Sample records for s channel

  1. Dark matter annihilation with s-channel internal Higgsstrahlung

    DOE PAGES

    Kumar, Jason; Liao, Jiajun; Marfatia, Danny

    2016-05-31

    We study the scenario of fermionic dark matter that annihilates to standard model fermions through an s-channel axial vector mediator. We point out that the well-known chirality suppression of the annihilation cross section can be alleviated by s-channel internal Higgsstrahlung. The shapes of the cosmic ray spectra are identical to that of t-channel internal Higgsstrahlung in the limit of a heavy mediating particle. Unlike the general case of t-channel bremsstrahlung, s-channel Higgsstrahlung can be the dominant annihilation process even for Dirac dark matter. Finally, since the s-channel mediator can be a standard model singlet, collider searches for the mediator aremore » easily circumvented.« less

  2. Dark matter annihilation with s-channel internal Higgsstrahlung

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kumar, Jason; Liao, Jiajun; Marfatia, Danny

    We study the scenario of fermionic dark matter that annihilates to standard model fermions through an s-channel axial vector mediator. We point out that the well-known chirality suppression of the annihilation cross section can be alleviated by s-channel internal Higgsstrahlung. The shapes of the cosmic ray spectra are identical to that of t-channel internal Higgsstrahlung in the limit of a heavy mediating particle. Unlike the general case of t-channel bremsstrahlung, s-channel Higgsstrahlung can be the dominant annihilation process even for Dirac dark matter. Finally, since the s-channel mediator can be a standard model singlet, collider searches for the mediator aremore » easily circumvented.« less

  3. On S-mixing entropy of quantum channels

    NASA Astrophysics Data System (ADS)

    Mukhamedov, Farrukh; Watanabe, Noboru

    2018-06-01

    In this paper, an S-mixing entropy of quantum channels is introduced as a generalization of Ohya's S-mixing entropy. We investigate several properties of the introduced entropy. Moreover, certain relations between the S-mixing entropy and the existing map and output entropies of quantum channels are investigated as well. These relations allowed us to find certain connections between separable states and the introduced entropy. Hence, there is a sufficient condition to detect entangled states. Moreover, several properties of the introduced entropy are investigated. Besides, entropies of qubit and phase-damping channels are calculated.

  4. Role of the S4-S5 linker in CNG channel activation.

    PubMed

    Kusch, Jana; Zimmer, Thomas; Holschuh, Jascha; Biskup, Christoph; Schulz, Eckhard; Nache, Vasilica; Benndorf, Klaus

    2010-10-20

    Cyclic nucleotide-gated (CNG) channels mediate sensory signal transduction in retinal and olfactory cells. The channels are activated by the binding of cyclic nucleotides to a cyclic nucleotide-binding domain (CNBD) in the C-terminus that is located at the intracellular side. The molecular events translating the ligand binding to the pore opening are still unknown. We investigated the role of the S4-S5 linker in the activation process by quantifying its interaction with other intracellular regions. To this end, we constructed chimeric channels in which the N-terminus, the S4-S5 linker, the C-linker, and the CNBD of the retinal CNGA1 subunit were systematically replaced by the respective regions of the olfactory CNGA2 subunit. Macroscopic concentration-response relations were analyzed, yielding the apparent affinity to cGMP and the Hill coefficient. The degree of functional coupling of intracellular regions in the activation gating was determined by thermodynamic double-mutant cycle analysis. We observed that all four intracellular regions, including the relatively short S4-S5 linker, are involved in controlling the apparent affinity of the channel to cGMP and, moreover, in determining the degree of cooperativity between the subunits, as derived from the Hill coefficient. The interaction energies reveal an interaction of the S4-S5 linker with both the N-terminus and the C-linker, but no interaction with the CNBD. Copyright © 2010 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  5. MscS-Like Mechanosensitive Channels in Plants and Microbes

    PubMed Central

    Wilson, Margaret E.; Maksaev, Grigory; Haswell, Elizabeth S.

    2013-01-01

    The challenge of osmotic stress is something all living organisms must face as a result of environmental dynamics. Over the past three decades, innovative research and cooperation across disciplines has irrefutably established that cells utilize mechanically gated ion channels to release osmolytes and prevent cell lysis during hypoosmotic stress. Early electrophysiological analysis of the inner membrane of Escherichia coli identified the presence of three distinct mechanosensitive activities. The subsequent discoveries of the genes responsible for two of these activities, the mechanosensitive channels of large (MscL) and small (MscS) conductance, led to the identification of two diverse families of mechanosensitive channels. The latter of these two families, the MscS family, is made up of members from bacteria, archaea, fungi, and plants. Genetic and electrophysiological analysis of these family members has provided insight into how organisms use mechanosensitive channels for osmotic regulation in response to changing environmental and developmental circumstances. Furthermore, solving the crystal structure of E. coli MscS and several homologs in several conformational states has contributed to the understanding of the gating mechanisms of these channels. Here we summarize our current knowledge of MscS homologs from all three domains of life, and address their structure, proposed physiological functions, electrophysiological behaviors, and topological diversity. PMID:23947546

  6. Periodic perturbations in Shaker K+ channel gating kinetics by deletions in the S3–S4 linker

    PubMed Central

    Gonzalez, Carlos; Rosenman, Eduardo; Bezanilla, Francisco; Alvarez, Osvaldo; Latorre, Ramon

    2001-01-01

    Upon depolarization positive charges contained in the transmembrane segment S4 of voltage-dependent channels are displaced from the cytoplasmic to the external milieu. This charge movement leads to channel opening. In Shaker K+ channels four positively charged arginines in the S4 domain are transferred from the internal to the external side of the channel during activation. The distance traveled by the S4 segment during activation is unknown, but large movements should be constrained by the S3–S4 linker. Constructing deletion mutants, we show that the activation time constant and the midpoint of the voltage activation curve of the Shaker K+ channel macroscopic currents becomes a periodic function of the S3–S4 linker length for linkers shorter than 7 aa residues. The periodicity is that typical of α-helices. Moreover, a linker containing only 3 aa is enough to recover the wild-type phenotype. The deletion method revealed the importance of the S3–S4 linker in determining the channel gating kinetics and indicated that the α-helical nature of S4 extends toward its N terminus. These results support the notion that a small displacement of the S4 segment suffices to displace the four gating charges involved in channel opening. PMID:11493701

  7. S1-S3 counter charges in the voltage sensor module of a mammalian sodium channel regulate fast inactivation.

    PubMed

    Groome, James R; Winston, Vern

    2013-05-01

    The movement of positively charged S4 segments through the electric field drives the voltage-dependent gating of ion channels. Studies of prokaryotic sodium channels provide a mechanistic view of activation facilitated by electrostatic interactions of negatively charged residues in S1 and S2 segments, with positive counterparts in the S4 segment. In mammalian sodium channels, S4 segments promote domain-specific functions that include activation and several forms of inactivation. We tested the idea that S1-S3 countercharges regulate eukaryotic sodium channel functions, including fast inactivation. Using structural data provided by bacterial channels, we constructed homology models of the S1-S4 voltage sensor module (VSM) for each domain of the mammalian skeletal muscle sodium channel hNaV1.4. These show that side chains of putative countercharges in hNaV1.4 are oriented toward the positive charge complement of S4. We used mutagenesis to define the roles of conserved residues in the extracellular negative charge cluster (ENC), hydrophobic charge region (HCR), and intracellular negative charge cluster (INC). Activation was inhibited with charge-reversing VSM mutations in domains I-III. Charge reversal of ENC residues in domains III (E1051R, D1069K) and IV (E1373K, N1389K) destabilized fast inactivation by decreasing its probability, slowing entry, and accelerating recovery. Several INC mutations increased inactivation from closed states and slowed recovery. Our results extend the functional characterization of VSM countercharges to fast inactivation, and support the premise that these residues play a critical role in domain-specific gating transitions for a mammalian sodium channel.

  8. Contribution of S4 segments and S4-S5 linkers to the low-voltage activation properties of T-type CaV3.3 channels.

    PubMed

    Sanchez-Sandoval, Ana Laura; Herrera Carrillo, Zazil; Díaz Velásquez, Clara Estela; Delgadillo, Dulce María; Rivera, Heriberto Manuel; Gomora, Juan Carlos

    2018-01-01

    Voltage-gated calcium channels contain four highly conserved transmembrane helices known as S4 segments that exhibit a positively charged residue every third position, and play the role of voltage sensing. Nonetheless, the activation range between high-voltage (HVA) and low-voltage (LVA) activated calcium channels is around 30-40 mV apart, despite the high level of amino acid similarity within their S4 segments. To investigate the contribution of S4 voltage sensors for the low-voltage activation characteristics of CaV3.3 channels we constructed chimeras by swapping S4 segments between this LVA channel and the HVA CaV1.2 channel. The substitution of S4 segment of Domain II in CaV3.3 by that of CaV1.2 (chimera IIS4C) induced a ~35 mV shift in the voltage-dependence of activation towards positive potentials, showing an I-V curve that almost overlaps with that of CaV1.2 channel. This HVA behavior induced by IIS4C chimera was accompanied by a 2-fold decrease in the voltage-dependence of channel gating. The IVS4 segment had also a strong effect in the voltage sensing of activation, while substitution of segments IS4 and IIIS4 moved the activation curve of CaV3.3 to more negative potentials. Swapping of IIS4 voltage sensor influenced additional properties of this channel such as steady-state inactivation, current decay, and deactivation. Notably, Domain I voltage sensor played a major role in preventing CaV3.3 channels to inactivate from closed states at extreme hyperpolarized potentials. Finally, site-directed mutagenesis in the CaV3.3 channel revealed a partial contribution of the S4-S5 linker of Domain II to LVA behavior, with synergic effects observed in double and triple mutations. These findings indicate that IIS4 and, to a lesser degree IVS4, voltage sensors are crucial in determining the LVA properties of CaV3.3 channels, although the accomplishment of this function involves the participation of other structural elements like S4-S5 linkers.

  9. Contribution of S4 segments and S4-S5 linkers to the low-voltage activation properties of T-type CaV3.3 channels

    PubMed Central

    Sanchez-Sandoval, Ana Laura; Herrera Carrillo, Zazil; Díaz Velásquez, Clara Estela; Delgadillo, Dulce María; Rivera, Heriberto Manuel

    2018-01-01

    Voltage-gated calcium channels contain four highly conserved transmembrane helices known as S4 segments that exhibit a positively charged residue every third position, and play the role of voltage sensing. Nonetheless, the activation range between high-voltage (HVA) and low-voltage (LVA) activated calcium channels is around 30–40 mV apart, despite the high level of amino acid similarity within their S4 segments. To investigate the contribution of S4 voltage sensors for the low-voltage activation characteristics of CaV3.3 channels we constructed chimeras by swapping S4 segments between this LVA channel and the HVA CaV1.2 channel. The substitution of S4 segment of Domain II in CaV3.3 by that of CaV1.2 (chimera IIS4C) induced a ~35 mV shift in the voltage-dependence of activation towards positive potentials, showing an I-V curve that almost overlaps with that of CaV1.2 channel. This HVA behavior induced by IIS4C chimera was accompanied by a 2-fold decrease in the voltage-dependence of channel gating. The IVS4 segment had also a strong effect in the voltage sensing of activation, while substitution of segments IS4 and IIIS4 moved the activation curve of CaV3.3 to more negative potentials. Swapping of IIS4 voltage sensor influenced additional properties of this channel such as steady-state inactivation, current decay, and deactivation. Notably, Domain I voltage sensor played a major role in preventing CaV3.3 channels to inactivate from closed states at extreme hyperpolarized potentials. Finally, site-directed mutagenesis in the CaV3.3 channel revealed a partial contribution of the S4-S5 linker of Domain II to LVA behavior, with synergic effects observed in double and triple mutations. These findings indicate that IIS4 and, to a lesser degree IVS4, voltage sensors are crucial in determining the LVA properties of CaV3.3 channels, although the accomplishment of this function involves the participation of other structural elements like S4-S5 linkers. PMID:29474447

  10. H{sub 2}S does not regulate proliferation via T-type Ca{sup 2+} channels

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Elies, Jacobo; Johnson, Emily; Boyle, John P.

    T-type Ca{sup 2+} channels (Cav3.1, 3.2 and 3.3) strongly influence proliferation of various cell types, including vascular smooth muscle cells (VSMCs) and certain cancers. We have recently shown that the gasotransmitter carbon monoxide (CO) inhibits T-type Ca{sup 2+} channels and, in so doing, attenuates proliferation of VSMC. We have also shown that the T-type Ca{sup 2+} channel Cav3.2 is selectively inhibited by hydrogen sulfide (H{sub 2}S) whilst the other channel isoforms (Cav3.1 and Cav3.3) are unaffected. Here, we explored whether inhibition of Cav3.2 by H{sub 2}S could account for the anti-proliferative effects of this gasotransmitter. H{sub 2}S suppressed proliferation inmore » HEK293 cells expressing Cav3.2, as predicted by our previous observations. However, H{sub 2}S was similarly effective in suppressing proliferation in wild type (non-transfected) HEK293 cells and those expressing the H{sub 2}S insensitive channel, Cav3.1. Further studies demonstrated that T-type Ca{sup 2+} channels in the smooth muscle cell line A7r5 and in human coronary VSMCs strongly influenced proliferation. In both cell types, H{sub 2}S caused a concentration-dependent inhibition of proliferation, yet by far the dominant T-type Ca{sup 2+} channel isoform was the H{sub 2}S-insensitive channel, Cav3.1. Our data indicate that inhibition of T-type Ca{sup 2+} channel-mediated proliferation by H{sub 2}S is independent of the channels’ sensitivity to H{sub 2}S. - Highlights: • T-type Ca{sup 2+} channels regulate proliferation and are sensitive to the gasotransmitters CO and H{sub 2}S. • H{sub 2}S reduced proliferation in HEK293 cells expressing the H{sub 2}S sensitive Cav3.2 channel. • H{sub 2}S also inhibited proliferation in non-transfected cells and HEK293 cells expressing Cav3.1. • Native smooth muscle cells primarily express Cav3.1. Their proliferation was also inhibited by H{sub 2}S. • Unlike CO, H{sub 2}S does not regulate smooth muscle proliferation via T-type Ca

  11. Compact Cr:ZnS Channel Waveguide Laser Operating at 2333 nm

    DTIC Science & Technology

    2014-03-24

    B. Mirov and V. V. Federov, “Mid-IR microchip laser : ZnS:Cr2+ laser with saturable absorber material,” (US Patent No 6,960,486., 2009). 23. A...Compact Cr:ZnS channel waveguide laser operating at 2333 nm John R. Macdonald,1* Stephen J. Beecher,2 Adam Lancaster,1 Patrick A. Berry,3 Kenneth...35294, USA *J.R.Macdonald@hw.ac.uk Abstract: A compact mid-infrared channel waveguide laser is demonstrated in Cr:ZnS with a view to power scaling

  12. Two MscS homologs provide mechanosensitive channel activities in the Arabidopsis root.

    PubMed

    Haswell, Elizabeth S; Peyronnet, Rémi; Barbier-Brygoo, Hélène; Meyerowitz, Elliot M; Frachisse, Jean-Marie

    2008-05-20

    In bacterial and animal systems, mechanosensitive (MS) ion channels are thought to mediate the perception of pressure, touch, and sound [1-3]. Although plants respond to a wide variety of mechanical stimuli, and although many mechanosensitive channel activities have been characterized in plant membranes by the patch-clamp method, the molecular nature of mechanoperception in plant systems has remained elusive [4]. Likely candidates are relatives of MscS (Mechanosensitive channel of small conductance), a well-characterized MS channel that serves to protect E. coli from osmotic shock [5]. Ten MscS-Like (MSL) proteins are found in the genome of the model flowering plant Arabidopsis thaliana[4, 6, 7]. MSL2 and MSL3, along with MSC1, a MscS family member from green algae, are implicated in the control of organelle morphology [8, 9]. Here, we characterize MSL9 and MSL10, two MSL proteins found in the plasma membrane of root cells. We use a combined genetic and electrophysiological approach to show that MSL9 and MSL10, along with three other members of the MSL family, are required for MS channel activities detected in protoplasts derived from root cells. This is the first molecular identification and characterization of MS channels in plant membranes.

  13. S-acylation dependent post-translational cross-talk regulates large conductance calcium- and voltage- activated potassium (BK) channels

    PubMed Central

    Shipston, Michael J.

    2014-01-01

    Mechanisms that control surface expression and/or activity of large conductance calcium-activated potassium (BK) channels are important determinants of their (patho)physiological function. Indeed, BK channel dysfunction is associated with major human disorders ranging from epilepsy to hypertension and obesity. S-acylation (S-palmitoylation) represents a major reversible, post-translational modification controlling the properties and function of many proteins including ion channels. Recent evidence reveals that both pore-forming and regulatory subunits of BK channels are S-acylated and control channel trafficking and regulation by AGC-family protein kinases. The pore-forming α-subunit is S-acylated at two distinct sites within the N- and C-terminus, each site being regulated by different palmitoyl acyl transferases (zDHHCs) and acyl thioesterases (APTs). S-acylation of the N-terminus controls channel trafficking and surface expression whereas S-acylation of the C-terminal domain determines regulation of channel activity by AGC-family protein kinases. S-acylation of the regulatory β4-subunit controls ER exit and surface expression of BK channels but does not affect ion channel kinetics at the plasma membrane. Furthermore, a significant number of previously identified BK-channel interacting proteins have been shown, or are predicted to be, S-acylated. Thus, the BK channel multi-molecular signaling complex may be dynamically regulated by this fundamental post-translational modification and thus S-acylation likely represents an important determinant of BK channel physiology in health and disease. PMID:25140154

  14. Quantum and quasiclassical dynamics of the multi-channel H + H2S reaction.

    PubMed

    Qi, Ji; Lu, Dandan; Song, Hongwei; Li, Jun; Yang, Minghui

    2017-03-28

    The prototypical multi-channel reaction H + H 2 S → H 2 + SH/H + H 2 S has been investigated using the full-dimensional quantum scattering and quasi-classical trajectory methods to unveil the underlying competition mechanism between different product channels and the mode specificity. This reaction favors the abstraction channel over the exchange channel. For both channels, excitations in the two stretching modes promote the reaction with nearly equal efficiency and are more efficient than the bending mode excitation. However, they are all less efficient than the translational energy. In addition, the experimentally observed non-Arrhenius temperature dependence of the thermal rate constants is reasonably reproduced by the quantum dynamics calculations, confirming that the non-Arrhenius behavior is caused by the pronounced quantum tunneling.

  15. Tyrosine Residues from the S4-S5 Linker of Kv11.1 Channels Are Critical for Slow Deactivation.

    PubMed

    Ng, Chai-Ann; Gravel, Andrée E; Perry, Matthew D; Arnold, Alexandre A; Marcotte, Isabelle; Vandenberg, Jamie I

    2016-08-12

    Slow deactivation of Kv11.1 channels is critical for its function in the heart. The S4-S5 linker, which joins the voltage sensor and pore domains, plays a critical role in this slow deactivation gating. Here, we use NMR spectroscopy to identify the membrane-bound surface of the S4S5 linker, and we show that two highly conserved tyrosine residues within the KCNH subfamily of channels are membrane-associated. Site-directed mutagenesis and electrophysiological analysis indicates that Tyr-542 interacts with both the pore domain and voltage sensor residues to stabilize activated conformations of the channel, whereas Tyr-545 contributes to the slow kinetics of deactivation by primarily stabilizing the transition state between the activated and closed states. Thus, the two tyrosine residues in the Kv11.1 S4S5 linker play critical but distinct roles in the slow deactivation phenotype, which is a hallmark of Kv11.1 channels. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  16. Charge-Transfer-Induced p-Type Channel in MoS2 Flake Field Effect Transistors.

    PubMed

    Min, Sung-Wook; Yoon, Minho; Yang, Sung Jin; Ko, Kyeong Rok; Im, Seongil

    2018-01-31

    The two-dimensional transition-metal dichalcogenide semiconductor MoS 2 has received extensive attention for decades because of its outstanding electrical and mechanical properties for next-generation devices. One weakness of MoS 2 , however, is that it shows only n-type conduction, revealing its limitations for homogeneous PN diodes and complementary inverters. Here, we introduce a charge-transfer method to modify the conduction property of MoS 2 from n- to p-type. We initially deposited an n-type InGaZnO (IGZO) film on top of the MoS 2 flake so that electron charges might be transferred from MoS 2 to IGZO during air ambient annealing. As a result, electron charges were depleted in MoS 2 . Such charge depletion lowered the MoS 2 Fermi level, which makes hole conduction favorable in MoS 2 when optimum source/drain electrodes with a high work function are selected. Our IGZO-supported MoS 2 flake field effect transistors (FETs) clearly display channel-type conversion from n- to p-channel in this way. Under short- and long-annealing conditions, n- and p-channel MoS 2 FETs are achieved, respectively, and a low-voltage complementary inverter is demonstrated using both channels in a single MoS 2 flake.

  17. A Cyclic Nucleotide-Gated Channel Mutation Associated with Canine Daylight Blindness Provides Insight into a Role for the S2 Segment Tri-Asp motif in Channel Biogenesis

    PubMed Central

    Tanaka, Naoto; Delemotte, Lucie; Klein, Michael L.; Komáromy, András M.; Tanaka, Jacqueline C.

    2014-01-01

    Cone cyclic nucleotide-gated channels are tetramers formed by CNGA3 and CNGB3 subunits; CNGA3 subunits function as homotetrameric channels but CNGB3 exhibits channel function only when co-expressed with CNGA3. An aspartatic acid (Asp) to asparagine (Asn) missense mutation at position 262 in the canine CNGB3 (D262N) subunit results in loss of cone function (daylight blindness), suggesting an important role for this aspartic acid residue in channel biogenesis and/or function. Asp 262 is located in a conserved region of the second transmembrane segment containing three Asp residues designated the Tri-Asp motif. This motif is conserved in all CNG channels. Here we examine mutations in canine CNGA3 homomeric channels using a combination of experimental and computational approaches. Mutations of these conserved Asp residues result in the absence of nucleotide-activated currents in heterologous expression. A fluorescent tag on CNGA3 shows mislocalization of mutant channels. Co-expressing CNGB3 Tri-Asp mutants with wild type CNGA3 results in some functional channels, however, their electrophysiological characterization matches the properties of homomeric CNGA3 channels. This failure to record heteromeric currents suggests that Asp/Asn mutations affect heteromeric subunit assembly. A homology model of S1–S6 of the CNGA3 channel was generated and relaxed in a membrane using molecular dynamics simulations. The model predicts that the Tri-Asp motif is involved in non-specific salt bridge pairings with positive residues of S3/S4. We propose that the D262N mutation in dogs with CNGB3-day blindness results in the loss of these inter-helical interactions altering the electrostatic equilibrium within in the S1–S4 bundle. Because residues analogous to Tri-Asp in the voltage-gated Shaker potassium channel family were implicated in monomer folding, we hypothesize that destabilizing these electrostatic interactions impairs the monomer folding state in D262N mutant CNG channels

  18. Angiotensin II stimulates basolateral 50-pS K channels in the thick ascending limb.

    PubMed

    Wang, Mingxiao; Luan, Haiyan; Wu, Peng; Fan, Lili; Wang, Lijun; Duan, Xinpeng; Zhang, Dandan; Wang, Wen-Hui; Gu, Ruimin

    2014-03-01

    We used the patch-clamp technique to examine the effect of angiotensin II (ANG II) on the basolateral K channels in the thick ascending limb (TAL) of the rat kidney. Application of ANG II increased the channel activity and the current amplitude of the basolateral 50-pS K channel. The stimulatory effect of ANG II on the K channels was completely abolished by losartan, an inhibitor of type 1 angiotensin receptor (AT1R), but not by PD123319, an AT2R antagonist. Moreover, inhibition of phospholipase C (PLC) and protein kinase C (PKC) also abrogated the stimulatory effect of ANG II on the basolateral K channels in the TAL. This suggests that the stimulatory effect of ANG II on the K channels was induced by activating PLC and PKC pathways. Western blotting demonstrated that ANG II increased the phosphorylation of c-Src at tyrosine residue 416, an indication of c-Src activation. This effect was mimicked by PKC stimulator but abolished by calphostin C. Moreover, inhibition of NADPH oxidase (NOX) also blocked the effect of ANG II on c-Src tyrosine phosphorylation. The role of Src-family protein tyrosine kinase (SFK) in mediating the effect of ANG II on the basolateral K channel was further suggested by the experiments in which inhibition of SFK abrogated the stimulatory effect of ANG II on the basolateral 50-pS K channel. We conclude that ANG II increases basolateral 50-pS K channel activity via AT1R and that activation of AT1R stimulates SFK by a PLC-PKC-NOX-dependent mechanism.

