

    Directory of Open Access Journals (Sweden)

    Isaac Maximiliano Bugueno

    Full Text Available Clinical studies demonstrated a potential link between atherosclerosis and periodontitis. Porphyromonas gingivalis (Pg, one of the main periodontal pathogen, has been associated to atheromatous plaque worsening. However, synergism between infection and other endothelial stressors such as oxidized-LDL or TNF-α especially on endothelial cell (EC death has not been investigated. This study aims to assess the role of Pg on EC death in an inflammatory context and to determine potential molecular pathways involved.Human umbilical vein ECs (HUVECs were infected with Pg (MOI 100 or stimulated by its lipopolysaccharide (Pg-LPS (1μg/ml for 24 to 48 hours. Cell viability was measured with AlamarBlue test, type of cell death induced was assessed using Annexin V/propidium iodide staining. mRNA expression regarding caspase-1, -3, -9, Bcl-2, Bax-1 and Apaf-1 has been evaluated with RT-qPCR. Caspases enzymatic activity and concentration of APAF-1 protein were evaluated to confirm mRNA results.Pg infection and Pg-LPS stimulation induced EC death. A cumulative effect has been observed in Ox-LDL pre-treated ECs infected or stimulated. This effect was not observed in TNF-α pre-treated cells. Pg infection promotes EC necrosis, however, in infected Ox-LDL pre-treated ECs, apoptosis was promoted. This effect was not observed in TNF-α pre-treated cells highlighting specificity of molecular pathways activated. Regarding mRNA expression, Pg increased expression of pro-apoptotic genes including caspases-1,-3,-9, Bax-1 and decreased expression of anti-apoptotic Bcl-2. In Ox-LDL pre-treated ECs, Pg increased significantly the expression of Apaf-1. These results were confirmed at the protein level.This study contributes to demonstrate that Pg and its Pg-LPS could exacerbate Ox-LDL and TNF-α induced endothelial injury through increase of EC death. Interestingly, molecular pathways are differentially modulated by the infection in function of the pre-stimulation.

  11. The theory of modulated hormone therapy for the treatment of breast cancer in pre- and post-menopausal women

    Science.gov (United States)

    Wiley, Teresa S.; Haraldsen, Jason T.

    2012-03-01

    We present a theory that questions the standard of care for pre- and post-menopausal women with breast cancer. Through the use of modulated hormones to mimic the natural multiphasic fluctuations of estrogen and progesterone cycles of healthy young women, it can be expected that patients will not only exhibit increased quality of life such as better sleep, well-being, and libido, but also memory improvement and less joint pain. Additionally, this regimen may engage genetic pathways that protect women in youth from breast cancers. We present a mathematical basis for the coupling of the hormone cycles through the use of Gaussian curves that provides the foundation of a new format of hormone replacement in women.

  12. The theory of modulated hormone therapy for the treatment of breast cancer in pre- and post-menopausal women

    Directory of Open Access Journals (Sweden)

    Teresa S. Wiley

    2012-03-01

    Full Text Available We present a theory that questions the standard of care for pre- and post-menopausal women with breast cancer. Through the use of modulated hormones to mimic the natural multiphasic fluctuations of estrogen and progesterone cycles of healthy young women, it can be expected that patients will not only exhibit increased quality of life such as better sleep, well-being, and libido, but also memory improvement and less joint pain. Additionally, this regimen may engage genetic pathways that protect women in youth from breast cancers. We present a mathematical basis for the coupling of the hormone cycles through the use of Gaussian curves that provides the foundation of a new format of hormone replacement in women.

  13. "Slow" Voltage-Dependent Inactivation of CaV2.2 Calcium Channels Is Modulated by the PKC Activator Phorbol 12-Myristate 13-Acetate (PMA.

    Directory of Open Access Journals (Sweden)

    Lei Zhu

    Full Text Available CaV2.2 (N-type voltage-gated calcium channels (Ca2+ channels play key roles in neurons and neuroendocrine cells including the control of cellular excitability, neurotransmitter / hormone secretion, and gene expression. Calcium entry is precisely controlled by channel gating properties including multiple forms of inactivation. "Fast" voltage-dependent inactivation is relatively well-characterized and occurs over the tens-to- hundreds of milliseconds timeframe. Superimposed on this is the molecularly distinct, but poorly understood process of "slow" voltage-dependent inactivation, which develops / recovers over seconds-to-minutes. Protein kinases can modulate "slow" inactivation of sodium channels, but little is known about if/how second messengers control "slow" inactivation of Ca2+ channels. We investigated this using recombinant CaV2.2 channels expressed in HEK293 cells and native CaV2 channels endogenously expressed in adrenal chromaffin cells. The PKC activator phorbol 12-myristate 13-acetate (PMA dramatically prolonged recovery from "slow" inactivation, but an inactive control (4α-PMA had no effect. This effect of PMA was prevented by calphostin C, which targets the C1-domain on PKC, but only partially reduced by inhibitors that target the catalytic domain of PKC. The subtype of the channel β-subunit altered the kinetics of inactivation but not the magnitude of slowing produced by PMA. Intracellular GDP-β-S reduced the effect of PMA suggesting a role for G proteins in modulating "slow" inactivation. We postulate that the kinetics of recovery from "slow" inactivation could provide a molecular memory of recent cellular activity and help control CaV2 channel availability, electrical excitability, and neurotransmission in the seconds-to-minutes timeframe.

  14. Sexual dimorphism and oestrogen regulation of KCNE3 expression modulates the functional properties of KCNQ1 K channels.

    LENUS (Irish Health Repository)

    Alzamora, Rodrigo

    2012-02-01

    -voltage relations elicited in CHO cells transfected with KCNQ1 and KCNE3 or KCNE1 cDNA. E2 (100 nM) reduced the currents mediated by the KCNQ1:KCNE3 potassium channel and had no effect on currents via KCNQ1:KCNE1 or KCNQ1 alone. Currents mediated by the complex formed by KCNQ1 and the mutant KCNE3-S82A beta-subunit (mutation of the site for PKCdelta-promoted phosphorylation and modulation of the activity of KCNE3) showed rapid run-down and insensitivity to E2. Together, these data suggest that oestrogen regulates the expression of the KCNE1 and KCNE3 and with it the gating and pharmacological properties of the K(+) conductance required for Cl(-) secretion. The decreased association of the KCNQ1:KCNE3 channel complex promoted by oestrogen exposure underlies the molecular mechanism for the sexual dimorphism and oestrous cycle dependence of the anti-secretory actions of oestrogen in the intestine.

  15. Design of a four-channel bolometer module for ASDEX upgrade and tore supra

    International Nuclear Information System (INIS)

    Mueller, E.R.; Weber, G.; Mast, F.; Schramm, G.; Buchelt, E.; Andelfinger, C.

    1985-10-01

    A new small-sized four-bolometer module for application in high-temperature plasma diagnostics has been designed. The four bolometers and the four reference bolometers shielded against radiation are placed side by side on one kapton foil, the entire arrangement occupying an area of 2.0x3.3 cm 2 . The central part of each bolometer consists of a 1.5x4 mm 2 large, 4 to 15 μm thick radiation absorber made of gold, a 7.5 μm thick kapton carrier foil, and a 0.05 μm thick meander-like gold resistor (conduction path width: 30 μm). It offers all the advantages already provided by the well-known ASDEX and JET bolometers, such as very high operating reliability and resistance to nuclear radiation damage. It is optional to enlarge the cooling time constant of the bolometer in a controlled way from a few milliseconds up to several hundreds, thus improving the sensitivity to very weak signals in the low-frequency (<=20 Hz) part of the radiation spectrum, by means of an additional (thin) gold layer that delays the heat losses from the bolometer foil to the cooling body. Since the bolometer is very suitable for AC-bridge electronics and all bridge resistors are arranged on a minimum area interference signals should be suppressed to extremely low levels. (orig.)

  16. Fertilizing ROSES through the STEM: Interdisciplinary Modules as Pre-service Research Experiences for Secondary STEM Educators (IMPRESS-Ed)

    Science.gov (United States)

    Magee, N. B.; Kavic, M.; Benoit, M. H.; Wiita, P.

    2011-12-01

    IMPRESS-Ed is a program designed to provide authentic summer research experiences in the space, earth, and atmospheric sciences for pre-service K-12 educators at The College of New Jersey (TCNJ). In 2011, the program involved five students and took place over eight weeks with recruitment occurring during the preceding academic year. The program was divided into two modules: A common core module and an individual mentored research experience. The common module consisted of three units focusing on data-driven pedagogical approaches in astrophysics, tectonophysics, and atmospheric science, respectively. The common module also featured training sessions in observational astronomy, and use of a 3D geowall and state of the art planetarium. Participants in the program are also offered the opportunity to utilize the available TCNJ facilities with their future students. Given that a large number of graduates from the TCNJ take positions in local New Jersey schools, the opportunity to make use of these facilities at a future time would be of great significance to them and their future students. The individual mentored research module matched student interests with potential projects. Research led by M.H. Benoit analyzed gravity data from the NASA-GRACE mission to find lithospheric density contrasts beneath the eastern US. A student working with N.B. Magee used data from NASA satellites CALIPSO, CloudSat, and AQUA-MODIS to study the dynamics of convective cloud tops. Research projects led by M. Kavic performed simulations to investigate the possibility of detecting superconducting cosmic strings using radio observations and also designed and constructed a radio interferometer based on the NASA's Radio-Jove program. P. Wiita supervised a research project studying star-forming regions of active galaxies through analysis of images from NASA's Hubble Space Telescope and GALEX. The research program was also incorporated into the framework of the TCNJ Mentored Undergraduate Summer

  17. Substitutions in the domain III voltage-sensing module enhance the sensitivity of an insect sodium channel to a scorpion beta-toxin.

    Science.gov (United States)

    Song, Weizhong; Du, Yuzhe; Liu, Zhiqi; Luo, Ningguang; Turkov, Michael; Gordon, Dalia; Gurevitz, Michael; Goldin, Alan L; Dong, Ke

    2011-05-06

    Scorpion β-toxins bind to the extracellular regions of the voltage-sensing module of domain II and to the pore module of domain III in voltage-gated sodium channels and enhance channel activation by trapping and stabilizing the voltage sensor of domain II in its activated state. We investigated the interaction of a highly potent insect-selective scorpion depressant β-toxin, Lqh-dprIT(3), from Leiurus quinquestriatus hebraeus with insect sodium channels from Blattella germanica (BgNa(v)). Like other scorpion β-toxins, Lqh-dprIT(3) shifts the voltage dependence of activation of BgNa(v) channels expressed in Xenopus oocytes to more negative membrane potentials but only after strong depolarizing prepulses. Notably, among 10 BgNa(v) splice variants tested for their sensitivity to the toxin, only BgNa(v)1-1 was hypersensitive due to an L1285P substitution in IIIS1 resulting from a U-to-C RNA-editing event. Furthermore, charge reversal of a negatively charged residue (E1290K) at the extracellular end of IIIS1 and the two innermost positively charged residues (R4E and R5E) in IIIS4 also increased the channel sensitivity to Lqh-dprIT(3). Besides enhancement of toxin sensitivity, the R4E substitution caused an additional 20-mV negative shift in the voltage dependence of activation of toxin-modified channels, inducing a unique toxin-modified state. Our findings provide the first direct evidence for the involvement of the domain III voltage-sensing module in the action of scorpion β-toxins. This hypersensitivity most likely reflects an increase in IIS4 trapping via allosteric mechanisms, suggesting coupling between the voltage sensors in neighboring domains during channel activation.

  18. Modulation of epithelial sodium channel trafficking and function by sodium 4-phenylbutyrate in human nasal epithelial cells.

    Science.gov (United States)

    Prulière-Escabasse, Virginie; Planès, Carole; Escudier, Estelle; Fanen, Pascale; Coste, André; Clerici, Christine

    2007-11-23

    Sodium 4-phenylbutyrate (4-PBA) has been shown to correct the cellular trafficking of several mutant or nonmutant plasma membrane proteins such as cystic fibrosis transmembrane conductance regulator through the expression of 70-kDa heat shock proteins. The objective of the study was to determine whether 4-PBA may influence the functional expression of epithelial sodium channels (ENaC) in human nasal epithelial cells (HNEC). Using primary cultures of HNEC, we demonstrate that 4-PBA (5 mm for 6 h) markedly stimulated amiloride-sensitive sodium channel activity and that this was related to an increased abundance of alpha-, beta-, and gamma-ENaC subunits in the apical membrane. The increase in ENaC cell surface expression (i) was due to insertion of newly ENaC subunits as determined by brefeldin A experiments and (ii) was not associated with cell surface retention of ENaC subunits because endocytosis of ENaC subunits was unchanged. In addition, we find that ENaC co-immunoprecipitated with the heat shock protein constitutively expressed Hsc70, that has been reported to modulate ENaC trafficking, and that 4-PBA decreased Hsc70 protein level. Finally, we report that in cystic fibrosis HNEC obtained from two cystic fibrosis patients, 4-PBA increased functional expression of ENaC as demonstrated by the increase in amiloride-sensitive sodium transport and in alpha-, beta-, and gamma-ENaC subunit expression in the apical membrane. Our results suggest that in HNEC, 4-PBA increases the functional expression of ENaC through the insertion of new alpha-, beta-, and gamma-ENaC subunits into the apical membrane and also suggest that 4-PBA could modify ENaC trafficking by reducing Hsc70 protein expression.

  19. Ion Channels Induced by Antimicrobial Agents in Model Lipid Membranes are Modulated by Plant Polyphenols Through Surrounding Lipid Media.

    Science.gov (United States)

    Efimova, Svetlana S; Zakharova, Anastasiia A; Medvedev, Roman Ya; Ostroumova, Olga S

    2018-03-16

    The potential therapeutic applications of plant polyphenols in various neurological, cardiovascular, metabolic and malignant disorders determine the relevance of studying the molecular mechanisms of their action on the cell membranes. Here, the quantitative changes in the physical parameters of model bilayer lipid membranes upon the adsorption of plant polyphenols were evaluated. It was shown that butein and naringenin significantly decreased the intrinsic dipole potential of cholesterol-free and cholesterol-enriched membranes. Cardamonin, 4'-hydroxychalcone, licochalcone A and liquiritigenin demonstrated the average efficiency, while resveratrol did not characterized by the ability to modulate the bilayer electrostatics. At the same time, the tested polyphenols affected melting of phospholipids with saturated acyl chains. The effects were attributed to the lipid disordering and a promotion of the positive curvature stress. According to DSC data and results of measurements of the threshold voltages that cause bilayer breakdown licochalcone A is the most effective agent. Furthermore, the role of the polyphenol induced changes in the electric and elastic properties of lipid host in the regulation of reconstituted ion channels was examined. The ability of the tested polyphenols to decrease the conductance of single ion channels produced by the antifungal cyclic lipopeptide syringomycin E was in agreement with their effects on the dipole potential of the lipid bilayers. The greatest effect of licochalcone A on the steady-state membrane conductance induced by the antifungal polyene macrolide antibiotic nystatin correlated with its greatest efficacy to induce the positive curvature stress. We also found that butein and naringenin bind specifically to a single pore formed by α-hemolysin from Staphylococcus aureus.

  20. Resveratrol, by modulating RNA processing factor levels, can influence the alternative splicing of pre-mRNAs.

    Directory of Open Access Journals (Sweden)

    M Andrea Markus

    Full Text Available Alternative pre-mRNA splicing defects can contribute to, or result from, various diseases, including cancer. Aberrant mRNAs, splicing factors and other RNA processing factors have therefore become targets for new therapeutic interventions. Here we report that the natural polyphenol resveratrol can modulate alternative splicing in a target-specific manner. We transfected minigenes of several alternatively spliceable primary mRNAs into HEK293 cells in the presence or absence of 1, 5, 20 and 50 µM resveratrol and measured exon levels by semi-quantitative PCR after separation by agarose gel electrophoresis. We found that 20 µg/ml and 50 µg/ml of resveratrol affected exon inclusion of SRp20 and SMN2 pre-mRNAs, but not CD44v5 or tau pre-mRNAs. By Western blotting and immunofluorescence we showed that this effect may be due to the ability of resveratrol to change the protein level but not the localization of several RNA processing factors. The processing factors that increased significantly were ASF/SF2, hnRNPA1 and HuR, but resveratrol did not change the levels of RBM4, PTBP1 and U2AF35. By means of siRNA-mediated knockdown we depleted cells of SIRT1, regarded as a major target of resveratrol, and showed that the effect on splicing was not dependent on SIRT1. Our results suggest that resveratrol might be an attractive small molecule to treat diseases in which aberrant splicing has been implicated, and justify more extensive research on the effects of resveratrol on the splicing machinery.

  1. Resveratrol, by modulating RNA processing factor levels, can influence the alternative splicing of pre-mRNAs.

    Science.gov (United States)

    Markus, M Andrea; Marques, Francine Z; Morris, Brian J

    2011-01-01

    Alternative pre-mRNA splicing defects can contribute to, or result from, various diseases, including cancer. Aberrant mRNAs, splicing factors and other RNA processing factors have therefore become targets for new therapeutic interventions. Here we report that the natural polyphenol resveratrol can modulate alternative splicing in a target-specific manner. We transfected minigenes of several alternatively spliceable primary mRNAs into HEK293 cells in the presence or absence of 1, 5, 20 and 50 µM resveratrol and measured exon levels by semi-quantitative PCR after separation by agarose gel electrophoresis. We found that 20 µg/ml and 50 µg/ml of resveratrol affected exon inclusion of SRp20 and SMN2 pre-mRNAs, but not CD44v5 or tau pre-mRNAs. By Western blotting and immunofluorescence we showed that this effect may be due to the ability of resveratrol to change the protein level but not the localization of several RNA processing factors. The processing factors that increased significantly were ASF/SF2, hnRNPA1 and HuR, but resveratrol did not change the levels of RBM4, PTBP1 and U2AF35. By means of siRNA-mediated knockdown we depleted cells of SIRT1, regarded as a major target of resveratrol, and showed that the effect on splicing was not dependent on SIRT1. Our results suggest that resveratrol might be an attractive small molecule to treat diseases in which aberrant splicing has been implicated, and justify more extensive research on the effects of resveratrol on the splicing machinery.

  2. Influence of Combined Ultrasound With Pre modulated interferential Current in Discogenic Sciatica

    International Nuclear Information System (INIS)

    Selem, A.I.; El Hafez, H.M.; Alshatoury, H.A.; Ismail, G.

    2016-01-01

    Background and purpose : Lumbar- spine disorders rank fifth among disease categories in the cost of hospital care and account for higher costs resulting in absence from work and disability than any other category. Sciatica is a common clinical condition that can be extremely painful, disabling and life changing. This study was conducted to find out the effectiveness of adding interferential current therapy to conventional treatment and to compare with conventional treatment only in patients with chronic discogenic sciatica. Methods : This randomized controlled trial was conducted at Ismailia General Hospital. Sixty patients (22 males and 38 females) aged between 20 and 40 years old and duration of illness of more than 3 months. They were classified randomly into two groups of equal number. The Experimental Group received interferential therapy (IFT) combined with conventional therapy while control Group received conventional therapy only, 3 times/ week for 4 weeks. Outcome measures : back and leg pain intensity was measured by numeric pain rating scale (0 - 10), functional disability was measured by Roland Morris disability questionnaire, range of motion (Rom) was measured by inclinometer and latency of H- reflex was measured by electromyography. The assessment was done twice for every subject (pre and post the treatment program). Results : Statistical interpretation showed significant improvement of both groups. But in case of experimental group, the amount of improvement was higher with decrease in pain, increasing functional ability, increasing range of motion and improvement in H- reflex latency when compared to control group

  3. Pre-Rationalized Parametric Designing of Roof Shells Formed by Repetitive Modules of Catalan Surfaces

    Directory of Open Access Journals (Sweden)

    Jolanta Dzwierzynska

    2018-04-01

    Full Text Available The aim of the study is to develop an original, methodical, and practical approach to the early stages of parametric design of roof shells formed by repetitive modules of Catalan surfaces. It is presented on the example of designing the roof shells compound of four concrete elements. The designing process proposed by us consists in linking geometric shaping of roofs’ models with their structural analysis and optimization. Contrary to other methods, which use optimization process in order to find free roof forms, we apply it in order to explore and improve design alternatives. It is realized with the application of designing tools working in Rhinoceros 3D software. The flexible scripts elaborated by us, in order to achieve roofs’ models of regular and symmetrical shapes, are converted into simulation models to perform structural analysis. It is mainly focused on how the roof shells perform dependently on their geometric characteristics. The simulation enables one to evaluate various roof shells’ shapes, as well as to select an optimal design solution. The proposed approach to the conceptual design process may drive the designing to achieve geometric and structural forms which not only follow the design intentions but also target better results.

  4. Direct Binding between Pre-S1 and TRP-like Domains in TRPP Channels Mediates Gating and Functional Regulation by PIP2

    OpenAIRE

    Wang Zheng; Ruiqi Cai; Laura Hofmann; Vasyl Nesin; Qiaolin Hu; Wentong Long; Mohammad Fatehi; Xiong Liu; Shaimaa Hussein; Tim Kong; Jingru Li; Peter E. Light; Jingfeng Tang; Veit Flockerzi; Leonidas Tsiokas

    2018-01-01

    Transient receptor potential (TRP) channels are regulated by diverse stimuli comprising thermal, chemical, and mechanical modalities. They are also commonly regulated by phosphatidylinositol-4,5-bisphosphate (PIP2), with underlying mechanisms largely unknown. We here revealed an intramolecular interaction of the TRPP3 N and C termini (N-C) that is functionally essential. The interaction was mediated by aromatic Trp81 in pre-S1 domain and cationic Lys568 in TRP-like domain. Structure-function ...

  5. 12.5 Gb/s multi-channel broadcasting transmission for free-space optical communication based on the optical frequency comb module.

    Science.gov (United States)

    Tan, Jun; Zhao, Zeping; Wang, Yuehui; Zhang, Zhike; Liu, Jianguo; Zhu, Ninghua

    2018-01-22

    A wide-spectrum, ultra-stable optical frequency comb (OFC) module with 100 GHz frequency intervals based on a quantum dot mode locked (QDML) laser is fabricated by our lab, and a scheme with 12.5 Gb/s multi-channel broadcasting transmission for free-space optical (FSO) communication is proposed based on the OFC module. The output power of the OFC is very stable, with the specially designed circuit and the flatness of the frequency comb over the span of 6 nm, which can be limited to 1.5 dB. Four channel wavelengths are chosen to demonstrate one-to-many channels for FSO communication, like optical wireless broadcast. The outdoor experiment is established to test the bit error rate (BER) and eye diagrams with 12.5 Gb/s on-off keying (OOK). The indoor experiment is used to test the highest traffic rate, which is up to 21 Gb/s for one-hop FSO communication. To the best of our knowledge, this scheme is the first to propose the realization of one-to-many broadcasting transmission for FSO communication based on the OFC module. The advantages of integration, miniaturization, channelization, low power consumption, and unlimited bandwidth of one-to-many broadcasting communication scheme, shows promising results on constructing the future space-air-ground-ocean (SAGO) FSO communication networks.

  6. Rhizosphere Microbiomes Modulated by Pre-crops Assisted Plants in Defense Against Plant-Parasitic Nematodes

    Directory of Open Access Journals (Sweden)

    Ahmed Elhady

    2018-06-01

    conclusion, this study highlights the importance of the rhizosphere microbiome in protecting crops against plant-parasitic nematodes. An effect of pre-crops on the rhizosphere microbiome might be harnessed to enhance the resistance of crops towards plant-parasitic nematodes. However, nematode-suppressive effects of a particular microbiome may not necessarily coincide with improvement of plant growth in the absence of plant-parasitic nematodes.

  7. Performance analysis of EM-based blind detection for ON-OFF keying modulation over atmospheric optical channels

    Science.gov (United States)

    Dabiri, Mohammad Taghi; Sadough, Seyed Mohammad Sajad

    2018-04-01

    In the free-space optical (FSO) links, atmospheric turbulence lead to scintillation in the received signal. Due to its ease of implementation, intensity modulation with direct detection (IM/DD) based on ON-OFF keying (OOK) is a popular signaling scheme in these systems. Over turbulence channel, to detect OOK symbols in a blind way, i.e., without sending pilot symbols, an expectation-maximization (EM)-based detection method was recently proposed in the literature related to free-space optical (FSO) communication. However, the performance of EM-based detection methods severely depends on the length of the observation interval (Ls). To choose the optimum values of Ls at target bit error rates (BER)s of FSO communications which are commonly lower than 10-9, Monte-Carlo simulations would be very cumbersome and require a very long processing time. To facilitate performance evaluation, in this letter we derive the analytic expressions for BER and outage probability. Numerical results validate the accuracy of our derived analytic expressions. Our results may serve to evaluate the optimum value for Ls without resorting to time-consuming Monte-Carlo simulations.

  8. Modulation of Kir4.1 and Kir4.1-Kir5.1 channels by extracellular cations

    DEFF Research Database (Denmark)

    Søe, Rikke; Andreasen, Mogens; Klærke, Dan Arne

    2009-01-01

    This work demonstrates that extracellular Na(+) modulates the cloned inwardly rectifying K(+) channels Kir4.1 and Kir4.1-Kir5.1. Whole-cell patch clamp studies on astrocytes have previously indicated that inward potassium currents are regulated by external Na(+). We expressed Kir4.1 and Kir4.1-Kir5.......1 in Xenopus oocytes to disclose if Kir4.1 and/or Kir4.1-Kir5.1 at the molecular level are responsible for the observed effect of [Na(+)](o) and to investigate the regulatory mechanism of external cations further. Our results showed that Na(+) has a biphasic modulatory effect on both Kir4.1 and Kir4.1-Kir5.......1 currents. Depending on the Na(+)-concentration and applied voltage, the inward Kir4.1/Kir4.1-Kir5.1 currents are either enhanced or reduced by extracellular Na(+). The Na(+) activation was voltage-independent, whereas the Na(+)-induced reduction of the Kir4.1 and Kir4.1-Kir5.1 currents was both...

  9. Roselle Polyphenols Exert Potent Negative Inotropic Effects via Modulation of Intracellular Calcium Regulatory Channels in Isolated Rat Heart.

    Science.gov (United States)

    Lim, Yi-Cheng; Budin, Siti Balkis; Othman, Faizah; Latip, Jalifah; Zainalabidin, Satirah

    2017-07-01

    Roselle (Hibiscus sabdariffa Linn.) calyces have demonstrated propitious cardioprotective effects in animal and clinical studies; however, little is known about its action on cardiac mechanical function. This study was undertaken to investigate direct action of roselle polyphenols (RP) on cardiac function in Langendorff-perfused rat hearts. We utilized RP extract which consists of 12 flavonoids and seven phenolic acids (as shown by HPLC profiling) and has a safe concentration range between 125 and 500 μg/ml in this study. Direct perfusion of RP in concentration-dependent manner lowered systolic function of the heart as shown by lowered LVDP and dP/dt max , suggesting a negative inotropic effect. RP also reduced heart rate (negative chronotropic action) while simultaneously increasing maximal velocity of relaxation (positive lusitropic action). Conversely, RP perfusion increased coronary pressure, an indicator for improvement in coronary blood flow. Inotropic responses elicited by pharmacological agonists for L-type Ca 2+ channel [(±)-Bay K 8644], ryanodine receptor (4-chloro-m-cresol), β-adrenergic receptor (isoproterenol) and SERCA blocker (thapsigargin) were all abolished by RP. In conclusion, RP elicits negative inotropic, negative chronotropic and positive lusitropic responses by possibly modulating calcium entry, release and reuptake in the heart. Our findings have shown the potential use of RP as a therapeutic agent to treat conditions like arrhythmia.

  10. Azadirachtin blocks the calcium channel and modulates the cholinergic miniature synaptic current in the central nervous system of Drosophila.

    Science.gov (United States)

    Qiao, Jingda; Zou, Xiaolu; Lai, Duo; Yan, Ying; Wang, Qi; Li, Weicong; Deng, Shengwen; Xu, Hanhong; Gu, Huaiyu

    2014-07-01

    Azadirachtin is a botanical pesticide, which possesses conspicuous biological actions such as insecticidal, anthelmintic, antifeedancy, antimalarial effects as well as insect growth regulation. Deterrent for chemoreceptor functions appears to be the main mechanism involved in the potent biological actions of Azadirachtin, although the cytotoxicity and subtle changes to skeletal muscle physiology may also contribute to its insecticide responses. In order to discover the effects of Azadirachtin on the central nervous system (CNS), patch-clamp recording was applied to Drosophila melanogaster, which has been widely used in neurological research. Here, we describe the electrophysiological properties of a local neuron located in the suboesophageal ganglion region of D. melanogaster using the whole brain. The patch-clamp recordings suggested that Azadirachtin modulates the properties of cholinergic miniature excitatory postsynaptic current (mEPSC) and calcium currents, which play important roles in neural activity of the CNS. The frequency of mEPSC and the peak amplitude of the calcium currents significantly decreased after application of Azadirachtin. Our study indicates that Azadirachtin can interfere with the insect's CNS via inhibition of excitatory cholinergic transmission and partly blocking the calcium channel. © 2013 Society of Chemical Industry.

  11. Substituted 4-phenyl-2-aminoimidazoles and 4-phenyl-4,5-dihydro-2-aminoimidazoles as voltage-gated sodium channel modulators.

    Science.gov (United States)

    Zidar, Nace; Jakopin, Žiga; Madge, David J; Chan, Fiona; Tytgat, Jan; Peigneur, Steve; Dolenc, Marija Sollner; Tomašić, Tihomir; Ilaš, Janez; Mašič, Lucija Peterlin; Kikelj, Danijel

    2014-03-03

    Voltage-gated sodium channels play an integral part in neurotransmission and their dysfunction is frequently a cause of various neurological disorders. On the basis of the structure of marine alkaloid clathrodin, twenty eight new analogs were designed, synthesized and tested for their ability to block human NaV1.3, NaV1.4 and NaV1.7 channels, as well as for their selectivity against human cardiac isoform NaV1.5, using automated patch clamp electrophysiological assay. Several compounds exhibited promising activities on different NaV channel isoforms in the medium micromolar range and some of the compounds showed also moderate isoform selectivities. The most promising results were obtained for the NaV1.3 channel, for which four compounds were found to possess IC₅₀ values lower than 15 μM. All of the active compounds bind to the open-inactivated states of the channels and therefore act as state-dependent modulators. The obtained results validate the approach of using natural products driven chemistry for drug discovery starting points and represent a good foundation for future design of selective NaV modulators. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  12. CaV1.3 L-type Ca2+ channels modulate depression-like behaviour in mice independent of deaf phenotype.

    Science.gov (United States)

    Busquet, Perrine; Nguyen, Ngoc Khoi; Schmid, Eduard; Tanimoto, Naoyuki; Seeliger, Mathias W; Ben-Yosef, Tamar; Mizuno, Fengxia; Akopian, Abram; Striessnig, Jörg; Singewald, Nicolas

    2010-05-01

    Mounting evidence suggests that voltage-gated L-type Ca2+ channels can modulate affective behaviour. We therefore explored the role of CaV1.3 L-type Ca2+ channels in depression- and anxiety-like behaviours using CaV1.3-deficient mice (CaV1.3-/-). We showed that CaV1.3-/- mice displayed less immobility in the forced swim test as well as in the tail suspension test, indicating an antidepressant-like phenotype. Locomotor activity in the home cage or a novel open-field test was not influenced. In the elevated plus maze (EPM), CaV1.3-/- mice entered the open arms more frequently and spent more time there indicating an anxiolytic-like phenotype which was, however, not supported in the stress-induced hyperthermia test. By performing parallel experiments in Claudin 14 knockout mice (Cldn14-/-), which like CaV1.3-/- mice are congenitally deaf, an influence of deafness on the antidepressant-like phenotype could be ruled out. On the other hand, a similar EPM behaviour indicative of an anxiolytic phenotype was also found in the Cldn14-/- animals. Using electroretinography and visual behavioural tasks we demonstrated that at least in mice, CaV1.3 channels do not significantly contribute to visual function. However, marked morphological changes were revealed in synaptic ribbons in the outer plexiform layer of CaV1.3-/- retinas by immunohistochemistry suggesting a possible role of this channel type in structural plasticity at the ribbon synapse. Taken together, our findings indicate that CaV1.3 L-type Ca2+ channels modulate depression-like behaviour but are not essential for visual function. The findings raise the possibility that selective modulation of CaV1.3 channels could be a promising new therapeutic concept for the treatment of mood disorders.

  13. Waveguide module comprising a first plate with a waveguide channel and a second plate with a raised portion in which a sealing layer is forced into the waveguide channel by the raised portion

    Science.gov (United States)

    Strassner, II, Bernd H.; Liedtke, Richard; McDonald, Jacob Jeremiah; Halligan, Matthew

    2018-04-17

    The various technologies presented herein relate to utilizing a sealing layer of malleable material to seal gaps, etc., at a joint between edges of a waveguide channel formed in a first plate and a surface of a clamping plate. A compression pad is included in the surface of the clamping plate and is dimensioned such that the upper surface of the pad is less than the area of the waveguide channel opening on the first plate. The sealing layer is placed between the waveguide plate and the clamping plate, and during assembly of the waveguide module, the compression pad deforms a portion of the sealing layer such that it ingresses into the waveguide channel opening. Deformation of the sealing layer results in the gaps, etc., to be filled, improving the operational integrity of the joint.

  14. Direct Binding between Pre-S1 and TRP-like Domains in TRPP Channels Mediates Gating and Functional Regulation by PIP2.

    Science.gov (United States)

    Zheng, Wang; Cai, Ruiqi; Hofmann, Laura; Nesin, Vasyl; Hu, Qiaolin; Long, Wentong; Fatehi, Mohammad; Liu, Xiong; Hussein, Shaimaa; Kong, Tim; Li, Jingru; Light, Peter E; Tang, Jingfeng; Flockerzi, Veit; Tsiokas, Leonidas; Chen, Xing-Zhen

    2018-02-06

    Transient receptor potential (TRP) channels are regulated by diverse stimuli comprising thermal, chemical, and mechanical modalities. They are also commonly regulated by phosphatidylinositol-4,5-bisphosphate (PIP2), with underlying mechanisms largely unknown. We here revealed an intramolecular interaction of the TRPP3 N and C termini (N-C) that is functionally essential. The interaction was mediated by aromatic Trp81 in pre-S1 domain and cationic Lys568 in TRP-like domain. Structure-function analyses revealed similar N-C interaction in TRPP2 as well as TRPM8/-V1/-C4 via highly conserved tryptophan and lysine/arginine residues. PIP2 bound to cationic residues in TRPP3, including K568, thereby disrupting the N-C interaction and negatively regulating TRPP3. PIP2 had similar negative effects on TRPP2. Interestingly, we found that PIP2 facilitates the N-C interaction in TRPM8/-V1, resulting in channel potentiation. The intramolecular N-C interaction might represent a shared mechanism underlying the gating and PIP2 regulation of TRP channels. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  15. Direct Binding between Pre-S1 and TRP-like Domains in TRPP Channels Mediates Gating and Functional Regulation by PIP2

    Directory of Open Access Journals (Sweden)

    Wang Zheng

    2018-02-01

    Full Text Available Transient receptor potential (TRP channels are regulated by diverse stimuli comprising thermal, chemical, and mechanical modalities. They are also commonly regulated by phosphatidylinositol-4,5-bisphosphate (PIP2, with underlying mechanisms largely unknown. We here revealed an intramolecular interaction of the TRPP3 N and C termini (N-C that is functionally essential. The interaction was mediated by aromatic Trp81 in pre-S1 domain and cationic Lys568 in TRP-like domain. Structure-function analyses revealed similar N-C interaction in TRPP2 as well as TRPM8/-V1/-C4 via highly conserved tryptophan and lysine/arginine residues. PIP2 bound to cationic residues in TRPP3, including K568, thereby disrupting the N-C interaction and negatively regulating TRPP3. PIP2 had similar negative effects on TRPP2. Interestingly, we found that PIP2 facilitates the N-C interaction in TRPM8/-V1, resulting in channel potentiation. The intramolecular N-C interaction might represent a shared mechanism underlying the gating and PIP2 regulation of TRP channels.

  16. Feasibility of Smartphone-Based Education Modules and Ecological Momentary Assessment/Intervention in Pre-bariatric Surgery Patients.

    Science.gov (United States)

    Mundi, Manpreet S; Lorentz, Paul A; Grothe, Karen; Kellogg, Todd A; Collazo-Clavell, Maria L

    2015-10-01

    Bariatric surgery is the most effective means of long-term weight loss. Knowledge gaps and lack of engagement in pre-operative patients can result in suboptimal outcome after surgery. Mobile technology, utilizing ecological momentary assessment (EMA)/intervention (EMI), has shown tremendous promise in changing behaviors. The primary objective of the study is to assess feasibility of using smartphone app with EMA/EMI functionality to prepare patients for bariatric surgery. Subjects seeking primary bariatric surgery were provided a smartphone app containing video-based education modules with linked assessments to evaluate mastery of topic. Subjects received algorithmic EMA text messages soliciting a response regarding lifestyle behavior. Upon answering, subjects received tailored EMI text messaging supporting healthy lifestyle. Thirty subjects (27 female and 3 male), with age of 41.3 ± 11.4 years and BMI of 46.3 ± 7.4 kg/m(2) were enrolled. Twenty subjects completed the study. Ten subjects withdrew. On average, seven out of nine education modules were completed (70.9 ± 27.3%), and 37.8/123 EMA were answered (30.7 ± 21.7%), with response time of 17.4 ± 4.4 min. Subjects reported high satisfaction with the app. Many felt that the app fit into their routine "somewhat easily" or "very easily" (n = 12), had "perfect" amount of EMA messages (n = 8), and was very helpful in preparing for surgery (n = 7). This study is the first to reveal the feasibility of using a smartphone app in the education and engagement of patients prior to bariatric surgery. The app was well-received based on subject satisfaction scores and revealed trends toward positive behavior change and increased weight loss. Randomized trials are necessary to delineate true efficacy.

  17. Pre-exposure to nitric oxide modulates the effect of ozone on oxidative defenses and volatile emissions in lima bean

    International Nuclear Information System (INIS)

    Souza, Silvia R.; Blande, James D.; Holopainen, Jarmo K.

    2013-01-01

    The roles that ozone and nitric oxide (NO), the chief O 3 precursor, play in the antioxidative balance and inducible volatile emissions of lima bean were assessed. Exposure to O 3 inhibited APX, CAT, and GR, decreased GSH content and induced emissions of (E)-β-ocimene, limonene, 1,8-cineole, linalool, (E)-4,8-dimethyl-1,3,7-nonatriene (E)-DMNT, 2-butanone and nonanal. O 3 did not induce emissions of (E)-β-caryophyllene and appeared to reduce the antioxidative capacity of plants to a greater extent than NO and NO followed by O 3 (NO/O 3 ) treatments. There were significant differences in emissions of (E)-β-ocimene and linalool between NO/O 3 treated plants and controls, but no differences in antioxidant concentrations. A model to explain the relationships between the ascorbate–glutathione cycle and O 3 and NO inducible volatiles was proposed. Our findings suggest that prior exposure to NO modulates the oxidative effect of ozone by the process of cross-tolerance, which might regulate the antioxidative system and induction of volatile organic compounds. -- Highlights: •NO and O 3 disturb antioxidant defenses and cause lipid peroxidation in lima bean plants. •Exposure to NO before exposure to O 3 does not alter the antioxidant defenses and malondialdehyde levels. •The total sum of induced volatiles is reduced in plants that are exposed to NO and then O 3 . •The antioxidant system and induced VOC emission were balanced by pre-exposure to NO before O 3 . -- Capsule: Nitric oxide modulates the ozone-induced oxidative stress in lima bean by cross-tolerance effect

  18. N-terminal arginines modulate plasma-membrane localization of Kv7.1/KCNE1 channel complexes.

    Directory of Open Access Journals (Sweden)

    Zenawit Girmatsion

    Full Text Available BACKGROUND AND OBJECTIVE: The slow delayed rectifier current (I(Ks is important for cardiac action potential termination. The underlying channel is composed of Kv7.1 α-subunits and KCNE1 β-subunits. While most evidence suggests a role of KCNE1 transmembrane domain and C-terminus for the interaction, the N-terminal KCNE1 polymorphism 38G is associated with reduced I(Ks and atrial fibrillation (a human arrhythmia. Structure-function relationship of the KCNE1 N-terminus for I(Ks modulation is poorly understood and was subject of this study. METHODS: We studied N-terminal KCNE1 constructs disrupting structurally important positively charged amino-acids (arginines at positions 32, 33, 36 as well as KCNE1 constructs that modify position 38 including an N-terminal truncation mutation. Experimental procedures included molecular cloning, patch-clamp recording, protein biochemistry, real-time-PCR and confocal microscopy. RESULTS: All KCNE1 constructs physically interacted with Kv7.1. I(Ks resulting from co-expression of Kv7.1 with non-atrial fibrillation '38S' was greater than with any other construct. Ionic currents resulting from co-transfection of a KCNE1 mutant with arginine substitutions ('38G-3xA' were comparable to currents evoked from cells transfected with an N-terminally truncated KCNE1-construct ('Δ1-38'. Western-blots from plasma-membrane preparations and confocal images consistently showed a greater amount of Kv7.1 protein at the plasma-membrane in cells co-transfected with the non-atrial fibrillation KCNE1-38S than with any other construct. CONCLUSIONS: The results of our study indicate that N-terminal arginines in positions 32, 33, 36 of KCNE1 are important for reconstitution of I(Ks. Furthermore, our results hint towards a role of these N-terminal amino-acids in membrane representation of the delayed rectifier channel complex.

  19. Calculation of the electron wave function in a graded-channel double-heterojunction modulation-doped field-effect transistor

    Science.gov (United States)

    Mui, D. S. L.; Patil, M. B.; Morkoc, H.

    1989-01-01

    Three double-heterojunction modulation-doped field-effect transistor structures with different channel composition are investigated theoretically. All of these transistors have an In(x)Ga(1-x)As channel sandwiched between two doped Al(0.3)Ga(0.7)As barriers with undoped spacer layers. In one of the structures, x varies from 0 from either heterojunction to 0.15 at the center of the channel quadratically; in the other two, constant values of x of 0 and 0.15 are used. The Poisson and Schroedinger equations are solved self-consistently for the electron wave function in all three cases. The results showed that the two-dimensional electron gas (2DEG) concentration in the channel of the quadratically graded structure is higher than the x = 0 one and slightly lower than the x = 0.15 one, and the mean distance of the 2DEG is closer to the center of the channel for this transistor than the other two. These two effects have important implications on the electron mobility in the channel.

  20. An In0.52Al0.48As/n+-In0.53Ga0.47As MISFET with a modulation-doped channel

    International Nuclear Information System (INIS)

    DelAlamo, J.A.

    1989-01-01

    A heterostructure metal-insulator-semiconductor field-effect transistor (MISFET) with a modulation-doped channel is proposed. In this device, a very thin undoped subchannel is located between the undoped wide-bandgap insulator and a thin heavily doped channel. In the depletion mode of operation, electron transport takes place along the heavily doped channel. When the device enters the accumulation mode of operation, electrons pile up against the heterointerface in the high-mobility undoped subchannel. This should result in markedly improved transport characteristics at the onset of accumulation. The concept is demonstrated in the In 0.52 Al 0.48 As/In 0.53 Ga 0.47 As system on InP

  1. Effect of the SK/IK channel modulator 4,5-dichloro-1,3-diethyl-1,3-dihydro-benzoimidazol-2-one (NS4591) on contractile force in rat, pig and human detrusor smooth muscle

    DEFF Research Database (Denmark)

    Nielsen, Jens Steen; Rode, Frederik; Rahbek, Mette

    2011-01-01

    • To investigate the importance of small (SK)- and intermediate (IK)-conductance Ca2(+) -activated K(+) channels on bladder function, by studying the effects of 4,5-dichloro-1,3-diethyl-1,3-dihydro-benzoimidazol-2-one (NS4591), a new modulator of SK/IK channels, on contractions induced by electri......• To investigate the importance of small (SK)- and intermediate (IK)-conductance Ca2(+) -activated K(+) channels on bladder function, by studying the effects of 4,5-dichloro-1,3-diethyl-1,3-dihydro-benzoimidazol-2-one (NS4591), a new modulator of SK/IK channels, on contractions induced...

  2. Pre-criticality testing of radiation monitors associated with protective and regulatory channels of PHWRs and related work

    International Nuclear Information System (INIS)

    Tripathi, S.M.; Rao, Suresh; Mahant, A.K.; Sathian, V.; Ghodke, Shobha; Satam, R.A.; Singh, Yashoda; Phadnis, U.V.; Shaha, V.V.

    2006-01-01

    The paper describes the various experiments that are regularly carried out for each PHWR since RAPS-2. The work involves performance evaluation of start-up counters and ion chambers used in Protective and Regulatory channels and start-up counters used both in-core and out of core. In addition, Radiation Safety Systems Division (RSSD) also carries out calibration of Delayed Neutron Monitors (DNM) and Self Powered Neutron Detectors (SPND). Except SPND, all other detectors are tested not only at BARC but also at reactor sites prior to initial flushing of heavy water, using the actual circuitry and control instruments at site. The performance evaluation of SPNDs is carried out at A-1 location of APSARA reactor core. Apart from these, RSSD also carries out calibration of zonal classification monitors and health physics related radiation monitors at BARC. (author)

  3. Real-Time Video Transmission Over Different Underwater Wireless Optical Channels Using a Directly Modulated 520  nm Laser Diode

    KAUST Repository

    Al-Halafi, Abdullah; Oubei, Hassan M.; Ooi, Boon S.; Shihada, Basem

    2017-01-01

    We experimentally demonstrate high-quality real-time video streaming over an underwater wireless optical communication (UWOC) link up to 5 m distance using phase-shift keying (PSK) modulation and quadrature amplitude modulation (QAM) schemes. The communication system uses software defined platforms connected to a commercial TO-9 packaged pigtailed 520 nm directly modulated laser diode (LD) with 1.2 GHz bandwidth as the optical transmitter and an avalanche photodiode (APD) module as the receiver. To simulate various underwater channels, we perform laboratory experiments on clear, coastal, harbor I, and harbor II ocean water types. The measured bit error rates of the received video streams are 1.0×10−9 for QPSK, 4-QAM, and 8-QAM and 9.9×10−9 for 8-PSK. We further evaluate the quality of the received live video images using structural similarity and achieve values of about 0.9 for the first three water types, and about 0.7 for harbor II. To the best of our knowledge, these results present the highest quality video streaming ever achieved in UWOC systems that resemble communication channels in real ocean water environments.

  4. Real-Time Video Transmission Over Different Underwater Wireless Optical Channels Using a Directly Modulated 520  nm Laser Diode

    KAUST Repository

    Al-Halafi, Abdullah

    2017-09-13

    We experimentally demonstrate high-quality real-time video streaming over an underwater wireless optical communication (UWOC) link up to 5 m distance using phase-shift keying (PSK) modulation and quadrature amplitude modulation (QAM) schemes. The communication system uses software defined platforms connected to a commercial TO-9 packaged pigtailed 520 nm directly modulated laser diode (LD) with 1.2 GHz bandwidth as the optical transmitter and an avalanche photodiode (APD) module as the receiver. To simulate various underwater channels, we perform laboratory experiments on clear, coastal, harbor I, and harbor II ocean water types. The measured bit error rates of the received video streams are 1.0×10−9 for QPSK, 4-QAM, and 8-QAM and 9.9×10−9 for 8-PSK. We further evaluate the quality of the received live video images using structural similarity and achieve values of about 0.9 for the first three water types, and about 0.7 for harbor II. To the best of our knowledge, these results present the highest quality video streaming ever achieved in UWOC systems that resemble communication channels in real ocean water environments.

  5. Optimized Irregular Low-Density Parity-Check Codes for Multicarrier Modulations over Frequency-Selective Channels

    Directory of Open Access Journals (Sweden)

    Valérian Mannoni

    2004-09-01

    Full Text Available This paper deals with optimized channel coding for OFDM transmissions (COFDM over frequency-selective channels using irregular low-density parity-check (LDPC codes. Firstly, we introduce a new characterization of the LDPC code irregularity called “irregularity profile.” Then, using this parameterization, we derive a new criterion based on the minimization of the transmission bit error probability to design an irregular LDPC code suited to the frequency selectivity of the channel. The optimization of this criterion is done using the Gaussian approximation technique. Simulations illustrate the good performance of our approach for different transmission channels.

  6. An S-type anion channel SLAC1 is involved in cryptogein-induced ion fluxes and modulates hypersensitive responses in tobacco BY-2 cells.

    Science.gov (United States)

    Kurusu, Takamitsu; Saito, Katsunori; Horikoshi, Sonoko; Hanamata, Shigeru; Negi, Juntaro; Yagi, Chikako; Kitahata, Nobutaka; Iba, Koh; Kuchitsu, Kazuyuki

    2013-01-01

    Pharmacological evidence suggests that anion channel-mediated plasma membrane anion effluxes are crucial in early defense signaling to induce immune responses and hypersensitive cell death in plants. However, their molecular bases and regulation remain largely unknown. We overexpressed Arabidopsis SLAC1, an S-type anion channel involved in stomatal closure, in cultured tobacco BY-2 cells and analyzed the effect on cryptogein-induced defense responses including fluxes of Cl(-) and other ions, production of reactive oxygen species (ROS), gene expression and hypersensitive responses. The SLAC1-GFP fusion protein was localized at the plasma membrane in BY-2 cells. Overexpression of SLAC1 enhanced cryptogein-induced Cl(-) efflux and extracellular alkalinization as well as rapid/transient and slow/prolonged phases of NADPH oxidase-mediated ROS production, which was suppressed by an anion channel inhibitor, DIDS. The overexpressor also showed enhanced sensitivity to cryptogein to induce downstream immune responses, including the induction of defense marker genes and the hypersensitive cell death. These results suggest that SLAC1 expressed in BY-2 cells mediates cryptogein-induced plasma membrane Cl(-) efflux to positively modulate the elicitor-triggered activation of other ion fluxes, ROS as well as a wide range of defense signaling pathways. These findings shed light on the possible involvement of the SLAC/SLAH family anion channels in cryptogein signaling to trigger the plasma membrane ion channel cascade in the plant defense signal transduction network.

  7. The KCNQ5 potassium channel from mouse: a broadly expressed M-current like potassium channel modulated by zinc, pH, and volume changes

    DEFF Research Database (Denmark)

    Jensen, Henrik Sindal; Callø, Kirstine; Jespersen, Thomas

    2005-01-01

    H-dependent potentiation by Zn2+ (EC50 = 21.8 microM at pH 7.4), inhibition by acidification (IC50 = 0.75 microM; pKa = 6.1), and regulation by small changes in cell volume. Furthermore, the channels are activated by the anti-convulsant drug retigabine (EC50 = 2.0 microM) and inhibited by the M-current blockers...... and hippocampus. This study shows that murine KCNQ5 channels, in addition to sharing biophysical and pharmacological characteristics with the human ortholog, are tightly regulated by physiological stimuli such as changes in extracellular Zn2+, pH, and tonicity, thus adding to the complex regulation...

  8. Effects of KCNQ channel modulators on the M-type potassium current in primate retinal pigment epithelium.

    Science.gov (United States)

    Pattnaik, Bikash R; Hughes, Bret A

    2012-03-01

    Recently, we demonstrated the expression of KCNQ1, KCNQ4, and KCNQ5 transcripts in monkey retinal pigment epithelium (RPE) and showed that the M-type current in RPE cells is blocked by the specific KCNQ channel blocker XE991. Using patch-clamp electrophysiology, we investigated the pharmacological sensitivity of the M-type current in isolated monkey RPE cells to elucidate the subunit composition of the channel. Most RPE cells exhibited an M-type current with a voltage for half-maximal activation of approximately -35 mV. The M-type current activation followed a double-exponential time course and was essentially complete within 1 s. The M-type current was inhibited by micromolar concentrations of the nonselective KCNQ channel blockers linopirdine and XE991 but was relatively insensitive to block by 10 μM chromanol 293B or 135 mM tetraethylammonium (TEA), two KCNQ1 channel blockers. The M-type current was activated by 1) 10 μM retigabine, an opener of all KCNQ channels except KCNQ1, 2) 10 μM zinc pyrithione, which augments all KCNQ channels except KCNQ3, and 3) 50 μM N-ethylmaleimide, which activates KCNQ2, KCNQ4, and KCNQ5, but not KCNQ1 or KCNQ3, channels. Application of cAMP, which activates KCNQ1 and KCNQ4 channels, had no significant effect on the M-type current. Finally, diclofenac, which activates KCNQ2/3 and KCNQ4 channels but inhibits KCNQ5 channels, inhibited the M-type current in the majority of RPE cells but activated it in others. The results indicate that the M-type current in monkey RPE is likely mediated by channels encoded by KCNQ4 and KCNQ5 subunits.

  9. In vivo and in vitro attenuation of naloxone-precipitated experimental opioid withdrawal syndrome by insulin and selective KATP channel modulator.

    Science.gov (United States)

    Singh, Prabhat; Sharma, Bhupesh; Gupta, Surbhi; Sharma, B M

    2015-01-01

    Opiate exposure for longer duration develops state of dependence in humans and animals, which is revealed by signs and symptoms of withdrawal precipitated by opioid receptor antagonists. The sudden withdrawal of opioids produces a withdrawal syndrome in opioid-dependent subjects. Insulin and ATP-sensitive potassium (KATP) channel-mediated glucose homeostasis have been shown to modulate morphine withdrawal. Present study has been structured to investigate the role of insulin and pharmacological modulator of KATP channel (gliclazide) in experimental morphine withdrawal syndrome, both invivo and invitro. In this study, naloxone-precipitated morphine withdrawal syndrome in mice (invivo) as well as in rat ileum (invitro) were utilized to assess opioid withdrawal phenomenon. Morphine withdrawal syndromes like jumping and rearing frequency, forepaw licking, circling, fore paw tremor, wet dog shake, sneezing, overall morphine withdrawal severity (OMWS), serum glucose, brain malondialdehyde (MDA), glutathione (GSH), nitrite/nitrate, and calcium (Ca(+2)) were assessed. Naloxone has significantly increased morphine withdrawal syndrome, both invivo and invitro. Insulin and gliclazide have significantly attenuated, naloxone induced behavioral changes like jumping and rearing frequency, forepaw licking, wet dog shake, sneezing, straightening, circling, OMWS, and various biochemical impairments such as serum glucose, brain MDA, GSH, nitrite/nitrate, and Ca(+2) in morphine-dependent animals (invivo). In vitro, insulin and gliclazide have significantly reduced naloxone-induced contraction in morphine-withdrawn rat ileum preparation. Insulin and gliclazide (KATP channel blocker) have attenuated naloxone-precipitated morphine withdrawal syndrome, both invivo and invitro. Thus, insulin and KATP channel modulation may provide new avenues for research in morphine withdrawal.

  10. Modulation of mammary gland development in pre-pubertal mice as affected by soya and milk protein supplements.

    Science.gov (United States)

    Alston-Mills, Brenda; Lepri, J J; Martin, C A

    2011-08-01

    The objective of the present study was to determine the effects of soya and whey milk protein, α-lactalbumin (α-LA), on mammary gland morphology and the structural support of the gland, in pre-pubertal mice after 7 d of treatment. In Expt 1, weaned (day 21) CD1 mice were given one of the four treatments, three included dietary supplements: (1) control diet, casein, (2) soya, (3) α-LA and (4) subcutaneous injection of 2·5 μg oestradiol benzoate in 20 μl maize oil and fed the control diet. All diets were isoenergetic with equal protein concentrations. All groups that were not treated with oestradiol received the vehicle. Whole-mount analyses were performed to determine longitudinal ductal growth and terminal end bud development. DNA was extracted from the gland and assessed by spectrophotometry (260/280 nm). Tissue extracts for extracellular matrix (ECM) proteins, matrix metalloproteinase-2 (MMP(2)), tissue inhibitor of MMP(2) (TIMP(2)), and serum oestradiol and mammary tissue epidermal growth factors (EGF) were measured by immunoassays. Expt 2 utilised the Her2/neu transgenic strain, with the same protocols. Statistical significance was determined by one-way ANOVA. From Expt 1 and 2, soya and α-LA significantly increased ductal elongation when compared with the oestrogen and control groups. These results were corroborated by data on total DNA and the ratio of MMP(2):TIMP(2). The ratio of MMP(2):TIMP(2) was affected by α-LA. Serum oestradiol was decreased only in the oestradiol-treated groups in both experiments. Soya is known to be oestrogenic and can act on epithelia directly. The mechanism by which α-LA affects glandular development is by modulating the ECM or by promoting the synthesis/activity of EGF.

  11. Making Earth Science Relevant in the K-8 Classroom. The Development of an Instructional Soils Module for Pre-Service Elementary Teachers Using the Next Generation Science Standards

    Science.gov (United States)

    Baldwin, K. A.; Hauge, R.; Dechaine, J. M.; Varrella, G.; Egger, A. E.

    2013-12-01

    The development and adoption of the Next Generation Science Standards (NGSS) raises a challenge in teacher preparation: few current teacher preparation programs prepare students to teach science the way it is presented in the NGSS, which emphasize systems thinking, interdisciplinary science, and deep engagement in the scientific process. In addition, the NGSS include more geoscience concepts and methods than previous standards, yet this is a topic area in which most college students are traditionally underprepared. Although nationwide, programmatic reform is needed, there are a few targets where relatively small, course-level changes can have a large effect. One of these targets is the 'science methods' course for pre-service elementary teachers, a requirement in virtually all teacher preparation programs. Since many elementary schools, both locally and across the country, have adopted a kit based science curriculum, examining kits is often a part of a science methods course. Unfortunately, solely relying on a kit based curriculum may leave gaps in science content curriculum as one prepares teachers to meet the NGSS. Moreover, kits developed at the national level often fall short in connecting geoscientific content to the locally relevant societal issues that engage students. This highlights the need to train pre-service elementary teachers to supplement kit curriculum with inquiry based geoscience investigations that consider relevant societal issues, promote systems thinking and incorporate connections between earth, life, and physical systems. We are developing a module that teaches geoscience concepts in the context of locally relevant societal issues while modeling effective pedagogy for pre-service elementary teachers. Specifically, we focus on soils, an interdisciplinary topic relevant to multiple geoscience-related societal grand challenges (e.g., water, food) that is difficult to engage students in. Module development is funded through InTeGrate, NSF

  12. Modulation of Potassium Channel Activity in the Balance of ROS and ATP Production by Durum Wheat Mitochondria - An amazing defence tool against hyperosmotic stress

    Directory of Open Access Journals (Sweden)

    Daniela eTrono

    2015-12-01

    Full Text Available In plants, the existence of a mitochondrial potassium channel was firstly demonstrated about fifteen years ago in durum wheat as an ATP-dependent potassium channel (PmitoKATP. Since then, both properties of the original PmitoKATP and occurrence of different mitochondrial potassium channels in a number of plant species (monocotyledonous and dicotyledonous and tissues/organs (etiolated and green have been shown. Here, an overview of the current knowledge is reported; in particular, the issue of PmitoKATP physiological modulation is addressed. Similarities and differences with other potassium channels, as well as possible cross-regulation with other mitochondrial proteins (Plant Uncoupling Protein, Alternative Oxidase, Plant Inner Membrane Anion Channel are also described. PmitoKATP is inhibited by ATP and activated by superoxide anion, as well as by free fatty acids (FFAs and acyl-CoAs. Interestingly, channel activation increases electrophoretic potassium uptake across the inner membrane towards the matrix, so collapsing membrane potential (ΔΨ, the main component of the protonmotive force (Δp in plant mitochondria; moreover, cooperation between PmitoKATP and the K+/H+ antiporter allows a potassium cycle able to dissipate also ΔpH. Interestingly, ΔΨ collapse matches with an active control of mitochondrial reactive oxygen species (ROS production. Fully open channel is able to lower superoxide anion up to 35-fold compared to a condition of ATP-inhibited channel. On the other hand, ΔΨ collapse by PmitoKATP was unexpectedly found to not affect ATP synthesis via oxidative phosphorylation. This may probably occur by means of a controlled collapse due to ATP inhibition of PmitoKATP; this brake to the channel activity may allow a loss of the bulk phase Δp, but may preserve a non-classically detectable localized driving force for ATP synthesis. This ability may become crucial under environmental/oxidative stress. In particular, under moderate

  13. Effect of the SK/IK channel modulator 4,5-dichloro-1,3-diethyl-1,3-dihydro-benzoimidazol-2-one (NS4591) on contractile force in rat, pig and human detrusor smooth muscle

    DEFF Research Database (Denmark)

    Nielsen, Jens Steen; Rode, Frederik; Rahbek, Mette

    2011-01-01

    • To investigate the importance of small (SK)- and intermediate (IK)-conductance Ca2(+) -activated K(+) channels on bladder function, by studying the effects of 4,5-dichloro-1,3-diethyl-1,3-dihydro-benzoimidazol-2-one (NS4591), a new modulator of SK/IK channels, on contractions induced by electri...

  14. ATP-modulated K+ channels sensitive to antidiabetic sulfonylureas are present in adenohypophysis and are involved in growth hormone release.

    OpenAIRE

    Bernardi, H; De Weille, J R; Epelbaum, J; Mourre, C; Amoroso, S; Slama, A; Fosset, M; Lazdunski, M

    1993-01-01

    The adenohypophysis contains high-affinity binding sites for antidiabetic sulfonylureas that are specific blockers of ATP-sensitive K+ channels. The binding protein has a M(r) of 145,000 +/- 5000. The presence of ATP-sensitive K+ channels (26 pS) has been demonstrated by electrophysiological techniques. Intracellular perfusion of adenohypophysis cells with an ATP-free medium to activate ATP-sensitive K+ channels induces a large hyperpolarization (approximately 30 mV) that is antagonized by an...

  15. Large-Eddy Simulation of Turbulent Flow and Heat Transfer in a Mildly Expanded Channel of IFMIF High Flux Test Module

    International Nuclear Information System (INIS)

    Shinji Ebara; Takehiko Yokomine; Akihiko Shimizu

    2006-01-01

    During irradiation test periods in the International Fusion Material Irradiation Facility (IFMIF), irradiated materials must be maintained at constant temperatures because irradiation characteristics of materials have a large dependency on temperature. In the high flux test module of the IFMIF, required performances for temperature control using gas-cooling and heater-heating are especially stringent because available space for temperature control is remarkably restricted due to very small irradiation volume of about 0.5 l. We proposed an alternative design of the test module with advantages of temperature monitoring and temperature uniformity in specimens. This design employs a rectangular duct as the vessel to pack capsules housing specimens compactly into the small irradiation volume. In the vessel the coolant flows between the capsules and vessel wall. In the basic design, both thickness of a vessel wall and a width of cooling channel are considered as 1.0 mm. Since inside the vessel gaseous helium of several atmospheric pressure flows as a coolant and a low vacuum environment is kept outside the vessel for safety requirements and thermal stress is foreseen to appear due to nuclear heating of the vessel itself, the vessel wall is considered to deform readily and this leads expansion of the cooling channels. It is also considered that a slight expansion of the vessel can have severe influence on the cooling performance due to the initial narrow channel width of 1.0 mm. Therefore, it is necessary to estimate cooling performances for the coolant flowing in the deformed channel. We conduct a finite element analysis of turbulent heat transfer in a mildly expanded channel using large-eddy simulation in this study. In a numerical system, fluid is enclosed by three-dimensionally expanded vessel wall and flat capsule wall, and flows into the system with a fully developed velocity profile. In this study, we focus not only on the cooling performances but also on change in

  16. Numerical study of turbulent channel flow perturbed by spanwise topographic heterogeneity: Amplitude and frequency modulation within low- and high-momentum pathways

    Science.gov (United States)

    Awasthi, Ankit; Anderson, William

    2018-04-01

    We have studied the effects of topographically driven secondary flows on inner-outer interaction in turbulent channel flow. Recent studies have revealed that large-scale motions in the logarithmic region impose an amplitude and frequency modulation on the dynamics of small-scale structures near the wall. This led to development of a predictive model for near-wall dynamics, which has practical relevance for large-eddy simulations. Existing work on amplitude modulation has focused on smooth-wall flows; however, Anderson [J. Fluid Mech. 789, 567 (2016), 10.1017/jfm.2015.744] addressed the problem of rough-wall turbulent channel flow in which the correlation profiles for amplitude modulation showed trends similar to those reported by Mathis et al. [Phys. Fluids 21, 111703 (2009), 10.1063/1.3267726]. For the present study, we considered flow over surfaces with a prominent spanwise heterogeneity, such that domain-scale turbulent secondary flows in the form of counter-rotating vortices are sustained within the flow. (We also show results for flow over a homogeneous roughness, which serves as a benchmark against the spanwise-perturbed cases.) The vortices are anchored to the topography such that prominent upwelling and downwelling occur above the low and high roughness, respectively. We have quantified the extent to which such secondary flows disrupt the distribution of spectral density across constituent wavelengths throughout the depth of the flow, which has direct implications for the existence of amplitude and frequency modulation. We find that the distinct outer peak associated with large-scale motions—the "modulators"—is preserved within the upwelling zone but vanishes in the downwelling zone. Within the downwelling zones, structures are steeper and shorter. Single- and two-point correlations for inner-outer amplitude and frequency modulation demonstrate insensitivity to resolution across cases. We also show a pronounced crossover between the single- and two

  17. Climate-modulated channel incision and rupture history of the San Andreas Fault in the Carrizo Plain.

    Science.gov (United States)

    Grant Ludwig, Lisa; Akçiz, Sinan O; Noriega, Gabriela R; Zielke, Olaf; Arrowsmith, J Ramón

    2010-02-26

    The spatial and temporal distribution of fault slip is a critical parameter in earthquake source models. Previous geomorphic and geologic studies of channel offset along the Carrizo section of the south central San Andreas Fault assumed that channels form more frequently than earthquakes occur and suggested that repeated large-slip earthquakes similar to the 1857 Fort Tejon earthquake illustrate typical fault behavior. We found that offset channels in the Carrizo Plain incised less frequently than they were offset by earthquakes. Channels have been offset by successive earthquakes with variable slip since ~1400. This nonuniform slip history reveals a more complex rupture history than previously assumed for the structurally simplest section of the San Andreas Fault.

  18. hERG1 channels are overexpressed in glioblastoma multiforme and modulate VEGF secretion in glioblastoma cell lines

    Science.gov (United States)

    Masi, A; Becchetti, A; Restano-Cassulini, R; Polvani, S; Hofmann, G; Buccoliero, A M; Paglierani, M; Pollo, B; Taddei, G L; Gallina, P; Di Lorenzo, N; Franceschetti, S; Wanke, E; Arcangeli, A

    2005-01-01

    Recent studies have led to considerable advancement in our understanding of the molecular mechanisms that underlie the relentless cell growth and invasiveness of human gliomas. Partial understanding of these mechanisms has (1) improved the classification for gliomas, by identifying prognostic subgroups, and (2) pointed to novel potential therapeutic targets. Some classes of ion channels have turned out to be involved in the pathogenesis and malignancy of gliomas. We studied the expression and properties of K+ channels in primary cultures obtained from surgical specimens: human ether a gò-gò related (hERG)1 voltage-dependent K+ channels, which have been found to be overexpressed in various human cancers, and human ether a gò-gò-like 2 channels, that share many of hERG1's biophysical features. The expression pattern of these two channels was compared to that of the classical inward rectifying K+ channels, IRK, that are widely expressed in astrocytic cells and classically considered a marker of astrocytic differentiation. In our study, hERG1 was found to be specifically overexpressed in high-grade astrocytomas, that is, glioblastoma multiforme (GBM). In addition, we present evidence that, in GBM cell lines, hERG1 channel activity actively contributes to malignancy by promoting vascular endothelial growth factor secretion, thus stimulating the neoangiogenesis typical of high-grade gliomas. Our data provide important confirmation for studies proposing the hERG1 channel as a molecular marker of tumour progression and a possible target for novel anticancer therapies. PMID:16175187

  19. Modulation of Ca(v)3.2 T-type calcium channel permeability by asparagine-linked glycosylation

    Czech Academy of Sciences Publication Activity Database

    Ondáčová, K.; Karmažínová, M.; Lazniewska, Joanna; Weiss, Norbert; Lacinová, L.

    2016-01-01

    Roč. 10, č. 3 (2016), s. 175-184 ISSN 1933-6950 R&D Projects: GA ČR GA15-13556S; GA MŠk 7AMB15FR015 Institutional support: RVO:61388963 Keywords : calcium channel * Ca(v)3.2 * gating * glycosylation * T-type channel Subject RIV: CE - Biochemistry Impact factor: 2.042, year: 2016

  20. Dynamic habitat corridors for marine predators; intensive use of a coastal channel by harbour seals is modulated by tidal currents.

    Science.gov (United States)

    Hastie, Gordon D; Russell, Deborah J F; Benjamins, Steven; Moss, Simon; Wilson, Ben; Thompson, Dave

    2016-01-01

    Previous studies have found that predators utilise habitat corridors to ambush prey moving through them. In the marine environment, coastal channels effectively act as habitat corridors for prey movements, and sightings of predators in such areas suggest that they may target these for foraging. Unlike terrestrial systems where the underlying habitat structure is generally static, corridors in marine systems are in episodic flux due to water movements created by tidal processes. Although these hydrographic features can be highly complex, there is generally a predictable underlying cyclic tidal pattern to their structure. For marine predators that must find prey that is often patchy and widely distributed, the underlying temporal predictability in potential foraging opportunities in marine corridors may be important drivers in their use. Here, we used data from land-based sightings and 19 harbour seals ( Phoca vitulina ) tagged with high-resolution GPS telemetry to investigate the spatial and temporal distribution patterns of seals in a narrow tidal channel. These seals showed a striking pattern in their distribution; all seals spent a high proportion of their time around the narrowest point of the channel. There was also a distinctive tidal pattern in the use of the channel; sightings of seals in the water peaked during the flood tide and were at a minimum during the ebb tide. This pattern is likely to be related to prey availability and/or foraging efficiency driven by the underlying tidal pattern in the water movements through the channel. To maximise foraging efficiency, predators often make use of narrow constrictions in habitat to intercept prey using these corridors for movement. In the marine environment, narrow channels may act as corridors, and sightings of predators suggest that they may target these for foraging. Despite this, there is little information on how individual predators use such areas. Here, we investigate how individual harbour seals use a

  1. Microwave-assisted convenient syntheses of 2-indolizine derivatives from Morita-Baylis-Hillman adducts: new in silico potential ion channel modulators

    International Nuclear Information System (INIS)

    Cunha, Saraghina M.D.; Oliveira, Ramon G. de; Vasconcellos, Mario L.A.A.

    2013-01-01

    In this work, a microwave-assisted synthesis study by microwave irradiation to produce indolizine-2-carbonitrile and indolizine-2-carboxylate in good to high yields (70 and 81%, respectively) in one step from Morita-Baylis-Hillman adducts (MBHA) is presented. These compounds were subsequently transformed to high yields (94 to 100%, respectively) in three 2-indolizine derivatives. The five synthesized compounds were designed in silico aiming to present potential selective activities as ion channel modulators. These activities were suggested by the score values using Molinspiration Cheminformatics program. (author)

  2. Microwave-assisted convenient syntheses of 2-indolizine derivatives from Morita-Baylis-Hillman adducts: new in silico potential ion channel modulators

    Energy Technology Data Exchange (ETDEWEB)

    Cunha, Saraghina M.D.; Oliveira, Ramon G. de; Vasconcellos, Mario L.A.A., E-mail: mlaav@quimica.ufpb.br [Universidade Federal da Paraiba (UFPB), Joao Pessoa, PB (Brazil). Departamento de Quimica

    2013-03-15

    In this work, a microwave-assisted synthesis study by microwave irradiation to produce indolizine-2-carbonitrile and indolizine-2-carboxylate in good to high yields (70 and 81%, respectively) in one step from Morita-Baylis-Hillman adducts (MBHA) is presented. These compounds were subsequently transformed to high yields (94 to 100%, respectively) in three 2-indolizine derivatives. The five synthesized compounds were designed in silico aiming to present potential selective activities as ion channel modulators. These activities were suggested by the score values using Molinspiration Cheminformatics program. (author)

  3. Modulation of the transient outward current (Ito) in rat cardiac myocytes and human Kv4.3 channels by mefloquine

    International Nuclear Information System (INIS)

    Perez-Cortes, E.J.; Islas, A.A.; Arevalo, J.P.; Mancilla, C.; Monjaraz, E.; Salinas-Stefanon, E.M.

    2015-01-01

    The antimalarial drug mefloquine, is known to be a potassium channel blocker, although its mechanism of action has not being elucidated and its effects on the transient outward current (I to ) and the molecular correlate, the K v 4.3 channel has not being studied. Here, we describe the mefloquine-induced inhibition of the rat ventricular I to and of CHO cells co-transfected with human K v 4.3 and its accessory subunit hKChIP2C by whole-cell voltage-clamp. Mefloquine inhibited rat I to and hK v 4.3 + KChIP2C currents in a concentration-dependent manner with a limited voltage dependence and similar potencies (IC 50 = 8.9 μM and 10.5 μM for cardiac myocytes and K v 4.3 channels, respectively). In addition, mefloquine did not affect the activation of either current but significantly modified the hK v 4.3 steady-state inactivation and recovery from inactivation. The effects of this drug was compared with that of 4-aminopyridine (4-AP), a well-known potassium channel blocker and its binding site does not seem to overlap with that of 4-AP. - Highlights: • Mefloquine inhibited ventricular I to and hK v 4.3 channels. IC 50 = 8.9 and 10.5 μM. • Inactivation and recovery from inactivation in the hK v 4.3 channels were modified by mefloquine. • Mefloquine displayed a higher affinity for the inactivated state. • The binding site for mefloquine may be located in the extracellular side of the channel.

  4. Fragile X mental retardation protein controls synaptic vesicle exocytosis by modulating N-type calcium channel density

    Science.gov (United States)

    Ferron, Laurent; Nieto-Rostro, Manuela; Cassidy, John S.; Dolphin, Annette C.

    2014-04-01

    Fragile X syndrome (FXS), the most common heritable form of mental retardation, is characterized by synaptic dysfunction. Synaptic transmission depends critically on presynaptic calcium entry via voltage-gated calcium (CaV) channels. Here we show that the functional expression of neuronal N-type CaV channels (CaV2.2) is regulated by fragile X mental retardation protein (FMRP). We find that FMRP knockdown in dorsal root ganglion neurons increases CaV channel density in somata and in presynaptic terminals. We then show that FMRP controls CaV2.2 surface expression by targeting the channels to the proteasome for degradation. The interaction between FMRP and CaV2.2 occurs between the carboxy-terminal domain of FMRP and domains of CaV2.2 known to interact with the neurotransmitter release machinery. Finally, we show that FMRP controls synaptic exocytosis via CaV2.2 channels. Our data indicate that FMRP is a potent regulator of presynaptic activity, and its loss is likely to contribute to synaptic dysfunction in FXS.

  5. TRPM8 ion channels differentially modulate proliferation and cell cycle distribution of normal and cancer prostate cells.

    Science.gov (United States)

    Valero, María Ll; Mello de Queiroz, Fernanda; Stühmer, Walter; Viana, Félix; Pardo, Luis A

    2012-01-01

    Overexpression of the cation-permeable channel TRPM8 in prostate cancers might represent a novel opportunity for their treatment. Inhibitors of TRPM8 reduce the growth of prostate cancer cells. We have used two recently described and highly specific blockers, AMTB and JNJ41876666, and RNAi to determine the relevance of TRPM8 expression in the proliferation of non-tumor and tumor cells. Inhibition of the expression or function of the channel reduces proliferation rates and proliferative fraction in all tumor cells tested, but not of non-tumor prostate cells. We observed no consistent acceleration of growth after stimulation of the channel with menthol or icilin, indicating that basal TRPM8 expression is enough to sustain growth of prostate cancer cells.

  6. TRPM8 ion channels differentially modulate proliferation and cell cycle distribution of normal and cancer prostate cells.