  19. S3b amino acid residues do not shuttle across the bilayer in voltage-dependent Shaker K+ channels

    PubMed Central

    Gonzalez, Carlos; Morera, Francisco J.; Rosenmann, Eduardo; Alvarez, Osvaldo; Latorre, Ramon

    2005-01-01

    In voltage-dependent channels, positive charges contained within the S4 domain are the voltage-sensing elements. The “voltage-sensor paddle” gating mechanism proposed for the KvAP K+ channel has been the subject of intense discussion regarding its general applicability to the family of voltage-gated channels. In this model, the voltage sensor composed of the S3b and the S4 segment shuttles across the lipid bilayer during channel activation. Guided by this mechanism, we assessed here the accessibility of residues in the S3 segment of the Shaker K+ channel by using cysteine-scanning mutagenesis. Mutants expressed robust K+ currents in Xenopus oocytes and reacted with methanethiosulfonate ethyltrimethylammonium in both closed and open conformations of the channel. Because Shaker has a long S3–S4 linker segment, we generated a deletion mutant with only three residues to emulate the KvAP structure. In this short linker mutant, all of the tested residues in the S3b were accessible to methanethiosulfonate ethyltrimethylammonium in both closed and open conformations. Because the S3b moves together with the S4 domain in the paddle model, we tested the effects of deleting two negative charges or adding a positive charge to this region of the channel. We found that altering the S3b net charge does not modify the total gating charge involved in channel activation. We conclude that the S3b segment is always exposed to the external milieu of the Shaker K+ channel. Our results are incompatible with any model involving a large membrane displacement of segment S3b. PMID:15774578

  20. Cytoplasmic Domain of MscS Interacts with Cell Division Protein FtsZ: A Possible Non-Channel Function of the Mechanosensitive Channel in Escherichia Coli.

    PubMed

    Koprowski, Piotr; Grajkowski, Wojciech; Balcerzak, Marcin; Filipiuk, Iwona; Fabczak, Hanna; Kubalski, Andrzej

    2015-01-01

    Bacterial mechano-sensitive (MS) channels reside in the inner membrane and are considered to act as emergency valves whose role is to lower cell turgor when bacteria enter hypo-osmotic environments. However, there is emerging evidence that members of the Mechano-sensitive channel Small (MscS) family play additional roles in bacterial and plant cell physiology. MscS has a large cytoplasmic C-terminal region that changes its shape upon activation and inactivation of the channel. Our pull-down and co-sedimentation assays show that this domain interacts with FtsZ, a bacterial tubulin-like protein. We identify point mutations in the MscS C-terminal domain that reduce binding to FtsZ and show that bacteria expressing these mutants are compromised in growth on sublethal concentrations of β-lactam antibiotics. Our results suggest that interaction between MscS and FtsZ could occur upon inactivation and/or opening of the channel and could be important for the bacterial cell response against sustained stress upon stationary phase and in the presence of β-lactam antibiotics.

  1. Cytoplasmic Domain of MscS Interacts with Cell Division Protein FtsZ: A Possible Non-Channel Function of the Mechanosensitive Channel in Escherichia Coli

    PubMed Central

    Koprowski, Piotr; Grajkowski, Wojciech; Balcerzak, Marcin; Filipiuk, Iwona; Fabczak, Hanna; Kubalski, Andrzej

    2015-01-01

    Bacterial mechano-sensitive (MS) channels reside in the inner membrane and are considered to act as emergency valves whose role is to lower cell turgor when bacteria enter hypo-osmotic environments. However, there is emerging evidence that members of the Mechano-sensitive channel Small (MscS) family play additional roles in bacterial and plant cell physiology. MscS has a large cytoplasmic C-terminal region that changes its shape upon activation and inactivation of the channel. Our pull-down and co-sedimentation assays show that this domain interacts with FtsZ, a bacterial tubulin-like protein. We identify point mutations in the MscS C-terminal domain that reduce binding to FtsZ and show that bacteria expressing these mutants are compromised in growth on sublethal concentrations of β-lactam antibiotics. Our results suggest that interaction between MscS and FtsZ could occur upon inactivation and/or opening of the channel and could be important for the bacterial cell response against sustained stress upon stationary phase and in the presence of β-lactam antibiotics. PMID:25996836

  2. A conserved threonine in the S1-S2 loop of KV7.2 and K V7.3 channels regulates voltage-dependent activation.

    PubMed

    Füll, Yvonne; Seebohm, Guiscard; Lerche, Holger; Maljevic, Snezana

    2013-06-01

    The voltage-gated potassium channels KV7.2 and KV7.3 (KCNQ2/3 genes) play an important role in regulating neuronal excitability. More than 50 KCNQ2/3 mutations have been identified to cause an inherited form of epilepsy in newborns. For two of those (E119G and S122L) found in the S1-S2 region of KV7.2, we previously showed a decreased channel availability mainly at action potential subthreshold voltages caused by a slight depolarizing shift of the activation curve. Interestingly, recent studies revealed that a threonine residue within the S1-S2 loop, highly conserved among different classes of KV channels, is crucial for both their function and surface expression. To investigate the functional role of the homologous threonine residues in KV7.2 (T114) and KV7.3 (T144) channels, we replaced them with alanine and examined the electrophysiological properties using heterologous expression in CHO cells and whole cell patch clamping. Channels comprising mutant subunits yielded decreased potassium currents with slowed activation and accelerated deactivation kinetics. However, the most striking effect was a depolarizing shift in the voltage dependence of activation reaching +30 mV upon co-expression of both mutant subunits. Potential interactions of T114 within the channel were analyzed by creating a 3D homology model of KV7.2 in an open state suggesting that this residue plays a central role in the formation of a stable interface between the S1-S2 and the S5 segment helices. This could be the explanation why substitution of the conserved threonine in KV7.2 and KV7.3 channels destabilizes the open and favors the closed state of these channels.

  3. Stabilization of the Activated hERG Channel Voltage Sensor by Depolarization Involves the S4-S5 Linker.

    PubMed

    Thouta, Samrat; Hull, Christina M; Shi, Yu Patrick; Sergeev, Valentine; Young, James; Cheng, Yen M; Claydon, Thomas W

    2017-01-24

    Slow deactivation of hERG channels is critical for preventing cardiac arrhythmia yet the mechanistic basis for the slow gating transition is unclear. Here, we characterized the temporal sequence of events leading to voltage sensor stabilization upon membrane depolarization. Progressive increase in step depolarization duration slowed voltage-sensor return in a biphasic manner (τ fast = 34 ms, τ slow  = 2.5 s). The faster phase of voltage-sensor return slowing correlated with the kinetics of pore opening. The slower component occurred over durations that exceeded channel activation and was consistent with voltage sensor relaxation. The S4-S5 linker mutation, G546L, impeded the faster phase of voltage sensor stabilization without attenuating the slower phase, suggesting that the S4-S5 linker is important for communications between the pore gate and the voltage sensor during deactivation. These data also demonstrate that the mechanisms of pore gate-opening-induced and relaxation-induced voltage-sensor stabilization are separable. Deletion of the distal N-terminus (Δ2-135) accelerated off-gating current, but did not influence the relative contribution of either mechanism of stabilization of the voltage sensor. Lastly, we characterized mode-shift behavior in hERG channels, which results from stabilization of activated channel states. The apparent mode-shift depended greatly on recording conditions. By measuring slow activation and deactivation at steady state we found the "true" mode-shift to be ∼15 mV. Interestingly, the "true" mode-shift of gating currents was ∼40 mV, much greater than that of the pore gate. This demonstrates that voltage sensor return is less energetically favorable upon repolarization than pore gate closure. We interpret this to indicate that stabilization of the activated voltage sensor limits the return of hERG channels to rest. The data suggest that this stabilization occurs as a result of reconfiguration of the pore gate upon opening

  4. CCSDS Advanced Orbiting Systems Virtual Channel Access Service for QoS MACHETE Model

    NASA Technical Reports Server (NTRS)

    Jennings, Esther H.; Segui, John S.

    2011-01-01

    To support various communications requirements imposed by different missions, interplanetary communication protocols need to be designed, validated, and evaluated carefully. Multimission Advanced Communications Hybrid Environment for Test and Evaluation (MACHETE), described in "Simulator of Space Communication Networks" (NPO-41373), NASA Tech Briefs, Vol. 29, No. 8 (August 2005), p. 44, combines various tools for simulation and performance analysis of space networks. The MACHETE environment supports orbital analysis, link budget analysis, communications network simulations, and hardware-in-the-loop testing. By building abstract behavioral models of network protocols, one can validate performance after identifying the appropriate metrics of interest. The innovators have extended the MACHETE model library to include a generic link-layer Virtual Channel (VC) model supporting quality-of-service (QoS) controls based on IP streams. The main purpose of this generic Virtual Channel model addition was to interface fine-grain flow-based QoS (quality of service) between the network and MAC layers of the QualNet simulator, a commercial component of MACHETE. This software model adds the capability of mapping IP streams, based on header fields, to virtual channel numbers, allowing extended QoS handling at link layer. This feature further refines the QoS v existing at the network layer. QoS at the network layer (e.g. diffserv) supports few QoS classes, so data from one class will be aggregated together; differentiating between flows internal to a class/priority is not supported. By adding QoS classification capability between network and MAC layers through VC, one maps multiple VCs onto the same physical link. Users then specify different VC weights, and different queuing and scheduling policies at the link layer. This VC model supports system performance analysis of various virtual channel link-layer QoS queuing schemes independent of the network-layer QoS systems.

  5. Observation of s-channel production of single top quarks at the Tevatron.

    PubMed

    Aaltonen, T; Abazov, V M; Abbott, B; Acharya, B S; Adams, M; Adams, T; Agnew, J P; Alexeev, G D; Alkhazov, G; Alton, A; Amerio, S; Amidei, D; Anastassov, A; Annovi, A; Antos, J; Apollinari, G; Appel, J A; Arisawa, T; Artikov, A; Asaadi, J; Ashmanskas, W; Askew, A; Atkins, S; Auerbach, B; Augsten, K; Aurisano, A; Avila, C; Azfar, F; Badaud, F; Badgett, W; Bae, T; Bagby, L; Baldin, B; Bandurin, D V; Banerjee, S; Barbaro-Galtieri, A; Barberis, E; Baringer, P; Barnes, V E; Barnett, B A; Barria, P; Bartlett, J F; Bartos, P; Bassler, U; Bauce, M; Bazterra, V; Bean, A; Bedeschi, F; Begalli, M; Behari, S; Bellantoni, L; Bellettini, G; Bellinger, J; Benjamin, D; Beretvas, A; Beri, S B; Bernardi, G; Bernhard, R; Bertram, I; Besançon, M; Beuselinck, R; Bhat, P C; Bhatia, S; Bhatnagar, V; Bhatti, A; Bland, K R; Blazey, G; Blessing, S; Bloom, K; Blumenfeld, B; Bocci, A; Bodek, A; Boehnlein, A; Boline, D; Boos, E E; Borissov, G; Bortoletto, D; Borysova, M; Boudreau, J; Boveia, A; Brandt, A; Brandt, O; Brigliadori, L; Brock, R; Bromberg, C; Bross, A; Brown, D; Brucken, E; Bu, X B; Budagov, J; Budd, H S; Buehler, M; Buescher, V; Bunichev, V; Burdin, S; Burkett, K; Busetto, G; Bussey, P; Buszello, C P; Butti, P; Buzatu, A; Calamba, A; Camacho-Pérez, E; Camarda, S; Campanelli, M; Canelli, F; Carls, B; Carlsmith, D; Carosi, R; Carrillo, S; Casal, B; Casarsa, M; Casey, B C K; Castilla-Valdez, H; Castro, A; Catastini, P; Caughron, S; Cauz, D; Cavaliere, V; Cavalli-Sforza, M; Cerri, A; Cerrito, L; Chakrabarti, S; Chan, K M; Chandra, A; Chapon, E; Chen, G; Chen, Y C; Chertok, M; Chiarelli, G; Chlachidze, G; Cho, K; Cho, S W; Choi, S; Chokheli, D; Choudhary, B; Cihangir, S; Claes, D; Clark, A; Clarke, C; Clutter, J; Convery, M E; Conway, J; Cooke, M; Cooper, W E; Corbo, M; Corcoran, M; Cordelli, M; Couderc, F; Cousinou, M-C; Cox, C A; Cox, D J; Cremonesi, M; Cruz, D; Cuevas, J; Culbertson, R; Cutts, D; Das, A; d'Ascenzo, N; Datta, M; Davies, G; de Barbaro, P; de Jong, S J; De La Cruz-Burelo, E; Déliot, F; Demina, R; Demortier, L; Deninno, M; Denisov, D; Denisov, S P; D'Errico, M; Desai, S; Deterre, C; DeVaughan, K; Devoto, F; Di Canto, A; Di Ruzza, B; Diehl, H T; Diesburg, M; Ding, P F; Dittmann, J R; Dominguez, A; Donati, S; D'Onofrio, M; Dorigo, M; Driutti, A; Dubey, A; Dudko, L V; Duperrin, A; Dutt, S; Eads, M; Ebina, K; Edgar, R; Edmunds, D; Elagin, A; Ellison, J; Elvira, V D; Enari, Y; Erbacher, R; Errede, S; Esham, B; Evans, H; Evdokimov, V N; Farrington, S; Feng, L; Ferbel, T; Fernández Ramos, J P; Fiedler, F; Field, R; Filthaut, F; Fisher, W; Fisk, H E; Flanagan, G; Forrest, R; Fortner, M; Fox, H; Franklin, M; Freeman, J C; Frisch, H; Fuess, S; Funakoshi, Y; Galloni, C; Garbincius, P H; Garcia-Bellido, A; García-González, J A; Garfinkel, A F; Garosi, P; Gavrilov, V; Geng, W; Gerber, C E; Gerberich, H; Gerchtein, E; Gershtein, Y; Giagu, S; Giakoumopoulou, V; Gibson, K; Ginsburg, C M; Ginther, G; Giokaris, N; Giromini, P; Giurgiu, G; Glagolev, V; Glenzinski, D; Gold, M; Goldin, D; Golossanov, A; Golovanov, G; Gomez, G; Gomez-Ceballos, G; Goncharov, M; González López, O; Gorelov, I; Goshaw, A T; Goulianos, K; Gramellini, E; Grannis, P D; Greder, S; Greenlee, H; Grenier, G; Grinstein, S; Gris, Ph; Grivaz, J-F; Grohsjean, A; Grosso-Pilcher, C; Group, R C; Grünendahl, S; Grünewald, M W; Guillemin, T; Guimaraes da Costa, J; Gutierrez, G; Gutierrez, P; Hahn, S R; Haley, J; Han, J Y; Han, L; Happacher, F; Hara, K; Harder, K; Hare, M; Harel, A; Harr, R F; Harrington-Taber, T; Hatakeyama, K; Hauptman, J M; Hays, C; Hays, J; Head, T; Hebbeker, T; Hedin, D; Hegab, H; Heinrich, J; Heinson, A P; Heintz, U; Hensel, C; Heredia-De La Cruz, I; Herndon, M; Herner, K; Hesketh, G; Hildreth, M D; Hirosky, R; Hoang, T; Hobbs, J D; Hocker, A; Hoeneisen, B; Hogan, J; Hohlfeld, M; Holzbauer, J L; Hong, Z; Hopkins, W; Hou, S; Howley, I; Hubacek, Z; Hughes, R E; Husemann, U; Hussein, M; Huston, J; Hynek, V; Iashvili, I; Ilchenko, Y; Illingworth, R; Introzzi, G; Iori, M; Ito, A S; Ivanov, A; Jabeen, S; Jaffré, M; James, E; Jang, D; Jayasinghe, A; Jayatilaka, B; Jeon, E J; Jeong, M S; Jesik, R; Jiang, P; Jindariani, S; Johns, K; Johnson, E; Johnson, M; Jonckheere, A; Jones, M; Jonsson, P; Joo, K K; Joshi, J; Jun, S Y; Jung, A W; Junk, T R; Juste, A; Kajfasz, E; Kambeitz, M; Kamon, T; Karchin, P E; Karmanov, D; Kasmi, A; Kato, Y; Katsanos, I; Kehoe, R; Kermiche, S; Ketchum, W; Keung, J; Khalatyan, N; Khanov, A; Kharchilava, A; Kharzheev, Y N; Kilminster, B; Kim, D H; Kim, H S; Kim, J E; Kim, M J; Kim, S H; Kim, S B; Kim, Y J; Kim, Y K; Kimura, N; Kirby, M; Kiselevich, I; Knoepfel, K; Kohli, J M; Kondo, K; Kong, D J; Konigsberg, J; Kotwal, A V; Kozelov, A V; Kraus, J; Kreps, M; Kroll, J; Kruse, M; Kuhr, T; Kumar, A; Kupco, A; Kurata, M; Kurča, T; Kuzmin, V A; Laasanen, A T; Lammel, S; Lammers, S; Lancaster, M; Lannon, K; Latino, G; Lebrun, P; Lee, H S; Lee, H S; Lee, J S; Lee, S W; Lee, W M; Lei, X; Lellouch, J; Leo, S; Leone, S; Lewis, J D; Li, D; Li, H; Li, L; Li, Q Z; Lim, J K; Limosani, A; Lincoln, D; Linnemann, J; Lipaev, V V; Lipeles, E; Lipton, R; Lister, A; Liu, H; Liu, H; Liu, Q; Liu, T; Liu, Y; Lobodenko, A; Lockwitz, S; Loginov, A; Lokajicek, M; Lopes de Sa, R; Lucchesi, D; Lucà, A; Lueck, J; Lujan, P; Lukens, P; Luna-Garcia, R; Lungu, G; Lyon, A L; Lys, J; Lysak, R; Maciel, A K A; Madar, R; Madrak, R; Maestro, P; Magaña-Villalba, R; Malik, S; Malik, S; Malyshev, V L; Manca, G; Manousakis-Katsikakis, A; Mansour, J; Marchese, L; Margaroli, F; Marino, P; Martínez-Ortega, J; Martínez, M; Matera, K; Mattson, M E; Mazzacane, A; Mazzanti, P; McCarthy, R; McGivern, C L; McNulty, R; Mehta, A; Mehtala, P; Meijer, M M; Melnitchouk, A; Menezes, D; Mercadante, P G; Merkin, M; Mesropian, C; Meyer, A; Meyer, J; Miao, T; Miconi, F; Mietlicki, D; Mitra, A; Miyake, H; Moed, S; Moggi, N; Mondal, N K; Moon, C S; Moore, R; Morello, M J; Mukherjee, A; Mulhearn, M; Muller, Th; Murat, P; Mussini, M; Nachtman, J; Nagai, Y; Naganoma, J; Nagy, E; Nakano, I; Napier, A; Narain, M; Nayyar, R; Neal, H A; Negret, J P; Nett, J; Neu, C; Neustroev, P; Nguyen, H T; Nigmanov, T; Nodulman, L; Noh, S Y; Norniella, O; Nunnemann, T; Oakes, L; Oh, S H; Oh, Y D; Oksuzian, I; Okusawa, T; Orava, R; Orduna, J; Ortolan, L; Osman, N; Osta, J; Pagliarone, C; Pal, A; Palencia, E; Palni, P; Papadimitriou, V; Parashar, N; Parihar, V; Park, S K; Parker, W; Partridge, R; Parua, N; Patwa, A; Pauletta, G; Paulini, M; Paus, C; Penning, B; Perfilov, M; Peters, Y; Petridis, K; Petrillo, G; Pétroff, P; Phillips, T J; Piacentino, G; Pianori, E; Pilot, J; Pitts, K; Plager, C; Pleier, M-A; Podstavkov, V M; Pondrom, L; Popov, A V; Poprocki, S; Potamianos, K; Pranko, A; Prewitt, M; Price, D; Prokopenko, N; Prokoshin, F; Ptohos, F; Punzi, G; Qian, J; Quadt, A; Quinn, B; Ranjan, N; Ratoff, P N; Razumov, I; Redondo Fernández, I; Renton, P; Rescigno, M; Rimondi, F; Ripp-Baudot, I; Ristori, L; Rizatdinova, F; Robson, A; Rodriguez, T; Rolli, S; Rominsky, M; Ronzani, M; Roser, R; Rosner, J L; Ross, A; Royon, C; Rubinov, P; Ruchti, R; Ruffini, F; Ruiz, A; Russ, J; Rusu, V; Sajot, G; Sakumoto, W K; Sakurai, Y; Sánchez-Hernández, A; Sanders, M P; Santi, L; Santos, A S; Sato, K; Savage, G; Saveliev, V; Savoy-Navarro, A; Sawyer, L; Scanlon, T; Schamberger, R D; Scheglov, Y; Schellman, H; Schlabach, P; Schmidt, E E; Schwanenberger, C; Schwarz, T; Schwienhorst, R; Scodellaro, L; Scuri, F; Seidel, S; Seiya, Y; Sekaric, J; Semenov, A; Severini, H; Sforza, F; Shabalina, E; Shalhout, S Z; Shary, V; Shaw, S; Shchukin, A A; Shears, T; Shepard, P F; Shimojima, M; Shochet, M; Shreyber-Tecker, I; Simak, V; Simonenko, A; Skubic, P; Slattery, P; Sliwa, K; Smirnov, D; Smith, J R; Snider, F D; Snow, G R; Snow, J; Snyder, S; Söldner-Rembold, S; Song, H; Sonnenschein, L; Sorin, V; Soustruznik, K; St Denis, R; Stancari, M; Stark, J; Stentz, D; Stoyanova, D A; Strauss, M; Strologas, J; Sudo, Y; Sukhanov, A; Suslov, I; Suter, L; Svoisky, P; Takemasa, K; Takeuchi, Y; Tang, J; Tecchio, M; Teng, P K; Thom, J; Thomson, E; Thukral, V; Titov, M; Toback, D; Tokar, S; Tokmenin, V V; Tollefson, K; Tomura, T; Tonelli, D; Torre, S; Torretta, D; Totaro, P; Trovato, M; Tsai, Y-T; Tsybychev, D; Tuchming, B; Tully, C; Ukegawa, F; Uozumi, S; Uvarov, L; Uvarov, S; Uzunyan, S; Van Kooten, R; van Leeuwen, W M; Varelas, N; Varnes, E W; Vasilyev, I A; Vázquez, F; Velev, G; Vellidis, C; Verkheev, A Y; Vernieri, C; Vertogradov, L S; Verzocchi, M; Vesterinen, M; Vidal, M; Vilanova, D; Vilar, R; Vizán, J; Vogel, M; Vokac, P; Volpi, G; Wagner, P; Wahl, H D; Wallny, R; Wang, M H L S; Wang, S M; Warchol, J; Waters, D; Watts, G; Wayne, M; Weichert, J; Welty-Rieger, L; Wester, W C; Whiteson, D; Wicklund, A B; Wilbur, S; Williams, H H; Williams, M R J; Wilson, G W; Wilson, J S; Wilson, P; Winer, B L; Wittich, P; Wobisch, M; Wolbers, S; Wolfe, H; Wood, D R; Wright, T; Wu, X; Wu, Z; Wyatt, T R; Xie, Y; Yamada, R; Yamamoto, K; Yamato, D; Yang, S; Yang, T; Yang, U K; Yang, Y C; Yao, W-M; Yasuda, T; Yatsunenko, Y A; Ye, W; Ye, Z; Yeh, G P; Yi, K; Yin, H; Yip, K; Yoh, J; Yorita, K; Yoshida, T; Youn, S W; Yu, G B; Yu, I; Yu, J M; Zanetti, A M; Zeng, Y; Zennamo, J; Zhao, T G; Zhou, B; Zhou, C; Zhu, J; Zielinski, M; Zieminska, D; Zivkovic, L; Zucchelli, S

    2014-06-13

    We report the first observation of single-top-quark production in the s channel through the combination of the CDF and D0 measurements of the cross section in proton-antiproton collisions at a center-of-mass energy of 1.96 TeV. The data correspond to total integrated luminosities of up to 9.7 fb(-1) per experiment. The measured cross section is σ(s) = 1.29(-0.24)(+0.26) pb. The probability of observing a statistical fluctuation of the background to a cross section of the observed size or larger is 1.8 × 10(-10), corresponding to a significance of 6.3 standard deviations for the presence of an s-channel contribution to the production of single-top quarks.