    Directory of Open Access Journals (Sweden)

    María Ll Valero

    Full Text Available Overexpression of the cation-permeable channel TRPM8 in prostate cancers might represent a novel opportunity for their treatment. Inhibitors of TRPM8 reduce the growth of prostate cancer cells. We have used two recently described and highly specific blockers, AMTB and JNJ41876666, and RNAi to determine the relevance of TRPM8 expression in the proliferation of non-tumor and tumor cells. Inhibition of the expression or function of the channel reduces proliferation rates and proliferative fraction in all tumor cells tested, but not of non-tumor prostate cells. We observed no consistent acceleration of growth after stimulation of the channel with menthol or icilin, indicating that basal TRPM8 expression is enough to sustain growth of prostate cancer cells.

  7. Mutation of I696 and W697 in the TRP box of vanilloid receptor subtype I modulates allosteric channel activation.

    Science.gov (United States)

    Gregorio-Teruel, Lucia; Valente, Pierluigi; González-Ros, José Manuel; Fernández-Ballester, Gregorio; Ferrer-Montiel, Antonio

    2014-03-01

    The transient receptor potential vanilloid receptor subtype I (TRPV1) channel acts as a polymodal sensory receptor gated by chemical and physical stimuli. Like other TRP channels, TRPV1 contains in its C terminus a short, conserved domain called the TRP box, which is necessary for channel gating. Substitution of two TRP box residues-I696 and W697-with Ala markedly affects TRPV1's response to all activating stimuli, which indicates that these two residues play a crucial role in channel gating. We systematically replaced I696 and W697 with 18 native l-amino acids (excluding cysteine) and evaluated the effect on voltage- and capsaicin-dependent gating. Mutation of I696 decreased channel activation by either voltage or capsaicin; furthermore, gating was only observed with substitution of hydrophobic amino acids. Substitution of W697 with any of the 18 amino acids abolished gating in response to depolarization alone, shifting the threshold to unreachable voltages, but not capsaicin-mediated gating. Moreover, vanilloid-activated responses of W697X mutants showed voltage-dependent gating along with a strong voltage-independent component. Analysis of the data using an allosteric model of activation indicates that mutation of I696 and W697 primarily affects the allosteric coupling constants of the ligand and voltage sensors to the channel pore. Together, our findings substantiate the notion that inter- and/or intrasubunit interactions at the level of the TRP box are critical for efficient coupling of stimulus sensing and gate opening. Perturbation of these interactions markedly reduces the efficacy and potency of the activating stimuli. Furthermore, our results identify these interactions as potential sites for pharmacological intervention.

  8. A Common Structural Component for β-Subunit Mediated Modulation of Slow Inactivation in Different KV Channels

    DEFF Research Database (Denmark)

    Strutz-Seebohm, Nathalie; Henrion, Ulrike; Schmitt, Nicole

    2013-01-01

    Background/Aims: Potassium channels are tetrameric proteins providing potassium selective passage through lipid embedded proteinaceous pores with highest fidelity. The selectivity results from binding to discrete potassium binding sites and stabilization of a hydrated potassium ion in a central...... internal cavity. The four potassium binding sites, generated by the conserved TTxGYGD signature sequence are formed by the backbone carbonyls of the amino acids TXGYG. Residues KV1.5-Val481, KV4.3-Leu368 and KV7.1- Ile 313 represent the amino acids in the X position of the respective channels. Methods...

  9. External pH modulates EAG superfamily K+ channels through EAG-specific acidic residues in the voltage sensor

    Science.gov (United States)

    Kazmierczak, Marcin; Zhang, Xiaofei; Chen, Bihan; Mulkey, Daniel K.; Shi, Yingtang; Wagner, Paul G.; Pivaroff-Ward, Kendra; Sassic, Jessica K.; Bayliss, Douglas A.

    2013-01-01

    The Ether-a-go-go (EAG) superfamily of voltage-gated K+ channels consists of three functionally distinct gene families (Eag, Elk, and Erg) encoding a diverse set of low-threshold K+ currents that regulate excitability in neurons and muscle. Previous studies indicate that external acidification inhibits activation of three EAG superfamily K+ channels, Kv10.1 (Eag1), Kv11.1 (Erg1), and Kv12.1 (Elk1). We show here that Kv10.2, Kv12.2, and Kv12.3 are similarly inhibited by external protons, suggesting that high sensitivity to physiological pH changes is a general property of EAG superfamily channels. External acidification depolarizes the conductance–voltage (GV) curves of these channels, reducing low threshold activation. We explored the mechanism of this high pH sensitivity in Kv12.1, Kv10.2, and Kv11.1. We first examined the role of acidic voltage sensor residues that mediate divalent cation block of voltage activation in EAG superfamily channels because protons reduce the sensitivity of Kv12.1 to Zn2+. Low pH similarly reduces Mg2+ sensitivity of Kv10.1, and we found that the pH sensitivity of Kv11.1 was greatly attenuated at 1 mM Ca2+. Individual neutralizations of a pair of EAG-specific acidic residues that have previously been implicated in divalent block of diverse EAG superfamily channels greatly reduced the pH response in Kv12.1, Kv10.2, and Kv11.1. Our results therefore suggest a common mechanism for pH-sensitive voltage activation in EAG superfamily channels. The EAG-specific acidic residues may form the proton-binding site or alternatively are required to hold the voltage sensor in a pH-sensitive conformation. The high pH sensitivity of EAG superfamily channels suggests that they could contribute to pH-sensitive K+ currents observed in vivo. PMID:23712551

  10. External pH modulates EAG superfamily K+ channels through EAG-specific acidic residues in the voltage sensor.

    Science.gov (United States)

    Kazmierczak, Marcin; Zhang, Xiaofei; Chen, Bihan; Mulkey, Daniel K; Shi, Yingtang; Wagner, Paul G; Pivaroff-Ward, Kendra; Sassic, Jessica K; Bayliss, Douglas A; Jegla, Timothy

    2013-06-01

    The Ether-a-go-go (EAG) superfamily of voltage-gated K(+) channels consists of three functionally distinct gene families (Eag, Elk, and Erg) encoding a diverse set of low-threshold K(+) currents that regulate excitability in neurons and muscle. Previous studies indicate that external acidification inhibits activation of three EAG superfamily K(+) channels, Kv10.1 (Eag1), Kv11.1 (Erg1), and Kv12.1 (Elk1). We show here that Kv10.2, Kv12.2, and Kv12.3 are similarly inhibited by external protons, suggesting that high sensitivity to physiological pH changes is a general property of EAG superfamily channels. External acidification depolarizes the conductance-voltage (GV) curves of these channels, reducing low threshold activation. We explored the mechanism of this high pH sensitivity in Kv12.1, Kv10.2, and Kv11.1. We first examined the role of acidic voltage sensor residues that mediate divalent cation block of voltage activation in EAG superfamily channels because protons reduce the sensitivity of Kv12.1 to Zn(2+). Low pH similarly reduces Mg(2+) sensitivity of Kv10.1, and we found that the pH sensitivity of Kv11.1 was greatly attenuated at 1 mM Ca(2+). Individual neutralizations of a pair of EAG-specific acidic residues that have previously been implicated in divalent block of diverse EAG superfamily channels greatly reduced the pH response in Kv12.1, Kv10.2, and Kv11.1. Our results therefore suggest a common mechanism for pH-sensitive voltage activation in EAG superfamily channels. The EAG-specific acidic residues may form the proton-binding site or alternatively are required to hold the voltage sensor in a pH-sensitive conformation. The high pH sensitivity of EAG superfamily channels suggests that they could contribute to pH-sensitive K(+) currents observed in vivo.

  11. Four-channel asymmetric Real-Time PCR hybridization probe assay: a rapid pre-screening method for critical BCR-ABL kinase domain mutations.

    Science.gov (United States)

    Martinez-Serra, Jordi; Gutiérrez, Antonio; Marcús, Toni F; Soverini, Simona; Amat, Juan Carlos; Navarro-Palou, María; Ros, Teresa; Bex, Teresa; Ballester, Carmen; Bauça, Josep Miquel; SanFelix, Sara; Novo, Andrés; Vidal, Carmen; Santos, Carmen; Besalduch, Joan

    2012-03-01

    Within the laboratory protocols, used for the study of BCR-ABL resistance mutations in chronic myeloid leukemia patients treated with Imatinib, direct sequencing remains the reference method. Since the incidence of patients with a mutation-related loss of response is not very high, it is very useful in the routine laboratory to perform a fast pre-screening method. With this in mind, we have designed a new technique, based on a single Real-Time FRET-based PCR, followed by a study of melting peaks. This new tool, developed in a LightCycler 2.0, combines four different fluorescence channels for the simultaneous detection, in a single close tube, of critical mutations within the ABL kinase domain. Assay evaluation performed on 33 samples, previously genotyped by sequentiation, resulted in full concordance of results. This new methodology detects in a few steps the presence of critical mutations associated to Imatinib resistance. Copyright © 2012 Elsevier Inc. All rights reserved.

  12. Caracterización del canal epitelial de sodio en sinciciotrofoblasto de placenta humana preeclamptica Characterization of the epithelial sodium channel in human pre-eclampsia syncytiotrophoblast

    Directory of Open Access Journals (Sweden)

    Silvana del Mónaco

    2006-02-01

    epithelial Na channel (ENaC in placental tissue from normal and pre-eclamptic women and in BeWo cell, a model of a human SCT. Changes in the expression of these proteins during sodium transport across the placenta may be related to the pathogeny of pre-eclampsia. The role that ENaC and Na+ transport deregulation play on human placental tissues still remains unknown although in aldosterone-responsive epithelial cells (kidney, colon, abnormalities upregulating its activity lead to increased Na+ uptake and hypertension (i.e. Liddle´s syndrome whereas a diminished channel activity can result in the pseudohypoaldosteronisn syndrome with salt loss and hypotension. Our results show that ENaC is expressed in the apical membrane of normal syncytiotrophoblast. The amplified fragment of a-ENaC was cloned and sequenced having a 100% identity with the sequence of a-ENaC obtained from GenBankTM (SCNN1A, accession number Z92981. We found that the transcription of the a-ENaC mRNA was not detectable in preeclamptic placentas and the protein was not observed with immunohistochemistry staining, probably indicating a low protein expression level. In BeWo cells ENac was found and its expression is regulated by aldosterone, vasopressin, progesterone and estradiol. With patch clamp techniques we studied the currents trough ENaC channels in Bewo cells. We observed currents that were blocked by 10 µM amiloride in cells incubated in 100 nM aldosterone for 12 hs. The amplitude of this current was 20-fold the basal current, a reversal potential of 3 mV and a conductance of 127 ± 26 pS/pF with pulses between -60 and -140 mV. These characteristics are similar to those reported in ENaC channels in several tissues. Although their roles in placenta are still poorly understood, the differences in the expression of ENaC in pre-eclamptic placentas may have consequences for ion transport and these data could lead to future studies concerning the mechanism involved in the pathophysiology of pre-eclampsia.

  13. Evaluation of 5G Modulation Candidates WCP-COQAM, GFDM-OQAM, and FBMC-OQAM in Low-Band Highly Dispersive Wireless Channels

    Directory of Open Access Journals (Sweden)

    Aitor Lizeaga

    2017-01-01

    Full Text Available We analyse some of the candidates for modulations for 5G: FBMC-OQAM, GFDM-OQAM, and WCP-COQAM. Unlike most of the related bibliographies, which are oriented to mobile communications, our research is focused on 5G in cognitive radio based industrial wireless communications. According to the ultrareliability and low-latency requirements of industrial communications, we simulate the aforementioned modulations in low-band transmissions (carrier frequencies below 6 GHz and a bandwidth narrower than 100 MHz through large indoor spaces and severe multipath channels that emulate industrial halls. Moreover, we give detailed information about WCP-COQAM and how the windowing affects the protection against multipath effect and reduces spectral efficiency compared to GFDM-OQAM. We also compare the aforementioned filtered multicarrier techniques and OFDM in terms of robustness against multipath channels, power spectral density, and spectral efficiency. Based on these results, we aim at providing an approximate idea about the suitability of 5G MCM candidates for industrial wireless communications based on CR.

  14. The acrylamide (S)-2 as a positive and negative modulator of Kv7 channels expressed in Xenopus laevis oocytes

    DEFF Research Database (Denmark)

    Blom, Sigrid Marie; Schmitt, Nicole; Jensen, Henrik Sindal

    2009-01-01

    Kv7.2-5, is now in clinical trial phase III for the treatment of partial onset seizures. One of the main obstacles in developing Kv7 channel active drugs has been to identify compounds that can discriminate between the neuronal subtypes, a feature that could help diminish side effects and increase...

  15. Modulation of the conductance of a 2,2′-bipyridine-functionalized peptidic ion channel by Ni2+

    Science.gov (United States)

    Pilz, Claudia S.

    2008-01-01

    An α-helical amphipathic peptide with the sequence H2N-(LSSLLSL)3-CONH2 was obtained by solid phase synthesis and a 2,2′-bipyridine was coupled to its N-terminus, which allows complexation of Ni2+. Complexation of the 2,2′-bipyridine residues was proven by UV/Vis spectroscopy. The peptide helices were inserted into lipid bilayers (nano black lipid membranes, nano-BLMs) that suspend the pores of porous alumina substrates with a pore diameter of 60 nm by applying a potential difference. From single channel recordings, we were able to distinguish four distinct conductance states, which we attribute to an increasing number of peptide helices participating in the conducting helix bundle. Addition of Ni2+ in micromolar concentrations altered the conductance behaviour of the formed ion channels in nano-BLMs considerably. The first two conductance states appear much more prominent demonstrating that the complexation of bipyridine by Ni2+ results in a considerable confinement of the observed multiple conductance states. However, the conductance levels were independent of the presence of Ni2+. Moreover, from a detailed analysis of the open lifetimes of the channels, we conclude that the complexation of Ni2+ diminishes the frequency of channel events with larger open times. Electronic supplementary material The online version of this article (doi:10.1007/s00249-008-0298-8) contains supplementary material, which is available to authorized users. PMID:18347789

  16. T-type Ca(2+) channels facilitate NO-formation, vasodilatation and NO-mediated modulation of blood pressure

    DEFF Research Database (Denmark)

    Svenningsen, Per; Andersen, Kenneth; Thuesen, Anne D

    2014-01-01

    nitric oxide synthase (eNOS) in arteries from wild type mice. Nitric oxide release measured as DAF fluorescence and cGMP levels were significantly lower in depolarized Cav3.1(-/-) compared to wild type arteries. In summary, the absence of T-type Cav3.1 channels attenuates NO-dependent dilatation...

  17. Structure-function relation of phospholamban: modulation of channel activity as a potential regulator of SERCA activity.

    Directory of Open Access Journals (Sweden)

    Serena Smeazzetto

    Full Text Available Phospholamban (PLN is a small integral membrane protein, which binds and inhibits in a yet unknown fashion the Ca(2+-ATPase (SERCA in the sarcoplasmic reticulum. When reconstituted in planar lipid bilayers PLN exhibits ion channel activity with a low unitary conductance. From the effect of non-electrolyte polymers on this unitary conductance we estimate a narrow pore with a diameter of ca. 2.2 Å for this channel. This value is similar to that reported for the central pore in the structure of the PLN pentamer. Hence the PLN pentamer, which is in equilibrium with the monomer, is the most likely channel forming structure. Reconstituted PLN mutants, which either stabilize (K27A and R9C or destabilize (I47A the PLN pentamer and also phosphorylated PLN still generate the same unitary conductance of the wt/non-phosphorylated PLN. However the open probability of the phosphorylated PLN and of the R9C mutant is significantly lower than that of the respective wt/non-phosphorylated control. In the context of data on PLN/SERCA interaction and on Ca(2+ accumulation in the sarcoplasmic reticulum the present results are consistent with the view that PLN channel activity could participate in the balancing of charge during Ca(2+ uptake. A reduced total conductance of the K(+ transporting PLN by phosphorylation or by the R9C mutation may stimulate Ca(2+ uptake in the same way as an inhibition of K(+ channels in the SR membrane. The R9C-PLN mutation, a putative cause of dilated cardiomyopathy, might hence affect SERCA activity also via its inherent low open probability.

  18. Statin therapy exacerbates alcohol-induced constriction of cerebral arteries via modulation of ethanol-induced BK channel inhibition in vascular smooth muscle.

    Science.gov (United States)

    Simakova, Maria N; Bisen, Shivantika; Dopico, Alex M; Bukiya, Anna N

    2017-12-01

    Statins constitute the most commonly prescribed drugs to decrease cholesterol (CLR). CLR is an important modulator of alcohol-induced cerebral artery constriction (AICAC). Using rats on a high CLR diet (2% CLR) we set to determine whether atorvastatin administration (10mg/kg daily for 18-23weeks) modified AICAC. Middle cerebral arteries were pressurized in vitro at 60mmHg and AICAC was evoked by 50mM ethanol, that is within the range of blood alcohol detected in humans following moderate-to-heavy drinking. AICAC was evident in high CLR+atorvastatin group but not in high CLR diet+placebo. Statin exacerbation of AICAC persisted in de-endothelialized arteries, and was blunted by CLR enrichment in vitro. Fluorescence imaging of filipin-stained arteries showed that atorvastatin decreased vascular smooth muscle (VSM) CLR when compared to placebo, this difference being reduced by CLR enrichment in vitro. Voltage- and calcium-gated potassium channels of large conductance (BK) are known VSM targets of ethanol, with their beta1 subunit being necessary for ethanol-induced channel inhibition and resulting AICAC. Ethanol-induced BK inhibition in excised membrane patches from freshly isolated myocytes was exacerbated in the high CLR diet+atorvastatin group when compared to high CLR diet+placebo. Unexpectedly, atorvastatin decreased the amount and function of BK beta1 subunit as documented by immunofluorescence imaging and functional patch-clamp studies. Atorvastatin exacerbation of ethanol-induced BK inhibition disappeared upon artery CLR enrichment in vitro. Our study demonstrates for the first time statin's ability to exacerbate the vascular effect of a widely consumed drug of abuse, this exacerbation being driven by statin modulation of ethanol-induced BK channel inhibition in the VSM via CLR-mediated mechanism. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Modulation of voltage-gated Ca2+ channels by G protein-coupled receptors in celiac-mesenteric ganglion neurons of septic rats.

    Directory of Open Access Journals (Sweden)

    Mohamed Farrag

    Full Text Available Septic shock, the most severe complication associated with sepsis, is manifested by tissue hypoperfusion due, in part, to cardiovascular and autonomic dysfunction. In many cases, the splanchnic circulation becomes vasoplegic. The celiac-superior mesenteric ganglion (CSMG sympathetic neurons provide the main autonomic input to these vessels. We used the cecal ligation puncture (CLP model, which closely mimics the hemodynamic and metabolic disturbances observed in septic patients, to examine the properties and modulation of Ca2+ channels by G protein-coupled receptors in acutely dissociated rat CSMG neurons. Voltage-clamp studies 48 hr post-sepsis revealed that the Ca2+ current density in CMSG neurons from septic rats was significantly lower than those isolated from sham control rats. This reduction coincided with a significant increase in membrane surface area and a negligible increase in Ca2+ current amplitude. Possible explanations for these findings include either cell swelling or neurite outgrowth enhancement of CSMG neurons from septic rats. Additionally, a significant rightward shift of the concentration-response relationship for the norepinephrine (NE-mediated Ca2+ current inhibition was observed in CSMG neurons from septic rats. Testing for the presence of opioid receptor subtypes in CSMG neurons, showed that mu opioid receptors were present in ~70% of CSMG, while NOP opioid receptors were found in all CSMG neurons tested. The pharmacological profile for both opioid receptor subtypes was not significantly affected by sepsis. Further, the Ca2+ current modulation by propionate, an agonist for the free fatty acid receptors GPR41 and GPR43, was not altered by sepsis. Overall, our findings suggest that CSMG function is affected by sepsis via changes in cell size and α2-adrenergic receptor-mediated Ca2+ channel modulation.

  20. ISSUES AND FEASIBILITY DEMONSTRATION OF CLIC SUPPORTING SYSTEM CHAIN ACTIVE PRE-ALIGNMENT USING A MULTI-MODULE TEST SETUP (MOCK-UP)

    CERN Document Server

    Sosin, Mateusz

    2016-01-01

    The implementation study of the CLIC (Compact LInear Collider) is under way at CERN with a focus on the challenging issues. The pre-alignment precision and accuracy requirements are part of these technical challenges: the permissible transverse position errors of the linac components are typically 14 micrometers over sliding windows of 200m. To validate the proposed methods and strategies, the Large Scale Metrology section at CERN has performed campaigns of measurements on the CLIC Two Beam Test Modules, focusing inter alia on the alignment performance of the CLIC “snake”- girders configuration and the Main Beam Quadrupoles supporting structures. This paper describes the activities and results of tests which were performed on the test mock-up for the qualification of the CLIC supporting system chain for active pre-alignment. The lessons learnt (“know how”), the issues encountered in the girder position determination as well as the behaviour of the mechanical components are presented.

  1. Modulation of CaV1.2 calcium channel by neuropeptide W regulates vascular myogenic tone via G protein-coupled receptor 7.

    Science.gov (United States)

    Ji, Li; Zhu, Huayuan; Chen, Hong; Fan, Wenyong; Chen, Junjie; Chen, Jing; Zhu, Guoqing; Wang, Juejin

    2015-12-01

    Neuropeptide W (NPW), an endogenous ligand for the G protein-coupled receptor 7 (GPR7), was first found to make important roles in central nerve system. In periphery, NPW was also present and regulated intracellular calcium homeostasis by L-type calcium channels. This study was designed to discover the effects of NPW-GPR7 on the function of CaV1.2 calcium channels in the vascular smooth muscle cells (VSMCs) and vasotone of arterial vessels. By whole-cell patch clamp, we studied the effects of NPW-23, the active form of NPW, on the CaV1.2 channels in the heterologously transfected human embryonic kidney 293 cells and VSMCs isolated from rat. Living system was used to explore the physiological function of NPW-23 in arterial myogenic tone. To investigate the pathological relevance, NPW mRNA level of mesenteric arteries was measured in the hypertensive and normotensive rats. NPW's receptor GPR7 was coexpressed with CaV1.2 channels in arterial smooth muscle. NPW-23 increased the ICa,L in transfected human embryonic kidney 293 cells and VSMCs via GPR7, which could be abrogated by phospholipase C (PLC)/protein kinase C (PKC) inhibitors, not protein kinase A or protein kinase G inhibitor. After NPW-23 application, the expression of pan phospho-PKC was increased; moreover, intracellular diacylglycerol level, the second messenger catalyzed by PLC, was increased 1.5-2-fold. Application with NPW-23 increased pressure-induced vasotone of the rat mesenteric arteries. Importantly, the expression of NPW was decreased in the hypertensive rats. NPW-23 regulates ICa,L via GPR7, which is mediated by PLC/PKC signaling, and such a mechanism plays a role in modulating vascular myogenic tone, which may involve in the development of vascular hypertension.

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

    Science.gov (United States)

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

    2008-06-01

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

  3. Pertussis toxin-sensitive alpha-adrenergic modulation of voltage - dependent calcium channels in spontaneously hypertensive rats (SHR)

    Czech Academy of Sciences Publication Activity Database

    Zicha, Josef; Pintérová, Mária; Dobešová, Zdenka; Líšková, Silvia; Kuneš, Jaroslav

    2006-01-01

    Roč. 24, č. S6 (2006), s. 34-34 ISSN 0263-6352. [Scientific Meeting of the International Society of Hypertension /21./. 15.10.2006-19.10.2006, Fukuoka] R&D Projects: GA MZd(CZ) NR7786 Institutional research plan: CEZ:AV0Z50110509 Keywords : pertussis toxin * alpha adrenergic vasoconstriction * voltage-dependent calcium channels * SHR rat Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery

  4. Killing of Candida albicans by Human Salivary Histatin 5 Is Modulated, but Not Determined, by the Potassium Channel TOK1

    OpenAIRE

    Baev, Didi; Rivetta, Alberto; Li, Xuewei S.; Vylkova, Slavena; Bashi, Esther; Slayman, Clifford L.; Edgerton, Mira

    2003-01-01

    Salivary histatin 5 (Hst 5), a potent toxin for the human fungal pathogen Candida albicans, induces noncytolytic efflux of cellular ATP, potassium, and magnesium in the absence of cytolysis, implicating these ion movements in the toxin's fungicidal activity. Hst 5 action on Candida resembles, in many respects, the action of the K1 killer toxin on Saccharomyces cerevisiae, and in that system the yeast plasma membrane potassium channel, Tok1p, has recently been reported to be a primary target o...

  5. Direct modulation of tracheal Cl--channel activity by 5,6- and 11,12-EET.

    Science.gov (United States)

    Salvail, D; Dumoulin, M; Rousseau, E

    1998-09-01

    Using microelectrode potential measurements, we tested the involvement of Cl- conductances in the hyperpolarization induced by 5,6- and 11,12-epoxyeicosatrienoic acid (EET) in airway smooth muscle (ASM) cells. 5,6-EET and 11,12-EET (0.75 microM) caused -5.4 +/- 1.1- and -3.34 +/- 0.95-mV hyperpolarizations, respectively, of rabbit tracheal cells (from a resting membrane potential of -53.25 +/- 0.44 mV), with significant residual repolarizations remaining after the Ca2+-activated K+ channels had been blocked by 10 nM iberiotoxin. In bilayer reconstitution experiments, we demonstrated that the EETs directly inhibit a Ca2+-insensitive Cl- channel from bovine ASM; 1 microM 5,6-EET and 1.5 microM 11,12-EET lowered the unitary current amplitude by 40 (n = 6 experiments) and 44.7% (n = 4 experiments), respectively. Concentration-dependent decreases in channel open probability were observed, with estimated IC50 values of 0.26 microM for 5,6- and 1.15 microM for 11,12-EET. Furthermore, pharmacomechanical tension measurements showed that both regioisomers induced significant bronchorelaxations in epithelium-denuded ASM strips. These results suggest that 5,6- and 11,12-EET can act in ASM as epithelium-derived hyperpolarizing factors.

  6. Modulating secretory pathway pH by proton channel co-expression can increase recombinant protein stability in plants.

    Science.gov (United States)

    Jutras, Philippe V; D'Aoust, Marc-André; Couture, Manon M-J; Vézina, Louis-Philippe; Goulet, Marie-Claire; Michaud, Dominique; Sainsbury, Frank

    2015-09-01

    Eukaryotic expression systems are used for the production of complex secreted proteins. However, recombinant proteins face considerable biochemical challenges along the secretory pathway, including proteolysis and pH variation between organelles. As the use of synthetic biology matures into solutions for protein production, various host-cell engineering approaches are being developed to ameliorate host-cell factors that can limit recombinant protein quality and yield. We report the potential of the influenza M2 ion channel as a novel tool to neutralize the pH in acidic subcellular compartments. Using transient expression in the plant host, Nicotiana benthamiana, we show that ion channel expression can significantly raise pH in the Golgi apparatus and that this can have a strong stabilizing effect on a fusion protein separated by an acid-susceptible linker peptide. We exemplify the utility of this effect in recombinant protein production using influenza hemagglutinin subtypes differentially stable at low pH; the expression of hemagglutinins prone to conformational change in mildly acidic conditions is considerably enhanced by M2 co-expression. The co-expression of a heterologous ion channel to stabilize acid-labile proteins and peptides represents a novel approach to increasing the yield and quality of secreted recombinant proteins in plants and, possibly, in other eukaryotic expression hosts. Copyright © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Pulse-Width Modulation Pre Emphasis applied in a Wireline Transmitter, achieving 33dB Loss Compensation at 5-Gb/s in 0.13-μm CMOS

    NARCIS (Netherlands)

    Schrader, J.H.R.; Klumperink, Eric A.M.; Visschers, J.L.; Nauta, Bram

    2006-01-01

    Abstract—A transmitter pre-emphasis technique for copper cable equalization is presented that is based on pulse-width modulation (PWM). This technique is an alternative to the usual 2-tap symbol-spaced FIR (SSF) pre-emphasis. The technique uses timing resolution instead of amplitude resolution to

  8. Pre-Statistical Process Control: Making Numbers Count! JobLink Winning at Work Instructor's Manual, Module 3.

    Science.gov (United States)

    Coast Community Coll. District, Costa Mesa, CA.

    This instructor's manual for workplace trainers contains the materials required to conduct a course in pre-statistical process control. The course consists of six lessons for workers and two lessons for supervisors that discuss the following: concepts taught in the six lessons; workers' progress in the individual lessons; and strategies for…

  9. Arylbenzazepines Are Potent Modulators for the Delayed Rectifier K+ Channel: A Potential Mechanism for Their Neuroprotective Effects

    Science.gov (United States)

    Chen, Xue-Qin; Zhang, Jing; Neumeyer, John L.; Jin, Guo-Zhang; Hu, Guo-Yuan; Zhang, Ao; Zhen, Xuechu

    2009-01-01

    (±) SKF83959, like many other arylbenzazepines, elicits powerful neuroprotection in vitro and in vivo. The neuroprotective action of the compound was found to partially depend on its D1-like dopamine receptor agonistic activity. The precise mechanism for the (±) SKF83959-mediated neuroprotection remains elusive. We report here that (±) SKF83959 is a potent blocker for delayed rectifier K+ channel. (±) SKF83959 inhibited the delayed rectifier K+ current (I K) dose-dependently in rat hippocampal neurons. The IC 50 value for inhibition of I K was 41.9±2.3 µM (Hill coefficient = 1.81±0.13, n = 6), whereas that for inhibition of I A was 307.9±38.5 µM (Hill coefficient = 1.37±0.08, n = 6). Thus, (±) SKF83959 is 7.3-fold more potent in suppressing I K than I A. Moreover, the inhibition of I K by (±) SKF83959 was voltage-dependent and not related to dopamine receptors. The rapidly onset of inhibition and recovery suggests that the inhibition resulted from a direct interaction of (±) SKF83959 with the K+ channel. The intracellular application of (±) SKF83959 had no effects of on I K, indicating that the compound most likely acts at the outer mouth of the pore of K+ channel. We also tested the enantiomers of (±) SKF83959, R-(+) SKF83959 (MCL-201), and S-(−) SKF83959 (MCL-202), as well as SKF38393; all these compounds inhibited I K. However, (±) SKF83959, at either 0.1 or 1 mM, exhibited the strongest inhibition on the currents among all tested drug. The present findings not only revealed a new potent blocker of I K , but also provided a novel mechanism for the neuroprotective action of arylbenzazepines such as (±) SKF83959. PMID:19503734

  10. AQP4 plasma membrane trafficking or channel gating is not significantly modulated by phosphorylation at C-terminal serine residues

    DEFF Research Database (Denmark)

    Assentoft, Mette; Larsen, Brian R; Olesen, Emma T B

    2014-01-01

    heterologous expression in Xenopus laevis oocytes (along with serine-to-aspartate mutants of the same residues to mimic a phosphorylation). None of the mutant AQP4 constructs displayed alterations in the unit water permeability. Thus phosphorylation of six different serine residues in the COOH terminus of AQP4....... Phosphorylation of aquaporins can regulate plasma membrane localization and, possibly, the unit water permeability via gating of the AQP channel itself. In vivo phosphorylation of six serine residues in the COOH terminus of AQP4 has been detected by mass spectrometry: Ser(276), Ser(285), Ser(315), Ser(316), Ser...

  11. Electron spin echo envelope modulation (ESEEM) reveals water and phosphate interactions with the KcsA potassium channel

    OpenAIRE

    Cieslak, John A.; Focia, Pamela J.; Gross, Adrian

    2010-01-01

    Electron spin-echo envelope modulation (ESEEM) spectroscopy is a well-established technique for the study of naturally occurring paramagnetic metal centers. The technique has been used to study copper complexes, hemes, enzyme mechanisms, micellar water content, and water permeation profiles in membranes, among other applications. In the present study, we combine ESEEM spectroscopy with site-directed spin labeling (SDSL) and X-ray crystallography in order to evaluate the technique's potential ...

  12. Modulation of mdm2 pre-mRNA splicing by 9-aminoacridine-PNA (peptide nucleic acid conjugates targeting intron-exon junctions

    Directory of Open Access Journals (Sweden)

    Nielsen Peter E

    2010-06-01

    Full Text Available Abstract Background Modulation of pre-mRNA splicing by antisense molecules is a promising mechanism of action for gene therapeutic drugs. In this study, we have examined the potential of peptide nucleic acid (PNA 9-aminoacridine conjugates to modulate the pre-mRNA splicing of the mdm2 human cancer gene in JAR cells. Methods We screened 10 different 15 mer PNAs targeting intron2 at both the 5' - and the 3'-splice site for their effects on the splicing of mdm2 using RT-PCR analysis. We also tested a PNA (2512 targeting the 3'-splice site of intron3 with a complementarity of 4 bases to intron3 and 11 bases to exon4 for its splicing modulation effect. This PNA2512 was further tested for the effects on the mdm2 protein level as well as for inhibition of cell growth in combination with the DNA damaging agent camptothecin (CPT. Results We show that several of these PNAs effectively inhibit the splicing thereby producing a larger mRNA still containing intron2, while skipping of exon3 was not observed by any of these PNAs. The most effective PNA (PNA2406 targeting the 3'-splice site of intron2 had a complementarity of 4 bases to intron2 and 11 bases to exon3. PNA (2512 targeting the 3'-splice site of intron3 induced both splicing inhibition (intron3 skipping and skipping of exon4. Furthermore, treatment of JAR cells with this PNA resulted in a reduction in the level of MDM2 protein and a concomitant increase in the level of tumor suppressor p53. In addition, a combination of this PNA with CPT inhibited cell growth more than CPT alone. Conclusion We have identified several PNAs targeting the 5'- or 3'-splice sites in intron2 or the 3'-splice site of intron3 of mdm2 pre-mRNA which can inhibit splicing. Antisense targeting of splice junctions of mdm2 pre-mRNA may be a powerful method to evaluate the cellular function of MDM2 splice variants as well as a promising approach for discovery of mdm2 targeted anticancer drugs.

  13. Study on a transportation and emplacement system of pre-assembled EBS module for HLW geological disposal

    International Nuclear Information System (INIS)

    Awano, Toshihiko; Kanno, Takeshi; Katsumata, Syunsuke; Kosuge, Kazuhiro

    2009-01-01

    HLW disposal is one of the largest issue to utilize Nuclear power safely. In the past study, the concept, which buffer materials and Overpacked waste were transported into underground respectively, have shown. The concept of pre-assembled engineered barrier has advantage to simplify the logistics and emplacement procedure, however there are difficulties to support heavy weight of pre-assembled package by equipment under the condition of little clearance between tunnel and package. In this study, Combination of air bearing and two degree-of-freedom wheels were suggested for transportation, and air jack was suggested for unloading and emplacement system. Also, whole system for transportation and emplacement procedure was designed, and Scale model test was examined to evaluate the feasibility of these concept and functions. (author)

  14. Radiation Hard Silicon Photonics Mach-Zehnder Modulator for HEP applications: all-Synopsys Sentaurus™ Pre-Irradiation Simulation

    CERN Document Server

    Cammarata, Simone

    2017-01-01

    Silicon Photonics may well provide the opportunity for new levels of integration between detectors and their readout electronics. This technology is thus being evaluated at CERN in order to assess its suitability for use in particle physics experiments. In order to check the agreement with measurements and the validity of previous device simulations, a pure Synopsys Sentaurus™ simulation of an un-irradiated Mach-Zehnder silicon modulator has been carried out during the Summer Student project.

  15. Modulation of leak K(+) channel in hypoglossal motoneurons of rats by serotonin and/or variation of pH value.

    Science.gov (United States)

    Xu, Xue-Feng; Tsai, Hao-Jan; Li, Lin; Chen, Yi-Fan; Zhang, Cheng; Wang, Guang-Fa

    2009-08-25

    The cloned TWIK-related acid-sensitive K(+) channel (TASK-1) is sensitive to the pH changes within physiological pH range (pK~7.4). Recently, the native TASK-1-like channel was suggested to be the main contributor to the background (or leak) K(+) conductance in the motoneurons of the brain stem. Serotonin (5-HT) and variation of pH value in perfused solution could modulate these currents. Here we aimed to examine the properties and modulation of the currents by serotonin or variation of pH value in hypoglossal motoneurons of rats. Transverse slices were prepared from the brainstem of neonatal Sprague-Dawley rats (postnatal days 7-8). Hypoglossal motoneurons were used for the study. The leak K(+) current (TASK-1-like current) and hyperpolarization-activated cationic current (I(h)) were recorded with the whole-cell patch-clamp technique. The results showed that these currents were inhibited by acidified artificial cerebrospinal fluid (ACSF, pH 6.0) and activated by alkalized ACSF (pH 8.5). 5-HT (10 mumol/L) significantly inhibited both leak K(+) current and I(h) with depolarization of membrane potential and the occurrence of oscillation and/or spikes. Bath application of Ketanserine, an antagonist of 5-HT₂ receptor, reversed or reduced the inhibitory effect of acidified solution on leak K(+) current and I(h). The results suggest that 5-HT₂ receptors mediate the effects of acidified media on leak K(+) current and I(h) in hypoglossal motoneurons.

  16. Performance Analysis of Heterodyne-Detected OCDMA Systems Using PolSK Modulation over a Free-Space Optical Turbulence Channel

    Directory of Open Access Journals (Sweden)

    Fan Bai

    2015-10-01

    Full Text Available This paper presents a novel model of heterodyne-detected optical code-division multiple-access (OCDMA systems employing polarization shift keying (PolSK modulation over a free-space optical (FSO turbulence channel. In this article, a new transceiver configuration and detailed analytical model for the proposed system are provided and discussed, taking into consideration the potential of heterodyne detection on mitigating the impact of turbulence-induced irradiance fluctuation on the performance of the proposed system under the gamma-gamma turbulence channel. Furthermore, we derived the closed-form expressions for the system error probability and outage probability, respectively. We determine the advantages of the proposed modeling by performing a comparison with a direct detection scheme obtained from an evaluation of link performance under the same environment conditions. The presented work also shows the most significant impact factor that degrades the performance of the proposed system and indicates that the proposed approach offers an optimum link performance compared to conventional cases.

  17. Modulation of voltage-gated Na+ and K+ channels by pumiliotoxin 251D: a "joint venture" alkaloid from arthropods and amphibians.

    Science.gov (United States)

    Vandendriessche, Thomas; Abdel-Mottaleb, Yousra; Maertens, Chantal; Cuypers, Eva; Sudau, Alexander; Nubbemeyer, Udo; Mebs, Dietrich; Tytgat, Jan

    2008-03-01

    Certain amphibians provide themselves with a chemical defense by accumulating lipophilic alkaloids into skin glands from dietary arthropods. Examples of such alkaloids are pumiliotoxins (PTXs). In general, PTXs are known as positive modulators of voltage-gated sodium channels (VGSCs). Unlike other PTXs, PTX 251D does not share this characteristic. However, mice and insect studies showed that PTX 251D is highly toxic and to date the basis of its toxicity remains unknown. In this work, we searched for the possible target of PTX 251D. The toxin was therefore made synthetically and tested on four VGSCs (mammalian rNa(v)1.2/beta(1), rNa(v)1.4/beta(1), hNa(v)1.5/beta(1) and insect Para/tipE) and five voltage-gated potassium channels (VGPCs) (mammalian rK(v)1.1-1.2, hK(v)1.3, hK(v)11.1 (hERG) and insect Shaker IR) expressed heterologously in Xenopus laevis oocytes, using the two-electrode voltage clamp technique. PTX 251D not only inhibited the Na(+) influx through the mammalian VGSCs but also affected the steady-state activation and inactivation. Interestingly, in the insect ortholog, the inactivation process was dramatically affected. Additionally, PTX 251D inhibited the K(+) efflux through all five tested VGPCs and slowed down the deactivation kinetics of the mammalian VGPCs. hK(v)1.3 was the most sensitive channel, with an IC(50) value 10.8+/-0.5 microM. To the best of our knowledge this is the first report of a PTX affecting VGPCs.

  18. Activation of CRH receptor type 1 expressed on glutamatergic neurons increases excitability of CA1 pyramidal neurons by the modulation of voltage-gated ion channels

    Directory of Open Access Journals (Sweden)

    Stephan eKratzer

    2013-07-01

    Full Text Available Corticotropin-releasing hormone (CRH plays an important role in a substantial number of patients with stress-related mental disorders, such as anxiety disorders and depression. CRH has been shown to increase neuronal excitability in the hippocampus, but the underlying mechanisms are poorly understood. The effects of CRH on neuronal excitability were investigated in acute hippocampal brain slices. Population spikes (PS and field excitatory postsynaptic potentials (fEPSP were evoked by stimulating Schaffer-collaterals and recorded simultaneously from the somatic and dendritic region of CA1 pyramidal neurons. CRH was found to increase PS amplitudes (mean  Standard error of the mean; 231.8  31.2% of control; n=10 while neither affecting fEPSPs (104.3 ± 4.2%; n=10 nor long-term potentiation (LTP. However, when Schaffer-collaterals were excited via action potentials (APs generated by stimulation of CA3 pyramidal neurons, CRH increased fEPSP amplitudes (119.8 ± 3.6%; n=8 and the magnitude of LTP in the CA1 region. Experiments in slices from transgenic mice revealed that the effect on PS amplitude is mediated exclusively by CRH receptor 1 (CRHR1 expressed on glutamatergic neurons. The effects of CRH on PS were dependent on phosphatase-2B, L- and T-type calcium channels and voltage-gated potassium channels but independent on intracellular Ca2+-elevation. In patch-clamp experiments, CRH increased the frequency and decay times of APs and decreased currents through A-type and delayed-rectifier potassium channels. These results suggest that CRH does not affect synaptic transmission per se, but modulates voltage-gated ion currents important for the generation of APs and hence elevates by this route overall neuronal activity.

  19. Anticonvulsant mechanism of saponins fraction from adventitious roots of Ficus religiosa: possible modulation of GABAergic, calcium and sodium channel functions

    Directory of Open Access Journals (Sweden)

    Damanpreet Singh

    Full Text Available ABSTRACT In our previous studies, quantified saponins-rich fraction from adventitious root extract of Ficus religiosa L., Moraceae, showed anticonvulsant effect in acute, as well as chronic mice models of epilepsy. The present study was designed to reveal putative anticonvulsant mechanism of quantified saponins-rich fraction using target specific animal models. The anticonvulsant effect of quantified saponins-rich fraction was initially studied in maximal electroshock and pentylenetetrazol test at 1, 2 and 4 mg/kg; i.p. doses. Based on the results of initial anticonvulsant testing, different groups of mice were injected with vehicle or quantified saponins-rich fraction (4 mg/kg; i.p., 30 min prior to an injection of N-methyl-D-aspartic acid (100 mg/kg; s.c., bicuculline (5 mg/kg; i.p., strychnine hydrochloride (2 mg/kg; i.p., BAY k-8644 (37.5 µg; i.c.v., veratridine (500 µg/kg; i.p. and the convulsive episodes were studied. Treatment with the extract (1, 2 and 4 mg/kg showed significant protection in maximal electroshock and pentylenetetrazol-induced convulsion tests, in a dose-dependent manner. Moreover, quantified saponins-rich fraction at 4 mg/kg dose showed significant increase in latency to clonic convulsions, decrease in seizure severity and increase in average wave amplitude in bicuculline, BAY k-8644 and veratridine tests, respectively, as compared to vehicle control. However, SRF treatment failed to abolish N-methyl-D-aspartic acid and strychnine-induced convulsions, indicated by insignificant change in the appearance of turning behavior and onset of tonic extension, respectively, as compared to vehicle control. From the results of present study, it is concluded that quantified saponins-rich fraction suppress maximal electroshock, pentylenetetrazol, bicuculline, BAY k-8644 and veratridine-induced convulsions, indicating its GABAergic, Na+ and Ca2+ channel modulatory effects. Further it can be correlated that quantified saponins

  20. Potential modulations of pre-monsoon aerosols during El Niño: impact on Indian summer monsoon

    Science.gov (United States)

    Fadnavis, S.; Roy, Chaitri; Sabin, T. P.; Ayantika, D. C.; Ashok, K.

    2017-10-01

    The potential role of aerosol loading on the Indian summer monsoon rainfall during the El Niño years are examined using satellite-derived observations and a state of the art fully interactive aerosol-chemistry-climate model. The Aerosol Index (AI) from TOMS (1978-2005) and Aerosol Optical Depth (AOD) from MISR spectroradiometer (2000-2010) indicate a higher-than-normal aerosol loading over the Indo-Gangetic plain (IGP) during the pre-monsoon season with a concurrent El Niño. Sensitivity experiments using ECHAM5-HAMMOZ climate model suggests that this enhanced loading of pre-monsoon absorbing aerosols over the Indo-Gangetic plain can reduce the drought during El Niño years by invoking the `Elevated-Heat-Pump' mechanism through an anomalous aerosol-induced warm core in the atmospheric column. This anomalous heating upshot the relative strengthening of the cross-equatorial moisture inflow associated with the monsoon and eventually reduces the severity of drought during El Niño years. The findings are subject to the usual limitations such as the uncertainties in observations, and limited number of El Niño years (during the study period).

  1. Differential Modulation of Rhythmic Brain Activity in Healthy Adults by a T-Type Calcium Channel Blocker: An MEG Study.

    Science.gov (United States)

    Walton, Kerry D; Maillet, Emeline L; Garcia, John; Cardozo, Timothy; Galatzer-Levy, Isaac; Llinás, Rodolfo R

    2017-01-01

    1-octanol is a therapeutic candidate for disorders involving the abnormal activation of the T-type calcium current since it blocks this current specifically. Such disorders include essential tremor and a group of neurological and psychiatric disorders resulting from thalamocortical dysrhythmia (TCD). For example, clinically, the observable phenotype in essential tremor is the tremor itself. The differential diagnostic of TCD is not based only on clinical signs and symptoms. Rather, TCD incorporates an electromagnetic biomarker, the presence of abnormal thalamocortical low frequency brain oscillations. The effect of 1-octanol on brain activity has not been tested. As a preliminary step to such a TCD study, we examined the short-term effects of a single dose of 1-octanol on resting brain activity in 32 healthy adults using magnetoencephalograpy. Visual inspection of baseline power spectra revealed that the subjects fell into those with strong low frequency activity (set 2, n = 11) and those without such activity, but dominated by an alpha peak (set 1, n = 22). Cross-validated linear discriminant analysis, using mean spectral density (MSD) in nine frequency bands as predictors, found overall that 82.5% of the subjects were classified as determined by visual inspection. The effect of 1-octanol on the MSD in narrow frequency bands differed between the two subject groups. In set 1 subjects the MSD increased in the 4.5-6.5Hz and 6.5-8.5 Hz bands. This was consistent with a widening of the alpha peak toward lower frequencies. In the set two subjects the MSD decrease in the 2.5-4.5 Hz and 4.5-6.5 Hz bands. This decreased power is consistent with the blocking effect of 1-octanol on T-type calcium channels. The subjects reported no adverse effects of the 1-octanol. Since stronger low frequency activity is characteristic of patients with TCD, 1-octanol and other T-type calcium channel blockers are good candidates for treatment of this group of disorders following a placebo

  2. Differential Modulation of Rhythmic Brain Activity in Healthy Adults by a T-Type Calcium Channel Blocker: An MEG Study

    Science.gov (United States)

    Walton, Kerry D.; Maillet, Emeline L.; Garcia, John; Cardozo, Timothy; Galatzer-Levy, Isaac; Llinás, Rodolfo R.

    2017-01-01

    1-octanol is a therapeutic candidate for disorders involving the abnormal activation of the T-type calcium current since it blocks this current specifically. Such disorders include essential tremor and a group of neurological and psychiatric disorders resulting from thalamocortical dysrhythmia (TCD). For example, clinically, the observable phenotype in essential tremor is the tremor itself. The differential diagnostic of TCD is not based only on clinical signs and symptoms. Rather, TCD incorporates an electromagnetic biomarker, the presence of abnormal thalamocortical low frequency brain oscillations. The effect of 1-octanol on brain activity has not been tested. As a preliminary step to such a TCD study, we examined the short-term effects of a single dose of 1-octanol on resting brain activity in 32 healthy adults using magnetoencephalograpy. Visual inspection of baseline power spectra revealed that the subjects fell into those with strong low frequency activity (set 2, n = 11) and those without such activity, but dominated by an alpha peak (set 1, n = 22). Cross-validated linear discriminant analysis, using mean spectral density (MSD) in nine frequency bands as predictors, found overall that 82.5% of the subjects were classified as determined by visual inspection. The effect of 1-octanol on the MSD in narrow frequency bands differed between the two subject groups. In set 1 subjects the MSD increased in the 4.5-6.5Hz and 6.5–8.5 Hz bands. This was consistent with a widening of the alpha peak toward lower frequencies. In the set two subjects the MSD decrease in the 2.5–4.5 Hz and 4.5–6.5 Hz bands. This decreased power is consistent with the blocking effect of 1-octanol on T-type calcium channels. The subjects reported no adverse effects of the 1-octanol. Since stronger low frequency activity is characteristic of patients with TCD, 1-octanol and other T-type calcium channel blockers are good candidates for treatment of this group of disorders following a

  3. SmD1 Modulates the miRNA Pathway Independently of Its Pre-mRNA Splicing Function.

    Directory of Open Access Journals (Sweden)

    Xiao-Peng Xiong

    2015-08-01

    Full Text Available microRNAs (miRNAs are a class of endogenous regulatory RNAs that play a key role in myriad biological processes. Upon transcription, primary miRNA transcripts are sequentially processed by Drosha and Dicer ribonucleases into ~22-24 nt miRNAs. Subsequently, miRNAs are incorporated into the RNA-induced silencing complexes (RISCs that contain Argonaute (AGO family proteins and guide RISC to target RNAs via complementary base pairing, leading to post-transcriptional gene silencing by a combination of translation inhibition and mRNA destabilization. Select pre-mRNA splicing factors have been implicated in small RNA-mediated gene silencing pathways in fission yeast, worms, flies and mammals, but the underlying molecular mechanisms are not well understood. Here, we show that SmD1, a core component of the Drosophila small nuclear ribonucleoprotein particle (snRNP implicated in splicing, is required for miRNA biogenesis and function. SmD1 interacts with both the microprocessor component Pasha and pri-miRNAs, and is indispensable for optimal miRNA biogenesis. Depletion of SmD1 impairs the assembly and function of the miRISC without significantly affecting the expression of major canonical miRNA pathway components. Moreover, SmD1 physically and functionally associates with components of the miRISC, including AGO1 and GW182. Notably, miRNA defects resulting from SmD1 silencing can be uncoupled from defects in pre-mRNA splicing, and the miRNA and splicing machineries are physically and functionally distinct entities. Finally, photoactivatable-ribonucleoside-enhanced crosslinking and immunoprecipitation (PAR-CLIP analysis identifies numerous SmD1-binding events across the transcriptome and reveals direct SmD1-miRNA interactions. Our study suggests that SmD1 plays a direct role in miRNA-mediated gene silencing independently of its pre-mRNA splicing activity and indicates that the dual roles of splicing factors in post-transcriptional gene regulation may be

  4. Nonlinear pre-coding apparatus of multi-antenna system, has pre-coding unit that extents original constellation points of modulated symbols to several constellation points by using limited perturbation vector

    DEFF Research Database (Denmark)

    2008-01-01

    A Coding/Modulating units (200-1-200-N) outputs modulated symbols by modulating coding bit streams based on certain modulation scheme. The limited perturbation vector is calculated by using distribution of perturbation vectors. The original constellation points of modulated symbols are extended t...

  5. Pre-infestation of Tomato Plants by Aphids Modulates Transmission-Acquisition Relationship among Whiteflies, Tomato Yellow Leaf Curl Virus (TYLCV and Plants

    Directory of Open Access Journals (Sweden)

    Xiao L. Tan

    2017-09-01

    Full Text Available Herbivory defense systems in plants are largely regulated by jasmonate-(JA and salicylate-(SA signaling pathways. Such defense mechanisms may impact insect feeding dynamic, may also affect the transmission-acquisition relationship among virus, plants and vectoring insects. In the context of the tomato – whitefly – Tomato Yellow Leaf Curl Virus (TYLCV biological model, we tested the impact of pre-infesting plants with a non-vector insect (aphid Myzus persicae on feeding dynamics of a vector insect (whitefly Bemisia tabaci as well as virus transmission-acquisition. We showed that an aphid herbivory period of 0–48 h led to a transient systemic increase of virus concentration in the host plant (root, stem, and leaf, with the same pattern observed in whiteflies feeding on aphid-infested plants. We used real-time quantitative PCR to study the expression of key genes of the SA- and JA-signaling pathways, as well as electrical penetration graph (EPG to characterize the impact of aphid pre-infestation on whitefly feeding during TYLCV transmission (whitefly to tomato and acquisition (tomato to whitefly. The impact of the duration of aphid pre-infestation (0, 24, or 48 h on phloem feeding by whitefly (E2 during the transmission phase was similar to that of global whitefly feeding behavior (E1, E2 and probing duration during the acquisition phase. In addition, we observed that a longer phase of aphid pre-infestation prior to virus transmission by whitefly led to the up-regulation and down-regulation of SA- and JA-signaling pathway genes, respectively. These results demonstrated a significant impact of aphid pre-infestation on the tomato – whitefly – TYLCV system. Transmission and acquisition of TYLCV was positively correlated with feeding activity of B. tabaci, and both were mediated by the SA- and JA-pathways. TYLCV concentration during the transmission phases was modulated by up- and down-regulation of SA- and JA-pathways, respectively. The two

  6. The use of blended learning to create a module about ill-health during childbirth for pre-registration midwifery students.

    Science.gov (United States)

    Young, Nicki; Randall, Jayne

    2014-01-01

    Reforms in the way higher education is delivered in order to address the needs of learners in the 21st century are increasingly being considered by university departments. This has led academics to combine e-learning with more traditional classroom based methods of teaching when designing new modules of study, a method commonly called blended learning. This paper will describe the different teaching and learning methods which were blended together to create a module for second year pre-registration midwifery students in England, which focused upon ill-health during pregnancy and childbearing. It is imperative that at the point of registration midwifery students possess the skills to identify deviations from normal, initiate immediate actions and make appropriate referrals. The health of women all over the world is of concern to health care professionals. Midwives are increasingly being upon to provide expert care. Midwives need a sound education to allow them to carry out their roles effectively. The International Confederation of Midwives global standards for midwifery education (2010) attempts to address the need for competent caring midwives to help women and families in every corner of the world. The paper will also cover the pedagogical issues considered when blending together the different elements of learning namely: traditional discursive lectures, small group work, e-learning, formative presentations and the use of simulation during a skills and drills day. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. Increased Patient Satisfaction and a Reduction in Pre-Analytical Errors Following Implementation of an Electronic Specimen Collection Module in Outpatient Phlebotomy.

    Science.gov (United States)

    Kantartjis, Michalis; Melanson, Stacy E F; Petrides, Athena K; Landman, Adam B; Bates, David W; Rosner, Bernard A; Goonan, Ellen; Bixho, Ida; Tanasijevic, Milenko J

    2017-08-01

    Patient satisfaction in outpatient phlebotomy settings typically depends on wait time and venipuncture experience, and many patients equate their experiences with their overall satisfaction with the hospital. We compared patient service times and preanalytical errors pre- and postimplementation of an integrated electronic health record (EHR)-laboratory information system (LIS) and electronic specimen collection module. We also measured patient wait time and assessed patient satisfaction using a 5-question survey. The percentage of patients waiting less than 10 minutes increased from 86% preimplementation to 93% postimplementation of the EHR-LIS (P ≤.001). The median total service time decreased significantly, from 6 minutes (IQR, 4-8 minutes), to 5 minutes (IQR, 3-6 minutes) (P = .005). The preanalytical errors decreased significantly, from 3.20 to 1.93 errors per 1000 specimens (P ≤.001). Overall patient satisfaction improved, with an increase in excellent responses for all 5 questions (P ≤.001). We found several benefits of implementing an electronic specimen collection module, including decreased wait and service times, improved patient satisfaction, and a reduction in preanalytical errors. © American Society for Clinical Pathology, 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

  8. Pre-apoptotic response to therapeutic DNA damage involves protein modulation of Mcl-1, Hdm2 and Flt3 in acute myeloid leukemia cells

    Directory of Open Access Journals (Sweden)

    Hovland Randi

    2007-05-01

    Full Text Available Abstract Background Acute myeloid leukemia (AML cells are characterized by non-mutated TP53, high levels of Hdm2, and frequent mutation of the Flt3 receptor tyrosine kinase. The juxtamembrane mutation of FLT3 is the strongest independent marker for disease relapse and is associated with elevated Bcl-2 protein and p53 hyper-phosphorylation in AML. DNA damage forms the basic mechanism of cancer cell eradication in current therapy of AML. Hdm2 and pro-apoptotic Bcl-2 members are among the most intensely induced genes immediately after chemotherapy and Hdm2 is proposed a role in receptor tyrosine kinase regulation. Thus we examined the DNA damage related modulation of these proteins in relation to FLT3 mutational status and induction of apoptosis. Results Within one hour after exposure to ionizing radiation (IR, the AML cells (NB4, MV4-11, HL-60, primary AML cells showed an increase in Flt3 protein independent of mRNA levels, while the Hdm2 protein decreased. The FLT3 mutant MV4-11 cells were resistant to IR accompanied by presence of both Mcl-1 and Hdm2 protein three hours after IR. In contrast, the FLT3 wild type NB4 cells responded to IR with apoptosis and pre-apoptotic Mcl-1 down regulation. Daunorubicin (DNR induced continuing down regulation of Hdm2 and Mcl-1 in both cell lines followed by apoptosis. Conclusion Both IR and DNR treatment resulted in concerted protein modulations of Mcl-1, Hdm2 and Flt3. Cell death induction was associated with persistent attenuation of Mcl-1 and Hdm2. These observations suggest that defining the pathway(s modulating Flt3, Hdm2 and Mcl-1 may propose new strategies to optimize therapy for the relapse prone FLT3 mutated AML patients.

  9. Differential expression of hERG1 channel isoforms reproduces properties of native I(Kr and modulates cardiac action potential characteristics.

    Directory of Open Access Journals (Sweden)

    Anders Peter Larsen

    Full Text Available BACKGROUND: The repolarizing cardiac rapid delayed rectifier current, I(Kr, is composed of ERG1 channels. It has been suggested that two isoforms of the ERG1 protein, ERG1a and ERG1b, both contribute to I(Kr. Marked heterogeneity in the kinetic properties of native I(Kr has been described. We hypothesized that the heterogeneity of native I(Kr can be reproduced by differential expression of ERG1a and ERG1b isoforms. Furthermore, the functional consequences of differential expression of ERG1 isoforms were explored as a potential mechanism underlying native heterogeneity of action potential duration (APD and restitution. METHODOLOGY/PRINCIPAL FINDINGS: The results show that the heterogeneity of native I(Kr can be reproduced in heterologous expression systems by differential expression of ERG1a and ERG1b isoforms. Characterization of the macroscopic kinetics of ERG1 currents demonstrated that these were dependent on the relative abundance of ERG1a and ERG1b. Furthermore, we used a computational model of the ventricular cardiomyocyte to show that both APD and the slope of the restitution curve may be modulated by varying the relative abundance of ERG1a and ERG1b. As the relative abundance of ERG1b was increased, APD was gradually shortened and the slope of the restitution curve was decreased. CONCLUSIONS/SIGNIFICANCE: Our results show that differential expression of ERG1 isoforms may explain regional heterogeneity of I(Kr kinetics. The data demonstrate that subunit dependent changes in channel kinetics are important for the functional properties of ERG1 currents and hence I(Kr. Importantly, our results suggest that regional differences in the relative abundance of ERG1 isoforms may represent a potential mechanism underlying the heterogeneity of both APD and APD restitution observed in mammalian hearts.

  10. Pre-specialization - Considerations for more focused and personalized educational modules in the twenty-first century.

    Science.gov (United States)

    Han, Jason J; Vapiwala, Neha

    2018-04-14

    This essay provides a multidisciplinary discussion of the current medical education curriculum and the increasing need to adapt it to our rapidly evolving and expanding healthcare environment. Thorough literature search on the topic of medical school curriculum, ranging from its historical origins to contemporary practice as well as statistics, was conducted. The authors give a brief historical overview of and rationale behind the current structure of the medical education system in America. The recent trends towards information overload and rapid evolution of the evidence-base are discussed. Specialization, as a means of responding to the burgeoning abundance of information in medicine, is described. The authors further provide current as well as foreseeable limitations of today's medical training paradigm as the trend towards specialization continues. The potential negative influences of a specialist-focused training paradigm on the overall length of training and the degree of autonomy exercised by generalists are described. A proposal toward pre-specialization at the level of medical school is introduced and elaborated upon. The authors incorporate social psychology principles and analyze trends toward career specialization, highlighting potential benefits to a different-size-for-all approach. The importance of optionality and flexibility of such a curriculum is emphasized. The authors describe the inevitable trend toward specialization, and the need to fundamentally re-configure American medical education system to behoove trainees' experiences and quality of training during the 21st century.

  11. An IMPI-compliant control system for the ATLAS TileCal Phase II Upgrade PreProcessor module

    CERN Document Server

    Zuccarello, Pedro Diego; The ATLAS collaboration

    2016-01-01

    TileCal is the Tile hadronic calorimeter of the ATLAS experiment at the LHC. The LHC upgrade program, currently under development, will culminate in the High Luminosity LHC (HL-LHC), which is expected to increase about five times the LHC nominal instantaneous luminosity. The readout electronics of the Tile calorimenter being redesigned introducing a new read-out strategy in order to accommodate the detector to the new HL-LHC parameters. The data generated inside the detector at every bunch crossing will be transmitted to the PreProcessor (PPR) boards before any event selection is applied. The PPRs will be located at off-detector sites. The PPR will be responsible of providing preprocessed trigger information to the ATLAS first level of trigger (L1). In overall it will represent the interface between the data acquisition, trigger and control systems and the on-detector electronics. The PPR, being an important part of the readout system, needs to be remotely accessed and monitored to prevent failures or, in cas...

  12. Pre-treatment with Bifidobacterium breve UCC2003 modulates Citrobacter rodentium-induced colonic inflammation and organ specificity.

    Science.gov (United States)

    Collins, James W; Akin, Ali R; Kosta, Artemis; Zhang, Ning; Tangney, Mark; Francis, Kevin P; Frankel, Gad

    2012-11-01

    Citrobacter rodentium, which colonizes the gut mucosa via formation of attaching and effacing (A/E) lesions, causes transmissible colonic hyperplasia. The aim of this study was to evaluate whether prophylactic treatment with Bifidobacterium breve UCC2003 can improve the outcome of C. rodentium infection. Six-week-old albino C57BL/6 mice were pre-treated for 3 days with B. breve, challenged with bioluminescent C. rodentium and administered B. breve or PBS-C for 8 days post-infection; control mice were either administered B. breve and mock-infected with PBS, or mock-treated with PBS-C and mock-infected with PBS. C. rodentium colonization was monitored by bacterial enumeration from faeces and by a combination of both 2D bioluminescence imaging (BLI) and composite 3D diffuse light imaging tomography with µCT imaging (DLIT-µCT). At day 8 post-infection, colons were removed and assessed for crypt hyperplasia, histology by light microscopy, bacterial colonization by immunofluorescence, and A/E lesion formation by electron microscopy. Prophylactic administration of B. breve did not prevent C. rodentium colonization or A/E lesion formation. However, this treatment did alter C. rodentium distribution within the large intestine and significantly reduced colonic crypt hyperplasia at the peak of bacterial infection. These results show that B. breve could not competitively exclude C. rodentium, but reduced pathogen-induced colonic inflammation.

  13. The long-term performance of the S-band klystron modulator system in the CERN LEP pre-injector

    CERN Document Server

    McMonagle, G; Rossat, G

    2000-01-01

    The Large Electron-Positron collider (LEP) is the final machine in a chain of four accelerators that are used to create particle collisions for high-energy physics experiments. LEP collides bunches of electrons (e/sup -/) with bunches of positrons (e/sup +/) that have originated in the LEP Injector Linac (LIL). These particles travel around the 27 km circumference of the LEP ring in opposite directions at velocities close to the speed of light. When bunches of particles collide, bursts of very high energy are created during a tiny fraction of a second, emulating the state of the early Universe. Four huge detector assemblies record the tracks of particles created in this way, and provide the physicists with a means of looking at the behaviour of matter at these high energies. LIL is at the front end of this chain and is used to produce the sequence of e/sup -/ and e/sup +/ beam pulses that are accumulated in 4 or 8 bunches, at a 100 Hz rate, in the Electron Positron Accumulator (EPA). The klystron- modulators,...

  14. Measuring oxygen tension modulation, induced by a new pre-radiotherapy therapeutic, in a mammary window chamber mouse model

    Science.gov (United States)

    Schafer, Rachel; Gmitro, Arthur F.

    2015-03-01

    Tumor regions under hypoxic or low oxygen conditions respond less effectively to many treatment strategies, including radiation therapy. A novel investigational therapeutic, NVX-108 (NuvOx Pharma), has been developed to increase delivery of oxygen through the use of a nano-emulsion of dodecofluoropentane. By raising pO2 levels prior to delivering radiation, treatment efficacy may be improved. To aid in evaluating the novel drug, oxygen tension was quantitatively measured, spatially and temporally, to record the effect of administrating NVX-108 in an orthotopic mammary window chamber mouse model of breast cancer. The oxygen tension was measured through the use of an oxygen-sensitive coating, comprised of phosphorescent platinum porphyrin dye embedded in a polystyrene matrix. The coating, applied to the surface of the coverslip of the window chamber through spin coating, is placed in contact with the mammary fat pad to record the oxygenation status of the surface tissue layer. Prior to implantation of the window chamber, a tumor is grown in the SCID mouse model by injection of MCF-7 cells into the mammary fat pad. Two-dimensional spatial distributions of the pO2 levels were obtained through conversion of measured maps of phosphorescent lifetime. The resulting information on the spatial and temporal variation of the induced oxygen modulation could provide valuable insight into the optimal timing between administration of NVX-108 and radiation treatment to provide the most effective treatment outcome.

  15. A 96-channel FPGA-based Time-to-Digital Converter (TDC) and fast trigger processor module with multi-hit capability and pipeline

    International Nuclear Information System (INIS)

    Bogdan, Mircea; Frisch, Henry; Heintz, Mary; Paramonov, Alexander; Sanders, Harold; Chappa, Steve; DeMaat, Robert; Klein, Rod; Miao, Ting; Wilson, Peter; Phillips, Thomas J.

    2005-01-01

    We describe an field-programmable gate arrays based (FPGA), 96-channel, Time-to-Digital converter (TDC) and trigger logic board intended for use with the Central Outer Tracker (COT) [T. Affolder et al., Nucl. Instr. and Meth. A 526 (2004) 249] in the CDF Experiment [The CDF-II detector is described in the CDF Technical Design Report (TDR), FERMILAB-Pub-96/390-E. The TDC described here is intended as a further upgrade beyond that described in the TDR] at the Fermilab Tevatron. The COT system is digitized and read out by 315 TDC cards, each serving 96 wires of the chamber. The TDC is physically configured as a 9U VME card. The functionality is almost entirely programmed in firmware in two Altera Stratix FPGAs. The special capabilities of this device are the availability of 840MHz LVDS inputs, multiple phase-locked clock modules, and abundant memory. The TDC system operates with an input resolution of 1.2ns, a minimum input pulse width of 4.8ns and a minimum separation of 4.8ns between pulses. Each input can accept up to 7 hits per collision. The time-to-digital conversion is done by first sampling each of the 96 inputs in 1.2-ns bins and filling a circular memory; the memory addresses of logical transitions (edges) in the input data are then translated into the time of arrival and width of the COT pulses. Memory pipelines with a depth of 5.5μs allow deadtime-less operation in the first-level trigger; the data are multiple-buffered to diminish deadtime in the second-level trigger. The complete process of edge-detection and filling of buffers for readout takes 12μs. The TDC VME interface allows a 64-bit Chain Block Transfer of multiple boards in a crate with transfer-rates up to 47Mbytes/s. The TDC module also produces prompt trigger data every Tevatron crossing via a deadtimeless fast logic path that can be easily reprogrammed. The trigger bits are clocked onto the P3 VME backplane connector with a 22-ns clock for transmission to the trigger. The full TDC design and

  16. Expression and effects of modulation of the K2P potassium channels TREK-1 (KCNK2) and TREK-2 (KCNK10) in the normal human ovary and epithelial ovarian cancer.

    Science.gov (United States)

    Innamaa, A; Jackson, L; Asher, V; van Schalkwyk, G; Warren, A; Keightley, A; Hay, D; Bali, A; Sowter, H; Khan, R

    2013-11-01

    Aberrant expression of potassium (K(+)) channels contributes to cancer cell proliferation and apoptosis, and K(+) channel blockers can inhibit cell proliferation. TREK-1 and -2 belong to the two-pore domain (K2P) superfamily. We report TREK-1 and -2 expression in ovarian cancer and normal ovaries, and the effects of TREK-1 modulators on cell proliferation and apoptosis. The cellular localisation of TREK-1 and -2 was investigated by immunofluorescence in SKOV-3 and OVCAR-3 cell lines and in cultured ovarian surface epithelium and cancer. Channel expression in normal ovaries and cancer was quantified by western blotting. Immunohistochemical analysis demonstrated the association between channel expression and disease prognosis, stage, and grade. TREK-1 modulation of cell proliferation in the cell lines was investigated with the MTS-assay and the effect on apoptosis determined using flow cytometry. Expression was identified in both cell lines, ovarian cancer (n = 22) and normal ovaries (n = 6). IHC demonstrated positive staining for TREK-1 and -2 in 95.7 % of tumours (n = 69) and 100 % of normal ovaries (n = 9). A reduction in cell proliferation (P ovaries and ovarian cancer. TREK-1 modulators have a significant effect on cell proliferation and apoptosis. We propose investigation of the therapeutic potential of TREK-1 blockers is warranted.

  17. Presynaptic muscarinic receptors, calcium channels, and protein kinase C modulate the functional disconnection of weak inputs at polyinnervated neonatal neuromuscular synapses.

    Science.gov (United States)

    Santafe, M M; Garcia, N; Lanuza, M A; Tomàs, M; Besalduch, N; Tomàs, J

    2009-04-01

    We studied the relation among calcium inflows, voltage-dependent calcium channels (VDCC), presynaptic muscarinic acetylcholine receptors (mAChRs), and protein kinase C (PKC) activity in the modulation of synapse elimination. We used intracellular recording to determine the synaptic efficacy in dually innervated endplates of the levator auris longus muscle of newborn rats during axonal competition in the postnatal synaptic elimination period. In these dual junctions, the weak nerve terminal was potentiated by partially reducing calcium entry (P/Q-, N-, or L-type VDCC-specific block or 500 muM magnesium ions), M1- or M4-type selective mAChR block, or PKC block. Moreover, reducing calcium entry or blocking PKC or mAChRs results in unmasking functionally silent nerve endings that now recover neurotransmitter release. Our results show interactions between these molecules and indicate that there is a release inhibition mechanism based on an mAChR-PKC-VDCC intracellular cascade. When it is fully active in certain weak motor axons, it can depress ACh release and even disconnect synapses. We suggest that this mechanism plays a central role in the elimination of redundant neonatal synapses, because functional axonal withdrawal can indeed be reversed by mAChRs, VDCCs, or PKC block.

  18. Breaking Through the Multi-Mesa-Channel Width Limited of Normally Off GaN HEMTs Through Modulation of the Via-Hole-Length.

    Science.gov (United States)

    Chien, Cheng-Yen; Wu, Wen-Hsin; You, Yao-Hong; Lin, Jun-Huei; Lee, Chia-Yu; Hsu, Wen-Ching; Kuan, Chieh-Hsiung; Lin, Ray-Ming

    2017-12-01

    We present new normally off GaN high-electron-mobility transistors (HEMTs) that overcome the typical limitations in multi-mesa-channel (MMC) width through modulation of the via-hole-length to regulate the charge neutrality screen effect. We have prepared enhancement-mode (E-mode) GaN HEMTs having widths of up to 300 nm, based on an enhanced surface pinning effect. E-mode GaN HEMTs having MMC structures and widths as well as via-hole-lengths of 100 nm/2 μm and 300 nm/6 μm, respectively, exhibited positive threshold voltages (V th ) of 0.79 and 0.46 V, respectively. The on-resistances of the MMC and via-hole-length structures were lower than those of typical tri-gate nanoribbon GaN HEMTs. In addition, the devices not only achieved the E-mode but also improved the power performance of the GaN HEMTs and effectively mitigated the device thermal effect. We controlled the via-hole-length sidewall surface pinning effect to obtain the E-mode GaN HEMTs. Our findings suggest that via-hole-length normally off GaN HEMTs have great potential for use in next-generation power electronics.

  19. Breaking Through the Multi-Mesa-Channel Width Limited of Normally Off GaN HEMTs Through Modulation of the Via-Hole-Length

    Science.gov (United States)

    Chien, Cheng-Yen; Wu, Wen-Hsin; You, Yao-Hong; Lin, Jun-Huei; Lee, Chia-Yu; Hsu, Wen-Ching; Kuan, Chieh-Hsiung; Lin, Ray-Ming

    2017-06-01

    We present new normally off GaN high-electron-mobility transistors (HEMTs) that overcome the typical limitations in multi-mesa-channel (MMC) width through modulation of the via-hole-length to regulate the charge neutrality screen effect. We have prepared enhancement-mode (E-mode) GaN HEMTs having widths of up to 300 nm, based on an enhanced surface pinning effect. E-mode GaN HEMTs having MMC structures and widths as well as via-hole-lengths of 100 nm/2 μm and 300 nm/6 μm, respectively, exhibited positive threshold voltages ( V th) of 0.79 and 0.46 V, respectively. The on-resistances of the MMC and via-hole-length structures were lower than those of typical tri-gate nanoribbon GaN HEMTs. In addition, the devices not only achieved the E-mode but also improved the power performance of the GaN HEMTs and effectively mitigated the device thermal effect. We controlled the via-hole-length sidewall surface pinning effect to obtain the E-mode GaN HEMTs. Our findings suggest that via-hole-length normally off GaN HEMTs have great potential for use in next-generation power electronics.

  20. SU-F-T-260: Using Portal Image Device for Pre-Treatment QA in Volumetric Modulated Arc Plans with Flattening Filter Free (FFF) Beams

    Energy Technology Data Exchange (ETDEWEB)

    Qu, H; Qi, P; Yu, N; Xia, P [The Cleveland Clinic Foundation, Cleveland, OH (United States)

    2016-06-15

    Purpose: To implement and validate a method of using electronic portal image device (EPID) for pre-treatment quality assurance (QA) of volumetric modulated arc therapy (VMAT) plans using flattering filter free (FFF) beams for stereotactic body radiotherapy (SBRT). Methods: On Varian Edge with 6MV FFF beam, open field (from 2×2 cm to 20×20 cm) EPID images were acquired with 200 monitor unit (MU) at the image device to radiation source distance of 150cm. With 10×10 open field and calibration unit (CU) provided by vendor to EPID image pixel, a dose conversion factor was determined by dividing the center dose calculated from the treatment planning system (TPS) to the corresponding CU readout on the image. Water phantom measured beam profile and the output factors for various field sizes were further correlated to those of EPID images. The dose conversion factor and correction factors were then used for converting the portal images to the planner dose distributions of clinical fields. A total of 28 VMAT fields of 14 SBRT plans (8 lung, 2 prostate, 2 liver and 2 spine) were measured. With 10% low threshold cutoff, the delivered dose distributions were compared to the reference doses calculated in water phantom from the TPS. A gamma index analysis was performed for the comparison in percentage dose difference/distance-to-agreement specifications. Results: The EPID device has a linear response to the open fields with increasing MU. For the clinical fields, the gamma indices between the converted EPID dose distributions and the TPS calculated 2D dose distributions were 98.7%±1.1%, 94.0%±3.4% and 70.3%±7.7% for the criteria of 3%/3mm, 2%/2mm and 1%/1mm, respectively. Conclusion: Using a portal image device, a high resolution and high accuracy portal dosimerty was achieved for pre-treatment QA verification for SBRT VMAT plans with FFF beams.