  6. Observation of s -Channel Production of Single Top Quarks at the Tevatron

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Aaltonen, T.; Abazov, V. M.; Abbott, B.

    2014-06-01

    We report the first observation of single-top-quark production in the s channel through the combination of the CDF and D0 measurements of the cross section in proton-antiproton collisions at a center-of-mass energy of 1.96 TeV. The data correspond to total integrated luminosities of up to 9.7 fb-1 per experiment. The measured cross section ismore » $$\\sigma_s = 1.29^{+0.26}_{-0.24}$$ pb. The probability of observing a statistical fluctuation of the background to a cross section of the observed size or larger is $$1.8 \\times 10^{-10}$$, corresponding to a significance of 6.3 standard deviations for the presence of an s-channel contribution to the production of single-top quarks.« less

  7. Intracellular segment between transmembrane helices S0 and S1 of BK channel α subunit contains two amphipathic helices connected by a flexible loop

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Shi, Pan; High Magnetic Field Laboratory, Chinese Academy of Sciences, Hefei, Anhui, 230031; Li, Dong

    2013-08-02

    Highlights: •The loop between S0 and S1 of BK channel was overexpressed and purified in DPC. •NMR studies indicated BK-IS1 contained two helices connected by a flexible loop. •Mg{sup 2+} titration of BK-IS1 indicated two possible binding sites of divalent ions. -- Abstract: The BK channel, a tetrameric potassium channel with very high conductance, has a central role in numerous physiological functions. The BK channel can be activated by intracellular Ca{sup 2+} and Mg{sup 2+}, as well as by membrane depolarization. Unlike other tetrameric potassium channels, the BK channel has seven transmembrane helices (S0–S6) including an extra helix S0. Themore » intracellular segment between S0 and S1 (BK-IS1) is essential to BK channel functions and Asp99 in BK-IS1 is reported to be responsible for Mg{sup 2+} coordination. In this study, BK-IS1 (44–113) was over-expressed using a bacterial system and purified in the presence of detergent micelles for multidimensional heteronuclear nuclear magnetic resonance (NMR) structural studies. Backbone resonance assignment and secondary structure analysis showed that BK-IS1 contains two amphipathic helices connected by a 36-residue loop. Amide {sup 1}H–{sup 15}N heteronuclear NOE analysis indicated that the loop is very flexible, while the two amphipathic helices are possibly stabilized through interaction with the membrane. A solution NMR-based titration assay of BK-IS1 was performed with various concentrations of Mg{sup 2+}. Two residues (Thr45 and Leu46) with chemical shift changes were observed but no, or very minor, chemical shift difference was observed for Asp99, indicating a possible site for binding divalent ions or other modulation partners.« less

  8. 22. SPILLWAY CHANNEL SLAB REINFORCEMENT DETAILS, NO. 1. Sheet S4, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    22. SPILLWAY CHANNEL SLAB REINFORCEMENT DETAILS, NO. 1. Sheet S-4, February, 1939. File no. SA 343/67. - Prado Dam, Spillway, Santa Ana River near junction of State Highways 71 & 91, Corona, Riverside County, CA

  9. Oscillation of Branching Ratios Between the D(2s)+D(1s) and the D(2p)+D(1s) Channels in Direct Photodissociation of D_{2}.

    PubMed

    Wang, Jie; Meng, Qingnan; Mo, Yuxiang

    2017-08-04

    The direct photodissociation of D_{2} at excitation energies above 14.76 eV occurs via two channels, D(2s)+D(1s) and D(2p)+D(1s). The branching ratios between the two have been measured from the dissociation threshold to 3200 cm^{-1} above it, and it is found that they show cosine oscillations as a function of the fragment wave vector magnitudes. The oscillation is due to an interference effect and can be simulated using the phase difference between the wave functions of the two channels, analogous to Young's double-slit experiment. By fitting the measured branching ratios, we have determined the depths and widths of the effective spherical potential wells related to the two channels, which are in agreement with the effective depths and widths of the ab initio interaction potentials. The results of this Letter illustrate the importance of the relative phase between the fragments in controlling the branching ratios of the photodissociation channels.

  10. Oscillation of Branching Ratios Between the D (2 s )+D (1 s ) and the D (2 p )+D (1 s ) Channels in Direct Photodissociation of D2

    NASA Astrophysics Data System (ADS)

    Wang, Jie; Meng, Qingnan; Mo, Yuxiang

    2017-08-01

    The direct photodissociation of D2 at excitation energies above 14.76 eV occurs via two channels, D (2 s )+D (1 s ) and D (2 p )+D (1 s ) . The branching ratios between the two have been measured from the dissociation threshold to 3200 cm-1 above it, and it is found that they show cosine oscillations as a function of the fragment wave vector magnitudes. The oscillation is due to an interference effect and can be simulated using the phase difference between the wave functions of the two channels, analogous to Young's double-slit experiment. By fitting the measured branching ratios, we have determined the depths and widths of the effective spherical potential wells related to the two channels, which are in agreement with the effective depths and widths of the ab initio interaction potentials. The results of this Letter illustrate the importance of the relative phase between the fragments in controlling the branching ratios of the photodissociation channels.

  11. Block of high-threshold calcium channels by the synthetic polyamines sFTX-3.3 and FTX-3.3.

    PubMed

    Norris, T M; Moya, E; Blagbrough, I S; Adams, M E

    1996-10-01

    A polyamine component of Agelenopsis aperta spider venom designated FTX is reported to be a selective antagonist of P-type calcium channels in the mammalian brain. Consequently, this component has frequently been used as a pharmacological tool to determine the presence, distribution, and function of P-type channels in physiological systems. We describe antagonism of calcium channels by the synthesized polyamine FTX-3.3, which has the proposed structure of natural FTX. We also examined a corresponding polyamine amide, sFTX-3.3. These polyamines are critically evaluated for antagonism of three high-threshold calcium channel subtypes in rat neurons through the use of the whole-cell patch-clamp technique. FTX-3.3 (IC50 = approximately 0.13 mM) is approximately twice as potent as sFTX-3.3 (IC50 = approximately 0.24 mM) against P-type channels and approximately 3-fold more potent against N-type channels (FTX-3.3, IC50 = approximately 0.24 mM; sFTX-3.3, IC50 = approximately 0.70 mM). Both polyamines also block L-type calcium channels with similar potencies. sFTX-3.3 (1 mM) and FTX-3.3 (0.5 mM) typically block 50% and 65% of Bay K8644-enhanced L-type current, respectively. Antagonism of each calcium channel subtype is voltage dependent, with less inhibition of Ba2+ currents at more-positive potentials. These data show that both sFTX-3.3 and FTX-3.3 antagonize P-, N-, and L-type calcium channels in mammalian Purkinje and superior cervical ganglia neurons with similar IC50 values.

  12. Mutation of a single residue in the S2-S3 loop of CNG channels alters the gating properties and sensitivity to inhibitors.

    PubMed

    Crary, J I; Dean, D M; Maroof, F; Zimmerman, A L

    2000-12-01

    We previously found that native cyclic nucleotide-gated (CNG) cation channels from amphibian rod cells are directly and reversibly inhibited by analogues of diacylglycerol (DAG), but little is known about the mechanism of this inhibition. We recently determined that, at saturating cGMP concentrations, DAG completely inhibits cloned bovine rod (Brod) CNG channels while only partially inhibiting cloned rat olfactory (Rolf) channels (Crary, J.I., D.M. Dean, W. Nguitragool, P.T. Kurshan, and A.L. Zimmerman. 2000. J. Gen. Phys. 116:755-768; in this issue). Here, we report that a point mutation at position 204 in the S2-S3 loop of Rolf and a mouse CNG channel (Molf) found in olfactory epithelium and heart, increased DAG sensitivity to that of the Brod channel. Mutation of this residue from the wild-type glycine to a glutamate (Molf G204E) or aspartate (Molf G204D) gave dramatic increases in DAG sensitivity without changing the apparent cGMP or cAMP affinities or efficacies. However, unlike the wild-type olfactory channels, these mutants demonstrated voltage-dependent gating with obvious activation and deactivation kinetics. Interestingly, the mutants were also more sensitive to inhibition by the local anesthetic, tetracaine. Replacement of the position 204 glycine with a tryptophan residue (Rolf G204W) not only gave voltage-dependent gating and an increased sensitivity to DAG and tetracaine, but also showed reduced apparent agonist affinity and cAMP efficacy. Sequence comparisons show that the glycine at position 204 in the S2-S3 loop is highly conserved, and our findings indicate that its alteration can have critical consequences for channel gating and inhibition.

  13. The effect of ratio between rigid plant height and water depth on the manning’s coefficient in open channel

    NASA Astrophysics Data System (ADS)

    Rizalihadi, M.; Ziana; Shaskia, Nina; Asharly, H.

    2018-05-01

    One of the important factors in channel dimension is the Manning’s coefficient ( n ). This coefficient is influenced not only by the channel roughness but also by the presence of plants in the channel. The aim of the study is to see the effect of the ratio between the height of the rigid plant and water depth on the Manning’s coefficient (n) in open channel. The study was conducted in open channel with 15.5 m long, 0.5 m wide and 1.0 m high, in which at the center of the channel is planted with the rigid plants with a density of 42 plants/m2. The flow was run with a discharge of 0.013 m3/s at 6 ratios of Hplants/Hwater, namely: 0; 0.2; 0.6; 0.8; 1,0 and 1,2, to obtain the velocity and water profiles. Then the value of n is analyzed using Manning’s equation. The results showed that the mean velocity becomes decrease 17.81-34.01% as increase the ratio of Hplants/Hwater. This results in increasing n value to become 1.22-1.52 times compared to the unplanted channel ( no =0.038). So, it can be concluded that the ratio between the rigid plant’s height and water depth in the open channel can affect the value of Manning coefficient.

  14. Deletion of the S3–S4 Linker in theShaker Potassium Channel Reveals Two Quenching Groups near the outside of S4

    PubMed Central

    Sørensen, J.B.; Cha, A.; Latorre, R.; Rosenman, E.; Bezanilla, F.

    2000-01-01

    When attached outside the voltage-sensing S4 segment of the Shaker potassium channel, the fluorescent probe tetramethylrhodamine (TMRM) undergoes voltage-dependent fluorescence changes (ΔF) due to differential interaction with a pH-titratable external protein-lined vestibule (Cha, A., and F. Bezanilla. 1998. J. Gen. Physiol. 112:391–408.). We attached TMRM at the same sites [corresponding to M356C and A359C in the wild-type (wt) channel] in a deletion mutant of Shaker where all but the five amino acids closest to S4 had been removed from the S3–S4 linker. In the deletion mutant, the maximal ΔF/F seen was diminished 10-fold, and the ΔF at M356C became pH independent, suggesting that the protein-lined vestibule is made up in large part by the S3–S4 linker. The residual ΔF showed that the probe still interacted with two putative quenching groups near the S4 segment. One group was detected by M356C-TMRM (located outside of S3 in the deletion mutant) and reported on deactivation gating charge movement when applying hyperpolarizing voltage steps from a holding potential of 0 mV. During activating voltage steps from a holding potential of −90 mV, the fluorescence lagged considerably behind the movement of gating charge over a range of potentials. Another putative quenching group was seen by probes attached closer to the S4 and caused a ΔF at extreme hyperpolarizations (more negative than −90 mV) only. A signal from the interaction with this group in the wt S3–S4 linker channel (at L361C) correlated with gating charge moving in the hyperpolarized part of the Q-V curve. Probe attached at A359C in the deletion mutant and at L361C in wt channel showed a biphasic ΔF as the probe oscillated between the two groups, revealing that there is a transient state of the voltage sensor in between, where the probe has maximal fluorescence. We conclude that the voltage sensor undergoes two distinct conformational changes as seen from probes attached outside the S4

  15. Proline Scan of the hERG Channel S6 Helix Reveals the Location of the Intracellular Pore Gate

    PubMed Central

    Thouta, Samrat; Sokolov, Stanislav; Abe, Yuki; Clark, Sheldon J.; Cheng, Yen M.; Claydon, Tom W.

    2014-01-01

    In Shaker-like channels, the activation gate is formed at the bundle crossing by the convergence of the inner S6 helices near a conserved proline-valine-proline motif, which introduces a kink that allows for electromechanical coupling with voltage sensor motions via the S4-S5 linker. Human ether-a-go-go-related gene (hERG) channels lack the proline-valine-proline motif and the location of the intracellular pore gate and how it is coupled to S4 movement is less clear. Here, we show that proline substitutions within the S6 of hERG perturbed pore gate closure, trapping channels in the open state. Performing a proline scan of the inner S6 helix, from Ile655 to Tyr667 revealed that gate perturbation occurred with proximal (I655P-Q664P), but not distal (R665P-Y667P) substitutions, suggesting that Gln664 marks the position of the intracellular gate in hERG channels. Using voltage-clamp fluorimetry and gating current analysis, we demonstrate that proline substitutions trap the activation gate open by disrupting the coupling between the voltage-sensing unit and the pore of the channel. We characterize voltage sensor movement in one such trapped-open mutant channel and demonstrate the kinetics of what we interpret to be intrinsic hERG voltage sensor movement. PMID:24606930

  16. The Cytoplasmic Region of Inner Helix S6 Is an Important Determinant of Cardiac Ryanodine Receptor Channel Gating.

    PubMed

    Sun, Bo; Guo, Wenting; Tian, Xixi; Yao, Jinjing; Zhang, Lin; Wang, Ruiwu; Chen, S R Wayne

    2016-12-09

    The ryanodine receptor (RyR) channel pore is formed by four S6 inner helices, with its intracellular gate located at the S6 helix bundle crossing region. The cytoplasmic region of the extended S6 helix is held by the U motif of the central domain and is thought to control the opening and closing of the S6 helix bundle. However, the functional significance of the S6 cytoplasmic region in channel gating is unknown. Here we assessed the role of the S6 cytoplasmic region in the function of cardiac RyR (RyR2) via structure-guided site-directed mutagenesis. We mutated each residue in the S6 cytoplasmic region of the mouse RyR2 ( 4876 QQEQVKEDM 4884 ) and characterized their functional impact. We found that mutations Q4876A, V4880A, K4881A, and M4884A, located mainly on one side of the S6 helix that faces the U motif, enhanced basal channel activity and the sensitivity to Ca 2+ or caffeine activation, whereas mutations Q4877A, E4878A, Q4879A, and D4883A, located largely on the opposite side of S6, suppressed channel activity. Furthermore, V4880A, a cardiac arrhythmia-associated mutation, markedly enhanced the frequency of spontaneous openings and the sensitivity to cytosolic and luminal Ca 2+ activation of single RyR2 channels. V4880A also increased the propensity and reduced the threshold for arrhythmogenic spontaneous Ca 2+ release in HEK293 cells. Collectively, our data suggest that interactions between the cytoplasmic region of S6 and the U motif of RyR2 are important for stabilizing the closed state of the channel. Mutations in the S6/U motif domain interface likely destabilize the closed state of RyR2, resulting in enhanced basal channel activity and sensitivity to activation and increased propensity for spontaneous Ca 2+ release and cardiac arrhythmias. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  17. Measurement of the B 0 s lifetime using the semileptonic decay channel B 0 s → D - sμ +vX

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lizarraga, Marco Antonio Carrasco

    2009-11-01

    We report a measurement of the B 0 s lifetime in the semileptonic decay channel BB 0 s → D - sμ +vX (and its charge conjugate), using approximately 0.4 fb -1 of data collected with the DØ detector during 2002–2004. Using 5176 reconstructed D - s μ + signal events, we have measured the B 0 s lifetime to be τ (B 0 s) = 1.398 ± 0.044 (stat) +0.028 -0.025 (syst) ps. This is the most precise measurement of the B 0 s lifetime to date.

  18. Search for s-channel single top-quark production in proton-proton collisions at √{ s} = 8 TeV with the ATLAS detector

    NASA Astrophysics Data System (ADS)