  1. Correlation between gamma index passing rate and clinical dosimetric difference for pre-treatment 2D and 3D volumetric modulated arc therapy dosimetric verification.

    Science.gov (United States)

    Jin, X; Yan, H; Han, C; Zhou, Y; Yi, J; Xie, C

    2015-03-01

    To investigate comparatively the percentage gamma passing rate (%GP) of two-dimensional (2D) and three-dimensional (3D) pre-treatment volumetric modulated arc therapy (VMAT) dosimetric verification and their correlation and sensitivity with percentage dosimetric errors (%DE). %GP of 2D and 3D pre-treatment VMAT quality assurance (QA) with different acceptance criteria was obtained by ArcCHECK® (Sun Nuclear Corporation, Melbourne, FL) for 20 patients with nasopharyngeal cancer (NPC) and 20 patients with oesophageal cancer. %DE were calculated from planned dose-volume histogram (DVH) and patients' predicted DVH calculated by 3DVH® software (Sun Nuclear Corporation). Correlation and sensitivity between %GP and %DE were investigated using Pearson's correlation coefficient (r) and receiver operating characteristics (ROCs). Relatively higher %DE on some DVH-based metrics were observed for both patients with NPC and oesophageal cancer. Except for 2%/2 mm criterion, the average %GPs for all patients undergoing VMAT were acceptable with average rates of 97.11% ± 1.54% and 97.39% ± 1.37% for 2D and 3D 3%/3 mm criteria, respectively. The number of correlations for 3D was higher than that for 2D (21 vs 8). However, the general correlation was still poor for all the analysed metrics (9 out of 26 for 3D 3%/3 mm criterion). The average area under the curve (AUC) of ROCs was 0.66 ± 0.12 and 0.71 ± 0.21 for 2D and 3D evaluations, respectively. There is a lack of correlation between %GP and %DE for both 2D and 3D pre-treatment VMAT dosimetric evaluation. DVH-based dose metrics evaluation obtained from 3DVH will provide more useful analysis. Correlation and sensitivity of %GP with %DE for VMAT QA were studied for the first time.

  2. Modulation of Kir4.1 and Kir4.1-Kir5.1 channels by small changes in cell volume

    DEFF Research Database (Denmark)

    Soe, Rikke; Macaulay, Nanna; Klaerke, Dan Arne

    2009-01-01

    in Kir4.1 and Kir4.1-Kir5.1 currents upon swelling of the oocytes and a reduction in the current when the oocytes were shrunk. The volume-dependent changes in channel activity were not due to changes in the kinetics of the channels. These findings implicate a putative functional interaction between...... the Kir channels and aquaporins via small, fast cell volume changes in the glial cells....... channels and aquaporins is therefore debated. To test a possible volume-sensitivity of the Kir channels, the Kir4.1 or Kir4.1-Kir5.1 channels were expressed in Xenopus oocytes with or without co-expression of aquaporins and subsequently exposed to cell volume alterations. Our results show an increase...

  3. Matching Dyadic Distributions to Channels

    OpenAIRE

    Böcherer, Georg; Mathar, Rudolf

    2010-01-01

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

  4. 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.

  5. SU-D-304-04: Pre-Clinical Feasibility Study for Intensity Modulated Grid Proton Therapy (IMgPT) Using a Newly Developed Delivery System

    International Nuclear Information System (INIS)

    Tsiamas, P; Moskvin, V; Shin, J; Axente, M; Pirlepesov, F; Krasin, M; Merchant, T; Farr, J

    2015-01-01

    Purpose: The purpose of the current study was to characterize and evaluate intensity-modulated proton grid therapy (IMgPT) using a clinical proton beam. Methods: A TOPAS MC model of a new developmental mode (pre-clinical) of the Hitachi proton therapy system (PROBEAT) was used for simulation and characterization of proton grid therapy. TOPAS simulations of different energy ranges, depths and spot separation distances were performed. LET spectra for various energies and depths were produced with FLUKA MC code for evaluation potential interplay between planning parameters and their effect on the characterization of areas (valley) between spots. IMgPT planning aspects (spot spacing, skin dose, peak-to-valley ratios, beam selection, etc.) were evaluated for different phantom and patient cases. Raysearch software (v4.51) was used to perform the evaluation. Results: Calculated beam peak-to-valley ratios scenarios showed strong energy and depth dependence with ratios to be larger for higher energies and shallower depths. Peak-to-valley ratios for R90 range and for spot spacing of 1cm varied from 30% (E = 221.3 MeV, depth 30.6 cm) to 80% (E = 70.3 MeV, depth 4 cm). LET spectra calculations showed spectral hardening with depth, which might potential increase, spot separation distance and improve peak-to-valley ratios. IMgPT optimization, using constant spot spacing, showed skin dose reduction between peak regions of dose due to the irradiation of less skin. Single beam for bulky shallower tumors might be a potential candidate for proton grid therapy. Conclusions: Proton grid therapy using a clinical beam is a promising technique that reduces skin dose between peak regions of dose and may be suitable for the treatment of shallow tumors. IMgPT may be considered for use when bystander effects in off peak regions would be appropriate

  6. SU-D-304-04: Pre-Clinical Feasibility Study for Intensity Modulated Grid Proton Therapy (IMgPT) Using a Newly Developed Delivery System

    Energy Technology Data Exchange (ETDEWEB)

    Tsiamas, P; Moskvin, V; Shin, J; Axente, M; Pirlepesov, F; Krasin, M; Merchant, T; Farr, J [St. Jude Children’s Research Hospital, Memphis, TN (United States)

    2015-06-15

    Purpose: The purpose of the current study was to characterize and evaluate intensity-modulated proton grid therapy (IMgPT) using a clinical proton beam. Methods: A TOPAS MC model of a new developmental mode (pre-clinical) of the Hitachi proton therapy system (PROBEAT) was used for simulation and characterization of proton grid therapy. TOPAS simulations of different energy ranges, depths and spot separation distances were performed. LET spectra for various energies and depths were produced with FLUKA MC code for evaluation potential interplay between planning parameters and their effect on the characterization of areas (valley) between spots. IMgPT planning aspects (spot spacing, skin dose, peak-to-valley ratios, beam selection, etc.) were evaluated for different phantom and patient cases. Raysearch software (v4.51) was used to perform the evaluation. Results: Calculated beam peak-to-valley ratios scenarios showed strong energy and depth dependence with ratios to be larger for higher energies and shallower depths. Peak-to-valley ratios for R90 range and for spot spacing of 1cm varied from 30% (E = 221.3 MeV, depth 30.6 cm) to 80% (E = 70.3 MeV, depth 4 cm). LET spectra calculations showed spectral hardening with depth, which might potential increase, spot separation distance and improve peak-to-valley ratios. IMgPT optimization, using constant spot spacing, showed skin dose reduction between peak regions of dose due to the irradiation of less skin. Single beam for bulky shallower tumors might be a potential candidate for proton grid therapy. Conclusions: Proton grid therapy using a clinical beam is a promising technique that reduces skin dose between peak regions of dose and may be suitable for the treatment of shallow tumors. IMgPT may be considered for use when bystander effects in off peak regions would be appropriate.

  7. Loss of Pnn expression attenuates expression levels of SR family splicing factors and modulates alternative pre-mRNA splicing in vivo

    International Nuclear Information System (INIS)

    Chiu Yali; Ouyang Pin

    2006-01-01

    SR and SR-related proteins have been implicated as trans-acting factors that play an important role in splice selection and are involved at specific stages of spliceosome formation. A well-established property of SR protein splicing factors is their ability to influence selection of alternative splice sites in a concentration-dependent manner. Identification of molecules that regulate SR family protein expression is therefore of vital importance in RNA biology. Here we report that depletion of Pnn expression, a SR-related protein with functions involved in pre-mRNA splicing and mRNA export, induces reduced expression of a subset of cellular proteins, especially that of SR family proteins, including SC35, SRm300, SRp55, and SRp40, but not that of other nuclear proteins, such as p53, Mdm2, and ki67. Knocking down Pnn expression was achieved in vitro by siRNA transfection. Expression levels of SR and SR-related proteins in Pnn-depleted cells as compared to those in control cells were evaluated by immunofluorescent staining and Western blot with specific antibodies. In addition, we also demonstrate that loss of Pnn expression could modulate splice site selection of model reporter gene in vivo. Our finding is significant in terms of regulation of SR protein cellular concentration because it reveals that Pnn may play a general role in the control of the cellular amount of family SR proteins through down-regulation of its own expression, thereby providing us with a better understanding of the cellular mechanism by which Pnn fulfills its biological function

  8. Antiarrhythmic effect of either negative modulation or blockade of small conductance Ca2+ activated K+ channels on ventricular fibrillation in guinea pig Langendorff perfused heart

    DEFF Research Database (Denmark)

    Diness, Jonas Goldin; Kirchhoff, Jeppe Egedal; Sheykhzade, Majid

    2015-01-01

    During recent years small conductance Ca activated K (SK) channels have been reported to play a role in cardiac electrophysiology. SK channels seem to be expressed in atria and ventricles but from a functional perspective atrial activity is predominant. A general notion seems to be that cardiac S...

  9. ATP Release Channels

    Directory of Open Access Journals (Sweden)

    Akiyuki Taruno

    2018-03-01

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

  10. 3D imaging of magnetic particles using the 7-channel magnetoencephalography device without pre-magnetization or displacement of the sample

    Energy Technology Data Exchange (ETDEWEB)

    Polikarpov, M.A., E-mail: polikarpov_imp@mail.ru [National Research Center “Kurchatov Institute”, Moscow (Russian Federation); Ustinin, M.N.; Rykunov, S.D. [Institute of Mathematical Problems of Biology, Russian Academy of Sciences, Pushchino (Russian Federation); Yurenya, A.Y. [National Research Center “Kurchatov Institute”, Moscow (Russian Federation); Faculty of Physics, Lomonosov Moscow State University, Moscow (Russian Federation); Naurzakov, S.P.; Grebenkin, A.P. [National Research Center “Kurchatov Institute”, Moscow (Russian Federation); Panchenko, V.Y. [National Research Center “Kurchatov Institute”, Moscow (Russian Federation); Faculty of Physics, Lomonosov Moscow State University, Moscow (Russian Federation)

    2017-04-01

    SQUID-based magnetoencephalography device was used for the measurement of a magnetic noise generated by ferrofluid in the stationary standing vial. It was found that a free surface of the ferrofluid generates spontaneous magnetic field sufficient to detect the presence of nanoparticles in the experimental setup. The spatial distribution of elementary magnetic sources was reconstructed by the frequency-pattern analysis of multichannel time series. The localization of ferrofluids was performed based on the analysis of quasirandom time series in two cases of oscillation source. One of them was infrasound from outer noise, and another one was the human heartbeat. These results are prospective for 3D imaging of magnetic particles without pre-magnetization. - Highlights: • A new method of imaging of magnetic nanoparticles in human body is proposed. • The method uses quasi-random fluctuations of the particles in geomagnetic field. • The use of heartbeats as a source of such fluctuations is demonstrated.

  11. On-coil multiple channel transmit system based on class-D amplification and pre-amplification with current amplitude feedback.

    Science.gov (United States)

    Gudino, Natalia; Heilman, Jeremiah A; Riffe, Matthew J; Heid, Oliver; Vester, Markus; Griswold, Mark A

    2013-07-01

    A complete high-efficiency transmit amplifier unit designed to be implemented in on-coil transmit arrays is presented. High power capability, low power dissipation, scalability, and cost minimization were some of the requirements imposed to the design. The system is composed of a current mode class-D amplifier output stage and a voltage mode class-D preamplification stage. The amplitude information of the radio frequency pulse was added through a customized step-down DC-DC converter with current amplitude feedback that connects to the current mode class-D stage. Benchtop measurements and imaging experiments were carried out to analyze system performance. Direct control of B1 was possible and its load sensitivity was reduced to less than 10% variation from unloaded to full loaded condition. When using the amplifiers in an array configuration, isolation above 20 dB was achieved between neighboring coils by the amplifier decoupling method. High output current operation of the transmitter was proved on the benchtop through output power measurements and in a 1.5T scanner through flip angle quantification. Finally, single and multiple channel excitations with the new hardware were demonstrated by receiving signal with the body coil of the scanner. Copyright © 2012 Wiley Periodicals, Inc.

  12. Non-basic amino acids in the ROMK1 channels via an appropriate distance modulate PIP2 regulated pHi-gating.

    Science.gov (United States)

    Lee, Chien-Hsing; Huang, Po-Tsang; Liou, Horng-Huei; Lin, Mei-Ying; Lou, Kuo-Long; Chen, Chung-Yi

    2016-04-22

    The ROMK1 (Kir1.1) channel activity is predominantly regulated by intracellular pH (pHi) and phosphatidylinositol 4,5-bisphosphate (PIP2). Although several residues were reported to be involved in the regulation of pHi associated with PIP2 interaction, the detailed molecular mechanism remains unclear. We perform experiments in ROMK1 pHi-gating with electrophysiology combined with mutational and structural analysis. In the present study, non basic residues of C-terminal region (S219, N215, I192, L216 and L220) in ROMK1 channels have been found to mediate channel-PIP2 interaction and pHi gating. Further, our structural results show these residues with an appropriate distance to interact with membrane PIP2. Meanwhile, a cluster of basic residues (R188, R217 and K218), which was previously discovered regarding the interaction with PIP2, exists in this appropriate distance to discriminate the regulation of channel-PIP2 interaction and pHi-gating. This appropriate distance can be observed with high conservation in the Kir channel family. Our results provide insight that an appropriate distance cooperates with the electrostatics interaction of channel-PIP2 to regulate pHi-gating. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Modulation of innate and learned sexual behaviors by the TRP channel Painless expressed in the fruit fly brain: behavioral genetic analysis and its implications

    Directory of Open Access Journals (Sweden)

    Shoma eSato

    2014-12-01

    Full Text Available Transient receptor potential (TRP channels have attracted considerable attention because of their vital roles in primary sensory neurons, mediating responses to a wide variety of external environmental stimuli. However, much less is known about how TRP channels in the brain respond to intrinsic signals and are involved in neurophysiological processes that control complex behaviors. Painless (Pain is the Drosophila TRP channel that was initially identified as a molecular sensor responsible for detecting noxious thermal and mechanical stimuli. Here, we review recent behavioral genetic studies demonstrating that Pain expressed in the brain plays a critical role in both innate and learned aspects of sexual behaviors. Several members of the TRP channel superfamily play evolutionarily conserved roles in sensory neurons as well as in other peripheral tissues. It is thus expected that brain TRP channels in vertebrates and invertebrates would have some common physiological functions. Studies of Pain in the Drosophila brain using a unique combination of genetics and physiological techniques should provide valuable insights into the fundamental principles concerning TRP channels expressed in the vertebrate and invertebrate brains.

  14. Specific features of design and electric circuit of the pulse modulator of the amplification channel of second-section linear accelerator for a meson factory

    International Nuclear Information System (INIS)

    Dyukov, L.V.; Fedorov, A.F.; Terekhov, V.F.

    1977-01-01

    The circuit and design of a modulator at pulse power of 15 MW and average power of 300 kW, intended for supplying a klystron generator, are described. The modulator is designed for operating in a lengthy mode. The capacitance storage-former is made in the form of three parallel sections of artificial shaping lines in order to lower the specific loads on the elements of the shaping line and thyristors. The thyristor spark gaps are made in the form of a unified water-cooled assembly composed of 12 series TD-320 thyristors. An assessment of the modulator reliability has shown that the average time-to-fault is 800 hr. Modulator tests confirm that the choice of the circuit solution is correct. The modulator total efficiency equals to approximately 0.9

  15. The specificity of Av3 sea anemone toxin for arthropods is determined at linker DI/SS2-S6 in the pore module of target sodium channels.

    Science.gov (United States)

    Gur Barzilai, Maya; Kahn, Roy; Regev, Noa; Gordon, Dalia; Moran, Yehu; Gurevitz, Michael

    2014-10-15

    Av3 is a peptide neurotoxin from the sea anemone Anemonia viridis that shows specificity for arthropod voltage-gated sodium channels (Navs). Interestingly, Av3 competes with a scorpion α-toxin on binding to insect Navs and similarly inhibits the inactivation process, and thus has been classified as 'receptor site-3 toxin', although the two peptides are structurally unrelated. This raises questions as to commonalities and differences in the way both toxins interact with Navs. Recently, site-3 was partly resolved for scorpion α-toxins highlighting S1-S2 and S3-S4 external linkers at the DIV voltage-sensor module and the juxtaposed external linkers at the DI pore module. To uncover channel determinants involved in Av3 specificity for arthropods, the toxin was examined on channel chimaeras constructed with the external linkers of the mammalian brain Nav1.2a, which is insensitive to Av3, in the background of the Drosophila DmNav1. This approach highlighted the role of linker DI/SS2-S6, adjacent to the channel pore, in determining Av3 specificity. Point mutagenesis at DI/SS2-S6 accompanied by functional assays highlighted Trp404 and His405 as a putative point of Av3 interaction with DmNav1. His405 conservation in arthropod Navs compared with tyrosine in vertebrate Navs may represent an ancient substitution that explains the contemporary selectivity of Av3. Trp404 and His405 localization near the membrane surface and the hydrophobic bioactive surface of Av3 suggest that the toxin possibly binds at a cleft by DI/S6. A partial overlap in receptor site-3 of both toxins nearby DI/S6 may explain their binding competition capabilities.

  16. Mechanism of the modulation of BK potassium channel complexes with different auxiliary subunit compositions by the omega-3 fatty acid DHA.

    Science.gov (United States)

    Hoshi, Toshinori; Tian, Yutao; Xu, Rong; Heinemann, Stefan H; Hou, Shangwei

    2013-03-19

    Large-conductance Ca(2+)- and voltage-activated K(+) (BK) channels are well known for their functional versatility, which is bestowed in part by their rich modulatory repertoire. We recently showed that long-chain omega-3 polyunsaturated fatty acids such as docosahexaenoic acid (DHA) found in oily fish lower blood pressure by activating vascular BK channels made of Slo1+β1 subunits. Here we examined the action of DHA on BK channels with different auxiliary subunit compositions. Neuronal Slo1+β4 channels were just as well activated by DHA as vascular Slo1+β1 channels. In contrast, the stimulatory effect of DHA was much smaller in Slo1+β2, Slo1+LRRC26 (γ1), and Slo1 channels without auxiliary subunits. Mutagenesis of β1, β2, and β4 showed that the large effect of DHA in Slo1+β1 and Slo1+β4 is conferred by the presence of two residues, one in the N terminus and the other in the first transmembrane segment of the β1 and β4 subunits. Transfer of this amino acid pair from β1 or β4 to β2 introduces a large response to DHA in Slo1+β2. The presence of a pair of oppositely charged residues at the aforementioned positions in β subunits is associated with a large response to DHA. The Slo1 auxiliary subunits are expressed in a highly tissue-dependent fashion. Thus, the subunit composition-dependent stimulation by DHA demonstrates that BK channels are effectors of omega-3 fatty acids with marked tissue specificity.

  17. A Pre- and Post-Evaluation of Integrating Sustainability Curriculum by Inserting Okala Modules into an Interior Design Materials and Methods Course

    Science.gov (United States)

    Schneiderman, Deborah; Freihoefer, Kara

    2012-01-01

    Purpose: The purpose of this paper is to examine the integration of Okala curriculum into Interior Design coursework. Okala, as a teaching package, is utilized extensively in industrial design education. However, this study examines the expansion and insertion of Okala modules in an existing interior design curriculum. The Okala modules included…

  18. Molecular determinants of interactions between the N-terminal domain and the transmembrane core that modulate hERG K+ channel gating.

    Directory of Open Access Journals (Sweden)

    Jorge Fernández-Trillo

    Full Text Available A conserved eag domain in the cytoplasmic amino terminus of the human ether-a-go-go-related gene (hERG potassium channel is critical for its slow deactivation gating. Introduction of gene fragments encoding the eag domain are able to restore normal deactivation properties of channels from which most of the amino terminus has been deleted, and also those lacking exclusively the eag domain or carrying a single point mutation in the initial residues of the N-terminus. Deactivation slowing in the presence of the recombinant domain is not observed with channels carrying a specific Y542C point mutation in the S4-S5 linker. On the other hand, mutations in some initial positions of the recombinant fragment also impair its ability to restore normal deactivation. Fluorescence resonance energy transfer (FRET analysis of fluorophore-tagged proteins under total internal reflection fluorescence (TIRF conditions revealed a substantial level of FRET between the introduced N-terminal eag fragments and the eag domain-deleted channels expressed at the membrane, but not between the recombinant eag domain and full-length channels with an intact amino terminus. The FRET signals were also minimized when the recombinant eag fragments carried single point mutations in the initial portion of their amino end, and when Y542C mutated channels were used. These data suggest that the restoration of normal deactivation gating by the N-terminal recombinant eag fragment is an intrinsic effect of this domain directed by the interaction of its N-terminal segment with the gating machinery, likely at the level of the S4-S5 linker.

  19. APETx4, a Novel Sea Anemone Toxin and a Modulator of the Cancer-Relevant Potassium Channel KV10.1

    Directory of Open Access Journals (Sweden)

    Lien Moreels

    2017-09-01

    Full Text Available The human ether-à-go-go channel (hEag1 or KV10.1 is a cancer-relevant voltage-gated potassium channel that is overexpressed in a majority of human tumors. Peptides that are able to selectively inhibit this channel can be lead compounds in the search for new anticancer drugs. Here, we report the activity-guided purification and electrophysiological characterization of a novel KV10.1 inhibitor from the sea anemone Anthopleura elegantissima. Purified sea anemone fractions were screened for inhibitory activity on KV10.1 by measuring whole-cell currents as expressed in Xenopus laevis oocytes using the two-microelectrode voltage clamp technique. Fractions that showed activity on Kv10.1 were further purified by RP-HPLC. The amino acid sequence of the peptide was determined by a combination of MALDI- LIFT-TOF/TOF MS/MS and CID-ESI-FT-ICR MS/MS and showed a high similarity with APETx1 and APETx3 and was therefore named APETx4. Subsequently, the peptide was electrophysiologically characterized on KV10.1. The selectivity of the toxin was investigated on an array of voltage-gated ion channels, including the cardiac human ether-à-go-go-related gene potassium channel (hERG or Kv11.1. The toxin inhibits KV10.1 with an IC50 value of 1.1 μM. In the presence of a similar toxin concentration, a shift of the activation curve towards more positive potentials was observed. Similar to the effect of the gating modifier toxin APETx1 on hERG, the inhibition of Kv10.1 by the isolated toxin is reduced at more positive voltages and the peptide seems to keep the channel in a closed state. Although the peptide also induces inhibitory effects on other KV and NaV channels, it exhibits no significant effect on hERG. Moreover, APETx4 induces a concentration-dependent cytotoxic and proapoptotic effect in various cancerous and noncancerous cell lines. This newly identified KV10.1 inhibitor can be used as a tool to further characterize the oncogenic channel KV10.1 or as a

  20. Power and Thermal Technologies for Air and Space-Scientific Research Program. Delivery Order 0017: Study of Microchip Power Module Materials Using Mini-Channel Heat Exchanger

    Science.gov (United States)

    2009-12-01

    at the mid-point of the channels. In fabricating the heat exchanger, a method of attaching the inlet and exit flow tubes (stainless- steel 625 ) to...and the inlet/exit tubing. The mixing chambers ( Inconel 600) were machined as two pieces which were later welded together to make one chamber. The

  1. Differential expression of hERG1 channel isoforms reproduces properties of native I(Kr) and modulates cardiac action potential characteristics

    DEFF Research Database (Denmark)

    Larsen, Anders Peter; Olesen, Søren-Peter

    2010-01-01

    The repolarizing cardiac rapid delayed rectifier current, I(Kr), is composed of ERG1 channels. It has been suggested that two isoforms of the ERG1 protein, ERG1a and ERG1b, both contribute to I(Kr). Marked heterogeneity in the kinetic properties of native I(Kr) has been described. We hypothesized...

  2. MacMARCKS interacts with the metabotropic glutamate receptor type 7 and modulates G protein-mediated constitutive inhibition of calcium channels

    Czech Academy of Sciences Publication Activity Database

    Bertaso, F.; Lill, Y.; Airas, J.M.; Espeut, J.; Blahoš, Jaroslav; Bockaert, J.; Fagni, L.; Betz, H.; Far, O.E.

    2006-01-01

    Roč. 99, - (2006), s. 288-298 ISSN 0022-3042 R&D Projects: GA ČR GA204/05/0920 Institutional research plan: CEZ:AV0Z50390512 Keywords : calmodulin * metabotropic glutamate receptor * calcium channel Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.260, year: 2006

  3. The L-Type Voltage-Gated Calcium Channel Ca [subscript V] 1.2 Mediates Fear Extinction and Modulates Synaptic Tone in the Lateral Amygdala

    Science.gov (United States)

    Temme, Stephanie J.; Murphy, Geoffrey G.

    2017-01-01

    L-type voltage-gated calcium channels (LVGCCs) have been implicated in both the formation and the reduction of fear through Pavlovian fear conditioning and extinction. Despite the implication of LVGCCs in fear learning and extinction, studies of the individual LVGCC subtypes, Ca[subscript V]1.2 and Ca[subscript V] 1.3, using transgenic mice have…

  4. N-Acetylcysteine-induced vasodilatation is modulated by KATP channels, Na+/K+-ATPase activity and intracellular calcium concentration: An in vitro study.

    Science.gov (United States)

    Vezir, Özden; Çömelekoğlu, Ülkü; Sucu, Nehir; Yalın, Ali Erdinç; Yılmaz, Şakir Necat; Yalın, Serap; Söğüt, Fatma; Yaman, Selma; Kibar, Kezban; Akkapulu, Merih; Koç, Meryem İlkay; Seçer, Didem

    2017-08-01

    In this study, we aimed to investigate the role of ATP-sensitive potassium (K ATP ) channel, Na + /K + -ATPase activity, and intracellular calcium levels on the vasodilatory effect of N-acetylcysteine (NAC) in thoracic aorta by using electrophysiological and molecular techniques. Rat thoracic aorta ring preparations and cultured thoracic aorta cells were divided into four groups as control, 2mM NAC, 5mM NAC, and 10mM NAC. Thoracic aorta rings were isolated from rats for measurements of relaxation responses and Na + /K + -ATPase activity. In the cultured thoracic aorta cells, we measured the currents of K ATP channel, the concentration of intracellular calcium and mRNA expression level of K ATP channel subunits (KCNJ8, KCNJ11, ABCC8 and ABCC9). The relaxation rate significantly increased in all NAC groups compared to control. Similarly, Na + /K + - ATPase activity also significantly decreased in NAC groups. Outward K ATP channel current significantly increased in all NAC groups compared to the control group. Intracellular calcium concentration decreased significantly in all groups with compared control. mRNA expression level of ABCC8 subunit significantly increased in all NAC groups compared to the control group. Pearson correlation analysis showed that relaxation rate was significantly associated with K ATP current, intracellular calcium concentration, Na + /K + -ATPase activity and mRNA expression level of ABCC8 subunit. Our findings suggest that NAC relaxes vascular smooth muscle cells through a direct effect on K ATP channels, by increasing outward K+ flux, partly by increasing mRNA expression of K ATP subunit ABCC8, by decreasing in intracellular calcium and by decreasing in Na + /K + -ATPase activity. Copyright © 2017 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  5. Construction and validation of a long-channel membrane test cell for representative monitoring of performance and characterization of fouling over the length of spiral-wound membrane modules

    KAUST Repository

    Siebdrath, Nadine; Ding, Wei; Pietsch, Elisabeth; Kruithof, Joop; Uhl, Wolfgang; Vrouwenvelder, Johannes S.

    2017-01-01

    A long-channel membrane test cell (LCMTC) with the same length as full-scale elements was developed to simulate performance and fouling in nanofiltration and reverse osmosis spiral-wound membrane modules (SWMs). The transparent LCMTC enabled simultaneous monitoring of SWM performance indicators: feed channel pressure drop, permeate flux and salt passage. Both permeate flux and salt passage were monitored over five sections of the test cell and were related to the amount and composition of the accumulated foulant in these five sections, illustrating the unique features of the test cell. Validation experiments at various feed pressures showed the same flow profile and the same hydraulic behaviour as SWMs used in practice, confirming the representativeness and suitability of the test cell to study SWM operation and fouling. The importance to apply feed spacers matching the flow channel height in test cell systems was demonstrated. Biofouling studies showed that the dosage of a biodegradable substrate to the feed of the LCMTC accelerated the gradual decrease of membrane performance and the accumulation of biomass on the spacer and membrane sheets. The strongest permeate flux decline and the largest amount of accumulated biomass was found in the first 18 cm of the test cell. The LCMTC showed to be suitable to study the impact of biofilm development and biofouling control strategies under representative conditions for full-scale membrane elements.

  6. Construction and validation of a long-channel membrane test cell for representative monitoring of performance and characterization of fouling over the length of spiral-wound membrane modules

    KAUST Repository

    Siebdrath, Nadine

    2017-12-03

    A long-channel membrane test cell (LCMTC) with the same length as full-scale elements was developed to simulate performance and fouling in nanofiltration and reverse osmosis spiral-wound membrane modules (SWMs). The transparent LCMTC enabled simultaneous monitoring of SWM performance indicators: feed channel pressure drop, permeate flux and salt passage. Both permeate flux and salt passage were monitored over five sections of the test cell and were related to the amount and composition of the accumulated foulant in these five sections, illustrating the unique features of the test cell. Validation experiments at various feed pressures showed the same flow profile and the same hydraulic behaviour as SWMs used in practice, confirming the representativeness and suitability of the test cell to study SWM operation and fouling. The importance to apply feed spacers matching the flow channel height in test cell systems was demonstrated. Biofouling studies showed that the dosage of a biodegradable substrate to the feed of the LCMTC accelerated the gradual decrease of membrane performance and the accumulation of biomass on the spacer and membrane sheets. The strongest permeate flux decline and the largest amount of accumulated biomass was found in the first 18 cm of the test cell. The LCMTC showed to be suitable to study the impact of biofilm development and biofouling control strategies under representative conditions for full-scale membrane elements.

  7. Phosphatidylinositol 4,5-bisphosphate, cholesterol, and fatty acids modulate the calcium-activated chloride channel TMEM16A (ANO1).

    Science.gov (United States)

    De Jesús-Pérez, José J; Cruz-Rangel, Silvia; Espino-Saldaña, Ángeles E; Martínez-Torres, Ataúlfo; Qu, Zhiqiang; Hartzell, H Criss; Corral-Fernandez, Nancy E; Pérez-Cornejo, Patricia; Arreola, Jorge

    2018-03-01

    The TMEM16A-mediated Ca 2+ -activated Cl - current drives several important physiological functions. Membrane lipids regulate ion channels and transporters but their influence on members of the TMEM16 family is poorly understood. Here we have studied the regulation of TMEM16A by phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2), cholesterol, and fatty acids using patch clamp, biochemistry and fluorescence microscopy. We found that depletion of membrane PI(4,5)P2 causes a decline in TMEM16A current that is independent of cytoskeleton, but is partially prevented by removing intracellular Ca 2+ . On the other hand, supplying PI(4,5)P2 to inside-out patches attenuated channel rundown and/or partially rescued activity after channel rundown. Also, depletion (with methyl-β-cyclodextrin M-βCD) or restoration (with M-βCD+cholesterol) of membrane cholesterol slows down the current decay observed after reduction of PI(4,5)P2. Neither depletion nor restoration of cholesterol change PI(4,5)P2 content. However, M-βCD alone transiently increases TMEM16A activity and dampens rundown whereas M-βCD+cholesterol increases channel rundown. Thus, PI(4,5)P2 is required for TMEM16A function while cholesterol directly and indirectly via a PI(4,5)P2-independent mechanism regulate channel function. Stearic, arachidonic, oleic, docosahexaenoic, and eicosapentaenoic fatty acids as well as methyl stearate inhibit TMEM16A in a dose- and voltage-dependent manner. Phosphatidylserine, a phospholipid whose hydrocarbon tails contain stearic and oleic acids also inhibits TMEM16A. Finally, we show that TMEM16A remains in the plasma membrane after treatment with M-βCD, M-βCD+cholesterol, oleic, or docosahexaenoic acids. Thus, we propose that lipids and fatty acids regulate TMEM16A channels through a membrane-delimited protein-lipid interaction. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. On the Capacity of the Dirty Paper Channel with Fast Fading and Discrete Channel States

    OpenAIRE

    Rini, Stefano; Shitz, Shlomo Shamai

    2016-01-01

    The "writing dirty paper" capacity result crucially dependents on the perfect channel knowledge at the transmitter as the presence of even a small uncertainty in the channel realization gravely hampers the ability of the transmitter to pre-code its transmission against the channel state. This is particularly disappointing as it implies that interference pre-coding in practical systems is effective only when the channel estimates at the users have very high precision, a condition which is gene...

  9. TDM/FM/FDMA - A modulation technique for multiple-beam satellites which precludes cochannel interference and allows non-uniform geographic distribution of user channels

    Science.gov (United States)

    Springett, J. C.

    1982-01-01

    The technique outlined in this paper is intended to eliminate the problems of cochannel interference and uniform geographic distribution of user channels which arise in conventional designs for a multiple spot beam communication satellite to serve mobile telephony users across the CONUS. By time multiplexing FM/FDMA signal ensembles so that only those beams operating on distinct frequency subbands are allowed to transmit concurrently, cochannel interference arising from simultaneous frequency subband reuse is precluded. Thus, time disjoint frequency reuse is accomplished over a repetitive sequence of fixed time slots. By assigning different size subbands to each time slot, a market of nonuniform users can be accommodated. The technique results in a greatly simplified antenna feed system design for the satellite, at a cost of imposing the need for time slot synchronization on the mobile FM receivers whose ability for rejecting adjacent channel interference is somewhat diminished.

  10. TDM/FM/FDMA - A modulation technique for multiple-beam satellites which precludes cochannel interference and allows non-uniform geographic distribution of user channels

    Science.gov (United States)

    Springett, J. C.

    The technique outlined in this paper is intended to eliminate the problems of cochannel interference and uniform geographic distribution of user channels which arise in conventional designs for a multiple spot beam communication satellite to serve mobile telephony users across the CONUS. By time multiplexing FM/FDMA signal ensembles so that only those beams operating on distinct frequency subbands are allowed to transmit concurrently, cochannel interference arising from simultaneous frequency subband reuse is precluded. Thus, time disjoint frequency reuse is accomplished over a repetitive sequence of fixed time slots. By assigning different size subbands to each time slot, a market of nonuniform users can be accommodated. The technique results in a greatly simplified antenna feed system design for the satellite, at a cost of imposing the need for time slot synchronization on the mobile FM receivers whose ability for rejecting adjacent channel interference is somewhat diminished.

  11. Individual variation and hormonal modulation of a sodium channel beta subunit in the electric organ correlate with variation in a social signal.

    Science.gov (United States)

    Liu, He; Wu, Ming-Ming; Zakon, Harold H

    2007-09-01

    The sodium channel beta1 subunit affects sodium channel gating and surface density, but little is known about the factors that regulate beta1 expression or its participation in the fine control of cellular excitability. In this study we examined whether graded expression of the beta1 subunit contributes to the gradient in sodium current inactivation, which is tightly controlled and directly related to a social behavior, the electric organ discharge (EOD), in a weakly electric fish Sternopygus macrurus. We found the mRNA and protein levels of beta1 in the electric organ both correlate with EOD frequency. We identified a novel mRNA splice form of this gene and found the splicing preference for this novel splice form also correlates with EOD frequency. Androgen implants lowered EOD frequency and decreased the beta1 mRNA level but did not affect splicing. Coexpression of each splice form in Xenopus oocytes with either the human muscle sodium channel gene, hNav1.4, or a Sternopygus ortholog, smNav1.4b, sped the rate of inactivation of the sodium current and shifted the steady-state inactivation toward less negative membrane potentials. The translational product of the novel mRNA splice form lacks a previously identified important tyrosine residue but still functions normally. The properties of the fish alpha and coexpressed beta1 subunits in the oocyte replicate those of the electric organ's endogenous sodium current. These data highlight the role of ion channel beta subunits in regulating cellular excitability.

  12. Ethanol modulation of mammalian BK channels in excitable tissues: molecular targets and their possible contribution to alcohol-induced altered behavior

    Directory of Open Access Journals (Sweden)

    Alex M. Dopico

    2014-12-01

    Full Text Available In most tissues, the function of calcium- and voltage-gated potassium (BK channels is modified in response to ethanol concentrations reached in human blood during alcohol intoxication. In general, modification of BK current from ethanol-naïve preparations in response to brief ethanol exposure results from changes in channel open probability without modification of unitary conductance or change in BK protein levels in the membrane. Protracted and/or repeated ethanol exposure, however, may evoke changes in BK expression. The final ethanol effect on BK open probability leading to either BK current potentiation or BK current reduction is determined by an orchestration of molecular factors, including levels of activating ligand (cytosolic calcium, BK subunit composition and posttranslational modifications, and the channel’s lipid microenvironment. These factors seem to allosterically regulate a direct interaction between ethanol and a recognition pocket of discrete dimensions recently mapped to the channel-forming (slo1 subunit. Type of ethanol exposure also plays a role in the final BK response to the drug: in several central nervous system regions (e.g., striatum, primary sensory neurons, and supraoptic nucleus, acute exposure to ethanol reduces neuronal excitability by enhancing BK activity. In contrast, protracted or repetitive ethanol administration may alter BK subunit composition and membrane expression, rendering the BK complex insensitive to further ethanol exposure. In neurohypophysial axon terminals, ethanol potentiation of BK channel activity leads to a reduction in neuropeptide release. In vascular smooth muscle, however, ethanol inhibition of BK current leads to cell contraction and vascular constriction.

  13. The value of integrating pre-clinical data to predict nausea and vomiting risk in humans as illustrated by AZD3514, a novel androgen receptor modulator

    Energy Technology Data Exchange (ETDEWEB)

    Grant, Claire, E-mail: claire.grant@astrazeneca.com [Drug Safety and Metabolism, AstraZeneca, Alderley Park, Macclesfield SK10 4TG (United Kingdom); Ewart, Lorna [Drug Safety and Metabolism, AstraZeneca, Da Vinci Building, Melbourn Science Park, Cambridge Road, Melbourn, Royston SG8 6HB (United Kingdom); Muthas, Daniel [Respiratory, Inflammation and Autoimmunity iMED, AstraZeneca, Pepparedsleden 1, 431 83 Mölndal (Sweden); Deavall, Damian [Drug Safety and Metabolism, AstraZeneca, Alderley Park, Macclesfield SK10 4TG (United Kingdom); Smith, Simon A. [Oncology Translational Medicine Unit, Early Clinical Development, AstraZeneca, Da Vinci Building, Melbourn Science Park, Melbourn, Royston SG8 6HB (United Kingdom); Clack, Glen [Translational Medicine Unit, Early Clinical Development, AstraZeneca, Alderley Park, Macclesfield SK10 4TG (United Kingdom); Newham, Pete [Drug Safety and Metabolism, AstraZeneca, Darwin Building, Cambridge Science Park, Milton Road, Cambridge CB4 0WG (United Kingdom)

    2016-04-01

    Nausea and vomiting are components of a complex mechanism that signals food avoidance and protection of the body against the absorption of ingested toxins. This response can also be triggered by pharmaceuticals. Predicting clinical nausea and vomiting liability for pharmaceutical agents based on pre-clinical data can be problematic as no single animal model is a universal predictor. Moreover, efforts to improve models are hampered by the lack of translational animal and human data in the public domain. AZD3514 is a novel, orally-administered compound that inhibits androgen receptor signaling and down-regulates androgen receptor expression. Here we have explored the utility of integrating data from several pre-clinical models to predict nausea and vomiting in the clinic. Single and repeat doses of AZD3514 resulted in emesis, salivation and gastrointestinal disturbances in the dog, and inhibited gastric emptying in rats after a single dose. AZD3514, at clinically relevant exposures, induced dose-responsive “pica” behaviour in rats after single and multiple daily doses, and induced retching and vomiting behaviour in ferrets after a single dose. We compare these data with the clinical manifestation of nausea and vomiting encountered in patients with castration-resistant prostate cancer receiving AZD3514. Our data reveal a striking relationship between the pre-clinical observations described and the experience of nausea and vomiting in the clinic. In conclusion, the emetic nature of AZD3514 was predicted across a range of pre-clinical models, and the approach presented provides a valuable framework for predicition of clinical nausea and vomiting. - Highlights: • Integrated pre-clinical data can be used to predict clinical nausea and vomiting. • Data integrated from standard toxicology studies is sufficient to make a prediction. • The use of the nausea algorithm developed by Parkinson (2012) aids the prediction. • Additional pre-clinical studies can be used

  14. Radiation Hard Silicon Photonics Mach-Zehnder Modulator for HEP applications: all-Synopsys SentaurusTM Pre-Irradiation Simulation

    CERN Document Server

    Cammarata, Simone

    2017-01-01

    Silicon Photonics may well provide the opportunity for new levels of integration between detectors and their readout electronics. This technology is thus being evaluated at CERN in order to assess its suitability for use in particle physics experiments. In order to check the agreement with measurements and the validity of previous device simulations, a pure Synopsys SentaurusTM simulation of an un-irradiated Mach-Zehnder silicon modulator has been carried out during the Summer Student project. Index Terms—Silicon Photonics, Mach-Zehnder modulator, electro-optic simulation, Synopsys SentaurusTM, electro-optic measurement, HEP.

  15. Modulation of the transient receptor potential vanilloid channel TRPV4 by 4alpha-phorbol esters: a structure-activity study

    DEFF Research Database (Denmark)

    Klausen, Thomas Kjaer; Pagani, Alberto; Minassi, Alberto

    2009-01-01

    The mechanism of activation of the transient receptor potential vanilloid 4 (TRPV4) channel by 4alpha-phorbol esters was investigated by combining information from chemical modification of 4alpha-phorbol-didecanoate (4alpha-PDD, 2a), site-directed mutagenesis, Ca(2+) imaging, and electrophysiology....... Binding of 4alpha-phorbol esters occurs in a loop in the TM3-TM4 domain of TRPV4 that is analogous to the capsaicin binding site of TRPV1, and the ester decoration of ring C and the A,B ring junction are critical for activity. The lipophilic ester groups on ring C serve mainly as a steering element...

  16. A digital multi-channel spectroscopy system with 100 MHz flash ADC module for the GENIUS-TF and GENIUS projects

    OpenAIRE

    Kihm, T.; Bobrakov, V. F.; Klapdor-Kleingrothaus, H. V.

    2003-01-01

    In this paper we will present the first results of applying a digital processing technology in low-level gamma spectroscopy with HPGE detectors. An experimental gamma spectrometer using Flash ADC module is built and tested. The test system is now under development and shows major advantages over the traditional analog technologies. It will be installed for the GENIUS-TF and GENIUS projects in Gran-Sasso in early 2003.

  17. A digital multi-channel spectroscopy system with 100 MHz flash ADC module for the GENIUS-TF and GENIUS projects

    International Nuclear Information System (INIS)

    Kihm, T.; Bobrakov, V.F.; Klapdor-Kleingrothaus, H.V.

    2003-01-01

    In this paper we present the first results of applying a digital processing technology in low-level gamma spectroscopy with HPGE detectors. An experimental gamma spectrometer using Flash ADC module is built and tested. The test system is now under development and shows major advantages over the traditional analog technologies. It will be installed for the GENIUS-TF and GENIUS projects in Gran-Sasso in early 2003

  18. Optical Communications Channel Combiner

    Science.gov (United States)

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

    2012-01-01

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

  19. Distinct abscisic acid signaling pathways for modulation of guard cell versus mesophyll cell potassium channels revealed by expression studies in Xenopus laevis oocytes

    Science.gov (United States)

    Sutton, F.; Paul, S. S.; Wang, X. Q.; Assmann, S. M.; Evans, M. L. (Principal Investigator)

    2000-01-01

    Regulation of guard cell ion transport by abscisic acid (ABA) and in particular ABA inhibition of a guard cell inward K(+) current (I(Kin)) is well documented. However, little is known concerning ABA effects on ion transport in other plant cell types. Here we applied patch clamp techniques to mesophyll cell protoplasts of fava bean (Vicia faba cv Long Pod) plants and demonstrated ABA inhibition of an outward K(+) current (I(Kout)). When mesophyll cell protoplast mRNA (mesophyll mRNA) was expressed in Xenopus laevis oocytes, I(Kout) was generated that displayed similar properties to I(Kout) observed from direct analysis of mesophyll cell protoplasts. I(Kout) expressed by mesophyll mRNA-injected oocytes was inhibited by ABA, indicating that the ABA signal transduction pathway observed in mesophyll cells was preserved in the frog oocytes. Co-injection of oocytes with guard cell protoplast mRNA and cRNA for KAT1, an inward K(+) channel expressed in guard cells, resulted in I(Kin) that was similarly inhibited by ABA. However, oocytes co-injected with mesophyll mRNA and KAT1 cRNA produced I(Kin) that was not inhibited by ABA. These results demonstrate that the mesophyll-encoded signaling mechanism could not substitute for the guard cell pathway. These findings indicate that mesophyll cells and guard cells use distinct and different receptor types and/or signal transduction pathways in ABA regulation of K(+) channels.

  20. 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...

  1. Discovery and Synthesis of Caracolamide A, an Ion Channel Modulating Dichlorovinylidene Containing Phenethylamide from a Panamanian Marine Cyanobacterium cf. Symploca Species.

    Science.gov (United States)

    Naman, C Benjamin; Almaliti, Jehad; Armstrong, Lorene; Caro-Díaz, Eduardo J; Pierce, Marsha L; Glukhov, Evgenia; Fenner, Amanda; Spadafora, Carmenza; Debonsi, Hosana M; Dorrestein, Pieter C; Murray, Thomas F; Gerwick, William H

    2017-08-25

    A recent untargeted metabolomics investigation into the chemical profile of 10 organic extracts from cf. Symploca spp. revealed several interesting chemical leads for further natural product drug discovery. Subsequent target-directed isolation efforts with one of these, a Panamanian marine cyanobacterium cf. Symploca sp., yielded a phenethylamide metabolite that terminates in a relatively rare gem-dichlorovinylidene moiety, caracolamide A (1), along with a known isotactic polymethoxy-1-alkene (2). Detailed NMR and HRESIMS analyses were used to determine the structures of these molecules, and compound 1 was confirmed by a three-step synthesis. Pure compound 1 was shown to have in vitro calcium influx and calcium channel oscillation modulatory activity when tested as low as 10 pM using cultured murine cortical neurons, but was not cytotoxic to NCI-H460 human non-small-cell lung cancer cells in vitro (IC 50 > 10 μM).

  2. Modulation of intracellular Ca2+ via L-type calcium channels in heart cells by the autoantibody directed against the second extracellular loop of the alpha1-adrenoceptors.

    Science.gov (United States)

    Bkaily, Ghassan; El-Bizri, Nesrine; Bui, Michel; Sukarieh, Rami; Jacques, Danielle; Fu, Michael L X

    2003-03-01

    The effects of methoxamine, a selective alpha1-adrenergic receptor agonist, and the autoantibody directed against the second extracellular loop of alpha1-adrenoceptors were studied on intracellular free Ca2+ levels using confocal microscopy and ionic currents using the whole-cell patch clamp technique in single cells of 10-day-old embryonic chick and 20-week-old fetal human hearts. We observed that like methoxamine, the autoantibody directed against the second extracellular loop of alpha1-adrenoreceptors significantly increased the L-type calcium current (I(Ca(L))) but had no effect on the T-type calcium current (I(Ca(T))), the delayed outward potassium current, or the fast sodium current. This effect of the autoantibody was prevented by a prestimulation of the receptors with methoxamine and vice versa. Moreover, treating the cells with prazosin, a selective alpha1-adrenergic receptor antagonist blocked the methoxamine and the autoantibody-induced increase in I(Ca(L)), respectively. In absence of prazosin, both methoxamine and the autoantibody showed a substantial enhancement in the frequency of cell contraction and that of the concomitant cytosolic and nuclear free Ca2+ variations. The subsequent addition of nifedipine, a specific L-type Ca2+ channel blocker, reversed not only the methoxamine or the autoantibody-induced effect but also completely abolished cell contraction. These results demonstrated that functional alpha1-adrenoceptors exist in both 10-day-old embryonic chick and 20-week-old human fetal hearts and that the autoantibody directed against the second extracellular loop of this type of receptors plays an important role in stimulating their activity via activation of L-type calcium channels. This loop seems to have a functional significance by being the target of alpha1-receptor agonists like methoxamine.

  3. Large-conductance Ca2+-activated K+ channel β1-subunit knockout mice are not hypertensive

    Science.gov (United States)

    Garver, Hannah; Galligan, James J.; Fink, Gregory D.

    2011-01-01

    Large-conductance Ca2+-activated K+ (BK) channels are composed of pore-forming α-subunits and accessory β1-subunits that modulate Ca2+ sensitivity. BK channels regulate arterial myogenic tone and renal Na+ clearance/K+ reabsorption. Previous studies using indirect or short-term blood pressure measurements found that BK channel β1-subunit knockout (BK β1-KO) mice were hypertensive. We evaluated 24-h mean arterial pressure (MAP) and heart rate in BK β1-KO mice using radiotelemetry. BK β1-KO mice did not have a higher 24-h average MAP when compared with wild-type (WT) mice, although MAP was ∼10 mmHg higher at night. The dose-dependent peak declines in MAP by nifedipine were only slightly larger in BK β1-KO mice. In BK β1-KO mice, giving 1% NaCl to mice to drink for 7 days caused a transient (5 days) elevation of MAP (∼5 mmHg); MAP returned to pre-saline levels by day 6. BK β1-KO mesenteric arteries in vitro demonstrated diminished contractile responses to paxilline, increased reactivity to Bay K 8644 and norepinephrine (NE), and maintained relaxation to isoproterenol. Paxilline and Bay K 8644 did not constrict WT or BK β1-KO mesenteric veins (MV). BK β1-subunits are not expressed in MV. The results indicate that BK β1-KO mice are not hypertensive on normal or high-salt intake. BK channel deficiency increases arterial reactivity to NE and L-type Ca2+ channel function in vitro, but the L-type Ca2+ channel modulation of MAP is not altered in BK β1-KO mice. BK and L-type Ca2+ channels do not modulate murine venous tone. It appears that selective loss of BK channel function in arteries only is not sufficient to cause sustained hypertension. PMID:21131476

  4. Athermal channeled spectropolarimeter

    Science.gov (United States)

    Jones, Julia Craven

    2015-12-08

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

  5. Pre-fermentative cold maceration, saignée, and various thermal treatments as options for modulating volatile aroma and phenol profiles of red wine.

    Science.gov (United States)

    Lukić, Igor; Budić-Leto, Irena; Bubola, Marijan; Damijanić, Kristijan; Staver, Mario

    2017-06-01

    The effects of six maceration treatments on volatile aroma and phenol composition of Teran red wine were studied: standard maceration (control C), cold pre-fermentation maceration (CPM), saignée (S), pre-fermentation heating with extended maceration (PHT) or juice fermentation (PHP), and post-fermentation heating (POH). PHP wine contained the highest amounts of esters, fatty acids and anthocyanins, and the lowest content of other phenols. Alternative treatments decreased higher alcohols in relation to control C. CPM treatment lowered the extraction of seed tannins, exhibited the highest acetaldehyde, ethyl acetate and C 6 -compounds levels, and had increased ester levels in relation to control C. POH wine contained the highest concentration of total phenols, flavonoids, monomeric, oligomeric and polymeric flavanols, and color intensity and hue. S and PHT wines contained lower amount of total phenols, but higher than in C and CPM wines. The calculated Odor Activity Values were used to establish significant differences between the treatments. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Tributyltin modulates 3,3',4,4',5-pentachlorobiphenyl (PCB-126)-induced hepatic CYP1A activity in channel catfish, Ictalurus punctatus.

    Science.gov (United States)

    Rice, C D; Roszell, L E

    1998-10-09

    Many harbor estuaries and their tributaries are contaminated with halogenated aromatic hydrocarbons (HAHs) and polycyclic aromatic hydrocarbons (PAHs). Planar congeners of these two classes initiate their toxic effects, including reproductive, developmental, and immunological dysfunction, primarily through the cytosolic arylhydrocabon receptor (Ahr). However, only rarely are aquatic environments contaminated with Ahr-binding contaminants alone. Instead, most are impacted by a variety of pollutants in mixture. Tributyltin (TBT), a common antifouling biocide, is also found in many harbor estuaries and their tributaries. Several reports indicate that TBT inhibits the cytochrome P-4501A system of fish, at least in vitro, and our recent studies with rodents indicate that TBT potentiates PCB-induced CYP1A. However, the effects of TBT on xenobiotic-induced CYP1A activity in aquatic organisms has been virtually unexplored. To this end, channel catfish, Ictalurus punctatus, were exposed to 3,3'4,4',5-pentachlorobiphenyl (PCB-126, PeCB), TBT, or both in combination, with corn oil (CO) serving as the carrier control. Immunoreactive CYP1A protein and ethoxyresorufin O-deethylase (EROD) activity were measured after (1) a single dose of 0.01, 0. 1, or 1 mg/kg of each or both in combination, and (2) 6 injections of 0.017, 1.7, or 17 microg/kg of each (or in combination) given every 3 d over a 16-d period to yield a cumulative dose of 0.01, 0.1, or 1 mg/kg. As expected, PeCB alone, but not TBT, greatly induced these two CYP1A parameters. Low and middle doses of TBT (0.01 and 0.1 mg/kg), but not the high dose, potentiated PeCB-induced activity at these same doses. This effect of TBT was even more pronounced in the repeated exposure study. Furthermore, EROD activity did not always reflect CYP1A protein induction; enzyme activity was inhibited by TBT at doses that potentiated protein induction (0.01 and 0.1 mg/kg). In summary, TBT potentiates PeCB-induced CYP1A in channel catfish at

  7. Electrophysiological evidence for voltage-gated calcium channel 2 (Cav2) modulation of mechano- and thermosensitive spinal neuronal responses in a rat model of osteoarthritis.

    Science.gov (United States)

    Rahman, W; Patel, R; Dickenson, A H

    2015-10-01

    Osteoarthritis (OA) remains one of the greatest healthcare burdens in western society, with chronic debilitating pain-dominating clinical presentation yet therapeutic strategies are inadequate in many patients. Development of better analgesics is contingent on improved understanding of the molecular mechanisms mediating OA pain. Voltage-gated calcium channels 2.2 (Cav2.2) play a critical role in spinal nociceptive transmission, therefore blocking Cav2.2 activity represents an attractive opportunity for OA pain treatment, but the only available licensed Cav2.2 antagonist ziconitide (PrilatTM) is of limited use. TROX-1 is an orally available, use dependent and state-selective Cav2 antagonist, exerting its analgesic effect primarily via Cav2.2 blockade, with an improved therapeutic window compared with ziconitide. Using a rat model of monosodium iodoacetate (MIA), 2 mg, induced OA we used in vivo electrophysiology to assess the effects of spinal or systemic administration of TROX-1 on the evoked activity of wide dynamic range spinal dorsal horn neurons in response to electrical, natural mechanical (dynamic brush and von Frey 2, 8, 26 and 6 g) and thermal (40, 45 and 45 °C) stimuli applied to the peripheral receptive field. MIA injection into the knee joint resulted in mechanical hypersensitivity of the ipsilateral hind paw and weight-bearing asymmetry. Spinal administration of TROX-1 (0.1 and 1 μg/50 μl) produced a significant dose-related inhibition of dynamic brush, mechanical (von Frey filament (vF) 8, 26 and 60 g) and noxious thermal-(45 and 48 °C) evoked neuronal responses in MIA rats only. Systemic administration of TROX-1 produced a significant inhibition of the mechanical-(vF 8, 26 and 60 g) evoked neuronal responses in MIA rats. TROX-1 did not produce any significant effect on any neuronal measure in Sham controls. Our in vivo electrophysiological results demonstrate a pathological state-dependent effect of TROX-1, which suggests an increased functional

  8. Ion channeling

    International Nuclear Information System (INIS)

    Erramli, H.; Blondiaux, G.

    1994-01-01

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

  9. Meet me on the other side: trans-bilayer modulation of a model voltage-gated ion channel activity by membrane electrostatics asymmetry.

    Directory of Open Access Journals (Sweden)

    Loredana Mereuta

    Full Text Available While it is accepted that biomembrane asymmetry is generated by proteins and phospholipids distribution, little is known about how electric changes manifested in a monolayer influence functional properties of proteins localized on the opposite leaflet. Herein we used single-molecule electrophysiology and investigated how asymmetric changes in the electrostatics of an artificial lipid membrane monolayer, generated oppositely from where alamethicin--a model voltage-gated ion channel--was added, altered peptide activity. We found that phlorizin, a membrane dipole potential lowering amphiphile, augmented alamethicin activity and transport features, whereas the opposite occurred with RH-421, which enhances the monolayer dipole potential. Further, the monolayer surface potential was decreased via adsorption of sodium dodecyl sulfate, and demonstrated that vectorial modification of it also affected the alamethicin activity in a predictive manner. A new paradigm is suggested according to which asymmetric changes in the monolayer dipole and surface potential extend their effects spatially by altering the intramembrane potential, whose gradient is sensed by distantly located peptides.

  10. SLAH1, a homologue of the slow type anion channel SLAC1, modulates shoot Cl − accumulation and salt tolerance in Arabidopsis thaliana

    KAUST Repository

    Qiu, Jiaen; Henderson, Sam W; Tester, Mark A.; Roy, Stuart J; Gilliham, Mathew

    2016-01-01

    Salinity tolerance is correlated with shoot chloride (Cl–) exclusion in multiple crops, but the molecular mechanisms of long-distance Cl– transport are poorly defined. Here, we characterize the in planta role of AtSLAH1 (a homologue of the slow type anion channel-associated 1 (SLAC1)). This protein, localized to the plasma membrane of root stelar cells, has its expression reduced by salt or ABA, which are key predictions for a protein involved with loading Cl– into the root xylem. Artificial microRNA knockdown mutants of AtSLAH1 had significantly reduced shoot Cl− accumulation when grown under low Cl–, whereas shoot Cl– increased and the shoot nitrate/chloride ratio decreased following AtSLAH1 constitutive or stelar-specific overexpression when grown in high Cl–. In both sets of overexpression lines a significant reduction in shoot biomass over the null segregants was observed under high Cl– supply, but not low Cl– supply. Further in planta data showed AtSLAH3 overexpression increased the shoot nitrate/chloride ratio, consistent with AtSLAH3 favouring nitrate transport. Heterologous expression of AtSLAH1 in Xenopus laevis oocytes led to no detectible transport, suggesting the need for post-translational modifications for AtSLAH1 to be active. Our in planta data are consistent with AtSLAH1 having a role in controlling root-to-shoot Cl– transport.

  11. SLAH1, a homologue of the slow type anion channel SLAC1, modulates shoot Cl − accumulation and salt tolerance in Arabidopsis thaliana

    KAUST Repository

    Qiu, Jiaen

    2016-06-23

    Salinity tolerance is correlated with shoot chloride (Cl–) exclusion in multiple crops, but the molecular mechanisms of long-distance Cl– transport are poorly defined. Here, we characterize the in planta role of AtSLAH1 (a homologue of the slow type anion channel-associated 1 (SLAC1)). This protein, localized to the plasma membrane of root stelar cells, has its expression reduced by salt or ABA, which are key predictions for a protein involved with loading Cl– into the root xylem. Artificial microRNA knockdown mutants of AtSLAH1 had significantly reduced shoot Cl− accumulation when grown under low Cl–, whereas shoot Cl– increased and the shoot nitrate/chloride ratio decreased following AtSLAH1 constitutive or stelar-specific overexpression when grown in high Cl–. In both sets of overexpression lines a significant reduction in shoot biomass over the null segregants was observed under high Cl– supply, but not low Cl– supply. Further in planta data showed AtSLAH3 overexpression increased the shoot nitrate/chloride ratio, consistent with AtSLAH3 favouring nitrate transport. Heterologous expression of AtSLAH1 in Xenopus laevis oocytes led to no detectible transport, suggesting the need for post-translational modifications for AtSLAH1 to be active. Our in planta data are consistent with AtSLAH1 having a role in controlling root-to-shoot Cl– transport.

  12. Trans-generational plasticity in physiological thermal tolerance is modulated by maternal pre-reproductive environment in the polychaete Ophryotrocha labronica.

    Science.gov (United States)

    Massamba-N'Siala, Gloria; Prevedelli, Daniela; Simonini, Roberto

    2014-06-01

    Maternal temperature is known to affect many aspects of offspring phenotype, but its effect on offspring physiological thermal tolerance has received less attention, despite the importance of physiological traits in defining organismal ability to cope with temperature changes. To fill this gap, we used the marine polychaete Ophryotrocha labronica to investigate the influence of maternal temperature on offspring upper and lower thermal tolerance limits, and assess whether maternal influence changed according to the stage of offspring pre-zygotic development at which a thermal cue was provided. Measurements were taken on adult offspring acclimated to 18 or 30°C, produced by mothers previously reared at 24°C and then exposed to 18 or 30°C at an early and late stage of oogenesis. When the shift from 24°C was provided early during oogenesis, mothers produced offspring with greater cold and heat tolerance whenever mother-offspring temperatures did not match, with respect to when they matched, suggesting the presence of an anticipatory maternal effect triggered by the thermal variation. Conversely, when the cue was provided later during oogenesis, more tolerant offspring were observed when temperatures persisted across generations. In this case, maternal exposure to 18 or 30°C may have benefited offspring performance, while limitations in the transmission of the thermal cue may account for the lack of correlation between maternal experiences and offspring performance when mother-offspring environments did not match. Our results provided evidence for a trans-generational effect of temperature on physiological performance characterised by a high context dependency, and are discussed in the light of maternal pre-reproductive experiences. © 2014. Published by The Company of Biologists Ltd.

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

    Directory of Open Access Journals (Sweden)

    Jennifer Thies

    2016-01-01

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

  14. Alterations in expression of Cat-315 epitope of perineuronal nets during normal ageing, and its modulation by an open-channel NMDA receptor blocker, memantine.

    Science.gov (United States)

    Yamada, Jun; Ohgomori, Tomohiro; Jinno, Shozo

    2017-06-15

    The perineuronal net (PNN), a specialized aggregate of the extracellular matrix, is involved in neuroprotection against oxidative stress, which is now recognized as a major contributor to age-related decline in brain functions. In this study, we investigated the age-related molecular changes of PNNs using monoclonal antibody Cat-315, which recognizes human natural killer-1 (HNK-1) glycan on aggrecan-based PNNs. Western blot analysis showed that the expression levels of Cat-315 epitope in the hippocampus were higher in middle-aged (MA, 12-month-old) mice than in young adult (YA, 2-month-old) mice. Although there were no differences in the expression levels of Cat-315 epitope between old age (OA, 20-month-old) and MA mice, Cat-315 immunoreactivity was also detected in astrocytes of OA mice. To focus on Cat-315 epitope in PNNs, we used YA and MA mice in the following experiments. Optical disector analysis showed that there were no differences in the numbers of Cat-315-positive (Cat-315 + ) PNNs between YA and MA mice. Fluorescence intensity analysis indicated that Cat-315 immunoreactivity in PNNs increased with age in the dorsal hippocampus, which is mainly involved in cognitive functions. Administration of an open-channel blocker of NMDA receptor, memantine, reduced the expression levels of Cat-315 epitope in the hippocampus. Furthermore, the numbers of glutamatergic and GABAergic terminals colocalized with Cat-315 epitope around parvalbumin-positive neurons were decreased by memantine. These findings provide novel insight into the involvement of PNNs in normal brain ageing, and suggest that memantine may counteract the age-related alterations in expression levels of Cat-315 epitope via regulation of its subcellular localization. © 2017 Wiley Periodicals, Inc.

  15. 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.

  16. Channel identification machines.

    Science.gov (United States)

    Lazar, Aurel A; Slutskiy, Yevgeniy B

    2012-01-01

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

  17. Channel box

    International Nuclear Information System (INIS)

    Tanabe, Akira.

    1993-01-01

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

  18. Analysis of synchronous digital-modulation schemes for satellite communication

    Science.gov (United States)

    Takhar, G. S.; Gupta, S. C.

    1975-01-01

    The multipath communication channel for space communications is modeled as a multiplicative channel. This paper discusses the effects of multiplicative channel processes on the symbol error rate for quadrature modulation (QM) digital modulation schemes. An expression for the upper bound on the probability of error is derived and numerically evaluated. The results are compared with those obtained for additive channels.

  19. Clofilium inhibits Slick and Slack potassium channels.

    Science.gov (United States)

    de Los Angeles Tejada, Maria; Stolpe, Kathleen; Meinild, Anne-Kristine; Klaerke, Dan A

    2012-01-01

    Slick and Slack high-conductance potassium channels have been recently discovered, and are found in the central nervous system and in the heart. Both channels are activated by Na(+) and Cl(-), and Slick channels are also inhibited by adenosine triphospate (ATP). An important role of setting the resting membrane potential and controlling the basal excitability of neurons has been suggested for these channels. In addition, no specific blockers for these channels are known up to the present. With the purpose of studying the pharmacological characteristics of Slick and Slack channels, the effects of exposure to the antiarrhythmic compound clofilium were evaluated. Clofilium was able to modulate the activity of Slick and Slack channels effectively, with a stronger effect on Slack than Slick channels. In order to evaluate the pharmacological behavior of Slick and Slack channels further, 38 commonly used potassium channel blockers were tested. Screening of these compounds did not reveal any modulators of Slick and Slack channels, except for clofilium. The present study provides a first approach towards elucidating the pharmacological characteristics of Slick and Slack channels and could be the basis for future studies aimed at developing potent and specific blockers and activators for these channels.

  20. Selective Estrogen Receptor Modulator (SERM)-like Activities of Diarylheptanoid, a Phytoestrogen from Curcuma comosa, in Breast Cancer Cells, Pre-osteoblast Cells, and Rat Uterine Tissues.

    Science.gov (United States)

    Thongon, Natthakan; Boonmuen, Nittaya; Suksen, Kanoknetr; Wichit, Patsorn; Chairoungdua, Arthit; Tuchinda, Patoomratana; Suksamrarn, Apichart; Winuthayanon, Wipawee; Piyachaturawat, Pawinee

    2017-05-03

    Diarylheptanoids from Curcuma comosa, of the Zingiberaceae family, exhibit diverse estrogenic activities. In this study we investigated the estrogenic activity of a major hydroxyl diarylheptanoid, 7-(3,4 -dihydroxyphenyl)-5-hydroxy-1-phenyl-(1E)-1-heptene (compound 092) isolated from C. comosa. The compound elicited different transcriptional activities of estrogen agonist at low concentrations (0.1-1 μM) and antagonist at high concentrations (10-50 μM) using luciferase reporter gene assay in HEK-293T cells. In human breast cancer (MCF-7) cells, compound 092 showed an anti-estrogenic activity by down-regulating ERα-signaling and suppressing estrogen-responsive genes, whereas it attenuated the uterotrophic effect of estrogen in immature ovariectomized rats. Of note, compound 092 promoted mouse pre-osteoblastic (MC3T3-E1) cell differentiation and the related bone markers, indicating its positive osteogenic effect. Our findings highlight a new, nonsteroidal, estrogen agonist/antagonist of catechol diarylheptanoid from C. comosa, which is scientific evidence supporting its potential as a dietary supplement to prevent bone loss with low risk of breast and uterine cancers in postmenopausal women.

  1. Surface channeling

    International Nuclear Information System (INIS)

    Sizmann, R.; Varelas, C.

    1976-01-01

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

  2. Spark Channels

    Energy Technology Data Exchange (ETDEWEB)

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

    1968-04-15

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

  3. Production of extended plasma channels in atmospheric air by amplitude-modulated UV radiation of GARPUN-MTW Ti : sapphire—KrF laser. Part 2. Accumulation of plasma electrons and electric discharge control

    Science.gov (United States)

    Zvorykin, V. D.; Ionin, Andrei A.; Levchenko, A. O.; Mesyats, Gennadii A.; Seleznev, L. V.; Sinitsyn, D. V.; Smetanin, Igor V.; Sunchugasheva, E. S.; Ustinovskii, N. N.; Shutov, A. V.

    2013-04-01

    The problem of the production of extended (~1 m) plasma channels is studied in atmospheric air by amplitude-modulated laser pulses of UV radiation, which are a superposition of a subpicosecond USP train amplified in a regenerative KrF amplifier with an unstable confocal resonator and a quasi-stationary lasing pulse. The USPs possess a high (0.2-0.3 TW) peak power and efficiently ionise oxygen molecules due to multiphoton ionisation, and the quasi-stationary lasing pulse, which has a relatively long duration (~100 ns), maintains the electron density at a level ne = (3-5) × 1014 cm—3 by suppressing electron attachment to oxygen. Experiments in laser triggering of high-voltage electric discharges suggest that the use of combined pulses results in a significant lowering of the breakdown threshold and enables controlling the discharge trajectory with a higher efficiency in comparison with smooth pulses. It was shown that controlled breakdowns may develop with a delay of tens of microseconds relative to the laser pulse, which is many orders of magnitude greater than the lifetime of free electrons in the laser-induced plasma. We propose a mechanism for this breakdown, which involves speeding-up of the avalanche ionisation of the air by negative molecular oxygen ions with a low electron binding energy (~0.5 eV) and a long lifetime (~1 ms), which are produced upon cessation of the laser pulse.

  4. 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.

  5. VAX CAMAC channel

    International Nuclear Information System (INIS)

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

    1980-10-01

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

  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. Solid state detector module

    International Nuclear Information System (INIS)

    Hoffman, D. M.

    1985-01-01

    A solid state detector in which each scintillator is optimally configured and coupled with its associated sensing diode in a way which exploits light piping effects to enhance efficiency, and at the same time provide a detector which is modular in nature. To achieve light piping, the scintillator crystal is oriented such that its sides conform with the crystal cleavage plane, and the sides are highly polished. An array of tungsten collimator plates define the individual channels. Multi-channel scintillator/diode modules are mounted behind and in registry with the plurality of collimator plates. A plurality of scintillators are bonded together after coating the surfaces thereof to minimize optical crosstalk. After lapping the face of the scintillator module, it is then bonded to a diode module with individual scintillators in registration with individual diodes. The module is then positioned in the detector array with collimator plates at the junctions between the scintillators

  8. Ascofuranone stimulates expression of adiponectin and peroxisome proliferator activated receptor through the modulation of mitogen activated protein kinase family members in 3T3-L1, murine pre-adipocyte cell line

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Young-Chae, E-mail: ycchang@cu.ac.kr [Research Institute of Biomedical Engineering and Department of Medicine, Catholic University of Daegu School of Medicine, Daegu 705-718 (Korea, Republic of); Cho, Hyun-Ji, E-mail: hjcho.dr@gmail.com [Research Institute of Biomedical Engineering and Department of Medicine, Catholic University of Daegu School of Medicine, Daegu 705-718 (Korea, Republic of)

    2012-06-08

    Highlights: Black-Right-Pointing-Pointer Ascofuranone increases expression of adiponectin and PPAR{gamma}. Black-Right-Pointing-Pointer Inhibitors for MEK and JNK increased the expression of adiponectin and PPAR{gamma}. Black-Right-Pointing-Pointer Ascofuranone significantly suppressed phosho-ERK, while increasing phospho-p38. -- Abstract: Ascofuranone, an isoprenoid antibiotic, was originally isolated as a hypolipidemic substance from a culture broth of the phytopathogenic fungus, Ascochyta visiae. Adiponectin is mainly synthesized by adipocytes. It relieves insulin resistance by decreasing the plasma triglycerides and improving glucose uptake, and has anti-atherogenic properties. Here, we found that ascofuranone increases expression of adiponectin and PPAR{gamma}, a major transcription factor for adiponectin, in 3T3-L1, murine pre-adipocytes cell line, without promoting accumulation of lipid droplets. Ascofuranone induced expression of adiponectin, and increases the promoter activity of adiponectin and PPRE, PPAR response element, as comparably as a PPAR{gamma} agonist, rosiglitazone, that stimulates lipid accumulation in the preadipocyte cell line. Moreover, inhibitors for MEK and JNK, like ascofuranone, considerably increased the expression of adiponectin and PPAR{gamma}, while a p38 inhibitor significantly suppressed. Ascofuranone significantly suppressed ERK phosphorylation, while increasing p38 phosphorylation, during adipocyte differentiation program. These results suggest that ascofuranone regulates the expression of adiponectin and PPAR{gamma} through the modulation of MAP kinase family members.

  9. Pre-trial quality assurance processes for an intensity-modulated radiation therapy (IMRT) trial: PARSPORT, a UK multicentre Phase III trial comparing conventional radiotherapy and parotid-sparing IMRT for locally advanced head and neck cancer.

    Science.gov (United States)

    Clark, C H; Miles, E A; Urbano, M T Guerrero; Bhide, S A; Bidmead, A M; Harrington, K J; Nutting, C M

    2009-07-01

    The purpose of this study was to compare conventional radiotherapy with parotid gland-sparing intensity-modulated radiation therapy (IMRT) using the PARSPORT trial. The validity of such a trial depends on the radiotherapy planning and delivery meeting a defined standard across all centres. At the outset, many of the centres had little or no experience of delivering IMRT; therefore, quality assurance processes were devised to ensure consistency and standardisation of all processes for comparison within the trial. The pre-trial quality assurance (QA) programme and results are described. Each centre undertook exercises in target volume definition and treatment planning, completed a resource questionnaire and produced a process document. Additionally, the QA team visited each participating centre. Each exercise had to be accepted before patients could be recruited into the trial. 10 centres successfully completed the quality assurance exercises. A range of treatment planning systems, linear accelerators and delivery methods were used for the planning exercises, and all the plans created reached the standard required for participation in this multicentre trial. All 10 participating centres achieved implementation of a comprehensive and robust IMRT programme for treatment of head and neck cancer.

  10. Ascofuranone stimulates expression of adiponectin and peroxisome proliferator activated receptor through the modulation of mitogen activated protein kinase family members in 3T3-L1, murine pre-adipocyte cell line

    International Nuclear Information System (INIS)

    Chang, Young-Chae; Cho, Hyun-Ji

    2012-01-01

    Highlights: ► Ascofuranone increases expression of adiponectin and PPARγ. ► Inhibitors for MEK and JNK increased the expression of adiponectin and PPARγ. ► Ascofuranone significantly suppressed phosho-ERK, while increasing phospho-p38. -- Abstract: Ascofuranone, an isoprenoid antibiotic, was originally isolated as a hypolipidemic substance from a culture broth of the phytopathogenic fungus, Ascochyta visiae. Adiponectin is mainly synthesized by adipocytes. It relieves insulin resistance by decreasing the plasma triglycerides and improving glucose uptake, and has anti-atherogenic properties. Here, we found that ascofuranone increases expression of adiponectin and PPARγ, a major transcription factor for adiponectin, in 3T3-L1, murine pre-adipocytes cell line, without promoting accumulation of lipid droplets. Ascofuranone induced expression of adiponectin, and increases the promoter activity of adiponectin and PPRE, PPAR response element, as comparably as a PPARγ agonist, rosiglitazone, that stimulates lipid accumulation in the preadipocyte cell line. Moreover, inhibitors for MEK and JNK, like ascofuranone, considerably increased the expression of adiponectin and PPARγ, while a p38 inhibitor significantly suppressed. Ascofuranone significantly suppressed ERK phosphorylation, while increasing p38 phosphorylation, during adipocyte differentiation program. These results suggest that ascofuranone regulates the expression of adiponectin and PPARγ through the modulation of MAP kinase family members.

  11. Multi-channel Kondo necklace

    International Nuclear Information System (INIS)

    Fazekas, P.; Kee Haeyoung.