    Aad, G.; Abbott, B.; Abdallah, J.; Abdel Khalek, S.; Abdinov, O.; Aben, R.; Abi, B.; Abolins, M.; Abouzeid, O. S.; Abramowicz, H.; Abreu, H.; Abreu, R.; Abulaiti, Y.; Acharya, B. S.; Adamczyk, L.; Adams, D. L.; Adelman, J.; Adomeit, S.; Adye, T.; Agatonovic-Jovin, T.; Aguilar-Saavedra, J. A.; Agustoni, M.; Ahlen, S. P.; Ahmadov, F.; Aielli, G.; Akerstedt, H.; Åkesson, T. P. A.; Akimoto, G.; Akimov, A. V.; Alberghi, G. L.; Albert, J.; Albrand, S.; Alconada Verzini, M. J.; Aleksa, M.; Aleksandrov, I. N.; Alexa, C.; Alexander, G.; Alexandre, G.; Alexopoulos, T.; Alhroob, M.; Alimonti, G.; Alio, L.; Alison, J.; Allbrooke, B. M. M.; Allison, L. J.; Allport, P. P.; Aloisio, A.; Alonso, A.; Alonso, F.; Alpigiani, C.; Altheimer, A.; Alvarez Gonzalez, B.; Alviggi, M. G.; Amako, K.; Amaral Coutinho, Y.; Amelung, C.; Amidei, D.; Amor Dos Santos, S. P.; Amorim, A.; Amoroso, S.; Amram, N.; Amundsen, G.; Anastopoulos, C.; Ancu, L. S.; Andari, N.; Andeen, T.; Anders, C. F.; Anders, G.; Anderson, K. J.; Andreazza, A.; Andrei, V.; Anduaga, X. S.; Angelidakis, S.; Angelozzi, I.; Anger, P.; Angerami, A.; Anghinolfi, F.; Anisenkov, A. V.; Anjos, N.; Annovi, A.; Antonaki, A.; Antonelli, M.; Antonov, A.; Antos, J.; Anulli, F.; Aoki, M.; Aperio Bella, L.; Apolle, R.; Arabidze, G.; Aracena, I.; Arai, Y.; Araque, J. P.; Arce, A. T. H.; Arduh, F. A.; Arguin, J.-F.; Argyropoulos, S.; Arik, M.; Armbruster, A. J.; Arnaez, O.; Arnal, V.; Arnold, H.; Arratia, M.; Arslan, O.; Artamonov, A.; Artoni, G.; Asai, S.; Asbah, N.; Ashkenazi, A.; Åsman, B.; Asquith, L.; Assamagan, K.; Astalos, R.; Atkinson, M.; Atlay, N. B.; Auerbach, B.; Augsten, K.; Aurousseau, M.; Avolio, G.; Axen, B.; Azuelos, G.; Azuma, Y.; Baak, M. A.; Baas, A. E.; Bacci, C.; Bachacou, H.; Bachas, K.; Backes, M.; Backhaus, M.; Backus Mayes, J.; Badescu, E.; Bagiacchi, P.; Bagnaia, P.; Bai, Y.; Bain, T.; Baines, J. T.; Baker, O. K.; Balek, P.; Balli, F.; Banas, E.; Banerjee, Sw.; Bannoura, A. A. E.; Bansal, V.; Bansil, H. S.; Barak, L.; Baranov, S. P.; Barberio, E. L.; Barberis, D.; Barbero, M.; Barillari, T.; Barisonzi, M.; Barklow, T.; Barlow, N.; Barnes, S. L.; Barnett, B. M.; Barnett, R. M.; Barnovska, Z.; Baroncelli, A.; Barone, G.; Barr, A. J.; Barreiro, F.; Barreiro Guimarães da Costa, J.; Bartoldus, R.; Barton, A. E.; Bartos, P.; Bartsch, V.; Bassalat, A.; Basye, A.; Bates, R. L.; Batista, S. J.; Batley, J. R.; Battaglia, M.; Battistin, M.; Bauer, F.; Bawa, H. S.; Beattie, M. D.; Beau, T.; Beauchemin, P. H.; Beccherle, R.; Bechtle, P.; Beck, H. P.; Becker, K.; Becker, S.; Beckingham, M.; Becot, C.; Beddall, A. J.; Beddall, A.; Bedikian, S.; Bednyakov, V. A.; Bee, C. P.; Beemster, L. J.; Beermann, T. A.; Begel, M.; Behr, K.; Belanger-Champagne, C.; Bell, P. J.; Bell, W. H.; Bella, G.; Bellagamba, L.; Bellerive, A.; Bellomo, M.; Belotskiy, K.; Beltramello, O.; Benary, O.; Benchekroun, D.; Bendtz, K.; Benekos, N.; Benhammou, Y.; Benhar Noccioli, E.; Benitez Garcia, J. A.; Benjamin, D. P.; Bensinger, J. R.; Bentvelsen, S.; Berge, D.; Bergeaas Kuutmann, E.; Berger, N.; Berghaus, F.; Beringer, J.; Bernard, C.; Bernat, P.; Bernius, C.; Bernlochner, F. U.; Berry, T.; Berta, P.; Bertella, C.; Bertoli, G.; Bertolucci, F.; Bertsche, C.; Bertsche, D.; Besana, M. I.; Besjes, G. J.; Bessidskaia, O.; Bessner, M.; Besson, N.; Betancourt, C.; Bethke, S.; Bhimji, W.; Bianchi, R. M.; Bianchini, L.; Bianco, M.; Biebel, O.; Bieniek, S. P.; Bierwagen, K.; Biesiada, J.; Biglietti, M.; Bilbao de Mendizabal, J.; Bilokon, H.; Bindi, M.; Binet, S.; Bingul, A.; Bini, C.; Black, C. W.; Black, J. E.; Black, K. M.; Blackburn, D.; Blair, R. E.; Blanchard, J.-B.; Blazek, T.; Bloch, I.; Blocker, C.; Blum, W.; Blumenschein, U.; Bobbink, G. J.; Bobrovnikov, V. S.; Bocchetta, S. S.; Bocci, A.; Bock, C.; Boddy, C. R.; Boehler, M.; Boek, T. T.; Bogaerts, J. A.; Bogdanchikov, A. G.; Bogouch, A.; Bohm, C.; Boisvert, V.; Bold, T.; Boldea, V.; Boldyrev, A. S.; Bomben, M.; Bona, M.; Boonekamp, M.; Borisov, A.; Borissov, G.; Borri, M.; Borroni, S.; Bortfeldt, J.; Bortolotto, V.; Bos, K.; Boscherini, D.; Bosman, M.; Boterenbrood, H.; Boudreau, J.; Bouffard, J.; Bouhova-Thacker, E. V.; Boumediene, D.; Bourdarios, C.; Bousson, N.; Boutouil, S.; Boveia, A.; Boyd, J.; Boyko, I. R.; Bozic, I.; Bracinik, J.; Brandt, A.; Brandt, G.; Brandt, O.; Bratzler, U.; Brau, B.; Brau, J. E.; Braun, H. M.; Brazzale, S. F.; Brelier, B.; Brendlinger, K.; Brennan, A. J.; Brenner, R.; Bressler, S.; Bristow, K.; Bristow, T. M.; Britton, D.; Brochu, F. M.; Brock, I.; Brock, R.; Bronner, J.; Brooijmans, G.; Brooks, T.; Brooks, W. K.; Brosamer, J.; Brost, E.; Brown, J.; Bruckman de Renstrom, P. A.; Bruncko, D.; Bruneliere, R.; Brunet, S.; Bruni, A.; Bruni, G.; Bruschi, M.; Bryngemark, L.; Buanes, T.; Buat, Q.; Bucci, F.; Buchholz, P.; Buckley, A. G.; Buda, S. I.; Budagov, I. A.; Buehrer, F.; Bugge, L.; Bugge, M. K.; Bulekov, O.; Bundock, A. C.; Burckhart, H.; Burdin, S.; Burghgrave, B.; Burke, S.; Burmeister, I.; Busato, E.; Büscher, D.; Büscher, V.; Bussey, P.; Buszello, C. P.; Butler, B.; Butler, J. M.; Butt, A. I.; Buttar, C. M.; Butterworth, J. M.; Butti, P.; Buttinger, W.; Buzatu, A.; Byszewski, M.; Cabrera Urbán, S.; Caforio, D.; Cakir, O.; Calafiura, P.; Calandri, A.; Calderini, G.; Calfayan, P.; Calkins, R.; Caloba, L. P.; Calvet, D.; Calvet, S.; Camacho Toro, R.; Camarda, S.; Cameron, D.; Caminada, L. M.; Caminal Armadans, R.; Campana, S.; Campanelli, M.; Campoverde, A.; Canale, V.; Canepa, A.; Cano Bret, M.; Cantero, J.; Cantrill, R.; Cao, T.; Capeans Garrido, M. D. M.; Caprini, I.; Caprini, M.; Capua, M.; Caputo, R.; Cardarelli, R.; Carli, T.; Carlino, G.; Carminati, L.; Caron, S.; Carquin, E.; Carrillo-Montoya, G. D.; Carter, J. R.; Carvalho, J.; Casadei, D.; Casado, M. P.; Casolino, M.; Castaneda-Miranda, E.; Castelli, A.; Castillo Gimenez, V.; Castro, N. F.; Catastini, P.; Catinaccio, A.; Catmore, J. R.; Cattai, A.; Cattani, G.; Caudron, J.; Cavaliere, V.; Cavalli, D.; Cavalli-Sforza, M.; Cavasinni, V.; Ceradini, F.; Cerio, B. C.; Cerny, K.; Cerqueira, A. S.; Cerri, A.; Cerrito, L.; Cerutti, F.; Cerv, M.; Cervelli, A.; Cetin, S. A.; Chafaq, A.; Chakraborty, D.; Chalupkova, I.; Chang, P.; Chapleau, B.; Chapman, J. D.; Charfeddine, D.; Charlton, D. G.; Chau, C. C.; Chavez Barajas, C. A.; Cheatham, S.; Chegwidden, A.; Chekanov, S.; Chekulaev, S. V.; Chelkov, G. A.; Chelstowska, M. A.; Chen, C.; Chen, H.; Chen, K.; Chen, L.; Chen, S.; Chen, X.; Chen, Y.; Cheng, H. C.; Cheng, Y.; Cheplakov, A.; Cherkaoui El Moursli, R.; Chernyatin, V.; Cheu, E.; Chevalier, L.; Chiarella, V.; Chiefari, G.; Childers, J. T.; Chilingarov, A.; Chiodini, G.; Chisholm, A. S.; Chislett, R. T.; Chitan, A.; Chizhov, M. V.; Chouridou, S.; Chow, B. K. B.; Chromek-Burckhart, D.; Chu, M. L.; Chudoba, J.; Chwastowski, J. J.; Chytka, L.; Ciapetti, G.; Ciftci, A. K.; Ciftci, R.; Cinca, D.; Cindro, V.; Ciocio, A.; Citron, Z. H.; Citterio, M.; Ciubancan, M.; Clark, A.; Clark, P. J.; Clarke, R. N.; Cleland, W.; Clemens, J. C.; Clement, C.; Coadou, Y.; Cobal, M.; Coccaro, A.; Cochran, J.; Coffey, L.; Cogan, J. G.; Cole, B.; Cole, S.; Colijn, A. P.; Collot, J.; Colombo, T.; Compostella, G.; Conde Muiño, P.; Coniavitis, E.; Connell, S. H.; Connelly, I. A.; Consonni, S. M.; Consorti, V.; Constantinescu, S.; Conta, C.; Conti, G.; Conventi, F.; Cooke, M.; Cooper, B. D.; Cooper-Sarkar, A. M.; Cooper-Smith, N. J.; Copic, K.; Cornelissen, T.; Corradi, M.; Corriveau, F.; Corso-Radu, A.; Cortes-Gonzalez, A.; Cortiana, G.; Costa, G.; Costa, M. J.; Costanzo, D.; Côté, D.; Cottin, G.; Cowan, G.; Cox, B. E.; Cranmer, K.; Cree, G.; Crépé-Renaudin, S.; Crescioli, F.; Cribbs, W. A.; Crispin Ortuzar, M.; Cristinziani, M.; Croft, V.; Crosetti, G.; Cuciuc, C.-M.; Cuhadar Donszelmann, T.; Cummings, J.; Curatolo, M.; Cuthbert, C.; Czirr, H.; Czodrowski, P.; D'Auria, S.; D'Onofrio, M.; da Cunha Sargedas de Sousa, M. J.; da Via, C.; Dabrowski, W.; Dafinca, A.; Dai, T.; Dale, O.; Dallaire, F.; Dallapiccola, C.; Dam, M.; Daniells, A. C.; Dano Hoffmann, M.; Dao, V.; Darbo, G.; Darmora, S.; Dassoulas, J.; Dattagupta, A.; Davey, W.; David, C.; Davidek, T.; Davies, E.; Davies, M.; Davignon, O.; Davison, A. R.; Davison, P.; Davygora, Y.; Dawe, E.; Dawson, I.; Daya-Ishmukhametova, R. K.; de, K.; de Asmundis, R.; de Castro, S.; de Cecco, S.; de Groot, N.; de Jong, P.; de la Torre, H.; de Lorenzi, F.; de Nooij, L.; de Pedis, D.; de Salvo, A.; de Sanctis, U.; de Santo, A.; de Vivie de Regie, J. B.; Dearnaley, W. J.; Debbe, R.; Debenedetti, C.; Dechenaux, B.; Dedovich, D. V.; Deigaard, I.; Del Peso, J.; Del Prete, T.; Deliot, F.; Delitzsch, C. M.; Deliyergiyev, M.; Dell'Acqua, A.; Dell'Asta, L.; Dell'Orso, M.; Della Pietra, M.; Della Volpe, D.; Delmastro, M.; Delsart, P. A.; Deluca, C.; Demarco, D. A.; Demers, S.; Demichev, M.; Demilly, A.; Denisov, S. P.; Derendarz, D.; Derkaoui, J. E.; Derue, F.; Dervan, P.; Desch, K.; Deterre, C.; Deviveiros, P. O.; Dewhurst, A.; Dhaliwal, S.; di Ciaccio, A.; di Ciaccio, L.; di Domenico, A.; di Donato, C.; di Girolamo, A.; di Girolamo, B.; di Mattia, A.; di Micco, B.; di Nardo, R.; di Simone, A.; di Sipio, R.; di Valentino, D.; Dias, F. A.; Diaz, M. A.; Diehl, E. B.; Dietrich, J.; Dietzsch, T. A.; Diglio, S.; Dimitrievska, A.; Dingfelder, J.; Dita, P.; Dita, S.; Dittus, F.; Djama, F.; Djobava, T.; Djuvsland, J. I.; Do Vale, M. A. B.; Dobos, D.; Doglioni, C.; Doherty, T.; Dohmae, T.; Dolejsi, J.; Dolezal, Z.; Dolgoshein, B. A.; Donadelli, M.; Donati, S.; Dondero, P.; Donini, J.; Dopke, J.; Doria, A.; Dova, M. T.; Doyle, A. T.; Dris, M.; Dubbert, J.; Dube, S.; Dubreuil, E.; Duchovni, E.; Duckeck, G.; Ducu, O. A.; Duda, D.; Dudarev, A.; Dudziak, F.; Duflot, L.; Duguid, L.; Dührssen, M.; Dunford, M.; Duran Yildiz, H.; Düren, M.; Durglishvili, A.; Dwuznik, M.; Dyndal, M.; Ebke, J.; Edson, W.; Edwards, N. C.; Ehrenfeld, W.; Eifert, T.; Eigen, G.; Einsweiler, K.; Ekelof, T.; El Kacimi, M.; Ellert, M.; Elles, S.; Ellinghaus, F.; Ellis, N.; Elmsheuser, J.; Elsing, M.; Emeliyanov, D.; Enari, Y.; Endner, O. C.; Endo, M.; Engelmann, R.; Erdmann, J.; Ereditato, A.; Eriksson, D.; Ernis, G.; Ernst, J.; Ernst, M.; Ernwein, J.; Errede, D.; Errede, S.; Ertel, E.; Escalier, M.; Esch, H.; Escobar, C.; Esposito, B.; Etienvre, A. I.; Etzion, E.; Evans, H.; Ezhilov, A.; Fabbri, L.; Facini, G.; Fakhrutdinov, R. M.; Falciano, S.; Falla, R. J.; Faltova, J.; Fang, Y.; Fanti, M.; Farbin, A.; Farilla, A.; Farooque, T.; Farrell, S.; Farrington, S. M.; Farthouat, P.; Fassi, F.; Fassnacht, P.; Fassouliotis, D.; Favareto, A.; Fayard, L.; Federic, P.; Fedin, O. L.; Fedorko, W.; Fehling-Kaschek, M.; Feigl, S.; Feligioni, L.; Feng, C.; Feng, E. J.; Feng, H.; Fenyuk, A. B.; Fernandez Perez, S.; Ferrag, S.; Ferrando, J.; Ferrari, A.; Ferrari, P.; Ferrari, R.; Ferreira de Lima, D. E.; Ferrer, A.; Ferrere, D.; Ferretti, C.; Ferretto Parodi, A.; Fiascaris, M.; Fiedler, F.; Filipčič, A.; Filipuzzi, M.; Filthaut, F.; Fincke-Keeler, M.; Finelli, K. D.; Fiolhais, M. C. N.; Fiorini, L.; Firan, A.; Fischer, A.; Fischer, J.; Fisher, W. C.; Fitzgerald, E. A.; Flechl, M.; Fleck, I.; Fleischmann, P.; Fleischmann, S.; Fletcher, G. T.; Fletcher, G.; Flick, T.; Floderus, A.; Flores Castillo, L. R.; Flowerdew, M. J.; Formica, A.; Forti, A.; Fortin, D.; Fournier, D.; Fox, H.; Fracchia, S.; Francavilla, P.; Franchini, M.; Franchino, S.; Francis, D.; Franconi, L.; Franklin, M.; Franz, S.; Fraternali, M.; French, S. T.; Friedrich, C.; Friedrich, F.; Froidevaux, D.; Frost, J. A.; Fukunaga, C.; Fullana Torregrosa, E.; Fulsom, B. G.; Fuster, J.; Gabaldon, C.; Gabizon, O.; Gabrielli, A.; Gabrielli, A.; Gadatsch, S.; Gadomski, S.; Gagliardi, G.; Gagnon, P.; Galea, C.; Galhardo, B.; Gallas, E. J.; Gallo, V.; Gallop, B. J.; Gallus, P.; Galster, G.; Gan, K. K.; Gao, J.; Gao, Y. S.; Garay Walls, F. M.; Garberson, F.; García, C.; García Navarro, J. E.; Garcia-Sciveres, M.; Gardner, R. W.; Garelli, N.; Garonne, V.; Gatti, C.; Gaudio, G.; Gaur, B.; Gauthier, L.; Gauzzi, P.; Gavrilenko, I. L.; Gay, C.; Gaycken, G.; Gazis, E. N.; Ge, P.; Gecse, Z.; Gee, C. N. P.; Geerts, D. A. A.; Geich-Gimbel, Ch.; Gellerstedt, K.; Gemme, C.; Gemmell, A.; Genest, M. H.; Gentile, S.; George, M.; George, S.; Gerbaudo, D.; Gershon, A.; Ghazlane, H.; Ghodbane, N.; Giacobbe, B.; Giagu, S.; Giangiobbe, V.; Giannetti, P.; Gianotti, F.; Gibbard, B.; Gibson, S. M.; Gilchriese, M.; Gillam, T. P. S.; Gillberg, D.; Gilles, G.; Gingrich, D. M.; Giokaris, N.; Giordani, M. P.; Giordano, R.; Giorgi, F. M.; Giorgi, F. M.; Giraud, P. F.; Giugni, D.; Giuliani, C.; Giulini, M.; Gjelsten, B. K.; Gkaitatzis, S.; Gkialas, I.; Gkougkousis, E. L.; Gladilin, L. K.; Glasman, C.; Glatzer, J.; Glaysher, P. C. F.; Glazov, A.; Glonti, G. L.; Goblirsch-Kolb, M.; Goddard, J. R.; Godlewski, J.; Goeringer, C.; Goldfarb, S.; Golling, T.; Golubkov, D.; Gomes, A.; Gomez Fajardo, L. S.; Gonçalo, R.; Goncalves Pinto Firmino da Costa, J.; Gonella, L.; González de La Hoz, S.; Gonzalez Parra, G.; Gonzalez-Sevilla, S.; Goossens, L.; Gorbounov, P. A.; Gordon, H. A.; Gorelov, I.; Gorini, B.; Gorini, E.; Gorišek, A.; Gornicki, E.; Goshaw, A. T.; Gössling, C.; Gostkin, M. I.; Gouighri, M.; Goujdami, D.; Goulette, M. P.; Goussiou, A. G.; Goy, C.; Grabas, H. M. X.; Graber, L.; Grabowska-Bold, I.; Grafström, P.; Grahn, K.-J.; Gramling, J.; Gramstad, E.; Grancagnolo, S.; Grassi, V.; Gratchev, V.; Gray, H. M.; Graziani, E.; Grebenyuk, O. G.; Greenwood, Z. D.; Gregersen, K.; Gregor, I. M.; Grenier, P.; Griffiths, J.; Grillo, A. A.; Grimm, K.; Grinstein, S.; Gris, Ph.; Grishkevich, Y. V.; Grivaz, J.-F.; Grohs, J. P.; Grohsjean, A.; Gross, E.; Grosse-Knetter, J.; Grossi, G. C.; Groth-Jensen, J.; Grout, Z. J.; Guan, L.; Guenther, J.; Guescini, F.; Guest, D.; Gueta, O.; Guicheney, C.; Guido, E.; Guillemin, T.; Guindon, S.; Gul, U.; Gumpert, C.; Guo, J.; Gupta, S.; Gutierrez, P.; Gutierrez Ortiz, N. G.; Gutschow, C.; Guttman, N.; Guyot, C.; Gwenlan, C.; Gwilliam, C. B.; Haas, A.; Haber, C.; Hadavand, H. K.; Haddad, N.; Haefner, P.; Hageböck, S.; Hajduk, Z.; Hakobyan, H.; Haleem, M.; Hall, D.; Halladjian, G.; Hallewell, G. D.; Hamacher, K.; Hamal, P.; Hamano, K.; Hamer, M.; Hamilton, A.; Hamilton, S.; Hamity, G. N.; Hamnett, P. G.; Han, L.; Hanagaki, K.; Hanawa, K.; Hance, M.; Hanke, P.; Hanna, R.; Hansen, J. B.; Hansen, J. D.; Hansen, P. H.; Hara, K.; Hard, A. 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T.; Poulard, G.; Poveda, J.; Pozdnyakov, V.; Pralavorio, P.; Pranko, A.; Prasad, S.; Pravahan, R.; Prell, S.; Price, D.; Price, J.; Price, L. E.; Prieur, D.; Primavera, M.; Proissl, M.; Prokofiev, K.; Prokoshin, F.; Protopapadaki, E.; Protopopescu, S.; Proudfoot, J.; Przybycien, M.; Przysiezniak, H.; Ptacek, E.; Puddu, D.; Pueschel, E.; Puldon, D.; Purohit, M.; Puzo, P.; Qian, J.; Qin, G.; Qin, Y.; Quadt, A.; Quarrie, D. R.; Quayle, W. B.; Queitsch-Maitland, M.; Quilty, D.; Qureshi, A.; Radeka, V.; Radescu, V.; Radhakrishnan, S. K.; Radloff, P.; Rados, P.; Ragusa, F.; Rahal, G.; Rajagopalan, S.; Rammensee, M.; Randle-Conde, A. S.; Rangel-Smith, C.; Rao, K.; Rauscher, F.; Rave, T. C.; Ravenscroft, T.; Raymond, M.; Read, A. L.; Readioff, N. P.; Rebuzzi, D. M.; Redelbach, A.; Redlinger, G.; Reece, R.; Reeves, K.; Rehnisch, L.; Reisin, H.; Relich, M.; Rembser, C.; Ren, H.; Ren, Z. L.; Renaud, A.; Rescigno, M.; Resconi, S.; Rezanova, O. L.; Reznicek, P.; Rezvani, R.; Richter, R.; Ridel, M.; Rieck, P.; Rieger, J.; Rijssenbeek, M.; Rimoldi, A.; Rinaldi, L.; Ritsch, E.; Riu, I.; Rizatdinova, F.; Rizvi, E.; Robertson, S. H.; Robichaud-Veronneau, A.; Robinson, D.; Robinson, J. E. M.; Robson, A.; Roda, C.; Rodrigues, L.; Roe, S.; Røhne, O.; Rolli, S.; Romaniouk, A.; Romano, M.; Romero Adam, E.; Rompotis, N.; Ronzani, M.; Roos, L.; Ros, E.; Rosati, S.; Rosbach, K.; Rose, M.; Rose, P.; Rosendahl, P. L.; Rosenthal, O.; Rossetti, V.; Rossi, E.; Rossi, L. P.; Rosten, R.; Rotaru, M.; Roth, I.; Rothberg, J.; Rousseau, D.; Royon, C. R.; Rozanov, A.; Rozen, Y.; Ruan, X.; Rubbo, F.; Rubinskiy, I.; Rud, V. I.; Rudolph, C.; Rudolph, M. S.; Rühr, F.; Ruiz-Martinez, A.; Rurikova, Z.; Rusakovich, N. A.; Ruschke, A.; Rutherfoord, J. P.; Ruthmann, N.; Ryabov, Y. F.; Rybar, M.; Rybkin, G.; Ryder, N. C.; Saavedra, A. F.; Sabato, G.; Sacerdoti, S.; Saddique, A.; Sadeh, I.; Sadrozinski, H. F.-W.; Sadykov, R.; Safai Tehrani, F.; Sakamoto, H.; Sakurai, Y.; Salamanna, G.; Salamon, A.; Saleem, M.; Salek, D.; Sales de Bruin, P. H.; Salihagic, D.; Salnikov, A.; Salt, J.; Salvatore, D.; Salvatore, F.; Salvucci, A.; Salzburger, A.; Sampsonidis, D.; Sanchez, A.; Sánchez, J.; Sanchez Martinez, V.; Sandaker, H.; Sandbach, R. L.; Sander, H. G.; Sanders, M. P.; Sandhoff, M.; Sandoval, T.; Sandoval, C.; Sandstroem, R.; Sankey, D. P. C.; Sansoni, A.; Santoni, C.; Santonico, R.; Santos, H.; Santoyo Castillo, I.; Sapp, K.; Sapronov, A.; Saraiva, J. G.; Sarrazin, B.; Sartisohn, G.; Sasaki, O.; Sasaki, Y.; Sauvage, G.; Sauvan, E.; Savard, P.; Savu, D. O.; Sawyer, C.; Sawyer, L.; Saxon, D. H.; Saxon, J.; Sbarra, C.; Sbrizzi, A.; Scanlon, T.; Scannicchio, D. A.; Scarcella, M.; Scarfone, V.; Schaarschmidt, J.; Schacht, P.; Schaefer, D.; Schaefer, R.; Schaepe, S.; Schaetzel, S.; Schäfer, U.; Schaffer, A. C.; Schaile, D.; Schamberger, R. D.; Scharf, V.; Schegelsky, V. A.; Scheirich, D.; Schernau, M.; Scherzer, M. I.; Schiavi, C.; Schieck, J.; Schillo, C.; Schioppa, M.; Schlenker, S.; Schmidt, E.; Schmieden, K.; Schmitt, C.; Schmitt, S.; Schneider, B.; Schnellbach, Y. J.; Schnoor, U.; Schoeffel, L.; Schoening, A.; Schoenrock, B. D.; Schorlemmer, A. L. S.; Schott, M.; Schouten, D.; Schovancova, J.; Schramm, S.; Schreyer, M.; Schroeder, C.; Schuh, N.; Schultens, M. J.; Schultz-Coulon, H.-C.; Schulz, H.; Schumacher, M.; Schumm, B. A.; Schune, Ph.; Schwanenberger, C.; Schwartzman, A.; Schwarz, T. A.; Schwegler, Ph.; Schwemling, Ph.; Schwienhorst, R.; Schwindling, J.; Schwindt, T.; Schwoerer, M.; Sciacca, F. G.; Scifo, E.; Sciolla, G.; Scuri, F.; Scutti, F.; Searcy, J.; Sedov, G.; Sedykh, E.; Seema, P.; Seidel, S. C.; Seiden, A.; Seifert, F.; Seixas, J. M.; Sekhniaidze, G.; Sekula, S. J.; Selbach, K. E.; Seliverstov, D. M.; Sellers, G.; Semprini-Cesari, N.; Serfon, C.; Serin, L.; Serkin, L.; Serre, T.; Seuster, R.; Severini, H.; Sfiligoj, T.; Sforza, F.; Sfyrla, A.; Shabalina, E.; Shamim, M.; Shan, L. Y.; Shang, R.; Shank, J. T.; Shapiro, M.; Shatalov, P. B.; Shaw, K.; Shehu, C. Y.; Sherwood, P.; Shi, L.; Shimizu, S.; Shimmin, C. O.; Shimojima, M.; Shiyakova, M.; Shmeleva, A.; Shochet, M. J.; Short, D.; Shrestha, S.; Shulga, E.; Shupe, M. A.; Shushkevich, S.; Sicho, P.; Sidiropoulou, O.; Sidorov, D.; Sidoti, A.; Siegert, F.; Sijacki, Dj.; Silva, J.; Silver, Y.; Silverstein, D.; Silverstein, S. B.; Simak, V.; Simard, O.; Simic, Lj.; Simion, S.; Simioni, E.; Simmons, B.; Simon, D.; Simoniello, R.; Sinervo, P.; Sinev, N. B.; Siragusa, G.; Sircar, A.; Sisakyan, A. N.; Sivoklokov, S. Yu.; Sjölin, J.; Sjursen, T. B.; Skottowe, H. P.; Skovpen, K. Yu.; Skubic, P.; Slater, M.; Slavicek, T.; Slawinska, M.; Sliwa, K.; Smakhtin, V.; Smart, B. H.; Smestad, L.; Smirnov, S. Yu.; Smirnov, Y.; Smirnova, L. N.; Smirnova, O.; Smith, K. M.; Smizanska, M.; Smolek, K.; Snesarev, A. A.; Snidero, G.; Snyder, S.; Sobie, R.; Socher, F.; Soffer, A.; Soh, D. A.; Solans, C. A.; Solar, M.; Solc, J.; Soldatov, E. Yu.; Soldevila, U.; Solodkov, A. A.; Soloshenko, A.; Solovyanov, O. V.; Solovyev, V.; Sommer, P.; Song, H. Y.; Soni, N.; Sood, A.; Sopczak, A.; Sopko, B.; Sopko, V.; Sorin, V.; Sosebee, M.; Soualah, R.; Soueid, P.; Soukharev, A. M.; South, D.; Spagnolo, S.; Spanò, F.; Spearman, W. R.; Spettel, F.; Spighi, R.; Spigo, G.; Spiller, L. A.; Spousta, M.; Spreitzer, T.; St. Denis, R. D.; Staerz, S.; Stahlman, J.; Stamen, R.; Stamm, S.; Stanecka, E.; Stanek, R. W.; Stanescu, C.; Stanescu-Bellu, M.; Stanitzki, M. M.; Stapnes, S.; Starchenko, E. A.; Stark, J.; Staroba, P.; Starovoitov, P.; Staszewski, R.; Stavina, P.; Steinberg, P.; Stelzer, B.; Stelzer, H. J.; Stelzer-Chilton, O.; Stenzel, H.; Stern, S.; Stewart, G. A.; Stillings, J. A.; Stockton, M. C.; Stoebe, M.; Stoicea, G.; Stolte, P.; Stonjek, S.; Stradling, A. R.; Straessner, A.; Stramaglia, M. E.; Strandberg, J.; Strandberg, S.; Strandlie, A.; Strauss, E.; Strauss, M.; Strizenec, P.; Ströhmer, R.; Strom, D. M.; Stroynowski, R.; Strubig, A.; Stucci, S. A.; Stugu, B.; Styles, N. A.; Su, D.; Su, J.; Subramaniam, R.; Succurro, A.; Sugaya, Y.; Suhr, C.; Suk, M.; Sulin, V. V.; Sultansoy, S.; Sumida, T.; Sun, S.; Sun, X.; Sundermann, J. E.; Suruliz, K.; Susinno, G.; Sutton, M. R.; Suzuki, Y.; Svatos, M.; Swedish, S.; Swiatlowski, M.; Sykora, I.; Sykora, T.; Ta, D.; Taccini, C.; Tackmann, K.; Taenzer, J.; Taffard, A.; Tafirout, R.; Taiblum, N.; Takai, H.; Takashima, R.; Takeda, H.; Takeshita, T.; Takubo, Y.; Talby, M.; Talyshev, A. A.; Tam, J. Y. C.; Tan, K. G.; Tanaka, J.; Tanaka, R.; Tanaka, S.; Tanaka, S.; Tanasijczuk, A. J.; Tannenwald, B. B.; Tannoury, N.; Tapprogge, S.; Tarem, S.; Tarrade, F.; Tartarelli, G. F.; Tas, P.; Tasevsky, M.; Tashiro, T.; Tassi, E.; Tavares Delgado, A.; Tayalati, Y.; Taylor, F. E.; Taylor, G. N.; Taylor, W.; Teischinger, F. A.; Teixeira Dias Castanheira, M.; Teixeira-Dias, P.; Temming, K. K.; Ten Kate, H.; Teng, P. K.; Teoh, J. J.; Terada, S.; Terashi, K.; Terron, J.; Terzo, S.; Testa, M.; Teuscher, R. J.; Therhaag, J.; Theveneaux-Pelzer, T.; Thomas, J. P.; Thomas-Wilsker, J.; Thompson, E. N.; Thompson, P. D.; Thompson, P. D.; Thompson, R. J.; Thompson, A. S.; Thomsen, L. A.; Thomson, E.; Thomson, M.; Thong, W. M.; Thun, R. P.; Tian, F.; Tibbetts, M. J.; Tikhomirov, V. O.; Tikhonov, Yu. A.; Timoshenko, S.; Tiouchichine, E.; Tipton, P.; Tisserant, S.; Todorov, T.; Todorova-Nova, S.; Tojo, J.; Tokár, S.; Tokushuku, K.; Tollefson, K.; Tolley, E.; Tomlinson, L.; Tomoto, M.; Tompkins, L.; Toms, K.; Topilin, N. D.; Torrence, E.; Torres, H.; Torró Pastor, E.; Toth, J.; Touchard, F.; Tovey, D. R.; Tran, H. L.; Trefzger, T.; Tremblet, L.; Tricoli, A.; Trigger, I. M.; Trincaz-Duvoid, S.; Tripiana, M. F.; Trischuk, W.; Trocmé, B.; Troncon, C.; Trottier-McDonald, M.; Trovatelli, M.; True, P.; Trzebinski, M.; Trzupek, A.; Tsarouchas, C.; Tseng, J. C.-L.; Tsiareshka, P. V.; Tsionou, D.; Tsipolitis, G.; Tsirintanis, N.; Tsiskaridze, S.; Tsiskaridze, V.; Tskhadadze, E. G.; Tsukerman, I. I.; Tsulaia, V.; Tsuno, S.; Tsybychev, D.; Tudorache, A.; Tudorache, V.; Tuna, A. N.; Tupputi, S. A.; Turchikhin, S.; Turecek, D.; Turk Cakir, I.; Turra, R.; Turvey, A. J.; Tuts, P. M.; Tykhonov, A.; Tylmad, M.; Tyndel, M.; Uchida, K.; Ueda, I.; Ueno, R.; Ughetto, M.; Ugland, M.; Uhlenbrock, M.; Ukegawa, F.; Unal, G.; Undrus, A.; Unel, G.; Ungaro, F. C.; Unno, Y.; Unverdorben, C.; Urban, J.; Urbaniec, D.; Urquijo, P.; Usai, G.; Usanova, A.; Vacavant, L.; Vacek, V.; Vachon, B.; Valencic, N.; Valentinetti, S.; Valero, A.; Valery, L.; Valkar, S.; Valladolid Gallego, E.; Vallecorsa, S.; Valls Ferrer, J. A.; van den Wollenberg, W.; van der Deijl, P. C.; van der Geer, R.; van der Graaf, H.; van der Leeuw, R.; van der Ster, D.; van Eldik, N.; van Gemmeren, P.; van Nieuwkoop, J.; van Vulpen, I.; van Woerden, M. C.; Vanadia, M.; Vandelli, W.; Vanguri, R.; Vaniachine, A.; Vankov, P.; Vannucci, F.; Vardanyan, G.; Vari, R.; Varnes, E. W.; Varol, T.; Varouchas, D.; Vartapetian, A.; Varvell, K. E.; Vazeille, F.; Vazquez Schroeder, T.; Veatch, J.; Veloso, F.; Velz, T.; Veneziano, S.; Ventura, A.; Ventura, D.; Venturi, M.; Venturi, N.; Venturini, A.; Vercesi, V.; Verducci, M.; Verkerke, W.; Vermeulen, J. C.; Vest, A.; Vetterli, M. C.; Viazlo, O.; Vichou, I.; Vickey, T.; Vickey Boeriu, O. E.; Viehhauser, G. H. A.; Viel, S.; Vigne, R.; Villa, M.; Villaplana Perez, M.; Vilucchi, E.; Vincter, M. G.; Vinogradov, V. B.; Virzi, J.; Vivarelli, I.; Vives Vaque, F.; Vlachos, S.; Vladoiu, D.; Vlasak, M.; Vogel, A.; Vogel, M.; Vokac, P.; Volpi, G.; Volpi, M.; von der Schmitt, H.; von Radziewski, H.; von Toerne, E.; Vorobel, V.; Vorobev, K.; Vos, M.; Voss, R.; Vossebeld, J. H.; Vranjes, N.; Vranjes Milosavljevic, M.; Vrba, V.; Vreeswijk, M.; Vu Anh, T.; Vuillermet, R.; Vukotic, I.; Vykydal, Z.; Wagner, P.; Wagner, W.; Wahlberg, H.; Wahrmund, S.; Wakabayashi, J.; Walder, J.; Walker, R.; Walkowiak, W.; Wall, R.; Waller, P.; Walsh, B.; Wang, C.; Wang, C.; Wang, F.; Wang, H.; Wang, H.; Wang, J.; Wang, J.; Wang, K.; Wang, R.; Wang, S. M.; Wang, T.; Wang, X.; Wanotayaroj, C.; Warburton, A.; Ward, C. P.; Wardrope, D. R.; Warsinsky, M.; Washbrook, A.; Wasicki, C.; Watkins, P. M.; Watson, A. T.; Watson, I. J.; Watson, M. F.; Watts, G.; Watts, S.; Waugh, B. M.; Webb, S.; Weber, M. S.; Weber, S. W.; Webster, J. S.; Weidberg, A. R.; Weinert, B.; Weingarten, J.; Weiser, C.; Weits, H.; Wells, P. S.; Wenaus, T.; Wendland, D.; Weng, Z.; Wengler, T.; Wenig, S.; Wermes, N.; Werner, M.; Werner, P.; Wessels, M.; Wetter, J.; Whalen, K.; White, A.; White, M. J.; White, R.; White, S.; Whiteson, D.; Wicke, D.; Wickens, F. J.; Wiedenmann, W.; Wielers, M.; Wienemann, P.; Wiglesworth, C.; Wiik-Fuchs, L. A. M.; Wijeratne, P. A.; Wildauer, A.; Wildt, M. A.; Wilkens, H. G.; Williams, H. H.; Williams, S.; Willis, C.; Willocq, S.; Wilson, A.; Wilson, J. A.; Wingerter-Seez, I.; Winklmeier, F.; Winter, B. T.; Wittgen, M.; Wittig, T.; Wittkowski, J.; Wollstadt, S. J.; Wolter, M. W.; Wolters, H.; Wosiek, B. K.; Wotschack, J.; Woudstra, M. J.; Wozniak, K. W.; Wright, M.; Wu, M.; Wu, S. L.; Wu, X.; Wu, Y.; Wulf, E.; Wyatt, T. R.; Wynne, B. M.; Xella, S.; Xiao, M.; Xu, D.; Xu, L.; Yabsley, B.; Yacoob, S.; Yakabe, R.; Yamada, M.; Yamaguchi, H.; Yamaguchi, Y.; Yamamoto, A.; Yamamoto, S.; Yamamura, T.; Yamanaka, T.; Yamauchi, K.; Yamazaki, Y.; Yan, Z.; Yang, H.; Yang, H.; Yang, U. K.; Yang, Y.; Yanush, S.; Yao, L.; Yao, W.-M.; Yasu, Y.; Yatsenko, E.; Yau Wong, K. H.; Ye, J.; Ye, S.; Yeletskikh, I.; Yen, A. L.; Yildirim, E.; Yilmaz, M.; Yoosoofmiya, R.; Yorita, K.; Yoshida, R.; Yoshihara, K.; Young, C.; Young, C. J. S.; Youssef, S.; Yu, D. R.; Yu, J.; Yu, J. M.; Yu, J.; Yuan, L.; Yurkewicz, A.; Yusuff, I.; Zabinski, B.; Zaidan, R.; Zaitsev, A. M.; Zaman, A.; Zambito, S.; Zanello, L.; Zanzi, D.; Zeitnitz, C.; Zeman, M.; Zemla, A.; Zengel, K.; Zenin, O.; Ženiš, T.; Zerwas, D.; Zevi Della Porta, G.; Zhang, D.; Zhang, F.; Zhang, H.; Zhang, J.; Zhang, L.; Zhang, R.; Zhang, X.; Zhang, Z.; Zhao, Y.; Zhao, Z.; Zhemchugov, A.; Zhong, J.; Zhou, B.; Zhou, L.; Zhou, N.; Zhu, C. G.; Zhu, H.; Zhu, J.; Zhu, Y.; Zhuang, X.; Zhukov, K.; Zibell, A.; Zieminska, D.; Zimine, N. I.; Zimmermann, C.; Zimmermann, R.; Zimmermann, S.; Zimmermann, S.; Zinonos, Z.; Ziolkowski, M.; Zobernig, G.; Zoccoli, A.; Zur Nedden, M.; Zurzolo, G.; Zutshi, V.; Zwalinski, L.; Atlas Collaboration