    1993-06-01

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

  12. Multi-channel Kondo necklace

    Energy Technology Data Exchange (ETDEWEB)

    Fazekas, P; Haeyoung, Kee

    1993-06-01

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

  13. Stimulated emission (4F3/2 → 4I11/2 channel) with LD and Xe-flashlamp pumping of tetragonal, incommensurately modulated Ca2MgSi2O7:Nd3+(Na+) – a new disordered laser crystal

    International Nuclear Information System (INIS)

    Kaminskii, A A; Nakao, H; Ueda, K; Shirakawa, A; Bohatý, L; Becker, P; Liebertz, J; Kleinschrodt, R

    2010-01-01

    Non-centrosymmetric tetragonal crystal Ca 2 MgSi 2 O 7 :Nd 3+ (Na + ) with incommensurately modulated melilite-type structure is presented as a new laser crystal. By LD and Xe-flashlamp pumping its CW and free-running pulsed stimulated emission of the 4 F 3/2 → 4 I 11/2 generation channel of Nd 3+ lasant ions was excited

  14. Osteopontin activates the diabetes-associated potassium channel TALK-1 in pancreatic β-cells.

    Directory of Open Access Journals (Sweden)

    Matthew T Dickerson

    Full Text Available Glucose-stimulated insulin secretion (GSIS relies on β-cell Ca2+ influx, which is modulated by the two-pore-domain K+ (K2P channel, TALK-1. A gain-of-function polymorphism in KCNK16, the gene encoding TALK-1, increases risk for developing type-2 diabetes. While TALK-1 serves an important role in modulating GSIS, the regulatory mechanism(s that control β-cell TALK-1 channels are unknown. Therefore, we employed a membrane-specific yeast two-hybrid (MYTH assay to identify TALK-1-interacting proteins in human islets, which will assist in determining signaling modalities that modulate TALK-1 function. Twenty-one proteins from a human islet cDNA library interacted with TALK-1. Some of these interactions increased TALK-1 activity, including intracellular osteopontin (iOPN. Intracellular OPN is highly expressed in β-cells and is upregulated under pre-diabetic conditions to help maintain normal β-cell function; however, the functional role of iOPN in β-cells is poorly understood. We found that iOPN colocalized with TALK-1 in pancreatic sections and coimmunoprecipitated with human islet TALK-1 channels. As human β-cells express two K+ channel-forming variants of TALK-1, regulation of these TALK-1 variants by iOPN was assessed. At physiological voltages iOPN activated TALK-1 transcript variant 3 channels but not TALK-1 transcript variant 2 channels. Activation of TALK-1 channels by iOPN also hyperpolarized resting membrane potential (Vm in HEK293 cells and in primary mouse β-cells. Intracellular OPN was also knocked down in β-cells to test its effect on β-cell TALK-1 channel activity. Reducing β-cell iOPN significantly decreased TALK-1 K+ currents and increased glucose-stimulated Ca2+ influx. Importantly, iOPN did not affect the function of other K2P channels or alter Ca2+ influx into TALK-1 deficient β-cells. These results reveal the first protein interactions with the TALK-1 channel and found that an interaction with iOPN increased

  15. 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

  16. 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.

  17. Magnetotransport, structural and optical characterization of p-type modulation doped heterostructures with high Ge content Si1-xGex channel grown by SS-MBE on Si1-yGey/Si(001) virtual substrates

    International Nuclear Information System (INIS)

    Myronov, M.

    2001-04-01

    This thesis is a report on experimental investigations of magnetotransport, structural and optical properties of p-type modulation doped (MOD) heterostructures with Si 1-x Ge x channel of high Ge content (0.6 1-y Ge y /Si(001) virtual substrate (VS). The active layers of MOD heterostructures were grown by solid source molecular beam epitaxy (SS-MBE). The VSs were grown either by SS-MBE or low-pressure chemical vapour deposition (LP-CVD). The influence of thermal annealing on magnetotransport, structural and optical properties of Si 1-x Ge x /Si 1-y Ge y heterostructures was studied by performing the post growth furnace thermal annealing (FTA) treatments in the temperature range of 600-900C for 30min and rapid thermal annealing (RTA) treatments at temperature 750C for 30sec. Structural and optical analysis of p-type MOD Si 1-x Ge x /Si 1-y Ge y heterostructures involved the techniques of cross-sectional transmission electron microscopy, ultra low energy secondary ion mass spectrometry, photoluminescence spectroscopy, micro-Raman spectroscopy and scanning white-light interferometry. From the combinations of experimental results obtained by these techniques the Ge composition in the SiGe heteroepilayers, their thicknesses, state of strain in the heteroepilayers and dislocations microstructure in VSs were obtained. After post growth thermal annealing treatments were observed broadening of the Si 1-x Ge x channel accompanied with the reduction of Ge content in the channel and smearing of Si 1-x Ge x /Si 1-y Ge y interfaces. The Si 0.7 Ge 0.3 on low-temperature Si buffer VSs with very good structural properties were designed and grown by SS-MBE. These include: relatively thin 850nm total thickness of VS, 4-6nm Peak-to-Valley values of surface roughness, less than 10 5 cm -2 threading dislocations density and more than 95% degree of relaxation in the top layers of VS. The Hall mobility and sheet carrier density of as-grown and annealed p-type MOD Si 1-x Ge x /Si 1-y Ge y

  18. Occupational Safety. Hand Tools. Pre-Apprenticeship Phase 1 Training.

    Science.gov (United States)

    Lane Community Coll., Eugene, OR.

    This self-paced student training module on safety when using hand tools is one of a number of modules developed for Pre-apprenticeship Phase 1 Training. Purpose of the module is to teach students the correct safety techniques for operating common hand- and arm-powered tools, including selection, maintenance, technique, and uses. The module may…

  19. Channelling and electromagnetic radiation of channelling particles

    International Nuclear Information System (INIS)

    Kalashnikov, N.

    1983-01-01

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

  20. Channel Modeling

    Science.gov (United States)

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

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

  1. Channeling experiment

    International Nuclear Information System (INIS)

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

    1990-07-01

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

  2. Design of a general purpose data collection module for the NuTel telescope

    International Nuclear Information System (INIS)

    Velikzhanin, Y.S.; Chi, Y.; Hou, W.S.; Hsu, C.C.; Shiu, J.G.; Ueno, K.; Wang, M.Z.; Yeh, P.

    2005-01-01

    We have developed a Data Collection Module (DCM) to digitize, store and select data from the NuTel telescope, which observes Cherenkov photons from near horizontal air showers. Multi-anode photo-multiplier tubes (MAPMT) are used as photon-sensitive devices. DCM processes 32 input signals from the charge-sensitive pre-amplifiers located close to the MAPMT. The module design uses 40-MHz 10-bit pipeline ADCs and medium-size FPGAs. A programmable gain/attenuation control x0.5-2 is applied to each channel before the ADC providing a comfortable operation with a multi-channel system using MAPMT as photon-sensitive device because the gain of MAPMT fluctuates from channel to channel as 1:3. DCM has a flexible on-board trigger inside FPGA firmware. The system design is made in 32-bit 33-MHz cPCI. Thirty-two DCMs housed in two crates process signals from the two telescopes of 512 channels each looking to the same direction for coincidence

  3. Resource-Efficient Fusion with Pre-Compensated Transmissions for Cooperative Spectrum Sensing

    Directory of Open Access Journals (Sweden)

    Dayan Adionel Guimarães

    2015-05-01

    Full Text Available Recently, a novel fusion scheme for cooperative spectrum sensing was proposed for saving resources in the control channel. Secondary users (SUs simultaneously report their decisions using binary modulations with the same carrier frequencies. The transmitted symbols add incoherently at the fusion centre (FC, leading to a larger set of symbols in which a subset is associated with the presence of the primary user (PU signal, and another subset is associated with the absence of such a signal. The decision criterion applied for discriminating these subsets works under the assumption that the channel gains are known at the FC. In this paper, we propose a new simultaneous transmission and decision scheme in which the task of channel estimation is shifted from the FC to the SUs, without the need for feeding-back of the estimates to the FC. The estimates are used at the SUs to pre-compensate for the reporting channel phase rotations and to partially compensate for the channel gains. This partial compensation is the result of signal clipping for peak-to-average power ratio (PAPR control. We show, analytically and with simulations, that this new scheme can produce large performance improvements, yet reduces the implementation complexity when compared with the original one.

  4. Retracted: Addition of a single methyl group to a small molecule sodium channel inhibitor introduces a new mode of gating modulation, by L Wang, SG Zellmer, DM Printzenhoff and NA Castle. British Journal of Pharmacology, volume 172(20): 4905-4918, published in October 2015; DOI 10.1111/bph.13259.

    Science.gov (United States)

    2018-07-01

    The above article, published by the British Journal of Pharmacology in October 2015 (https://bpspubs.onlinelibrary.wiley.com/doi/full/10.1111/bph.13259), has been retracted by agreement between the authors, the journal Editor in Chief and John Wiley & Sons Limited. The retraction has been agreed owing to the discovery of errors in the chemical structure of the synthetic compounds generated. The corrected structure is now available in the article PF-06526290 can both enhance and inhibit conduction through voltage gated sodium channels by L Wang, SG Zellmer, DM Printzenhoff and NA Castle, 2018, https://bpspubs.onlinelibrary.wiley.com/doi/full/10.1111/bph.14338. Reference Wang L, Zellmer SG, Printzenhoff DM, Castle NA (2015). Addition of a single methyl group to a small molecule sodium channel inhibitor introduces a new mode of gating modulation. Br J Pharmacol 172: 4905-4918. https://doi.org/10.1111/bph.13259. © 2018 The British Pharmacological Society.

  5. Components of cross-frequency modulation in health and disease

    Directory of Open Access Journals (Sweden)

    Elena A Allen

    2011-07-01

    Full Text Available The cognitive deficits associated with schizophrenia are commonly believed to arise from the abnormal temporal integration of information, however a quantitative approach to assess network coordination is lacking. Here, we propose to use cross-frequency modulation, the dependence of local high-frequency activity on the phase of widespread low-frequency oscillations, as an indicator of network coordination and functional integration. In an exploratory analysis based on pre-existing data, we measured cross-frequency modulation from multi-channel EEG recordings acquired while schizophrenia patients (n = 47 and healthy controls (n = 130 performed an auditory oddball task. Novel application of independent component analysis (ICA to modulation data delineated components with specific spatial and spectral profiles, the weights of which showed co-variation with diagnosis. Global cross-frequency modulation was significantly greater in healthy controls (F1,175=9.25, P<0.005, while modulation at fronto-temporal electrodes was greater in patients (F1,175 =17.5, P<0.0001. We further found that the weights of schizophrenia-relevant components were associated with genetic polymorphisms at previously identified risk loci. Global cross-frequency modulation decreased with copies of 957C allele in the gene for the dopamine D2 receptor (r = −0.20, P < 0.01 across all subjects. Additionally, greater ‘aberrant’ fronto-temporal modulation in schizophrenia patients was correlated with several polymorphisms in the gene for the α2-subunit of the GABAA receptor (GABRA2 as well as the total number of risk alleles in GABRA2 (r = 0.45, P < 0.01. Overall, our results indicate great promise for this approach in establishing patterns of cross-frequency modulation in health and disease and elucidating the roles of oscillatory interactions in functional connectivity.

  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. Note: Optical receiver system for 152-channel magnetoencephalography

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-11-15

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

  8. Spinal Gap Junction Channels in Neuropathic Pain

    OpenAIRE

    Jeon, Young Hoon; Youn, Dong Ho

    2015-01-01

    Damage to peripheral nerves or the spinal cord is often accompanied by neuropathic pain, which is a complex, chronic pain state. Increasing evidence indicates that alterations in the expression and activity of gap junction channels in the spinal cord are involved in the development of neuropathic pain. Thus, this review briefly summarizes evidence that regulation of the expression, coupling, and activity of spinal gap junction channels modulates pain signals in neuropathic pain states induced...

  9. Upgrade of the PreProcessor System for the ATLAS Level-1 Calorimeter Trigger

    CERN Document Server

    Khomich, A

    2010-01-01

    The ATLAS Level-1 Calorimeter Trigger is a hardware-based pipelined system designed to identify high-pT objects in the ATLAS calorimeters within a fixed latency of 2.5\\,us. It consists of three subsystems: the PreProcessor which conditions and digitizes analogue signals and two digital processors. The majority of the PreProcessor's tasks are performed on a dense Multi-Chip Module(MCM) consisting of FADCs, a time-adjustment and digital processing ASICs, and LVDS serialisers designed and implemented in ten years old technologies. An MCM substitute, based on today's components (dual channel FADCs and FPGA), is being developed to profit from state-of-the-art electronics and to enhance the flexibility of the digital processing. Development and first test results are presented.

  10. Upgrade of the PreProcessor System for the ATLAS LVL1 Calorimeter Trigger

    CERN Document Server

    Khomich, A; The ATLAS collaboration

    2010-01-01

    The ATLAS Level-1 Calorimeter Trigger is a hardware-based pipelined system designed to identify high-pT objects in the ATLAS calorimeters within a fixed latency of 2.5us. It consists of three subsystems: the PreProcessor which conditions and digitizes analogue signals and two digital processors. The majority of the PreProcessor's tasks are performed on a dense Multi-Chip Module(MCM) consisting of FADCs, a time-adjustment and digital processing ASICs, and LVDS serializers designed and implemented in ten years old technologies. An MCM substitute, based on today's components (dual channel FADCs and FPGA), is being developed to profit from state-of-the-art electronics and to enhance the flexibility of the digital processing. Development and first test results are presented.

  11. Opioid inhibition of N-type Ca2+ channels and spinal analgesia couple to alternative splicing.

    Science.gov (United States)

    Andrade, Arturo; Denome, Sylvia; Jiang, Yu-Qiu; Marangoudakis, Spiro; Lipscombe, Diane

    2010-10-01

    Alternative pre-mRNA splicing occurs extensively in the nervous systems of complex organisms, including humans, considerably expanding the potential size of the proteome. Cell-specific alternative pre-mRNA splicing is thought to optimize protein function for specialized cellular tasks, but direct evidence for this is limited. Transmission of noxious thermal stimuli relies on the activity of N-type Ca(V)2.2 calcium channels in nociceptors. Using an exon-replacement strategy in mice, we show that mutually exclusive splicing patterns in the Ca(V)2.2 gene modulate N-type channel function in nociceptors, leading to a change in morphine analgesia. Exon 37a (e37a) enhances μ-opioid receptor-mediated inhibition of N-type calcium channels by promoting activity-independent inhibition. In the absence of e37a, spinal morphine analgesia is weakened in vivo but the basal response to noxious thermal stimuli is not altered. Our data suggest that highly specialized, discrete cellular responsiveness in vivo can be attributed to alternative splicing events regulated at the level of individual neurons.

  12. Design and development of CAMAC test module

    International Nuclear Information System (INIS)

    Kulkarni, S.G.; Gore, J. A.; Gupta, A.K.; Saxena, A.

    2015-01-01

    Various Computer automated measurement and control (CAMAC) modules are used in control and monitoring of Pelletron Accelerator. 24 channels CAMAC Input Gate is used for getting the ON/OFF status of various devices in the Pelletron Accelerator. If a channel has 24 V then the status is 'ON' and if the channel receives 0 V then the status is 'OFF'. Hence we can get the status of 24 different channels though one CAMAC Input Gate module. The status is transported to the PC via CAMAC controller. The manual testing of CAMAC Input Gate involves connection of 24 V to each channel and checking the status of each channel with Graphical user interface (GUI) software. This process of checking input gate is automated by developing a CAMAC Test module which is connected to CAMAC Input Gate with a 50 pin ribbon cable. The Test module automatically generates 24 V /0 V on each channel to be tested depending on the software GUI buttons labeled as 'ON'/'OFF' in labview. The status of CAMAC Input Gate is displayed on GUI for all 24 channels. Hence the user can check the working of each channel on GUI written in labview. This automated process of checking the CAMAC Input Gate saves time to debug problems in module and identifying the bad channel which can be subsequently repaired. The CAMAC Test module uses Spartan 2 FPGA which is connected to 24 transistors which in turn operates 24 relays. 24 V supply is connected to the relay secondary contacts which open/close as per the transistor inputs. The 24 V contacts are connected to the module output connector which should be connected to CAMAC Input Gate which is to be tested. (author)

  13. 矿井预掘回撤通道顶板支护技术研究及应用%Mine pre-dug channel retracement of the roof support technology research and application

    Institute of Scientific and Technical Information of China (English)

    郭玉峰

    2015-01-01

    Oblique coal mine 23101 working face for the ifrst time with pre-dug retracement passage through to peep around the rock structure and surrounding rock strength tests, the extent of damage the tunnel roof are mainly located in shallow 2.4m, with the help of the Ministry of coal within the range 0~1.3m to determine the scientiifc support designed to strengthen the rock pressure observation to ensure that the rapid closure of the mine safety purposes.%斜沟煤矿23101工作面首次采用预掘回撤通道,通过围对岩结构窥视和围岩强度的测试,得出巷道顶板的破坏范围主要位于浅部2.4 m,煤帮部0~1.3 m范围内,确定了科学的支护设计,加强矿压观测,确保了矿井安全快速收尾的目的。

  14. FInal Technical Repot of the Project: Design and Implementation of Low-Power 10Gb/s/channel Laser/Silicon Photonics Modulator Drivers with SEU Tolerance for HL-LHC

    Energy Technology Data Exchange (ETDEWEB)

    Gui, Ping [Southern Methodist Univ., Dallas, TX (United States)

    2017-08-09

    During the funding period of this award from May 1, 2014 through March 30, 2016, we have accomplished the design, implementation and measurement results of two laser driver chips: LpGBLD10+ which is a low-power single-channel 10Gb/s laser driver IC, and LDQ10P, which is a 4x10Gb/s driver array chip for High Energy Physics (HEP) applications. With new circuit techniques, the driver consumes a record-low power consumption, 31 mW @10Gb/s/channel and occupies a small area of 400 µm × 1750 µm for the single-channel driver IC and 1900umx1700um for the LDQ10P chip. These characteristics allow for both the LpGBLD10+ ICs and LDQ10P suitable candidate for the Versatile Link PLUS (VL+) project, offering flexibility in configuring multiple Transmitters and receivers.

  15. Dysfunctional HCN ion channels in neurological diseases

    Directory of Open Access Journals (Sweden)

    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

  16. Components of cross-frequency modulation in health and disease.

    Science.gov (United States)

    Allen, Elena A; Liu, Jingyu; Kiehl, Kent A; Gelernter, Joel; Pearlson, Godfrey D; Perrone-Bizzozero, Nora I; Calhoun, Vince D

    2011-01-01

    The cognitive deficits associated with schizophrenia are commonly believed to arise from the abnormal temporal integration of information, however a quantitative approach to assess network coordination is lacking. Here, we propose to use cross-frequency modulation (cfM), the dependence of local high-frequency activity on the phase of widespread low-frequency oscillations, as an indicator of network coordination and functional integration. In an exploratory analysis based on pre-existing data, we measured cfM from multi-channel EEG recordings acquired while schizophrenia patients (n = 47) and healthy controls (n = 130) performed an auditory oddball task. Novel application of independent component analysis (ICA) to modulation data delineated components with specific spatial and spectral profiles, the weights of which showed covariation with diagnosis. Global cfM was significantly greater in healthy controls (F(1,175) = 9.25, P modulation at fronto-temporal electrodes was greater in patients (F(1,175) = 17.5, P modulation in schizophrenia patients was correlated with several polymorphisms in the gene for the α2-subunit of the GABA(A) receptor (GABRA2) as well as the total number of risk alleles in GABRA2 (r = 0.45, P < 0.01). Overall, our results indicate great promise for this approach in establishing patterns of cfM in health and disease and elucidating the roles of oscillatory interactions in functional connectivity.

  17. Rapid effects of 17beta-estradiol on TRPV5 epithelial Ca2+ channels in rat renal cells.

    LENUS (Irish Health Repository)

    Irnaten, Mustapha

    2009-08-01

    The renal distal tubules and collecting ducts play a key role in the control of electrolyte and fluid homeostasis. The discovery of highly calcium selective channels, Transient Receptor Potential Vanilloid 5 (TRPV5) of the TRP superfamily, has clarified the nature of the calcium entry channels. It has been proposed that this channel mediates the critical Ca(2+) entry step in transcellular Ca(2+) re-absorption in the kidney. The regulation of transmembrane Ca(2+) flux through TRPV5 is of particular importance for whole body calcium homeostasis.In this study, we provide evidence that the TRPV5 channel is present in rat cortical collecting duct (RCCD(2)) cells at mRNA and protein levels. We demonstrate that 17beta-estradiol (E(2)) is involved in the regulation of Ca(2+) influx in these cells via the epithelial Ca(2+) channels TRPV5. By combining whole-cell patch-clamp and Ca(2+)-imaging techniques, we have characterized the electrophysiological properties of the TRPV5 channel and showed that treatment with 20-50nM E(2) rapidly (<5min) induced a transient increase in inward whole-cell currents and intracellular Ca(2+) via TRPV5 channels. This rise was significantly prevented when cells were pre-treated with ruthenium red and completely abolished in cells treated with siRNA specifically targeting TRPV5.These data demonstrate for the first time, a novel rapid modulation of endogenously expressed TRPV5 channels by E(2) in kidney cells. Furthermore, the results suggest calcitropic effects of E(2). The results are discussed in relation to present concepts of non-genomic actions of E(2) in Ca(2+) homeostasis.

  18. Quantum entanglement enhances the capacity of bosonic channels with memory

    International Nuclear Information System (INIS)

    Cerf, Nicolas J.; Clavareau, Julien; Macchiavello, Chiara; Roland, Jeremie

    2005-01-01

    The bosonic quantum channels have recently attracted a growing interest, motivated by the hope that they open a tractable approach to the generally hard problem of evaluating quantum channel capacities. These studies, however, have always been restricted to memoryless channels. Here, it is shown that the classical capacity of a bosonic Gaussian channel with memory can be significantly enhanced if entangled symbols are used instead of product symbols. For example, the capacity of a photonic channel with 70%-correlated thermal noise of one-third the shot noise is enhanced by about 11% when using 3.8-dB entangled light with a modulation variance equal to the shot noise

  19. Occupational Safety. Hygiene Safety. Pre-Apprenticeship Phase 1 Training.

    Science.gov (United States)

    Lane Community Coll., Eugene, OR.

    This self-paced student training module on hygiene safety is one of a number of modules developed for Pre-apprenticeship Phase 1 Training. Purpose of the module is to familiarize students with the different types of airborne contaminants--including noise--which may be health hazards and with the proper hygienic measures for dealing with them. The…

  20. 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,

  1. In-Service Inspection system for coolant channels of Indian PHWRS - evolution and experience

    International Nuclear Information System (INIS)

    Puri, R.K.; Singh, M.

    2006-01-01

    In-Service Inspection (ISI) is the most important of all periodic monitoring and surveillance activities for assuring the structural integrity of coolant channels in the life extension and management of pressurized heavy water reactors (PHWR-CANDU). Indian PHWRs (220 MWe) are characterized by consists by 306 coolant channels in each unit. These channels have to be inspected for various parameters over the operating life of the reactor. ISI of coolant channels necessitated the indigenous development of an inspection system called BARCIS (BARC Channel Inspection System) at Bhabha Atomic Research Center. BARCIS consists of mainly three parts; drive and control unit, special sealing plug and an inspection head carrying various NDT sensors. Five such systems have been built and deployed at various power plants. The paper deals with the development of the BARCIS system for meeting the ISI requirements of coolant channels, development cycle of this system from its conception to evolution to the present state, challenges, data generated and experience gained (ISI of nearly 900 coolant channels has been completed). Prior to BARCIS, pressure tube gauging equipment for pre-service inspection of coolant tubes was developed in 1980. Moreover a tool for ISI of coolant channels in dry condition was developed in 1990. The paper also describes evolution of various contingency procedures and devices developed over the last one decade. Future plans taking into account technological advancement, changes in the scope of inspection due to design and operating experiences and plant layout will also be covered. The paper describes the efforts put in to develop drive and control mechanism to suit the different vault layouts. The drive mechanism is responsible for linear and rotary movement of the inspection head to carry out 100% volumetric inspection. Special emphasis has been laid on the safety devices required during the inspection activity. Special measures for heavy water retention in

  2. Reliability Improved Design for a Safety System Channel

    International Nuclear Information System (INIS)

    Oh, Eung Se; Kim, Yun Goo

    2016-01-01

    Nowadays, these systems are implemented with a same platform type, such as a qualified programmable logic controller (PLC). The platform intensively uses digital communication with fiber-optic links to reduce cabling costs and to achieve effective signal isolation. These communication interface and redundancies within a channel increase the complexness of an overall system design. This paper proposes a simpler channel architecture design to reduce the complexity and to enhance overall channel reliability. Simplified safety channel configuration is proposed and the failure probabilities are compared with baseline safety channel configuration using an estimated generic value. The simplified channel configuration achieves 40 percent failure reduction compare to baseline safety channel configuration. If this configuration can be implemented within a processor module, overall safety channel reliability is increase and costs of fabrication and maintenance will be greatly reduced

  3. Reliability Improved Design for a Safety System Channel

    Energy Technology Data Exchange (ETDEWEB)

    Oh, Eung Se; Kim, Yun Goo [KHNP, Daejeon (Korea, Republic of)

    2016-05-15

    Nowadays, these systems are implemented with a same platform type, such as a qualified programmable logic controller (PLC). The platform intensively uses digital communication with fiber-optic links to reduce cabling costs and to achieve effective signal isolation. These communication interface and redundancies within a channel increase the complexness of an overall system design. This paper proposes a simpler channel architecture design to reduce the complexity and to enhance overall channel reliability. Simplified safety channel configuration is proposed and the failure probabilities are compared with baseline safety channel configuration using an estimated generic value. The simplified channel configuration achieves 40 percent failure reduction compare to baseline safety channel configuration. If this configuration can be implemented within a processor module, overall safety channel reliability is increase and costs of fabrication and maintenance will be greatly reduced.

  4. Waveform Sampler CAMAC Module

    International Nuclear Information System (INIS)

    Freytag, D.R.; Haller, G.M.; Kang, H.; Wang, J.

    1985-09-01

    A Waveform Sampler Module (WSM) for the measurement of signal shapes coming from the multi-hit drift chambers of the SLAC SLC detector is described. The module uses a high speed, high resolution analog storage device (AMU) developed in collaboration between SLAC and Stanford University. The AMU devices together with high speed TTL clocking circuitry are packaged in a hybrid which is also suitable for mounting on the detector. The module is in CAMAC format and provides eight signal channels, each recording signal amplitude versus time in 512 cells at a sampling rate of up to 360 MHz. Data are digitized by a 12-bit ADC with a 1 μs conversion time and stored in an on-board memory accessible through CAMAC

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

    OpenAIRE

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

    2017-01-01

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

  6. A compact four channel scaler with display

    International Nuclear Information System (INIS)

    Ingelman, S.; Wannberg, G.

    1977-03-01

    This note describes the construction of a simple-to-make and inexpensive four channel, four decade scaler with display. The unit is intended for use with standard NIM modules in nuclear counting experiments where counting rates are fairly moderate. (Auth.)

  7. A Fast Channel Switching Method in EPON System for IPTV Service

    Science.gov (United States)

    Nie, Yaling; Yoshiuchi, Hideya

    This paper presents a fast channel switching method in Ethernet Passive Optical Network (EPON) system for IPTV service. Fast channel switching is one of the important features of successful IPTV systems. Users surely prefer IPTV systems with small channel switching time rather than a longer one. Thus a channel switching control module and a channel/permission list in EPON system’s ONU or OLT is designed. When EPON system receives channel switching message from IPTV end user, the channel switching control module will catch the message and search the channel list and permission list maintained in EPON system, then got the matching parameter of EPON for the new channel. The new channel’s data transmission will be enabled by directly updating the optical filter of the ONU that end user connected. By using this method in EPON system, it provides a solution for dealing with channel switching delays in IPTV service.

  8. Integration of 128 channels for monitoring, acquisition and control with existing LHCD DAC system

    International Nuclear Information System (INIS)

    Joshi, Ramesh; Virani, Chetan; Wadhwani, Archana; Sharma, P.K.

    2015-01-01

    Lower Hybrid Current Drive (LHCD) data acquisition system needs to be upgraded for additional channel requirement. The existing VME based DAC has been used since long with 32 analog input channels for data monitoring and control. Additional 128 channels require integrating with existing DAC. There are four layers of waveguides which deliver final output power into tokamak. Each layer requires 32 channels for power measurement. For the same requirement 128 analog input channels have been integrated with the help of carrier board and IP modules. Acromag IP330 modules have been procured and finally integrated with additional carrier board with existing VME hardware. Each module provides 32 analog input channels. Device driver has been developed for each module and integrated with existing program. LHCD DAC system has been upgraded with additional 128 channels requirement. It has been successfully testing with recent SST-1 campaign. (author)

  9. Index modulation for 5G wireless communications

    CERN Document Server

    Wen, Miaowen; Yang, Liuqing

    2017-01-01

    This book presents a thorough examination of index modulation, an emerging 5G modulation technique. It includes representative transmitter and receiver design, optimization, and performance analysis of index modulation in various domains. First, the basic spatial modulation system for the spatial domain is introduced. Then, the development of a generalized pre-coding aided quadrature spatial modulation system as well as a virtual spatial modulation system are presented. For the space-time domain, a range of differential spatial modulation systems are examined, along with the pre-coding design. Both basic and enhanced index modulated OFDM systems for the frequency domain are discussed, focusing on the verification of their strong capabilities in inter-carrier interference mitigation. Finally, key open problems are highlighted and future research directions are considered. Designed for researchers and professionals, this book is essential for anyone working in communications networking, 5G, and system design. A...

  10. CAMAC interface module for PACE ADC system

    Energy Technology Data Exchange (ETDEWEB)

    Dalton, C G; Mischke, R E [Los Alamos Scientific Lab., N.Mex. (USA); Scott, D T

    1977-03-15

    This report describes a CAMAC module designed to buffer and transfer data from the Tennelec multiplexed ADC system called PACE to a computer. It can be operated in either of two modes: as an eight-deep, first-in-first-out (FIFO) circular buffer, or in channel mode with a single buffer reserved for each PACE channel.

  11. Dental enamel cells express functional SOCE channels.

    Science.gov (United States)

    Nurbaeva, Meerim K; Eckstein, Miriam; Concepcion, Axel R; Smith, Charles E; Srikanth, Sonal; Paine, Michael L; Gwack, Yousang; Hubbard, Michael J; Feske, Stefan; Lacruz, Rodrigo S

    2015-10-30

    Dental enamel formation requires large quantities of Ca(2+) yet the mechanisms mediating Ca(2+) dynamics in enamel cells are unclear. Store-operated Ca(2+) entry (SOCE) channels are important Ca(2+) influx mechanisms in many cells. SOCE involves release of Ca(2+) from intracellular pools followed by Ca(2+) entry. The best-characterized SOCE channels are the Ca(2+) release-activated Ca(2+) (CRAC) channels. As patients with mutations in the CRAC channel genes STIM1 and ORAI1 show abnormal enamel mineralization, we hypothesized that CRAC channels might be an important Ca(2+) uptake mechanism in enamel cells. Investigating primary murine enamel cells, we found that key components of CRAC channels (ORAI1, ORAI2, ORAI3, STIM1, STIM2) were expressed and most abundant during the maturation stage of enamel development. Furthermore, inositol 1,4,5-trisphosphate receptor (IP3R) but not ryanodine receptor (RyR) expression was high in enamel cells suggesting that IP3Rs are the main ER Ca(2+) release mechanism. Passive depletion of ER Ca(2+) stores with thapsigargin resulted in a significant raise in [Ca(2+)]i consistent with SOCE. In cells pre-treated with the CRAC channel blocker Synta-66 Ca(2+) entry was significantly inhibited. These data demonstrate that enamel cells have SOCE mediated by CRAC channels and implicate them as a mechanism for Ca(2+) uptake in enamel formation.

  12. A Micromechanical RF Channelizer

    Science.gov (United States)

    Akgul, Mehmet

    applications that must be stable against environmental perturbations, such as acceleration or power supply variations. Measurements on fabricated devices in fact confirm predictions by the new model of up to 4x improvement in frequency stability against DC-bias voltage variations for contour-mode disk resonators as the resistance loading their ports increases. By enhancing circuit visualization, this circuit model makes more obvious the circuit design procedures and topologies most beneficial for certain mechanical circuits, e.g., filters and oscillators. The second method enables simultaneous low motional resistance ( Rx 70,000) at 61 MHz using an improved ALD-partial electrode-to-resonator gap filling technique that reduces the Q-limiting surface losses of previous renditions by adding an alumina pre-coating before ALD of the gap-filling high-k dielectric. This effort increases the Q over the ˜10,000 of previous renditions by more than 6x towards demonstration of the first VHF micromechanical resonators in any material, piezoelectric or not, to meet the simultaneous high Q (>50,000) and low motional resistance Rx (gap spacing. Finally, the experimental results introduce a 39nm-gap capacitive transducer, voltage-controlled frequency tuning, and a stress relieving coupled array design that enable a 0.09% bandwidth 223.4 MHz channel-select filter with only 2.7dB of in-band insertion loss and 50dB rejection of out-of-band interferers. This amount of rejection is more than 23dB better than previous capacitive-gap transduced filter designs that did not benefit from sub-50nm gaps. It also comes in tandem with a 20dB shape factor of 2.7 realized by a hierarchical mechanical circuit design utilizing 206 micromechanical circuit elements, all contained in an area footprint of only 600mumx420mum. The key to such low insertion loss for this tiny percent bandwidth is Q's>8,800 supplied by polysilicon disk resonators employing for the first time capacitive transducer gaps small enough to

  13. Flavonoid Regulation of HCN2 Channels*

    Science.gov (United States)

    Carlson, Anne E.; Rosenbaum, Joel C.; Brelidze, Tinatin I.; Klevit, Rachel E.; Zagotta, William N.

    2013-01-01

    The hyperpolarization-activated cyclic nucleotide-modulated (HCN) channels are pacemaker channels whose currents contribute to rhythmic activity in the heart and brain. HCN channels open in response to hyperpolarizing voltages, and the binding of cAMP to their cyclic nucleotide-binding domain (CNBD) facilitates channel opening. Here, we report that, like cAMP, the flavonoid fisetin potentiates HCN2 channel gating. Fisetin sped HCN2 activation and shifted the conductance-voltage relationship to more depolarizing potentials with a half-maximal effective concentration (EC50) of 1.8 μm. When applied together, fisetin and cAMP regulated HCN2 gating in a nonadditive fashion. Fisetin did not potentiate HCN2 channels lacking their CNBD, and two independent fluorescence-based binding assays reported that fisetin bound to the purified CNBD. These data suggest that the CNBD mediates the fisetin potentiation of HCN2 channels. Moreover, binding assays suggest that fisetin and cAMP partially compete for binding to the CNBD. NMR experiments demonstrated that fisetin binds within the cAMP-binding pocket, interacting with some of the same residues as cAMP. Together, these data indicate that fisetin is a partial agonist for HCN2 channels. PMID:24085296

  14. Functional modulation of cerebral gamma-aminobutyric acidA receptor/benzodiazepine receptor/chloride ion channel complex with ethyl beta-carboline-3-carboxylate: Presence of independent binding site for ethyl beta-carboline-3-carboxylate

    Energy Technology Data Exchange (ETDEWEB)

    Taguchi, J.; Kuriyama, K. (Kyoto Prefectural Univ. of Medicine (Japan))

    1990-05-01

    Effect of ethyl beta-carboline-3-carboxylate (beta-CCE) on the function of gamma-aminobutyric acid (GABA)A receptor/benzodiazepine receptor/chloride ion channel complex was studied. Beta-CCE noncompetitively and competitively inhibited (3H)flunitrazepam binding to benzodiazepine receptor, but not (3H)muscimol binding to GABAA receptor as well as t-(3H)butylbicycloorthobenzoate (( 3H) TBOB) binding to chloride ion channel, in particulate fraction of the mouse brain. Ro15-1788 also inhibited competitively (3H) flunitrazepam binding. On the other hand, the binding of beta-(3H)CCE was inhibited noncompetitively and competitively by clonazepam and competitively by Ro15-1788. In agreement with these results, benzodiazepines-stimulated (3H)muscimol binding was antagonized by beta-CCE and Ro15-1788. Gel column chromatography for the solubilized fraction from cerebral particulate fraction by 0.2% sodium deoxycholate (DOC-Na) in the presence of 1 M KCl indicated that beta-(3H)CCE binding site was eluted in the same fraction (molecular weight, 250,000) as the binding sites for (3H)flunitrazepam, (3H)muscimol and (3H)TBOB. GABA-stimulated 36Cl- influx into membrane vesicles prepared from the bovine cerebral cortex was stimulated and attenuated by flunitrazepam and beta-CCE, respectively. These effects of flunitrazepam and beta-CCE on the GABA-stimulated 36Cl- influx were antagonized by Ro15-1788. The present results suggest that the binding site for beta-CCE, which resides on GABAA receptor/benzodiazepine receptor/chloride ion channel complex, may be different from that for benzodiazepine. Possible roles of beta-CCE binding site in the allosteric inhibitions on benzodiazepine binding site as well as on the functional coupling between chloride ion channel and GABAA receptor are also suggested.

  15. Chronic electroconvulsive stimulation but not chronic restraint stress modulates mRNA expression of voltage-dependent potassium channels Kv7.2 and Kv11.1 in the rat piriform cortex

    DEFF Research Database (Denmark)

    Hjæresen, Marie-Louise; Hageman, Ida; Wörtwein, Gitta

    2008-01-01

    The mechanisms by which stress and electroconvulsive therapy exert opposite effects on the course of major depression are not known. Potential candidates might include the voltage-dependent potassium channels. Potassium channels play an important role in maintaining the resting membrane potential...... and controlling neuronal excitability. To explore this hypothesis, we examined the effects of one or several electroconvulsive stimulations and chronic restraint stress (6 h/day for 21 days) on the expression of voltage-dependent potassium channel Kv7.2, Kv11.1, and Kv11.3 mRNA in the rat brain using in situ...... hybridization. Repeated, but not acute, electroconvulsive stimulation increased Kv7.2 and Kv11.1 mRNA levels in the piriform cortex. In contrast, restraint stress had no significant effect on mRNA expression of Kv7.2, Kv11.1, or Kv11.3 in any of the brain regions examined. Thus, it appears that the investigated...