    2015-01-01

    This Letter presents a search at the LHC for s-channel single top-quark production in proton-proton collisions at a centre-of-mass energy of 8 TeV. The analyzed data set was recorded by the ATLAS detector and corresponds to an integrated luminosity of 20.3 fb-1. Selected events contain one charged lepton, large missing transverse momentum and exactly two b-tagged jets. A multivariate event classifier based on boosted decision trees is developed to discriminate s-channel single top-quark events from the main background contributions. The signal extraction is based on a binned maximum-likelihood fit of the output classifier distribution. The analysis leads to an upper limit on the s-channel single top-quark production cross-section of 14.6 pb at the 95% confidence level. The fit gives a cross-section of σs = 5.0 ± 4.3 pb, consistent with the Standard Model expectation.

  19. Search for s-channel single top-quark production in proton-proton collisions at √ s=8 TeV with the ATLAS detector

    DOE PAGES

    Aad, G.; Abbott, B.; Abdallah, J.; ...

    2015-01-05

    This Letter presents a search at the LHC for s-channel single top-quark production in proton–proton collisions at a centre-of-mass energy of 8 TeV. The analyzed data set was recorded by the ATLAS detector and corresponds to an integrated luminosity of 20.3 fb -1. The selected events contain one charged lepton, large missing transverse momentum and exactly two b-tagged jets. A multivariate event classifier based on boosted decision trees is developed to discriminate s-channel single top-quark events from the main background contributions. The signal extraction is based on a binned maximum-likelihood fit of the output classifier distribution. The analysis leads tomore » an upper limit on the s-channel single top-quark production cross-section of 14.6 pb at the 95% confidence level. The fit gives a cross-section of σ s=5.0 ± 4.3 pb, consistent with the Standard Model expectation.« less

  20. The topogenic function of S4 promotes membrane insertion of the voltage-sensor domain in the KvAP channel.

    PubMed

    Mishima, Eriko; Sato, Yoko; Nanatani, Kei; Hoshi, Naomi; Lee, Jong-Kook; Schiller, Nina; von Heijne, Gunnar; Sakaguchi, Masao; Uozumi, Nobuyuki

    2016-12-01

    Voltage-dependent K + (K V ) channels control K + permeability in response to shifts in the membrane potential. Voltage sensing in K V channels is mediated by the positively charged transmembrane domain S4. The best-characterized K V channel, KvAP, lacks the distinct hydrophilic region corresponding to the S3-S4 extracellular loop that is found in other K + channels. In the present study, we evaluated the topogenic properties of the transmembrane regions within the voltage-sensing domain in KvAP. S3 had low membrane insertion activity, whereas S4 possessed a unique type-I signal anchor (SA-I) function, which enabled it to insert into the membrane by itself. S4 was also found to function as a stop-transfer signal for retention in the membrane. The length and structural nature of the extracellular S3-S4 loop affected the membrane insertion of S3 and S4, suggesting that S3 membrane insertion was dependent on S4. Replacement of charged residues within the transmembrane regions with residues of opposite charge revealed that Asp 72 in S2 and Glu 93 in S3 contributed to membrane insertion of S3 and S4, and increased the stability of S4 in the membrane. These results indicate that the SA-I function of S4, unique among K + channels studied to date, promotes the insertion of S3 into the membrane, and that the charged residues essential for voltage sensing contribute to the membrane-insertion of the voltage sensor domain in KvAP. © 2016 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

  1. The S4–S5 Linker Acts as a Signal Integrator for hERG K+ Channel Activation and Deactivation Gating

    PubMed Central

    Ng, Chai Ann; Perry, Matthew D.; Tan, Peter S.; Hill, Adam P.; Kuchel, Philip W.; Vandenberg, Jamie I.

    2012-01-01

    Human ether-à-go-go-related gene (hERG) K+ channels have unusual gating kinetics. Characterised by slow activation/deactivation but rapid inactivation/recovery from inactivation, the unique gating kinetics underlie the central role hERG channels play in cardiac repolarisation. The slow activation and deactivation kinetics are regulated in part by the S4–S5 linker, which couples movement of the voltage sensor domain to opening of the activation gate at the distal end of the inner helix of the pore domain. It has also been suggested that cytosolic domains may interact with the S4–S5 linker to regulate activation and deactivation kinetics. Here, we show that the solution structure of a peptide corresponding to the S4–S5 linker of hERG contains an amphipathic helix. The effects of mutations at the majority of residues in the S4–S5 linker of hERG were consistent with the previously identified role in coupling voltage sensor movement to the activation gate. However, mutations to Ser543, Tyr545, Gly546 and Ala548 had more complex phenotypes indicating that these residues are involved in additional interactions. We propose a model in which the S4–S5 linker, in addition to coupling VSD movement to the activation gate, also contributes to interactions that stabilise the closed state and a separate set of interactions that stabilise the open state. The S4–S5 linker therefore acts as a signal integrator and plays a crucial role in the slow deactivation kinetics of the channel. PMID:22359612

  2. 47 CFR 80.57 - Canada/U.S.A. channeling arrangement for VHF maritime public correspondence.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Island within the Canada/U.S.A. Coordination Zone. (5) Inland Waters Primary Channel. A channel intended... (Canada) 26 24 Juan de Fuca East (Canada) 86 84 Gulf Islands 27 1 Strait of Georgia South 26 86 Howe Sound 24 84 Strait of Georgia North 26 87 Campbell River 28 85 Washington (Coastal Waters): Cape Johnson 26...

  3. 47 CFR 80.57 - Canada/U.S.A. channeling arrangement for VHF maritime public correspondence.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Island within the Canada/U.S.A. Coordination Zone. (5) Inland Waters Primary Channel. A channel intended... (Canada) 26 24 Juan de Fuca East (Canada) 86 84 Gulf Islands 27 1 Strait of Georgia South 26 86 Howe Sound 24 84 Strait of Georgia North 26 87 Campbell River 28 85 Washington (Coastal Waters): Cape Johnson 26...

  4. 47 CFR 80.57 - Canada/U.S.A. channeling arrangement for VHF maritime public correspondence.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... Island within the Canada/U.S.A. Coordination Zone. (5) Inland Waters Primary Channel. A channel intended... (Canada) 26 24 Juan de Fuca East (Canada) 86 84 Gulf Islands 27 1 Strait of Georgia South 26 86 Howe Sound 24 84 Strait of Georgia North 26 87 Campbell River 28 85 Washington (Coastal Waters): Cape Johnson 26...

  5. 47 CFR 80.57 - Canada/U.S.A. channeling arrangement for VHF maritime public correspondence.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... Island within the Canada/U.S.A. Coordination Zone. (5) Inland Waters Primary Channel. A channel intended... (Canada) 26 24 Juan de Fuca East (Canada) 86 84 Gulf Islands 27 1 Strait of Georgia South 26 86 Howe Sound 24 84 Strait of Georgia North 26 87 Campbell River 28 85 Washington (Coastal Waters): Cape Johnson 26...

  6. 47 CFR 80.57 - Canada/U.S.A. channeling arrangement for VHF maritime public correspondence.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... Island within the Canada/U.S.A. Coordination Zone. (5) Inland Waters Primary Channel. A channel intended... (Canada) 26 24 Juan de Fuca East (Canada) 86 84 Gulf Islands 27 1 Strait of Georgia South 26 86 Howe Sound 24 84 Strait of Georgia North 26 87 Campbell River 28 85 Washington (Coastal Waters): Cape Johnson 26...