  16. Oscillatory magnetoconductance of quantum double-well channels

    International Nuclear Information System (INIS)

    Rojo, A.G.; Kumar, N.; Balseiro, C.A.

    1988-07-01

    The recently observed flux-periodic interference effect between parallel quantum double-well channels is theoretically studied in a discrete model that takes into account tunneling between channels. We obtain oscillatory magnetoconductance with small modulations which is attributable to the tunneling. Our treatment includes the effect of evanescent modes. (author). 7 refs, 2 figs

  17. The PDZ motif of the α1C subunit is not required for surface trafficking and adrenergic modulation of CaV1.2 channel in the heart.

    Science.gov (United States)

    Yang, Lin; Katchman, Alexander; Weinberg, Richard L; Abrams, Jeffrey; Samad, Tahmina; Wan, Elaine; Pitt, Geoffrey S; Marx, Steven O

    2015-01-23

    Voltage-gated Ca(2+) channels play a key role in initiating muscle excitation-contraction coupling, neurotransmitter release, gene expression, and hormone secretion. The association of CaV1.2 with a supramolecular complex impacts trafficking, localization, turnover, and, most importantly, multifaceted regulation of its function in the heart. Several studies hint at an important role for the C terminus of the α1C subunit as a hub for multidimensional regulation of CaV1.2 channel trafficking and function. Recent studies have demonstrated an important role for the four-residue PDZ binding motif at the C terminus of α1C in interacting with scaffold proteins containing PDZ domains, in the subcellular localization of CaV1.2 in neurons, and in the efficient signaling to cAMP-response element-binding protein in neurons. However, the role of the α1C PDZ ligand domain in the heart is not known. To determine whether the α1C PDZ motif is critical for CaV1.2 trafficking and function in cardiomyocytes, we generated transgenic mice with inducible expression of an N-terminal FLAG epitope-tagged dihydropyridine-resistant α1C with the PDZ motif deleted (ΔPDZ). These mice were crossed with α-myosin heavy chain reverse transcriptional transactivator transgenic mice, and the double-transgenic mice were fed doxycycline. The ΔPDZ channels expressed, trafficked to the membrane, and supported robust excitation-contraction coupling in the presence of nisoldipine, a dihydropyridine Ca(2+) channel blocker, providing functional evidence that they appropriately target to dyads. The ΔPDZ Ca(2+) channels were appropriately regulated by isoproterenol and forskolin. These data indicate that the α1C PDZ motif is not required for surface trafficking, localization to the dyad, or adrenergic stimulation of CaV1.2 in adult cardiomyocytes. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  18. Multicarrier Modulation Techniques for 5G Communications

    OpenAIRE

    QIANYU JIN

    2018-01-01

    This thesis focuses on multicarrier modulation techniques for 5G wireless communications. We study different properties of current multicarrier modulation techniques and propose methodologies to improve them in order to meet the demands of 5G wireless, e.g., low out-of-band radiation, low latency, relaxed synchronization, and stable performance against phase noise with low complexity over a wireless channel.

  19. Aberrant Splicing Induced by Dysregulated Rbfox2 Produces Enhanced Function of CaV1.2 Calcium Channel and Vascular Myogenic Tone in Hypertension.

    Science.gov (United States)

    Zhou, Yingying; Fan, Jia; Zhu, Huayuan; Ji, Li; Fan, Wenyong; Kapoor, Isha; Wang, Yue; Wang, Yuan; Zhu, Guoqing; Wang, Juejin

    2017-12-01

    Calcium influx from activated voltage-gated calcium channel Ca V 1.2 in vascular smooth muscle cells is indispensable for maintaining myogenic tone and blood pressure. The function of Ca V 1.2 channel can be optimized by alternative splicing, one of post-transcriptional modification mechanisms. The splicing factor Rbfox2 is known to regulate the Ca V 1.2 pre-mRNA alternative splicing events during neuronal development. However, Rbfox2's roles in modulating the key function of vascular Ca V 1.2 channel and in the pathogenesis of hypertension remain elusive. Here, we report that the proportion of Ca V 1.2 channels with alternative exon 9* is increased by 10.3%, whereas that with alternative exon 33 is decreased by 10.5% in hypertensive arteries. Surprisingly, the expression level of Rbfox2 is increased ≈3-folds, presumably because of the upregulation of a dominant-negative isoform of Rbfox2. In vascular smooth muscle cells, we find that knockdown of Rbfox2 dynamically increases alternative exon 9*, whereas decreases exon 33 inclusion of Ca V 1.2 channels. By patch-clamp studies, we show that diminished Rbfox2-induced alternative splicing shifts the steady-state activation and inactivation curves of vascular Ca V 1.2 calcium channel to hyperpolarization, which makes the window current potential to more negative. Moreover, siRNA-mediated knockdown of Rbfox2 increases the pressure-induced vascular myogenic tone of rat mesenteric artery. Taken together, our data indicate that Rbfox2 modulates the functions of vascular Ca V 1.2 calcium channel by dynamically regulating the expressions of alternative exons 9* and 33, which in turn affects the vascular myogenic tone. Therefore, our work suggests a key role for Rbfox2 in hypertension, which provides a rational basis for designing antihypertensive therapies. © 2017 American Heart Association, Inc.

  20. High precision 16K, 16 channel peak sensing CAMAC ADC

    International Nuclear Information System (INIS)

    Jain, Mamta; Subramaniam, E.T

    2013-01-01

    A high density, peak sensing, analog to digital converter (ADC) double width module with CAMAC back plane has been developed for nuclear physics experiments with a large number of detectors. This module has sixteen independent channels in plug-in daughter card mother board mode

  1. CLIC Quadrupole Module final report

    CERN Document Server

    Artoos, K; Mainaud-Durand, H

    2013-01-01

    Future Linear colliders will need particle beam sizes in the nanometre range. The beam also needs to be stable all along the beam line. The CLIC Main Beam Quadrupole (MBQ) module has been defined and studied. It is meant as a test stand for stabilisation and pre-alignment with a MB Quadrupole. The main topic that has been tackled concerns the Quadrupole magnet stabilisation to 1nm at 1Hz. This is needed to obtain the desired CLIC luminosity of 2.1034 cm-2m-1. The deliverable was demonstrated by procuring a MBQ and by stabilising a powered and cooled CLIC MBQ quadrupole. In addition, the stabilisation system has to be compatible with the pre-alignment procedures. Pre-alignment movement resolution has been demonstrated to 1m. The last step is the combined test of stability with a quadrupole on a CLIC Module with the pre-alignment.

  2. USACE Navigation Channels 2012

    Data.gov (United States)

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

  3. Calcium channel blocker overdose

    Science.gov (United States)

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

  4. Playing with Opening and Closing of Heterocycles: Using the Cusmano-Ruccia Reaction to Develop a Novel Class of Oxadiazolothiazinones, Active as Calcium Channel Modulators and P-Glycoprotein Inhibitors

    Directory of Open Access Journals (Sweden)

    Domenico Spinelli

    2014-10-01

    Full Text Available As a result of the ring-into-ring conversion of nitrosoimidazole derivatives, we obtained a molecular scaffold that, when properly decorated, is able to decrease inotropy by blocking L-type calcium channels. Previously, we used this scaffold to develop a quantitative structure-activity relationship (QSAR model, and we used the most potent oxadiazolothiazinone as a template for ligand-based virtual screening. Here, we enlarge the diversity of chemical decorations, present the synthesis and in vitro data for 11 new derivatives, and develop a new 3D-QSAR model with recent in silico techniques. We observed a key role played by the oxadiazolone moiety: given the presence of positively charged calcium ions in the transmembrane channel protein, we hypothesize the formation of a ternary complex between the oxadiazolothiazinone, the Ca2+ ion and the protein. We have supported this hypothesis by means of pharmacophore generation and through the docking of the pharmacophore into a homology model of the protein. We also studied with docking experiments the interaction with a homology model of P-glycoprotein, which is inhibited by this series of molecules, and provided further evidence toward the relevance of this scaffold in biological interactions.

  5. Labeling by ( sup 3 H)1,3-di(2-tolyl)guanidine of two high affinity binding sites in guinea pig brain: Evidence for allosteric regulation by calcium channel antagonists and pseudoallosteric modulation by sigma ligands

    Energy Technology Data Exchange (ETDEWEB)

    Rothman, R.B.; Reid, A.; Mahboubi, A.; Kim, C.H.; De Costa, B.R.; Jacobson, A.E.; Rice, K.C. (National Institute of Mental Health, Bethesda, MD (USA))

    1991-02-01

    Equilibrium binding studies with the sigma receptor ligand ({sup 3}H)1,3-di(2-tolyl)guanidine (({sup 3}H)DTG) demonstrated two high affinity binding sites in membranes prepared from guinea pig brain. The apparent Kd values of DTG for sites 1 and 2 were 11.9 and 37.6 nM, respectively. The corresponding Bmax values were 1045 and 1423 fmol/mg of protein. Site 1 had high affinity for (+)-pentazocine, haloperidol, (R)-(+)-PPP, carbepentane, and other sigma ligands, suggesting a similarity with the dextromethorphan/sigma 1 binding site described by Musacchio et al. (Life Sci. 45:1721-1732 (1989)). Site 2 had high affinity for DTG and haloperidol (Ki = 36.1 nM) and low affinity for most other sigma ligands. Kinetic experiments demonstrated that ({sup 3}H)DTG dissociated in a biphasic manner from both site 1 and site 2. DTG and haloperidol increased the dissociation rate of ({sup 3}H)DTG from site 1 and site 2, demonstrating the presence of pseudoallosteric interactions. Inorganic calcium channel blockers such as Cd2+ selectively increased the dissociation rate of ({sup 3}H)DTG from site 2, suggesting an association of this binding site with calcium channels.

  6. Labeling by [3H]1,3-di(2-tolyl)guanidine of two high affinity binding sites in guinea pig brain: Evidence for allosteric regulation by calcium channel antagonists and pseudoallosteric modulation by sigma ligands

    International Nuclear Information System (INIS)

    Rothman, R.B.; Reid, A.; Mahboubi, A.; Kim, C.H.; De Costa, B.R.; Jacobson, A.E.; Rice, K.C.

    1991-01-01

    Equilibrium binding studies with the sigma receptor ligand [ 3 H]1,3-di(2-tolyl)guanidine ([ 3 H]DTG) demonstrated two high affinity binding sites in membranes prepared from guinea pig brain. The apparent Kd values of DTG for sites 1 and 2 were 11.9 and 37.6 nM, respectively. The corresponding Bmax values were 1045 and 1423 fmol/mg of protein. Site 1 had high affinity for (+)-pentazocine, haloperidol, (R)-(+)-PPP, carbepentane, and other sigma ligands, suggesting a similarity with the dextromethorphan/sigma 1 binding site described by Musacchio et al. [Life Sci. 45:1721-1732 (1989)]. Site 2 had high affinity for DTG and haloperidol (Ki = 36.1 nM) and low affinity for most other sigma ligands. Kinetic experiments demonstrated that [ 3 H]DTG dissociated in a biphasic manner from both site 1 and site 2. DTG and haloperidol increased the dissociation rate of [ 3 H]DTG from site 1 and site 2, demonstrating the presence of pseudoallosteric interactions. Inorganic calcium channel blockers such as Cd2+ selectively increased the dissociation rate of [ 3 H]DTG from site 2, suggesting an association of this binding site with calcium channels

  7. Gigascale Silicon Photonic Transmitters Integrating HBT-based Carrier-injection Electroabsorption Modulator Structures

    Science.gov (United States)

    Fu, Enjin

    Demand for more bandwidth is rapidly increasing, which is driven by data intensive applications such as high-definition (HD) video streaming, cloud storage, and terascale computing applications. Next-generation high-performance computing systems require power efficient chip-to-chip and intra-chip interconnect yielding densities on the order of 1Tbps/cm2. The performance requirements of such system are the driving force behind the development of silicon integrated optical interconnect, providing a cost-effective solution for fully integrated optical interconnect systems on a single substrate. Compared to conventional electrical interconnect, optical interconnects have several advantages, including frequency independent insertion loss resulting in ultra wide bandwidth and link latency reduction. For high-speed optical transmitter modules, the optical modulator is a key component of the optical I/O channel. This thesis presents a silicon integrated optical transmitter module design based on a novel silicon HBT-based carrier injection electroabsorption modulator (EAM), which has the merits of wide optical bandwidth, high speed, low power, low drive voltage, small footprint, and high modulation efficiency. The structure, mechanism, and fabrication of the modulator structure will be discussed which is followed by the electrical modeling of the post-processed modulator device. The design and realization of a 10Gbps monolithic optical transmitter module integrating the driver circuit architecture and the HBT-based EAM device in a 130nm BiCMOS process is discussed. For high power efficiency, a 6Gbps ultra-low power driver IC implemented in a 130nm BiCMOS process is presented. The driver IC incorporates an integrated 27-1 pseudo-random bit sequence (PRBS) generator for reliable high-speed testing, and a driver circuit featuring digitally-tuned pre-emphasis signal strength. With outstanding drive capability, the driver module can be applied to a wide range of carrier

  8. Degenerated-Inverse-Matrix-Based Channel Estimation for OFDM Systems

    Directory of Open Access Journals (Sweden)

    Makoto Yoshida

    2009-01-01

    Full Text Available This paper addresses time-domain channel estimation for pilot-symbol-aided orthogonal frequency division multiplexing (OFDM systems. By using a cyclic sinc-function matrix uniquely determined by Nc transmitted subcarriers, the performance of our proposed scheme approaches perfect channel state information (CSI, within a maximum of 0.4 dB degradation, regardless of the delay spread of the channel, Doppler frequency, and subcarrier modulation. Furthermore, reducing the matrix size by splitting the dispersive channel impulse response into clusters means that the degenerated inverse matrix estimator (DIME is feasible for broadband, high-quality OFDM transmission systems. In addition to theoretical analysis on normalized mean squared error (NMSE performance of DIME, computer simulations over realistic nonsample spaced channels also showed that the DIME is robust for intersymbol interference (ISI channels and fast time-invariant channels where a minimum mean squared error (MMSE estimator does not work well.

  9. KCNMA1 encoded cardiac BK channels afford protection against ischemia-reperfusion injury

    DEFF Research Database (Denmark)

    Soltysinska, Ewa; Bentzen, Bo Hjorth; Barthmes, Maria

    2014-01-01

    Mitochondrial potassium channels have been implicated in myocardial protection mediated through pre-/postconditioning. Compounds that open the Ca2+- and voltage-activated potassium channel of big-conductance (BK) have a pre-conditioning-like effect on survival of cardiomyocytes after ischemia/rep...

  10. Quantum Channels With Memory

    International Nuclear Information System (INIS)

    Rybar, T.

    2012-01-01

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

  11. Eight channel fast scalar

    Energy Technology Data Exchange (ETDEWEB)

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

    1977-11-01

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

  12. 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...

  13. Mapping the interaction site for the tarantula toxin hainantoxin-IV (β-TRTX-Hn2a) in the voltage sensor module of domain II of voltage-gated sodium channels.

    Science.gov (United States)

    Cai, Tianfu; Luo, Ji; Meng, Er; Ding, Jiuping; Liang, Songping; Wang, Sheng; Liu, Zhonghua

    2015-06-01

    Peptide toxins often have pharmacological applications and are powerful tools for investigating the structure-function relationships of voltage-gated sodium channels (VGSCs). Although a group of potential VGSC inhibitors have been reported from tarantula venoms, little is known about the mechanism of their interaction with VGSCs. In this study, we showed that hainantoxin-IV (β-TRTX-Hn2a, HNTX-IV in brief), a 35-residue peptide from Ornithoctonus hainana venom, preferentially inhibited rNav1.2, rNav1.3 and hNav1.7 compared with rNav1.4 and hNav1.5. hNav1.7 was the most sensitive to HNTX-IV (IC50∼21nM). In contrast to many other tarantula toxins that affect VGSCs, HNTX-IV at subsaturating concentrations did not alter activation and inactivation kinetics in the physiological range of voltages, while very large depolarization above +70mV could partially activate toxin-bound hNav1.7 channel, indicating that HNTX-IV acts as a gating modifier rather than a pore blocker. Site-directed mutagenesis indicated that the toxin bound to site 4, which was located on the extracellular S3-S4 linker of hNav1.7 domain II. Mutants E753Q, D816N and E818Q of hNav1.7 decreased toxin affinity for hNav1.7 by 2.0-, 3.3- and 130-fold, respectively. In silico docking indicated that a three-toed claw substructure formed by residues with close contacts in the interface between HNTX-IV and hNav1.7 domain II stabilized the toxin-channel complex, impeding movement of the domain II voltage sensor and inhibiting hNav1.7 activation. Our data provide structural details for structure-based drug design and a useful template for the design of highly selective inhibitors of a specific subtype of VGSCs. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Voltage gating of mechanosensitive PIEZO channels.

    Science.gov (United States)

    Moroni, Mirko; Servin-Vences, M Rocio; Fleischer, Raluca; Sánchez-Carranza, Oscar; Lewin, Gary R

    2018-03-15

    Mechanosensitive PIEZO ion channels are evolutionarily conserved proteins whose presence is critical for normal physiology in multicellular organisms. Here we show that, in addition to mechanical stimuli, PIEZO channels are also powerfully modulated by voltage and can even switch to a purely voltage-gated mode. Mutations that cause human diseases, such as xerocytosis, profoundly shift voltage sensitivity of PIEZO1 channels toward the resting membrane potential and strongly promote voltage gating. Voltage modulation may be explained by the presence of an inactivation gate in the pore, the opening of which is promoted by outward permeation. Older invertebrate (fly) and vertebrate (fish) PIEZO proteins are also voltage sensitive, but voltage gating is a much more prominent feature of these older channels. We propose that the voltage sensitivity of PIEZO channels is a deep property co-opted to add a regulatory mechanism for PIEZO activation in widely different cellular contexts.

  15. GMSK Modulation for Deep Space Applications

    Science.gov (United States)

    Shambayati, Shervin; Lee, Dennis K.

    2012-01-01

    Due to scarcity of spectrum at 8.42 GHz deep space Xband allocation, many deep space missions are now considering the use of higher order modulation schemes instead of the traditional binary phase shift keying (BPSK). One such scheme is pre-coded Gaussian minimum shift keying (GMSK). GMSK is an excellent candidate for deep space missions. GMSK is a constant envelope, bandwidth efficien modulation whose frame error rate (FER) performance with perfect carrier tracking and proper receiver structure is nearly identical to that of BPSK. There are several issues that need to be addressed with GMSK however. Specificall, we are interested in the combined effects of spectrum limitations and receiver structure on the coded performance of the X-band link using GMSK. The receivers that are typically used for GMSK demodulations are variations on offset quadrature phase shift keying (OQPSK) receivers. In this paper we consider three receivers: the standard DSN OQPSK receiver, DSN OQPSK receiver with filte ed input, and an optimum OQPSK receiver with filte ed input. For the DSN OQPSK receiver we show experimental results with (8920, 1/2), (8920, 1/3) and (8920, 1/6) turbo codes in terms of their error rate performance. We also consider the tracking performance of this receiver as a function of data rate, channel code and the carrier loop signal-to-noise ratio (SNR). For the other two receivers we derive theoretical results that will show that for a given loop bandwidth, a receiver structure, and a channel code, there is a lower data rate limit on the GMSK below which a higher SNR than what is required to achieve the required FER on the link is needed. These limits stem from the minimum loop signal-to-noise ratio requirements on the receivers for achieving lock. As a result of this, for a given channel code and a given FER, there could be a gap between the maximum data rate that BPSK can support without violating the spectrum limits and the minimum data rate that GMSK can support

  16. T-type Ca(2+) channels and Autoregulation of Local Blood Flow

    DEFF Research Database (Denmark)

    Jensen, Lars Jørn; Nielsen, Morten Schak; Salomonsson, Max

    2017-01-01

    L-type voltage gated Ca(2+) channels are considered to be the primary source of calcium influx during the myogenic response. However, many vascular beds also express T-type voltage gated Ca(2+) channels. Recent studies suggest that these channels may also play a role in autoregulation. At low pre...

  17. The Sodium-Activated Potassium Channel Slack Is Required for Optimal Cognitive Flexibility in Mice

    Science.gov (United States)

    Bausch, Anne E.; Dieter, Rebekka; Nann, Yvette; Hausmann, Mario; Meyerdierks, Nora; Kaczmarek, Leonard K.; Ruth, Peter; Lukowski, Robert

    2015-01-01

    "Kcnt1" encoded sodium-activated potassium channels (Slack channels) are highly expressed throughout the brain where they modulate the firing patterns and general excitability of many types of neurons. Increasing evidence suggests that Slack channels may be important for higher brain functions such as cognition and normal intellectual…

  18. Charged and Neutral Particles Channeling Phenomena Channeling 2008

    Science.gov (United States)

    Dabagov, Sultan B.; Palumbo, Luigi

    2010-04-01

    -- Probing channeling radiation influenced by ultrasound / W. Wagner ... [et al.] -- Radiation characteristics under electrons planar channeling and quasichanneling in complex crystals / L. Gevorgian -- Formation of relativistic positron atoms by axially channeled positrons and their decay on [symbol]-rays / A. Gevorkyan, A. R. Mkrtchyan and K. Oganesyan -- New features of diffracted channeling radiation from electrons in Si and LiF Crystals / K. B. Korotchenko, Yu. L. Pivovarov and T. A. Tukhfatullin -- Modulated particle beam in a crystal channel / A. Kostyuk ... [et al.] -- Computer simulations of resonant coherent excitation of heavy hydrogenlike ions under planar channeling / A. A. Babaev and Yu. L. Pivovarov -- Parametric x-ray and diffracted transition radiation of 4.5 GeV electrons in diamond / R. O. Avakian ... [et al.] -- Possible use of small accelerators in student laboratory for engineering education / I. Endo, M. Tanaka and T. Yoshimura.The Status of the SPARC Project / A. Cianchi -- Laser-plasma acceleration: first experimental results from the Plasmon-X Project / L. A. Gizzi ... [et al.] -- The powerful nanosecond duration electron beam effect on the crystalline tungsten target / Y. N. Adischev ... [et al.] -- "Shadowing" of the electromagnetic field of a relativistic electron / G. Naumenko ... [et al.] -- The acceleration of the charged particles in a low temperature acoustoplasma / A. S. Abrahamyan, A. R. Mkrtchyan and R. B. Kostanyan -- The experimental study of the surface current excitation by a relativistic electron electromagnetic field / G. A. Naumenko ... [et al.] -- Synchrotron radiation from a charge moving along helical orbit around a dielectric cylinder / A. A. Saharian and A. S. Kotanjyan -- Particle acceleration in a helical wave guide / X. Artru and C. Ray -- Effect of heavy ion charge fluctuations on Cherenkov radiation / V. S. Malyshevsky -- Hard photons powerful radiation of electron bunch interacting with plasma beat waves / A. Shamamian

  19. Fine Channel Networks

    Science.gov (United States)

    1997-01-01

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

  20. MODULACIÓN DE LA SINTESIS DE METALOTIONINAS EN Perna viridis PREEXPUESTOS A COBRE Y EXPUESTOS A CADMIO | MODULATION OF METALLOTHIONEIN SYNTHESIS IN Perna viridis PRE EXPOSED TO COPPER AND EXPOSED TO CADMIUM

    Directory of Open Access Journals (Sweden)

    Marín Lemus,

    2014-02-01

    Full Text Available The metallothioneins (Mts have been used as biomarkers because toxic metals such as Hg, Cd, Cu can induce their synthesis; however, environmental factors and the presence of other xenobiotics can determine the magnitude of the response in future exposures to metal ions. Metallothionein concentration was determinate in the soft tissue of Perna viridis juveniles pre-exposed to Cu and exposed to Cd (Cu/Cd for 21 days. For this, three experimental groups were established: exposed to Cd, pre-exposed to Cu and exposed to Cd and the control group (no metal. Cadmium accumulation in tissues of P. viridis was significantly higher in pre-exposed organisms to Cu, with an average value of 6.6 ± 1.9 mg/g, while in those exposed to Cd, was 4.7 ± 2.4 mg/g. Mts concentrations were also higher in the Cu/Cd experimental group, with a value of 1.36 ± 0.52 mg/g in relation to those exposed to Cd which had a value of 0.79 ± 0.47 mg/g. The relationship between Mts and bioaccumulation of Cd was significant in the group exposed to Cd, but not in the exposed Cu/Cd. These results suggest that Cu possibly acted as an inducer of Mts in the body, which led to increased accumulation of Cd in P. viridis and increase in Mts concentration. Tolerance and bioaccumulation of Cd in P. viridis was determined by previous exposure of the organism and hence its response on levels of MTs also depends on it.

  1. Ion channels in plants.

    Science.gov (United States)

    Hedrich, Rainer

    2012-10-01

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

  2. VME Data Acquisition Modules for MINERvA Experiment

    Energy Technology Data Exchange (ETDEWEB)

    Baldin, B.; /fermilab

    2010-01-01

    This document describes two VME modules developed for MINERvA experiment at Fermilab. The Chain ReadOut Controller (CROC) module has four serial data channels and can interface with up to 48 front-ends using standard CAT5e networking cable. The data transmission rate of each channel is 160 Mbit/s. The maximum data transmission rate via VME bus is {approx}18 MB/s. The Chain Readout Interface Module (CRIM) is designed to provide various interface functions for the CROC module. It is compatible with MINOS MTM timing module and can be used to distribute timing signals to four CROC modules. The CRIM module also has a data port compatible with the CROC serial data interface. The data port can be used for diagnostic purpose and can generate triggers from front-end events. The CRIM module is a standard D08(O) interrupter module.

  3. Combined Coding And Modulation Using Runlength Limited Error ...

    African Journals Online (AJOL)

    In this paper we propose a Combined Coding and Modulation (CCM) scheme employing RLL/ECCs and MPSK modulation as well as RLL/ECC codes and BFSK/MPSK modulation with a view to optimise on channel bandwidth. The CCM codes and their trellis are designed and their error performances simulated in AWGN ...

  4. Construction and performance of the ATLAS silicon microstrip barrel modules

    International Nuclear Information System (INIS)

    Kondo, T.; Apsimon, R.; Beck, G.A.; Bell, P.; Brenner, R.; Bruckman de Renstrom, P.; Carter, A.A.; Carter, J.R.; Charlton, D.; Dabrowski, W.; Dorholt, O.; Ekelof, T.; Eklund, L.; Gibson, M.; Gadomski, S.; Grillo, A.; Grosse-Knetter, J.; Haber, C.; Hara, K.; Hill, J.C.; Ikegami, Y.; Iwata, Y.; Johansen, L.G.; Kohriki, T.; Macpherson, A.; McMahon, S.; Moorhead, G.; Morin, J.; Morris, J.; Morrissey, M.; Nagai, K.; Nakano, I.; Pater, J.; Pernegger, H.; Perrin, E.; Phillips, P.; Robinson, D.; Skubic, B.; Spencer, N.; Stapnes, S.; Stugu, B.; Takashima, R.; Terada, S.; Tyndel, M.; Ujiie, N.; Unno, Y.; Vos, M.

    2002-01-01

    The ATLAS Semiconductor Tracker (SCT) consists of four barrel cylinders and 18 end-cap disks. This paper describes the SCT modules of the barrel region, of which more than 2000 are about to be constructed. The module design is fixed. Its design concept is given together with the electrical, thermal and mechanical specifications. The pre-series production of the barrel modules is underway using mass-production procedures and jigs. The pre-series modules have given satisfactory performances on noise, noise occupancy, electrical as well as mechanical and thermal properties. In addition, irradiated modules were demonstrated to work successfully. Also first results from a 10-module system test are given

  5. In vitro progesterone modulation on bacterial endotoxin-induced production of IL-1β, TNFα, IL-6, IL-8, IL-10, MIP-1α, and MMP-9 in pre-labor human term placenta.

    Science.gov (United States)

    Garcia-Ruíz, G; Flores-Espinosa, P; Preciado-Martínez, E; Bermejo-Martínez, L; Espejel-Nuñez, A; Estrada-Gutierrez, G; Maida-Claros, R; Flores-Pliego, A; Zaga-Clavellina, Veronica

    2015-10-07

    During human pregnancy, infection/inflammation represents an important factor that increases the risk of developing preterm labor. The purpose of this study was to determine if pre-treatment with progesterone has an immunomodulatory effect on human placenta production of endotoxin-induced inflammation and degradation of extracellular matrix markers. Placentas were obtained under sterile conditions from pregnancies delivered at term before the onset of labor by cesarean section. Explants from central cotyledons of 10 human placentas were pre-treated with different concentrations of progesterone (0.01, 01, 1.0 μM) and then stimulated with 1000 ng/mL of LPS of Escherichia coli. Cytokines TNFα, IL-1β, IL-6, IL-8, MIP-1α, IL-10 concentrations in the culture medium were then measured by specific ELISA. Secretion profile of MMP-9 was evaluated by ELISA and zymogram. Statistical differences were determined by one-way ANOVA followed by the appropriate ad hoc test; P progesterone significantly blunted (73, 56, 56, 75, 25, 48 %) the secretion of TNF-α, IL-1β, IL-6, IL-8, MIP-1α, IL-10, respectively. The MMP-9 induced by LPS treatment was inhibited only with the highest concentration of progesterone. Mifepristone (RU486) blocked the immunosuppressive effect of progesterone. The present results support the concept that progesterone could be part of the compensatory mechanism that limits the inflammation-induced cytotoxic effects associated with an infection process during gestation.

  6. Multiuser Diversity with Adaptive Modulation in Non-Identically Distributed Nakagami Fading Environments

    KAUST Repository

    Rao, Anlei; Alouini, Mohamed-Slim

    2012-01-01

    In this paper, we analyze the performance of adaptive modulation with single-cell multiuser scheduling over independent but not identical distributed (i.n.i.d.) Nakagami fading channels. Closed-form expressions are derived for the average channel

  7. Compound Wiretap Channels

    Directory of Open Access Journals (Sweden)

    Shlomo Shamai (Shitz

    2009-01-01

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

  8. 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.

  9. A Mathematical Model of Membrane Gas Separation with Energy Transfer by Molecules of Gas Flowing in a Channel to Molecules Penetrating this Channel from the Adjacent Channel

    Directory of Open Access Journals (Sweden)

    Szwast Maciej

    2015-06-01

    Full Text Available The paper presents the mathematical modelling of selected isothermal separation processes of gaseous mixtures, taking place in plants using membranes, in particular nonporous polymer membranes. The modelling concerns membrane modules consisting of two channels - the feeding and the permeate channels. Different shapes of the channels cross-section were taken into account. Consideration was given to co-current and counter-current flows, for feeding and permeate streams, respectively, flowing together with the inert gas receiving permeate. In the proposed mathematical model it was considered that pressure of gas changes along the length of flow channels was the result of both - the drop of pressure connected with flow resistance, and energy transfer by molecules of gas flowing in a given channel to molecules which penetrate this channel from the adjacent channel. The literature on membrane technology takes into account only the drop of pressure connected with flow resistance. Consideration given to energy transfer by molecules of gas flowing in a given channel to molecules which penetrate this channel from the adjacent channel constitute the essential novelty in the current study. The paper also presents results of calculations obtained by means of a computer program which used equations of the derived model. Physicochemical data concerning separation of the CO2/CH4 mixture with He as the sweep gas and data concerning properties of the membrane made of PDMS were assumed for calculations.

  10. A Simulator of Periodically Switching Channels for Power Line Communications

    Science.gov (United States)

    Hayasaki, Taro; Umehara, Daisuke; Denno, Satoshi; Morikura, Masahiro

    An indoor power line is one of the most attractive media for in-home networks. However, there are many technical problems for achieving in-home power line communication (PLC) with high rate and high reliability. One of such problem is the degradation in the performance of the in-home PLC caused by periodically time-varying channel responses, particularly when connecting the switching power supply equipment. We present a measurement method for power line channel responses and reveal the switching of the channel responses synchronized with power-frequency voltage when connecting switching power supply equipment in sending or receiving outlets. In this paper, we term them periodically switching channel responses. The performance of PLC adapters is seriously affected by the periodically switching channel responses. Therefore, we provide a modeling of the periodically switching channel responses by using finite impulse response (FIR) filters with a shared channel memory and construct a simulator for in-home power line channels including the periodically switching channel responses in order to evaluate the various communication systems through the power line. We present the validity of the proposed simulator through the performance evaluation of OFDM/64QAM over periodically switching channels with additive white Gaussian noise. Furthermore, we evaluate the influence of the periodically switching channel responses on the communication quality of a time-invariant modulation scheme by using the proposed simulator.

  11. Volume Regulated Channels

    DEFF Research Database (Denmark)

    Klausen, Thomas Kjær

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

  12. Mechanosensitive gating of Kv channels.

    Directory of Open Access Journals (Sweden)

    Catherine E Morris

    Full Text Available K-selective voltage-gated channels (Kv are multi-conformation bilayer-embedded proteins whose mechanosensitive (MS Popen(V implies that at least one conformational transition requires the restructuring of the channel-bilayer interface. Unlike Morris and colleagues, who attributed MS-Kv responses to a cooperative V-dependent closed-closed expansion↔compaction transition near the open state, Mackinnon and colleagues invoke expansion during a V-independent closed↔open transition. With increasing membrane tension, they suggest, the closed↔open equilibrium constant, L, can increase >100-fold, thereby taking steady-state Popen from 0→1; "exquisite sensitivity to small…mechanical perturbations", they state, makes a Kv "as much a mechanosensitive…as…a voltage-dependent channel". Devised to explain successive gK(V curves in excised patches where tension spontaneously increased until lysis, their L-based model falters in part because of an overlooked IK feature; with recovery from slow inactivation factored in, their g(V datasets are fully explained by the earlier model (a MS V-dependent closed-closed transition, invariant L≥4. An L-based MS-Kv predicts neither known Kv time courses nor the distinctive MS responses of Kv-ILT. It predicts Kv densities (hence gating charge per V-sensor several-fold different from established values. If opening depended on elevated tension (L-based model, standard gK(V operation would be compromised by animal cells' membrane flaccidity. A MS V-dependent transition is, by contrast, unproblematic on all counts. Since these issues bear directly on recent findings that mechanically-modulated Kv channels subtly tune pain-related excitability in peripheral mechanoreceptor neurons we undertook excitability modeling (evoked action potentials. Kvs with MS V-dependent closed-closed transitions produce nuanced mechanically-modulated excitability whereas an L-based MS-Kv yields extreme, possibly excessive

  13. HIPPI and Fibre Channel

    International Nuclear Information System (INIS)

    Tolmie, D.E.

    1992-01-01

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

  14. Nuclear reactor coolant channels

    International Nuclear Information System (INIS)

    Macbeth, R.V.

    1978-01-01

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

  15. Ion Permeation and Mechanotransduction Mechanisms of Mechanosensitive Piezo Channels.

    Science.gov (United States)

    Zhao, Qiancheng; Wu, Kun; Geng, Jie; Chi, Shaopeng; Wang, Yanfeng; Zhi, Peng; Zhang, Mingmin; Xiao, Bailong

    2016-03-16

    Piezo proteins have been proposed as the long-sought-after mechanosensitive cation channels in mammals that play critical roles in various mechanotransduction processes. However, the molecular bases that underlie their ion permeation and mechanotransduction have remained functionally undefined. Here we report our finding of the miniature pore-forming module of Piezo1 that resembles the pore architecture of other trimeric channels and encodes the essential pore properties. We further identified specific residues within the pore module that determine unitary conductance, pore blockage and ion selectivity for divalent and monovalent cations and anions. The non-pore-containing region of Piezo1 confers mechanosensitivity to mechano-insensitive trimeric acid-sensing ion channels, demonstrating that Piezo1 channels possess intrinsic mechanotransduction modules separate from their pore modules. In conclusion, this is the first report on the bona fide pore module and mechanotransduction components of Piezo channels, which define their ion-conducting properties and gating by mechanical stimuli, respectively. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. New Channels, New Possibilities

    DEFF Research Database (Denmark)

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

    2017-01-01

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

  17. Calcium Channel Blockers

    Science.gov (United States)

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

  18. A channel profile analyser

    International Nuclear Information System (INIS)

    Gobbur, S.G.

    1983-01-01

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

  19. Ligand Access Channels in Cytochrome P450 Enzymes: A Review

    Directory of Open Access Journals (Sweden)

    Philippe Urban

    2018-05-01

    Full Text Available Quantitative structure-activity relationships may bring invaluable information on structural elements of both enzymes and substrates that, together, govern substrate specificity. Buried active sites in cytochrome P450 enzymes are connected to the solvent by a network of channels exiting at the distal surface of the protein. This review presents different in silico tools that were developed to uncover such channels in P450 crystal structures. It also lists some of the experimental evidence that actually suggest that these predicted channels might indeed play a critical role in modulating P450 functions. Amino acid residues at the entrance of the channels may participate to a first global ligand recognition of ligands by P450 enzymes before they reach the buried active site. Moreover, different P450 enzymes show different networks of predicted channels. The plasticity of P450 structures is also important to take into account when looking at how channels might play their role.

  20. Command and Service Module Communications

    Science.gov (United States)

    Interbartolo, Michael

    2009-01-01

    This viewgraph presentation examines Command and Service Module (CSM) Communications. The communication system's capabilities are defined, including CSM-Earth, CSM-Lunar Module and CSM-Extravehicular crewman communications. An overview is provided for S-band communications, including data transmission and receiving rates, operating frequencies and major system components (pre-modulation processors, unified S-band electronics, S-band power amplifier and S-band antennas). Additionally, data transmission rates, operating frequencies and the capabilities of VHF communications are described. Major VHF components, including transmitters and receivers, and the VHF multiplexer and antennas are also highlighted. Finally, communications during pre-launch, ascent, in-flight and entry are discussed. Overall, the CSM communication system was rated highly by flight controllers and crew. The system was mostly autonomous for both crew and flight controllers and no major issues were encountered during flight.