  7. Dual Channel S-Band Frequency Modulated Continuous Wave Through-Wall Radar Imaging

    PubMed Central

    Oh, Daegun; Kim, Sunwoo; Chong, Jong-Wha

    2018-01-01

    This article deals with the development of a dual channel S-Band frequency-modulated continuous wave (FMCW) system for a through-the-wall imaging (TWRI) system. Most existing TWRI systems using FMCW were developed for synthetic aperture radar (SAR) which has many drawbacks such as the need for several antenna elements and movement of the system. Our implemented TWRI system comprises a transmitting antenna and two receiving antennas, resulting in a significant reduction of the number of antenna elements. Moreover, a proposed algorithm for range-angle-Doppler 3D estimation based on a 3D shift invariant structure is utilized in our implemented dual channel S-band FMCW TWRI system. Indoor and outdoor experiments were conducted to image the scene beyond a wall for water targets and person targets, respectively. The experimental results demonstrate that high-quality imaging can be achieved under both experimental scenarios. PMID:29361777

  8. Evidence for s-channel single-top-quark production in events with one charged lepton and two jets at CDF.

    PubMed

    Aaltonen, T; Amerio, S; Amidei, D; Anastassov, A; Annovi, A; Antos, J; Apollinari, G; Appel, J A; Arisawa, T; Artikov, A; Asaadi, J; Ashmanskas, W; Auerbach, B; Aurisano, A; Azfar, F; Badgett, W; Bae, T; Barbaro-Galtieri, A; Barnes, V E; Barnett, B A; Barria, P; Bartos, P; Bauce, M; Bedeschi, F; Behari, S; Bellettini, G; Bellinger, J; Benjamin, D; Beretvas, A; Bhatti, A; Bland, K R; Blumenfeld, B; Bocci, A; Bodek, A; Bortoletto, D; Boudreau, J; Boveia, A; Brigliadori, L; Bromberg, C; Brucken, E; Budagov, J; Budd, H S; Burkett, K; Busetto, G; Bussey, P; Butti, P; Buzatu, A; Calamba, A; Camarda, S; Campanelli, M; Canelli, F; Carls, B; Carlsmith, D; Carosi, R; Carrillo, S; Casal, B; Casarsa, M; Castro, A; Catastini, P; Cauz, D; Cavaliere, V; Cavalli-Sforza, M; Cerri, A; Cerrito, L; Chen, Y C; Chertok, M; Chiarelli, G; Chlachidze, G; Cho, K; Chokheli, D; Clark, A; Clarke, C; Convery, M E; Conway, J; Corbo, M; Cordelli, M; Cox, C A; Cox, D J; Cremonesi, M; Cruz, D; Cuevas, J; Culbertson, R; d'Ascenzo, N; Datta, M; de Barbaro, P; Demortier, L; Deninno, M; D'Errico, M; Devoto, F; Di Canto, A; Di Ruzza, B; Dittmann, J R; Donati, S; D'Onofrio, M; Dorigo, M; Driutti, A; Ebina, K; Edgar, R; Elagin, A; Erbacher, R; Errede, S; Esham, B; Farrington, S; Fernández Ramos, J P; Field, R; Flanagan, G; Forrest, R; Franklin, M; Freeman, J C; Frisch, H; Funakoshi, Y; Galloni, C; Garfinkel, A F; Garosi, P; Gerberich, H; Gerchtein, E; Giagu, S; Giakoumopoulou, V; Gibson, K; Ginsburg, C M; Giokaris, N; Giromini, P; Giurgiu, G; Glagolev, V; Glenzinski, D; Gold, M; Goldin, D; Golossanov, A; Gomez, G; Gomez-Ceballos, G; Goncharov, M; González López, O; Gorelov, I; Goshaw, A T; Goulianos, K; Gramellini, E; Grinstein, S; Grosso-Pilcher, C; Group, R C; Guimaraes da Costa, J; Hahn, S R; Han, J Y; Happacher, F; Hara, K; Hare, M; Harr, R F; Harrington-Taber, T; Hatakeyama, K; Hays, C; Heinrich, J; Herndon, M; Hocker, A; Hong, Z; Hopkins, W; Hou, S; Hughes, R E; Husemann, U; Hussein, M; Huston, J; Introzzi, G; Iori, M; Ivanov, A; James, E; Jang, D; Jayatilaka, B; Jeon, E J; Jindariani, S; Jones, M; Joo, K K; Jun, S Y; Junk, T R; Kambeitz, M; Kamon, T; Karchin, P E; Kasmi, A; Kato, Y; Ketchum, W; Keung, J; Kilminster, B; Kim, D H; Kim, H S; Kim, J E; Kim, M J; Kim, S H; Kim, S B; Kim, Y J; Kim, Y K; Kimura, N; Kirby, M; Knoepfel, K; Kondo, K; Kong, D J; Konigsberg, J; Kotwal, A V; Kreps, M; Kroll, J; Kruse, M; Kuhr, T; Kurata, M; Laasanen, A T; Lammel, S; Lancaster, M; Lannon, K; Latino, G; Lee, H S; Lee, J S; Leo, S; Leone, S; Lewis, J D; Limosani, A; Lipeles, E; Lister, A; Liu, H; Liu, Q; Liu, T; Lockwitz, S; Loginov, A; Lucchesi, D; Lucà, A; Lueck, J; Lujan, P; Lukens, P; Lungu, G; Lys, J; Lysak, R; Madrak, R; Maestro, P; Malik, S; Manca, G; Manousakis-Katsikakis, A; Marchese, L; Margaroli, F; Marino, P; Martínez, M; Matera, K; Mattson, M E; Mazzacane, A; Mazzanti, P; McNulty, R; Mehta, A; Mehtala, P; Mesropian, C; Miao, T; Mietlicki, D; Mitra, A; Miyake, H; Moed, S; Moggi, N; Moon, C S; Moore, R; Morello, M J; Mukherjee, A; Muller, Th; Murat, P; Mussini, M; Nachtman, J; Nagai, Y; Naganoma, J; Nakano, I; Napier, A; Nett, J; Neu, C; Nigmanov, T; Nodulman, L; Noh, S Y; Norniella, O; Oakes, L; Oh, S H; Oh, Y D; Oksuzian, I; Okusawa, T; Orava, R; Ortolan, L; Pagliarone, C; Palencia, E; Palni, P; Papadimitriou, V; Parker, W; Pauletta, G; Paulini, M; Paus, C; Phillips, T J; Piacentino, G; Pianori, E; Pilot, J; Pitts, K; Plager, C; Pondrom, L; Poprocki, S; Potamianos, K; Pranko, A; Prokoshin, F; Ptohos, F; Punzi, G; Ranjan, N; Redondo Fernández, I; Renton, P; Rescigno, M; Rimondi, F; Ristori, L; Robson, A; Rodriguez, T; Rolli, S; Ronzani, M; Roser, R; Rosner, J L; Ruffini, F; Ruiz, A; Russ, J; Rusu, V; Sakumoto, W K; Sakurai, Y; Santi, L; Sato, K; Saveliev, V; Savoy-Navarro, A; Schlabach, P; Schmidt, E E; Schwarz, T; Scodellaro, L; Scuri, F; Seidel, S; Seiya, Y; Semenov, A; Sforza, F; Shalhout, S Z; Shears, T; Shepard, P F; Shimojima, M; Shochet, M; Shreyber-Tecker, I; Simonenko, A; Sliwa, K; Smith, J R; Snider, F D; Song, H; Sorin, V; St Denis, R; Stancari, M; Stentz, D; Strologas, J; Sudo, Y; Sukhanov, A; Suslov, I; Takemasa, K; Takeuchi, Y; Tang, J; Tecchio, M; Teng, P K; Thom, J; Thomson, E; Thukral, V; Toback, D; Tokar, S; Tollefson, K; Tomura, T; Tonelli, D; Torre, S; Torretta, D; Totaro, P; Trovato, M; Ukegawa, F; Uozumi, S; Velev, G; Vellidis, C; Vernieri, C; Vidal, M; Vilar, R; Vizán, J; Vogel, M; Volpi, G; Vázquez, F; Wagner, P; Wallny, R; Wang, S M; Waters, D; Wester, W C; Whiteson, D; Wicklund, A B; Wilbur, S; Williams, H H; Wilson, J S; Wilson, P; Winer, B L; Wittich, P; Wolbers, S; Wolfe, H; Wright, T; Wu, X; Wu, Z; Yamamoto, K; Yamato, D; Yang, T; Yang, U K; Yang, Y C; Yao, W-M; Yeh, G P; Yi, K; Yoh, J; Yorita, K; Yoshida, T; Yu, G B; Yu, I; Zanetti, A M; Zeng, Y; Zhou, C; Zucchelli, S

    2014-06-13

    We report evidence for s-channel single-top-quark production in proton-antiproton collisions at center-of-mass energy sqrt[s] = 1.96 TeV using a data set that corresponds to an integrated luminosity of 9.4 fb(-1) collected by the Collider Detector at Fermilab. We select events consistent with the s-channel process including two jets and one leptonically decaying W boson. The observed significance is 3.8 standard deviations with respect to the background-only prediction. Assuming a top-quark mass of 172.5 GeV/c(2), we measure the s-channel cross section to be 1.41(-0.42)(+0.44) pb.

  9. Tryptophan scanning mutagenesis of the HERG K+ channel: the S4 domain is loosely packed and likely to be lipid exposed

    PubMed Central

    Subbiah, Rajesh N; Kondo, Mari; Campbell, Terence J; Vandenberg, Jamie I

    2005-01-01

    Inherited mutations or drug-induced block of voltage-gated ion channels, including the human ether-à-go-go-related gene (HERG) K+ channel, are significant causes of malignant arrhythmias and sudden death. The fourth transmembrane domain (S4) of these channels contains multiple positive charges that move across the membrane electric field in response to changes in transmembrane voltage. In HERG K+ channels, the movement of the S4 domain across the transmembrane electric field is particularly slow. To examine the basis of the slow movement of the HERG S4 domain and specifically to probe the relationship between the S4 domain with the lipid bilayer and rest of the channel protein, we individually mutated each of the S4 amino acids in HERG (L524–L539) to tryptophan, and characterized the activation and deactivation properties of the mutant channels in Xenopus oocytes, using two-electrode voltage-clamp methods. Tryptophan has a large bulky hydrophobic sidechain and so should be tolerated at positions that interact with lipid, but not at positions involved in close protein–protein interactions. Significantly, we found that all S4 tryptophan mutants were functional. These data indicate that the S4 domain is loosely packed within the rest of the voltage sensor domain and is likely to be lipid exposed. Further, we identified residues K525, R528 and K538 as being the most important for slow activation of the channels. PMID:16166152

  10. The channels of Mars

    NASA Technical Reports Server (NTRS)

    Baker, Victor R.

    1988-01-01

    The geomorphology of Mars is discussed, focusing on the Martian channels. The great flood channels of Mars, the processes of channel erosion, and dendritic channel networks, are examined. The topography of the Channeled Scabland region of the northwestern U.S. is described and compared to the Martian channels. The importance of water in the evolution of the channel systems is considered.

  11. A limited 4 Å radial displacement of the S4-S5 linker is sufficient for internal gate closing in Kv channels.

    PubMed

    Faure, Élise; Starek, Greg; McGuire, Hugo; Bernèche, Simon; Blunck, Rikard

    2012-11-16

    Voltage-gated ion channels are responsible for the generation of action potentials in our nervous system. Conformational rearrangements in their voltage sensor domains in response to changes of the membrane potential control pore opening and thus ion conduction. Crystal structures of the open channel in combination with a wealth of biophysical data and molecular dynamics simulations led to a consensus on the voltage sensor movement. However, the coupling between voltage sensor movement and pore opening, the electromechanical coupling, occurs at the cytosolic face of the channel, from where no structural information is available yet. In particular, the question how far the cytosolic pore gate has to close to prevent ion conduction remains controversial. In cells, spectroscopic methods are hindered because labeling of internal sites remains difficult, whereas liposomes or detergent solutions containing purified ion channels lack voltage control. Here, to overcome these problems, we controlled the state of the channel by varying the lipid environment. This way, we directly measured the position of the S4-S5 linker in both the open and the closed state of a prokaryotic Kv channel (KvAP) in a lipid environment using Lanthanide-based resonance energy transfer. We were able to reconstruct the movement of the covalent link between the voltage sensor and the pore domain and used this information as restraints for molecular dynamics simulations of the closed state structure. We found that a small decrease of the pore radius of about 3-4 Å is sufficient to prevent ion permeation through the pore.

  12. E-Cigarette Market Trends in Traditional U.S. Retail Channels, 2012-2013.

    PubMed

    Giovenco, Daniel P; Hammond, David; Corey, Catherine G; Ambrose, Bridget K; Delnevo, Cristine D

    2015-10-01

    E-cigarette sales continue to increase in the United States. To date, little surveillance research has documented the specific product attributes driving growth. This study uses national market scanner data to describe sales trends in traditional U.S. tobacco retail channels between 2012 and 2013 and identifies product features associated with sales increases. Data on e-cigarette sales in convenience stores, drug stores, grocery stores, and mass merchandisers in the United States were obtained from the Nielsen Company. Each product was coded for attributes such as brand, flavor, and unit size. Total sales volume, market share, and percent growth were calculated for various product attributes. E-cigarette sales more than doubled between 2012 and 2013, from $273.6 million to $636.2 million, respectively. Growth was particularly strong in the convenience store channel. Blu eCigs quickly emerged as the best-selling brand and in 2013 constituted nearly half (44.1%) of overall sales. Although fruit-flavored and other flavored products experienced marked growth, unflavored and menthol e-cigarettes overwhelmingly dominated the market. Sales of single unit products (likely disposable e-cigarettes) increased by 216.4%, a much faster rate than multi-unit packs and cartridge refills. In traditional U.S. retail channels, particularly the convenience store channel, sales of e-cigarettes continue to grow, with brands like blu and disposable products as the likely drivers. Given the rapidly-changing market, expanded surveillance is needed to monitor sales not only in traditional retail locations, but sales online and in specialty "vape shops," as well. © The Author 2014. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  13. E-Cigarette Market Trends in Traditional U.S. Retail Channels, 2012–2013

    PubMed Central

    Hammond, David; Corey, Catherine G.; Ambrose, Bridget K.; Delnevo, Cristine D.

    2015-01-01

    Introduction: E-cigarette sales continue to increase in the United States. To date, little surveillance research has documented the specific product attributes driving growth. This study uses national market scanner data to describe sales trends in traditional U.S. tobacco retail channels between 2012 and 2013 and identifies product features associated with sales increases. Methods: Data on e-cigarette sales in convenience stores, drug stores, grocery stores, and mass merchandisers in the United States were obtained from the Nielsen Company. Each product was coded for attributes such as brand, flavor, and unit size. Total sales volume, market share, and percent growth were calculated for various product attributes. Results: E-cigarette sales more than doubled between 2012 and 2013, from $273.6 million to $636.2 million, respectively. Growth was particularly strong in the convenience store channel. Blu eCigs quickly emerged as the best-selling brand and in 2013 constituted nearly half (44.1%) of overall sales. Although fruit-flavored and other flavored products experienced marked growth, unflavored and menthol e-cigarettes overwhelmingly dominated the market. Sales of single unit products (likely disposable e-cigarettes) increased by 216.4%, a much faster rate than multi-unit packs and cartridge refills. Conclusions: In traditional U.S. retail channels, particularly the convenience store channel, sales of e-cigarettes continue to grow, with brands like blu and disposable products as the likely drivers. Given the rapidly-changing market, expanded surveillance is needed to monitor sales not only in traditional retail locations, but sales online and in specialty “vape shops,” as well. PMID:25542918

  14. Computational investigation of drug-resistant mutant of M2 proton channel (S31N) against rimantadine.

    PubMed

    Karthick, V; Ramanathan, K

    2014-11-01

    M2 proton channel is the target for treating the patients who ere suffering from influenza A infection, which facilitates the spread of virions. Amantadine and rimantadine are adamantadine-based drugs, which target M2 proton channel and inhibit the viral replication. Preferably, rimantadine drug is used more than amantadine because of its fewer side effects. However, S31N mutation in the M2 proton channel was highly resistant to the rimantadine drug. Therefore, in the present study, we focused to understand the drug-resistance mechanism of S31N mutation with the aid of molecular docking and dynamics approach. The docking analysis undoubtedly indicates that affinity for rimantadine with mutant-type M2 proton channel is significantly lesser than the native-type M2 proton channel. In addition, RMSD, RMSF, and principal component analysis suggested that the mutation shows increased flexibility. Furthermore, the intermolecular hydrogen bonds analysis showed that there is a complete loss of hydrogen bonds in the mutant complex. On the whole, we conclude that the intermolecular contact was maintained by D-44, a key residue for stable binding of rimantadine. These findings are certainly helpful for better understanding of drug-resistance mechanism and also helpful for designing new drugs for treating influenza infection against drug-resistance target.

  15. Connectivity of Secondary Channels in the Floodplain of a Low-Gradient Midwestern U.S. Agricultural River

    NASA Astrophysics Data System (ADS)

    Czuba, J. A.; David, S. R.; Edmonds, D. A.

    2016-12-01

    Floodplains of low-gradient Midwestern U.S. agricultural rivers are commonly dissected by a network of secondary channels that convey flow only during flood events. These networks of secondary channels have only recently been revealed by high resolution digital elevation models. Secondary channels, as referred to here, span multiple meander wavelengths and appear fundamentally different from chute channels. While secondary channels have been described to some extent in other river systems, our focus here is on those found in Indiana, which are revealed by state-wide LiDAR data acquired in 2011. In this work, we quantify how the network connectivity of the secondary channels in the floodplain develops as a function of flow stage. Secondary channels begin conveying water at stages just below bankfull, become an interconnected web of flow pathways above bankfull stage, and are completely inundated at higher stages. We construct a two-dimensional numerical model of the river/floodplain system from LiDAR data and from main-channel river bathymetry in order to obtain the extent of floodplain inundation at various flows. The inundated area within the secondary channels is then converted into a river/floodplain flow-channel network and quantified using various network metrics. Future work will explore the morphodynamics of this river/floodplain system extended to 100-1,000 year timescales. The goal is to develop a simple model to test hypotheses about how these floodplain channels evolve. Relevant research questions include: do secondary channels serve as preferential avulsion pathways? Or could secondary channels evolve to create a multi-channeled anabranching system? Furthermore, under what hydrologic and sedimentologic conditions would a river/floodplain system evolve to one state or another?

  16. R- and S-terbutaline activate large conductance and Ca2+ dependent K+ (BKCa) channel through interacting with β2 and M receptor respectively.

    PubMed

    Fan, Zhuo; Lin, Wei; Lv, Nanying; Ye, Yanrui; Tan, Wen

    2016-11-01

    This study investigated the effect of the β 2 receptor agonist terbutaline on the single channel activity of BK Ca channel. The effects of racemate and two isomers of terbutaline were all assessed. β 2 adrenoceptors were stably overexpressed on HEK293 cells by lentiviral transduction method and chicken BK Ca channels were transiently expressed on normal HEK293 cell line or HEK293 cells overexpressing β 2 receptors. Data showed that terbutaline significantly increased the single channel open probability of BK Ca channel within 10min. The channel activating effects of terbutaline are stereoselective and mainly stay with the R-enantiomers. The opening probability of BK Ca channel at 10min after drug application normalized to that just before drug application (Po10/Po0s) for R- and S-terbutaline were 7.85±3.20 and 1.06±0.45 respectively at 1μM concentration, corresponding to 28.37±9.96 and 2.68±1.09 at the higher concentration of 10μM. ICI 118551 blocked the effect of R- but not S-terbutaline (10μM), whereas atropine blocked the channel activating effects of S-terbutaline of higher concentration. In addition, the muscarinic receptor agonist carbachol increased the BK Ca channel activity in an atropine-sensitive manner as an positive control experiment, which indicate the involvement of M receptor in the channel activating effect of S-terbutaline. Copyright © 2016. Published by Elsevier B.V.

  17. [Effects of phoxim and fenvalerate on TTX-S and TTX-R sodium channels in the DRG neurons of adult rat].

    PubMed

    Wang, X; Xiao, H; Dai, X; Liu, X; Yu, X; Wu, J

    2000-05-01

    To study the joint neurotoxic effects of phoxim (Pho) and fenvalerate (Fen) on tetrodotoxin-sensitive (TTX-S) and tetrodotoxin-resistant (TTX-R) Na(+) currents in dorsal root ganglion (DRG) neurons of adult rat. Whole cell patch clamp technique was used to test the effects of Pho and Fen on TTX-S and TTX-R sodium currents in DRG neurons. The inactivation of TTX-R sodium channel was obviously slowed down by Fen. The tau(Na) of peak currents at doses of 10, 50 and 100 micromol/L Fen and control groups were (8.10 +/- 2.41) ms, (11.78 +/- 2.76) ms, P < 0.01, (8.76 +/-1.94) ms, P < 0.05 and (6.41 +/- 1.32) ms respectively. The inactivation of TTX-R sodium channel tail currents was also significantly delayed by Fen. The tau(Na) of the tail currents at doses of 10, 50, 100 micromol/L Fen and control groups were 6.11 +/- 0.52 (P < 0.05), 7.82 +/- 0.82 (P < 0.05), 7.23 +/- 1.09 (P < 0.05) and (4.91 +/- 0.97) ms separately. As compared with TTX-R sodium channel, the TTX-S sodium channel was less responsive to Fen exposure, which only led to slowly decay TTX-S sodium tail currents. There was no any effect of Pho on the TTX-S and TTX-R sodium channels. The mixed treatment of a Pho and Fen did not show joint effect on the sodium currents. Both the peak and tail currents are changed by Fen, however, Fen has more remarkable effects on TTX-R than on TTX-S sodium channel. The combined exposure to Pho and Fen shows no joint effect on the sodium channel.

  18. S-glutathionylation of an auxiliary subunit confers redox sensitivity to Kv4 channel inactivation.

    PubMed

    Jerng, Henry H; Pfaffinger, Paul J

    2014-01-01

    Reactive oxygen species (ROS) regulate ion channels, modulate neuronal excitability, and contribute to the etiology of neurodegenerative disorders. ROS differentially suppress fast "ball-and-chain" N-type inactivation of cloned Kv1 and Kv3 potassium channels but not of Kv4 channels, likely due to a lack of reactive cysteines in Kv4 N-termini. Recently, we discovered that N-type inactivation of Kv4 channel complexes can be independently conferred by certain N-terminal variants of Kv4 auxiliary subunits (DPP6a, DPP10a). Here, we report that both DPP6a and DPP10a, like Kv subunits with redox-sensitive N-type inactivation, contain a highly conserved cysteine in their N-termini (Cys-13). To test if N-type inactivation mediated by DPP6a or DPP10a is redox sensitive, Xenopus oocyte recordings were performed to examine the effects of two common oxidants, tert-butyl hydroperoxide (tBHP) and diamide. Both oxidants markedly modulate DPP6a- or DPP10a-conferred N-type inactivation of Kv4 channels, slowing the overall inactivation and increasing the peak current. These functional effects are fully reversed by the reducing agent dithiothreitol (DTT) and appear to be due to a selective modulation of the N-type inactivation mediated by these auxiliary subunits. Mutation of DPP6a Cys-13 to serine eliminated the tBHP or diamide effects, confirming the importance of Cys-13 to the oxidative regulation. Biochemical studies designed to elucidate the underlying molecular mechanism show no evidence of protein-protein disulfide linkage formation following cysteine oxidation. Instead, using a biotinylated glutathione (BioGEE) reagent, we discovered that oxidation by tBHP or diamide leads to S-glutathionylation of Cys-13, suggesting that S-glutathionylation underlies the regulation of fast N-type inactivation by redox. In conclusion, our studies suggest that Kv4-based A-type current in neurons may show differential redox sensitivity depending on whether DPP6a or DPP10a is highly expressed

  19. Water Dynamics and Dewetting Transitions in the Small Mechanosensitive Channel MscS

    PubMed Central

    Anishkin, Andriy; Sukharev, Sergei

    2004-01-01

    The dynamics of confined water in capillaries and nanotubes suggests that gating of ion channels may involve not only changes of the pore geometry, but also transitions between water-filled and empty states in certain locations. The recently solved heptameric structure of the small mechanosensitive channel of Escherichia coli, MscS, has revealed a relatively wide (7–15 Å) yet highly hydrophobic transmembrane pore. Continuum estimations based on the properties of pore surface suggest low conductance and a thermodynamic possibility of dewetting. To test the predictions we performed molecular dynamics simulations of MscS filled with flexible TIP3P water. Irrespective to the initial conditions, several independent 6-ns simulations converged to the same stable state with the pore water-filled in the wider part, but predominantly empty in the narrow hydrophobic part, displaying intermittent vapor-liquid transitions. The polar gain-of-function substitution L109S in the constriction resulted in a stable hydration of the entire pore. Steered passages of Cl− ions through the narrow part of the pore consistently produced partial ion dehydration and required a force of 200–400 pN to overcome an estimated barrier of 10–20 kcal/mole, implying negligibly low conductance. We conclude that the crystal structure of MscS does not represent an open state. We infer that MscS gate, which is similar to that of the nicotinic ACh receptor, involves a vapor-lock mechanism where limited changes of geometry or surface polarity can locally switch the regime between water-filled (conducting) and empty (nonconducting) states. PMID:15111405

  20. Charged and Neutral Particles Channeling Phenomena Channeling 2008

    NASA Astrophysics Data System (ADS)

    Dabagov, Sultan B.; Palumbo, Luigi

    2010-04-01

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

  1. The hitchhiker’s guide to the voltage-gated sodium channel galaxy

    PubMed Central

    2016-01-01

    Eukaryotic voltage-gated sodium (Nav) channels contribute to the rising phase of action potentials and served as an early muse for biophysicists laying the foundation for our current understanding of electrical signaling. Given their central role in electrical excitability, it is not surprising that (a) inherited mutations in genes encoding for Nav channels and their accessory subunits have been linked to excitability disorders in brain, muscle, and heart; and (b) Nav channels are targeted by various drugs and naturally occurring toxins. Although the overall architecture and behavior of these channels are likely to be similar to the more well-studied voltage-gated potassium channels, eukaryotic Nav channels lack structural and functional symmetry, a notable difference that has implications for gating and selectivity. Activation of voltage-sensing modules of the first three domains in Nav channels is sufficient to open the channel pore, whereas movement of the domain IV voltage sensor is correlated with inactivation. Also, structure–function studies of eukaryotic Nav channels show that a set of amino acids in the selectivity filter, referred to as DEKA locus, is essential for Na+ selectivity. Structures of prokaryotic Nav channels have also shed new light on mechanisms of drug block. These structures exhibit lateral fenestrations that are large enough to allow drugs or lipophilic molecules to gain access into the inner vestibule, suggesting that this might be the passage for drug entry into a closed channel. In this Review, we will synthesize our current understanding of Nav channel gating mechanisms, ion selectivity and permeation, and modulation by therapeutics and toxins in light of the new structures of the prokaryotic Nav channels that, for the time being, serve as structural models of their eukaryotic counterparts. PMID:26712848

  2. Differential inhibition of Ca2+ channels in mature rat cerebellar Purkinje cells by sFTX-3.3 and FTX-3.3.

    PubMed

    Dupere, J R; Moya, E; Blagbrough, I S; Usowicz, M M

    1996-01-01

    Synthetic funnel web spider toxin (sFTX-3.3) is a polyamine amide analogue of FTX, a toxin fraction isolated from the venom of the funnel web spider, Agelenopsis aperta, that blocks P-type Ca2+ channels. The structures of these polyamine containing compounds are not identical: sFTX-3.3 contains an amide carbonyl oxygen that is absent from the predicted structure of native FTX. Recently, a compound called FTX-3.3 was synthesized with the structure predicted for native FTX. We have compared the effects of polyamine amide sFTX-3.3 and polyamine FTX-3.3, on Ca2+ channel currents in the soma of mature rat cerebellar Purkinje neurons, in which the predominant Ca2+ channels are defined as P-type. Differential inhibition by sFTX-3.3 and FTX-3.3 revealed three populations of Ca2+ channels. One group, mediating approximately 66% of the current, was blocked by sFTX-3.3 with an IC50 (concentration producing half maximal inhibition) of 33 nM or by FTX-3.3 with an IC50 of 55 pM. A second population (5-25% of the total current) was inhibited by sFTX-3.3 with an IC50 of 33 nM, but was insensitive to FTX-3.3, while a third (10-30%) was blocked by FTX-3.3 with an IC50 of 125 nM and was resistant to sFTX-3.3. These channels also showed distinctive current-voltage relationships. Our results suggest that P-type Ca2+ channels in mature rat cerebellar Purkinje cells may be subdivided according to pharmacological and biophysical properties.

  3. The external pore loop interacts with S6 and S3-S4 linker in domain 4 to assume an essential role in gating control and anticonvulsant action in the Na+ channel

    PubMed Central

    Yang, Ya-Chin; Hsieh, Jui-Yi

    2009-01-01

    Carbamazepine, phenytoin, and lamotrigine are widely prescribed anticonvulsants in neurological clinics. These drugs bind to the same receptor site, probably with the diphenyl motif in their structure, to inhibit the Na+ channel. However, the location of the drug receptor remains controversial. In this study, we demonstrate close proximity and potential interaction between an external aromatic residue (W1716 in the external pore loop) and an internal aromatic residue (F1764 in the pore-lining part of the sixth transmembrane segment, S6) of domain 4 (D4), both being closely related to anticonvulsant and/or local anesthetic binding to the Na+ channel. Double-mutant cycle analysis reveals significant cooperativity between the two phenyl residues for anticonvulsant binding. Concomitant F1764C mutation evidently decreases the susceptibility of W1716C to external Cd2+ and membrane-impermeable methanethiosulfonate reagents. Also, the W1716E/F1764R and G1715E/F1764R double mutations significantly alter the selectivity for Na+ over K+ and markedly shift the activation curve, respectively. W1716 and F1764 therefore very likely form a link connecting the outer and inner compartments of the Na+ channel pore (in addition to the selectivity filter). Anticonvulsants and local anesthetics may well traverse this “S6 recess” without trespassing on the selectivity filter. Furthermore, we found that Y1618K, a point mutation in the S3-4 linker (the extracellular extension of D4S4), significantly alters the consequences of carbamazepine binding to the Na+ channel. The effect of Y1618K mutation, however, is abolished by concomitant point mutations in the vicinity of Y1618, but not by those in the internally located inactivation machinery, supporting a direct local rather than a long-range allosteric action. Moreover, Y1618 could interact with D4 pore residues W1716 and L1719 to have a profound effect on both channel gating and anticonvulsant action. We conclude that there are direct

  4. The external pore loop interacts with S6 and S3-S4 linker in domain 4 to assume an essential role in gating control and anticonvulsant action in the Na(+) channel.

    PubMed

    Yang, Ya-Chin; Hsieh, Jui-Yi; Kuo, Chung-Chin

    2009-08-01

    Carbamazepine, phenytoin, and lamotrigine are widely prescribed anticonvulsants in neurological clinics. These drugs bind to the same receptor site, probably with the diphenyl motif in their structure, to inhibit the Na(+) channel. However, the location of the drug receptor remains controversial. In this study, we demonstrate close proximity and potential interaction between an external aromatic residue (W1716 in the external pore loop) and an internal aromatic residue (F1764 in the pore-lining part of the sixth transmembrane segment, S6) of domain 4 (D4), both being closely related to anticonvulsant and/or local anesthetic binding to the Na(+) channel. Double-mutant cycle analysis reveals significant cooperativity between the two phenyl residues for anticonvulsant binding. Concomitant F1764C mutation evidently decreases the susceptibility of W1716C to external Cd(2+) and membrane-impermeable methanethiosulfonate reagents. Also, the W1716E/F1764R and G1715E/F1764R double mutations significantly alter the selectivity for Na(+) over K(+) and markedly shift the activation curve, respectively. W1716 and F1764 therefore very likely form a link connecting the outer and inner compartments of the Na(+) channel pore (in addition to the selectivity filter). Anticonvulsants and local anesthetics may well traverse this "S6 recess" without trespassing on the selectivity filter. Furthermore, we found that Y1618K, a point mutation in the S3-4 linker (the extracellular extension of D4S4), significantly alters the consequences of carbamazepine binding to the Na(+) channel. The effect of Y1618K mutation, however, is abolished by concomitant point mutations in the vicinity of Y1618, but not by those in the internally located inactivation machinery, supporting a direct local rather than a long-range allosteric action. Moreover, Y1618 could interact with D4 pore residues W1716 and L1719 to have a profound effect on both channel gating and anticonvulsant action. We conclude that there

  5. Electrophysiological Features of Single Store-Operated Calcium Channels in HEK S4 Cell Line with Stable STIM1 Protein Knockdown.

    PubMed

    Shalygin, A V; Vigont, V A; Glushankova, L N; Zimina, O A; Kolesnikov, D O; Skopin, A Yu; Kaznacheeva, E V

    2017-07-01

    An important role in intracellular calcium signaling is played by store-operated channels activated by STIM proteins, calcium sensors of the endoplasmic reticulum. In stable STIM1 knockdown HEK S4 cells, single channels activated by depletion of intracellular calcium stores were detected by cell-attached patch-clamp technique and their electrophysiological parameters were described. Comparison of the properties of single channels in HEK293 and HEK S4 cells revealed no significant differences in their current-voltage curves, while regulation of store-operated calcium channels in these cell lines depended on the level of STIM1 expression. We can conclude that electrophysiological peculiarities of store-regulated calcium entry observed in different cells can be explained by differences in STIM1 expression.

  6. Purification of the small mechanosensitive channel of Escherichia coli (MscS): the subunit structure, conduction, and gating characteristics in liposomes

    NASA Technical Reports Server (NTRS)

    Sukharev, Sergei

    2002-01-01

    The small mechanosensitive channel, MscS, is a part of the turgor-driven solute efflux system that protects bacteria from lysis in the event of osmotic downshift. It has been identified in Escherichia coli as a product of the orphan yggB gene, now called mscS (Levina et al., 1999, EMBO J. 18:1730). Here I show that that the isolated 31-kDa MscS protein is sufficient to form a functional mechanosensitive channel gated directly by tension in the lipid bilayer. MscS-6His complexes purified in the presence of octylglucoside and lipids migrate in a high-resolution gel-filtration column as particles of approximately 200 kDa. Consistent with that, the protein cross-linking patterns predict a hexamer. The channel reconstituted in soybean asolectin liposomes was activated by pressures of 20-60 mm Hg and displayed the same asymmetric I-V curve and slight anionic preference as in situ. At the same time, the single-channel conductance is proportional to the buffer conductivity in a wide range of salt concentrations. The rate of channel activation in response to increasing pressure gradient across the patch was slower than the rate of closure in response to decreasing steps of pressure gradient. Therefore, the open probability curves were recorded with descending series of pressures. Determination of the curvature of patches by video imaging permitted measurements of the channel activity as a function of membrane tension (gamma). Po(gamma) curves had the midpoint at 5.5 +/- 0.1 dyne/cm and gave estimates for the energy of opening DeltaG = 11.4 +/- 0.5 kT, and the transition-related area change DeltaA = 8.4 +/- 0.4 nm(2) when fitted with a two-state Boltzmann model. The correspondence between channel properties in the native and reconstituted systems is discussed.

  7. Reconstructive techniques for creation of catheterizable channels: tunneled and nipple valve channels

    PubMed Central

    Levy, Mya E.

    2016-01-01

    Cutaneous catheterizable channels allow for continent bladder emptying when an alternate route is desired. The goals of channel creation in the neurogenic bladder population are successful urine elimination, renal preservation, continence and lastly cosmesis. In addition to a particular surgeon’s comfort and experience with a given procedure, individual patient factors such as medical comorbidities, anatomic factors, and occupational function should be central to the selection of a surgical approach. An ideal channel is one that is short, straight, and well supported by associated blood supply and surrounding adventitia, so as to minimize difficulty with catheterization. Two types of channel continence mechanisms are discussed at length in this review—the tunneled channel, and the nipple valve. The appendicovesicostomy (Mitrofanoff), and reconfigured ileum (Yang-Monti) are both tunneled channels. The ileocecal valve is a commonly used nipple valve and provides continence when reinforced. The continent catheterizable ileal cecocystoplasty (CCIC) is an example of this channel technique. This method couples a tapered ileal limb as a catheterizable channel, the ileocecal valve as the continence mechanism, and the cecum and ascending colon as a bladder augmentation. While this procedure has higher perioperative complications relative to a simple tunneled channel, it has increased channel length flexibility and is also coupled with a bladder augment, which is completely performed using one bowel segment. Continent channel creation in adults can improve quality of life and minimize morbidity associated with neurogenic bladder. However, the decision to proceed with creation of a catheterizable channel should be made only after careful consideration of the patient’s medical comorbidities, physical abilities social support, and surgeon experience. PMID:26904419

  8. 500  Gb/s free-space optical transmission over strong atmospheric turbulence channels.

    PubMed

    Qu, Zhen; Djordjevic, Ivan B

    2016-07-15

    We experimentally demonstrate a high-spectral-efficiency, large-capacity, featured free-space-optical (FSO) transmission system by using low-density, parity-check (LDPC) coded quadrature phase shift keying (QPSK) combined with orbital angular momentum (OAM) multiplexing. The strong atmospheric turbulence channel is emulated by two spatial light modulators on which four randomly generated azimuthal phase patterns yielding the Andrews spectrum are recorded. The validity of such an approach is verified by reproducing the intensity distribution and irradiance correlation function (ICF) from the full-scale simulator. Excellent agreement of experimental, numerical, and analytical results is found. To reduce the phase distortion induced by the turbulence emulator, the inexpensive wavefront sensorless adaptive optics (AO) is used. To deal with remaining channel impairments, a large-girth LDPC code is used. To further improve the aggregate data rate, the OAM multiplexing is combined with WDM, and 500 Gb/s optical transmission over the strong atmospheric turbulence channels is demonstrated.

  9. CFTR Cl- channel and CFTR-associated ATP channel: distinct pores regulated by common gates.

    PubMed Central

    Sugita, M; Yue, Y; Foskett, J K

    1998-01-01

    The cystic fibrosis transmembrane conductance regulator (CFTR) is a chloride channel that is regulated by phosphorylation of the R domain and ATP hydrolysis at two nucleotide-binding domains (NBDs). It is controversial whether CFTR conducts ATP or whether CFTR might be closely associated with a separate ATP conductance. To characterize ATP channels associated with CFTR, we analyzed Cl- and ATP single channel-currents in excised inside-out membrane patches from MDCK epithelial cells transiently expressing CFTR. With 100 mM ATP in the pipette and 140 mM Cl- in the bath, ATP channels were associated with CFTR Cl- channels in two-thirds of patches that included CFTR. CFTR Cl- channels and CFTR-associated ATP channels had slope conductances of 7.4 pS and 5.2 pS, respectively, and had distinct reversal potentials and sensitivities to channel blockers. CFTR-associated ATP channels exhibited slow gating kinetics that depended on the presence of protein kinase A and cytoplasmic ATP, similar to CFTR Cl- channels. Gating kinetics of the ATP channels as well as the CFTR Cl- channels were similarly affected by non-hydrolyzable ATP analogues and mutations in the CFTR R domain and NBDs. Our results indicate that phosphorylation- and nucleotide-hydrolysis-dependent gating of CFTR is directly involved in gating of an associated ATP channel. However, the permeation pathways for Cl- and ATP are distinct and the ATP conduction pathway is not obligatorily associated with the expression of CFTR. PMID:9463368

  10. Compound-Specific Effects of Mutations at Val787 in DII-S6 of Nav1.4 Sodium Channels on the Action of Sodium Channel Inhibitor Insecticides

    PubMed Central

    von Stein, Richard T.; Soderlund, David M.

    2012-01-01

    Sodium channel inhibitor (SCI) insecticides are hypothesized to inhibit voltage-gated sodium channels by binding selectively to the slow-inactivated state. Replacement of valine at position 787 in the S6 segment of homology domain II of the rat Nav1.4 sodium channel by lysine (V787K) enchances slow inactivation of this channel whereas replacement by alanine or cysteine (V787A, V787C) inhibits slow inactivation. To test the hypothesis that SCI insecticides bind selectively to the slow-inactivated state, we constructed mutated Nav1.4/V787A, Nav1.4/V787C, and Nav1.4/V787K cDNAs, expressed wildtype and mutated channels with the auxiliary β1 subunit in Xenopus oocytes, and used the two-electrode voltage clamp technique to examine the effects of these mutations on channel inhibition by four SCI insecticides (indoxacarb, its bioactivated metabolite DCJW, metaflumizone, and RH3421). Mutations at Val787 affected SCI insecticide sensitivity in a manner that was independent of mutation-induced changes in slow inactivation gating. Sensitivity to inhibition by 10 μM indoxacarb was significantly increased in all three mutated channels, whereas sensitivity to inhibition by 10 μM metaflumizone was significantly reduced in Nav1.4/V787A channels and completely abolished in Nav1.4/V787K channels. The effects of Val787 mutations on metaflumizone were correlated with the hydrophobicity of the substituted amino acid rather than the extent of slow inactivation. None of the mutations at Val787 significantly affected the sensitivity to inhibition by DCJW or RH3421. These results demonstrate that the impact of mutations at Val787 on sodium channel inhibition by SCI insecticides depends on the specific insecticide examined and is independent of mutation-induced changes in slow inactivation gating. We propose that Val787 may be a unique determinant of metaflumizone binding. PMID:22983119

  11. Channel and Interface Management in a Heterogeneous Multi-Channel Multi-Radio Wireless Network

    DTIC Science & Technology

    2009-03-01

    its channel is changed, the change is advertised to neighbors. An R-interface is also used for transmitting packets that are to be sent on its...Agrawal, S. Banerjee, and S. Ganguly, “Distributed channel management in uncoordinated wireless environments.” in MOBI - COM, 2006, pp. 170–181. [18] W. Wang

  12. River channel adjustments in Southern Italy over the past 150 years and implications for channel recovery

    NASA Astrophysics Data System (ADS)

    Scorpio, Vittoria; Aucelli, Pietro P. C.; Giano, Salvatore I.; Pisano, Luca; Robustelli, Gaetano; Rosskopf, Carmen M.; Schiattarella, Marcello

    2015-12-01

    Multi-temporal GIS analysis of topographic maps and aerial photographs along with topographic and geomorphological surveys are used to assess evolutionary trends and key control factors of channel adjustments for five major rivers in southern Italy (the Trigno, Biferno, Volturno, Sinni and Crati rivers) to support assessment of channel recovery and river restoration. Three distinct phases of channel adjustment are identified over the past 150 years primarily driven by human disturbances. Firstly, slight channel widening dominated from the last decades of the nineteenth century to the 1950s. Secondly, from the 1950s to the end of the 1990s, altered sediment fluxes induced by in-channel mining and channel works brought about moderate to very intense incision (up to 6-7 m) accompanied by strong channel narrowing (up to 96%) and changes in channel configuration from multi-threaded to single-threaded patterns. Thirdly, the period from around 2000 to 2015 has been characterized by channel stabilization and local widening. Evolutionary trajectories of the rivers studied are quite similar to those reconstructed for other Italian rivers, particularly regarding the second phase of channel adjustments and ongoing transitions towards channel recovery in some reaches. Analyses of river dynamics, recovery potential and connectivity with sediment sources of the study reaches, framed in their catchment context, can be used as part of a wider interdisciplinary approach that views effective river restoration alongside sustainable and risk-reduced river management.

  13. Effects of cochlear-implant pulse rate and inter-channel timing on channel interactions and thresholds

    NASA Astrophysics Data System (ADS)

    Middlebrooks, John C.

    2004-07-01

    Interactions among the multiple channels of a cochlear prosthesis limit the number of channels of information that can be transmitted to the brain. This study explored the influence on channel interactions of electrical pulse rates and temporal offsets between channels. Anesthetized guinea pigs were implanted with 2-channel scala-tympani electrode arrays, and spike activity was recorded from the auditory cortex. Channel interactions were quantified as the reduction of the threshold for pulse-train stimulation of the apical channel by sub-threshold stimulation of the basal channel. Pulse rates were 254 or 4069 pulses per second (pps) per channel. Maximum threshold reductions averaged 9.6 dB when channels were stimulated simultaneously. Among nonsimultaneous conditions, threshold reductions at the 254-pps rate were entirely eliminated by a 1966-μs inter-channel offset. When offsets were only 41 to 123 μs, however, maximum threshold shifts averaged 3.1 dB, which was comparable to the dynamic ranges of cortical neurons in this experimental preparation. Threshold reductions at 4069 pps averaged up to 1.3 dB greater than at 254 pps, which raises some concern in regard to high-pulse-rate speech processors. Thresholds for various paired-pulse stimuli, pulse rates, and pulse-train durations were measured to test possible mechanisms of temporal integration.

  14. Measuring the Non-Line-of-Sight Ultra-High-Frequency Channel in Mountainous Terrain: A Spread-Spectrum, Portable Channel Sounder

    DTIC Science & Technology

    2018-03-01

    ER D C/ CR RE L TR -1 8- 3 ERDC 6.1 Basic Research Measuring the Non-Line-of-Sight Ultra- High - Frequency Channel in Mountainous Terrain... High - Frequency Channel in Mountainous Terrain A Spread-Spectrum, Portable Channel Sounder Samuel S. Streeter and Daniel J. Breton U.S. Army...spread-spectrum, portable channel sounder specifically designed to meas- ure the non-line-of-sight, ultra- high -frequency channel in mountainous terrain

  15. State-dependent block of CNG channels by dequalinium.

    PubMed

    Rosenbaum, Tamara; Gordon-Shaag, Ariela; Islas, León D; Cooper, Jeremy; Munari, Mika; Gordon, Sharona E

    2004-03-01

    Cyclic nucleotide-gated (CNG) ion channels are nonselective cation channels with a high permeability for Ca(2+). Not surprisingly, they are blocked by a number of Ca(2+) channel blockers including tetracaine, pimozide, and diltiazem. We studied the effects of dequalinium, an extracellular blocker of the small conductance Ca(2+)-activated K(+) channel. We previously noted that dequalinium is a high-affinity blocker of CNGA1 channels from the intracellular side, with little or no state dependence at 0 mV. Here we examined block by dequalinium at a broad range of voltages in both CNGA1 and CNGA2 channels. We found that dequalinium block was mildly state dependent for both channels, with the affinity for closed channels 3-5 times higher than that for open channels. Mutations in the S4-S5 linker did not alter the affinity of open channels for dequalinium, but increased the affinity of closed channels by 10-20-fold. The state-specific effect of these mutations raises the question of whether/how the S4-S5 linker alters the binding of a blocker within the ion permeation pathway.

  16. Optical Communications Channel Combiner

    NASA Technical Reports Server (NTRS)

    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.

  17. Aromatic–aromatic interactions between residues in KCa3.1 pore helix and S5 transmembrane segment control the channel gating process

    PubMed Central

    Garneau, Line; Klein, Hélène; Lavoie, Marie-France; Brochiero, Emmanuelle; Parent, Lucie

    2014-01-01

    The Ca2+-activated potassium channel KCa3.1 is emerging as a therapeutic target for a large variety of health disorders. One distinguishing feature of KCa3.1 is that the channel open probability at saturating Ca2+ concentrations (Pomax) is low, typically 0.1–0.2 for KCa3.1 wild type. This observation argues for the binding of Ca2+ to the calmodulin (CaM)–KCa3.1 complex, promoting the formation of a preopen closed-state configuration leading to channel opening. We have previously shown that the KCa3.1 active gate is most likely located at the level of the selectivity filter. As Ca2+-dependent gating of KCa3.1 originates from the binding of Ca2+ to CaM in the C terminus, the hypothesis of a gate located at the level of the selectivity filter requires that the conformational change initiated in the C terminus be transmitted to the S5 and S6 transmembrane helices, with a resulting effect on the channel pore helix directly connected to the selectivity filter. A study was thus undertaken to determine to what extent the interactions between the channel pore helix with the S5 and S6 transmembrane segments contribute to KCa3.1 gating. Molecular dynamics simulations first revealed that the largest contact area between the pore helix and the S5 plus S6 transmembrane helices involves residue F248 at the C-terminal end of the pore helix. Unitary current recordings next confirmed that modulating aromatic–aromatic interactions between F248 and W216 of the S5 transmembrane helical segment and/or perturbing the interactions between F248 and residues in S6 surrounding the glycine hinge G274 cause important changes in Pomax. This work thus provides the first evidence for a key contribution of the pore helix in setting Pomax by stabilizing the channel closed configuration through aromatic–aromatic interactions involving F248 of the pore helix. We propose that the interface pore helix/S5 constitutes a promising site for designing KCa3.1 potentiators. PMID:24470490

  18. Understanding Coulomb Scattering Mechanism in Monolayer MoS2 Channel in the Presence of h-BN Buffer Layer.

    PubMed

    Joo, Min-Kyu; Moon, Byoung Hee; Ji, Hyunjin; Han, Gang Hee; Kim, Hyun; Lee, Gwanmu; Lim, Seong Chu; Suh, Dongseok; Lee, Young Hee

    2017-02-08

    As the thickness becomes thinner, the importance of Coulomb scattering in two-dimensional layered materials increases because of the close proximity between channel and interfacial layer and the reduced screening effects. The Coulomb scattering in the channel is usually obscured mainly by the Schottky barrier at the contact in the noise measurements. Here, we report low-temperature (T) noise measurements to understand the Coulomb scattering mechanism in the MoS 2 channel in the presence of h-BN buffer layer on the silicon dioxide (SiO 2 ) insulating layer. One essential measure in the noise analysis is the Coulomb scattering parameter (α SC ) which is different for channel materials and electron excess doping concentrations. This was extracted exclusively from a 4-probe method by eliminating the Schottky contact effect. We found that the presence of h-BN on SiO 2 provides the suppression of α SC twice, the reduction of interfacial traps density by 100 times, and the lowered Schottky barrier noise by 50 times compared to those on SiO 2 at T = 25 K. These improvements enable us to successfully identify the main noise source in the channel, which is the trapping-detrapping process at gate dielectrics rather than the charged impurities localized at the channel, as confirmed by fitting the noise features to the carrier number and correlated mobility fluctuation model. Further, the reduction in contact noise at low temperature in our system is attributed to inhomogeneous distributed Schottky barrier height distribution in the metal-MoS 2 contact region.

  19. S-matrix decomposition, natural reaction channels, and the quantum transition state approach to reactive scattering

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Manthe, Uwe, E-mail: uwe.manthe@uni-bielefeld.de; Ellerbrock, Roman, E-mail: roman.ellerbrock@uni-bielefeld.de

    2016-05-28

    A new approach for the quantum-state resolved analysis of polyatomic reactions is introduced. Based on the singular value decomposition of the S-matrix, energy-dependent natural reaction channels and natural reaction probabilities are defined. It is shown that the natural reaction probabilities are equal to the eigenvalues of the reaction probability operator [U. Manthe and W. H. Miller, J. Chem. Phys. 99, 3411 (1993)]. Consequently, the natural reaction channels can be interpreted as uniquely defined pathways through the transition state of the reaction. The analysis can efficiently be combined with reactive scattering calculations based on the propagation of thermal flux eigenstates. Inmore » contrast to a decomposition based straightforwardly on thermal flux eigenstates, it does not depend on the choice of the dividing surface separating reactants from products. The new approach is illustrated studying a prototypical example, the H + CH{sub 4} → H{sub 2} + CH{sub 3} reaction. The natural reaction probabilities and the contributions of the different vibrational states of the methyl product to the natural reaction channels are calculated and discussed. The relation between the thermal flux eigenstates and the natural reaction channels is studied in detail.« less

  20. Summary report, Flexible VSR`s and VSR channel sleeve development programs

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kempf, F.J.

    1963-11-15

    (VSR = vertical safety rod.) This report summarizes results of development programs which have evaluated vertical rod channel sleeving materials and provided flexible vertical rods, acceptable for both interim use before rod channel sleeving, and for subsequent use in sleeved channels. B{sub 4}C is the rod material; graphite and Al oxide are among the sleeve materials.

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

    PubMed

    Cheng, Lan; Sanguinetti, Michael C

    2009-05-01

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

  2. Tip-localized Ca2+ -permeable channels control pollen tube growth via kinase-dependent R- and S-type anion channel regulation.

    PubMed

    Gutermuth, Timo; Herbell, Sarah; Lassig, Roman; Brosché, Mikael; Romeis, Tina; Feijó, José Alberto; Hedrich, Rainer; Konrad, Kai Robert

    2018-05-01

    Pollen tubes (PTs) are characterized by having tip-focused cytosolic calcium ion (Ca 2+ ) concentration ([Ca 2+ ] cyt ) gradients, which are believed to control PT growth. However, the mechanisms by which the apical [Ca 2+ ] cyt orchestrates PT growth are not well understood. Here, we aimed to identify these mechanisms by combining reverse genetics, cell biology, electrophysiology, and live-cell Ca 2+ and anion imaging. We triggered Ca 2+ -channel activation by applying hyperpolarizing voltage pulses and observed that the evoked [Ca 2+ ] cyt increases were paralleled by high anion channel activity and a decrease in the cytosolic anion concentration at the PT tip. We confirmed a functional correlation between these patterns by showing that inhibition of Ca 2+ -permeable channels eliminated the [Ca 2+ ] cyt increase, resulting in the abrogation of anion channel activity via Ca 2+ -dependent protein kinases (CPKs). Functional characterization of CPK and anion-channel mutants revealed a CPK2/20/6-dependent activation of SLAH3 and ALMT12/13/14 anion channels. The impaired growth phenotypes of anion channel and CPK mutants support the physiological significance of a kinase- and Ca 2+ -dependent pathway to control PT growth via anion channel activation. Other than unveiling this functional link, our membrane hyperpolarization method allows for unprecedented manipulation of the [Ca 2+ ] cyt gradient or oscillations in the PT tips and opens an array of opportunities for channel screenings. © 2018 The Authors. New Phytologist © 2018 New Phytologist Trust.

  3. A probabilistic approach for channel initiation

    Treesearch

    Erkan Istanbulluoglu; David G. Tarboton; Robert T. Pack; Charles H. Luce

    2002-01-01

    The channel head represents an important transition point from hillslope to fluvial processes. There is a nonlinear threshold transition across the channel head with sediment transport much larger in channels than on hillslopes. Deterministic specific catchment area, a, thresholds for channel initiation, sometimes dependent on slope, S...

  4. Channel Analysis for a 6.4 Gb s-1 DDR5 Data Buffer Receiver Front-End

    NASA Astrophysics Data System (ADS)

    Lehmann, Stefanie; Gerfers, Friedel

    2017-09-01

    In this contribution, the channel characteristic of the next generation DDR5-SDRAM architecture and possible approaches to overcome channel impairments are analysed. Because modern enterprise server applications and networks demand higher memory bandwidth, throughput and capacity, the DDR5-SDRAM specification is currently under development as a follow-up of DDR4-SDRAM technology. In this specification, the data rate is doubled to DDR5-6400 per IO as compared to the former DDR4-3200 architecture, resulting in a total per DIMM data rate of up to 409.6 Gb s-1. The single-ended multi-point-to-point CPU channel architecture in DDRX technology remains the same for DDR5 systems. At the specified target data rate, insertion loss, reflections, cross-talk as well as power supply noise become more severe and have to be considered. Using the data buffer receiver front-end of a load-reduced memory module, sophisticated equalisation techniques can be applied to ensure target BER at the increased data rate. In this work, the worst case CPU back-plane channel is analysed to derive requirements for receiver-side equalisation from the channel response characteristics. First, channel impairments such as inter-symbol-interference, reflections from the multi-point channel structure, and crosstalk from neighboring lines are analysed in detail. Based on these results, different correction methods for DDR5 data buffer front-ends are discussed. An architecture with 1-tap FFE in combination with a multi-tap DFE is proposed. Simulation of the architecture using a random input data stream is used to reveal the required DFE tap filter depth to effectively eliminate the dominant ISI and reflection based error components.

  5. A Pre-Emptive Horizontal Channel Borrowing and Vertical Traffic Overflowing Channel Allocation Scheme for Overlay Networks

    NASA Astrophysics Data System (ADS)

    Zhao, Fang-Ming; Jiang, Ling-Ge; He, Chen

    In this paper, a channel allocation scheme is studied for overlay wireless networks to optimize connection-level QoS. The contributions of our work are threefold. First, a channel allocation strategy using both horizontal channel borrowing and vertical traffic overflowing (HCBVTO) is presented and analyzed. When all the channels in a given macrocell are used, high-mobility real-time handoff requests can borrow channels from adjacent homogeneous cells. In case that the borrowing requests fail, handoff requests may also be overflowed to heterogeneous cells, if possible. Second, high-mobility real-time service is prioritized by allowing it to preempt channels currently used by other services. And third, to meet the high QoS requirements of some services and increase the utilization of radio resources, certain services can be transformed between real-time services and non-real-time services as necessary. Simulation results demonstrate that the proposed schemes can improve system performance.

  6. From membrane tension to channel gating: A principal energy transfer mechanism for mechanosensitive channels.

    PubMed

    Zhang, Xuejun C; Liu, Zhenfeng; Li, Jie

    2016-11-01

    Mechanosensitive (MS) channels are evolutionarily conserved membrane proteins that play essential roles in multiple cellular processes, including sensing mechanical forces and regulating osmotic pressure. Bacterial MscL and MscS are two prototypes of MS channels. Numerous structural studies, in combination with biochemical and cellular data, provide valuable insights into the mechanism of energy transfer from membrane tension to gating of the channel. We discuss these data in a unified two-state model of thermodynamics. In addition, we propose a lipid diffusion-mediated mechanism to explain the adaptation phenomenon of MscS. © 2016 The Protein Society.

  7. Orientations and Proximities of the Extracellular Ends of Transmembrane Helices S0 and S4 in Open and Closed BK Potassium Channels

    PubMed Central

    Wu, Roland S.; Chudasama, Neelesh; Zakharov, Sergey I.; Karlin, Arthur; Marx, Steven O.

    2013-01-01

    The large-conductance potassium channel (BK) α subunit contains a transmembrane (TM) helix S0 preceding the canonical TM helices S1 through S6. S0 lies between S4 and the TM2 helix of the regulatory β1 subunit. Pairs of Cys were substituted in the first helical turns in the membrane of BK α S0 and S4 and in β1 TM2. One such pair, W22C in S0 and W203C in S4, was 95% crosslinked endogenously. Under voltage-clamp conditions in outside-out patches, this crosslink was reduced by DTT and reoxidized by a membrane-impermeant bis-quaternary ammonium derivative of diamide. The rate constants for this reoxidation were not significantly different in the open and closed states of the channel. Thus, these two residues are approximately equally close in the two states. In addition, 90% crosslinking of a second pair, R20C in S0 and W203C in S4, had no effect on the V50 for opening. Taken together, these findings indicate that separation between residues at the extracellular ends of S0 and S4 is not required for voltage-sensor activation. On the contrary, even though W22C and W203C were equally likely to form a disulfide in the activated and deactivated states, relative immobilization by crosslinking of these two residues favored the activated state. Furthermore, the efficiency of recrosslinking of W22C and W203C on the cell surface was greater in the presence of the β1 subunit than in its absence, consistent with β1 acting through S0 to stabilize its immobilization relative to α S4. PMID:23472181

  8. Comparison of cloned Kir2 channels with native inward rectifier K+ channels from guinea-pig cardiomyocytes

    PubMed Central

    Xin Liu, Gong; Derst, Christian; Schlichthörl, Günter; Heinen, Steffen; Seebohm, Guiscard; Brüggemann, Andrea; Kummer, Wolfgang; Veh, Rüdiger W; Daut, Jürgen; Preisig-Müller, Regina

    2001-01-01

    The aim of the study was to compare the properties of cloned Kir2 channels with the properties of native rectifier channels in guinea-pig (gp) cardiac muscle. The cDNAs of gpKir2.1, gpKir2.2, gpKir2.3 and gpKir2.4 were obtained by screening a cDNA library from guinea-pig cardiac ventricle. A partial genomic structure of all gpKir2 genes was deduced by comparison of the cDNAs with the nucleotide sequences derived from a guinea-pig genomic library. The cell-specific expression of Kir2 channel subunits was studied in isolated cardiomyocytes using a multi-cell RT-PCR approach. It was found that gpKir2.1, gpKir2.2 and gpKir2.3, but not gpKir2.4, are expressed in cardiomyocytes. Immunocytochemical analysis with polyclonal antibodies showed that expression of Kir2.4 is restricted to neuronal cells in the heart. After transfection in human embryonic kidney cells (HEK293) the mean single-channel conductance with symmetrical K+ was found to be 30.6 pS for gpKir2.1, 40.0 pS for gpKir2.2 and 14.2 pS for Kir2.3. Cell-attached measurements in isolated guinea-pig cardiomyocytes (n = 351) revealed three populations of inwardly rectifying K+ channels with mean conductances of 34.0, 23.8 and 10.7 pS. Expression of the gpKir2 subunits in Xenopus oocytes showed inwardly rectifying currents. The Ba2+ concentrations required for half-maximum block at -100 mV were 3.24 μm for gpKir2.1, 0.51 μm for gpKir2.2, 10.26 μm for gpKir2.3 and 235 μm for gpKir2.4. Ba2+ block of inward rectifier channels of cardiomyocytes was studied in cell-attached recordings. The concentration and voltage dependence of Ba2+ block of the large-conductance inward rectifier channels was virtually identical to that of gpKir2.2 expressed in Xenopus oocytes. Our results suggest that the large-conductance inward rectifier channels found in guinea-pig cardiomyocytes (34.0 pS) correspond to gpKir2.2. The intermediate-conductance (23.8 pS) and low-conductance (10.7 pS) channels described here may correspond to gpKir2

  9. Anion channels: master switches of stress responses.

    PubMed

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

    2012-04-01

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

  10. Search for s-channel single-top-quark production in events with missing energy plus jets in pp collisions at sqrt[s] = 1.96 TeV.

    PubMed

    Aaltonen, T; Amerio, S; Amidei, D; Anastassov, A; Annovi, A; Antos, J; Apollinari, G; Appel, J A; Arisawa, T; Artikov, A; Asaadi, J; Ashmanskas, W; Auerbach, B; Aurisano, A; Azfar, F; Badgett, W; Bae, T; Barbaro-Galtieri, A; Barnes, V E; Barnett, B A; Barria, P; Bartos, P; Bauce, M; Bedeschi, F; Behari, S; Bellettini, G; Bellinger, J; Benjamin, D; Beretvas, A; Bhatti, A; Bland, K R; Blumenfeld, B; Bocci, A; Bodek, A; Bortoletto, D; Boudreau, J; Boveia, A; Brigliadori, L; Bromberg, C; Brucken, E; Budagov, J; Budd, H S; Burkett, K; Busetto, G; Bussey, P; Butti, P; Buzatu, A; Calamba, A; Camarda, S; Campanelli, M; Canelli, F; Carls, B; Carlsmith, D; Carosi, R; Carrillo, S; Casal, B; Casarsa, M; Castro, A; Catastini, P; Cauz, D; Cavaliere, V; Cavalli-Sforza, M; Cerri, A; Cerrito, L; Chen, Y C; Chertok, M; Chiarelli, G; Chlachidze, G; Cho, K; Chokheli, D; Clark, A; Clarke, C; Convery, M E; Conway, J; Corbo, M; Cordelli, M; Cox, C A; Cox, D J; Cremonesi, M; Cruz, D; Cuevas, J; Culbertson, R; d'Ascenzo, N; Datta, M; de Barbaro, P; Demortier, L; Deninno, M; D'Errico, M; Devoto, F; Di Canto, A; Di Ruzza, B; Dittmann, J R; Donati, S; D'Onofrio, M; Dorigo, M; Driutti, A; Ebina, K; Edgar, R; Elagin, A; Erbacher, R; Errede, S; Esham, B; Farrington, S; Fernández Ramos, J P; Field, R; Flanagan, G; Forrest, R; Franklin, M; Freeman, J C; Frisch, H; Funakoshi, Y; Galloni, C; Garfinkel, A F; Garosi, P; Gerberich, H; Gerchtein, E; Giagu, S; Giakoumopoulou, V; Gibson, K; Ginsburg, C M; Giokaris, N; Giromini, P; Giurgiu, G; Glagolev, V; Glenzinski, D; Gold, M; Goldin, D; Golossanov, A; Gomez, G; Gomez-Ceballos, G; Goncharov, M; González López, O; Gorelov, I; Goshaw, A T; Goulianos, K; Gramellini, E; Grinstein, S; Grosso-Pilcher, C; Group, R C; Guimaraes da Costa, J; Hahn, S R; Han, J Y; Happacher, F; Hara, K; Hare, M; Harr, R F; Harrington-Taber, T; Hatakeyama, K; Hays, C; Heinrich, J; Herndon, M; Hocker, A; Hong, Z; Hopkins, W; Hou, S; Hughes, R E; Husemann, U; Hussein, M; Huston, J; Introzzi, G; Iori, M; Ivanov, A; James, E; Jang, D; Jayatilaka, B; Jeon, E J; Jindariani, S; Jones, M; Joo, K K; Jun, S Y; Junk, T R; Kambeitz, M; Kamon, T; Karchin, P E; Kasmi, A; Kato, Y; Ketchum, W; Keung, J; Kilminster, B; Kim, D H; Kim, H S; Kim, J E; Kim, M J; Kim, S H; Kim, S B; Kim, Y J; Kim, Y K; Kimura, N; Kirby, M; Knoepfel, K; Kondo, K; Kong, D J; Konigsberg, J; Kotwal, A V; Kreps, M; Kroll, J; Kruse, M; Kuhr, T; Kurata, M; Laasanen, A T; Lammel, S; Lancaster, M; Lannon, K; Latino, G; Lee, H S; Lee, J S; Leo, S; Leone, S; Lewis, J D; Limosani, A; Lipeles, E; Lister, A; Liu, H; Liu, Q; Liu, T; Lockwitz, S; Loginov, A; Lucchesi, D; Lucà, A; Lueck, J; Lujan, P; Lukens, P; Lungu, G; Lys, J; Lysak, R; Madrak, R; Maestro, P; Malik, S; Manca, G; Manousakis-Katsikakis, A; Marchese, L; Margaroli, F; Marino, P; Martínez, M; Matera, K; Mattson, M E; Mazzacane, A; Mazzanti, P; McNulty, R; Mehta, A; Mehtala, P; Mesropian, C; Miao, T; Mietlicki, D; Mitra, A; Miyake, H; Moed, S; Moggi, N; Moon, C S; Moore, R; Morello, M J; Mukherjee, A; Muller, Th; Murat, P; Mussini, M; Nachtman, J; Nagai, Y; Naganoma, J; Nakano, I; Napier, A; Nett, J; Neu, C; Nigmanov, T; Nodulman, L; Noh, S Y; Norniella, O; Oakes, L; Oh, S H; Oh, Y D; Oksuzian, I; Okusawa, T; Orava, R; Ortolan, L; Pagliarone, C; Palencia, E; Palni, P; Papadimitriou, V; Parker, W; Pauletta, G; Paulini, M; Paus, C; Phillips, T J; Piacentino, G; Pianori, E; Pilot, J; Pitts, K; Plager, C; Pondrom, L; Poprocki, S; Potamianos, K; Pranko, A; Prokoshin, F; Ptohos, F; Punzi, G; Ranjan, N; Redondo Fernández, I; Renton, P; Rescigno, M; Rimondi, F; Ristori, L; Robson, A; Rodriguez, T; Rolli, S; Ronzani, M; Roser, R; Rosner, J L; Ruffini, F; Ruiz, A; Russ, J; Rusu, V; Sakumoto, W K; Sakurai, Y; Santi, L; Sato, K; Saveliev, V; Savoy-Navarro, A; Schlabach, P; Schmidt, E E; Schwarz, T; Scodellaro, L; Scuri, F; Seidel, S; Seiya, Y; Semenov, A; Sforza, F; Shalhout, S Z; Shears, T; Shepard, P F; Shimojima, M; Shochet, M; Shreyber-Tecker, I; Simonenko, A; Sliwa, K; Smith, J R; Snider, F D; Song, H; Sorin, V; St Denis, R; Stancari, M; Stentz, D; Strologas, J; Sudo, Y; Sukhanov, A; Suslov, I; Takemasa, K; Takeuchi, Y; Tang, J; Tecchio, M; Teng, P K; Thom, J; Thomson, E; Thukral, V; Toback, D; Tokar, S; Tollefson, K; Tomura, T; Tonelli, D; Torre, S; Torretta, D; Totaro, P; Trovato, M; Ukegawa, F; Uozumi, S; Velev, G; Vellidis, C; Vernieri, C; Vidal, M; Vilar, R; Vizán, J; Vogel, M; Volpi, G; Vázquez, F; Wagner, P; Wallny, R; Wang, S M; Waters, D; Wester, W C; Whiteson, D; Wicklund, A B; Wilbur, S; Williams, H H; Wilson, J S; Wilson, P; Winer, B L; Wittich, P; Wolbers, S; Wolfe, H; Wright, T; Wu, X; Wu, Z; Yamamoto, K; Yamato, D; Yang, T; Yang, U K; Yang, Y C; Yao, W-M; Yeh, G P; Yi, K; Yoh, J; Yorita, K; Yoshida, T; Yu, G B; Yu, I; Zanetti, A M; Zeng, Y; Zhou, C; Zucchelli, S

    2014-06-13

    The first search for single-top-quark production from the exchange of an s-channel virtual W boson using events with an imbalance in the total transverse energy, b-tagged jets, and no identified leptons is presented. Assuming the electroweak production of top quarks of mass 172.5 GeV/c(2) in the s channel, a cross section of 1.12(-0.57)(+0.61) (stat+syst) pb with a significance of 1.9 standard deviations is measured. This measurement is combined with the result obtained from events with an imbalance in total transverse momentum, b-tagged jets, and exactly one identified lepton, yielding a cross section of 1.36(-0.32)(+0.37) (stat+syst) pb, with a significance of 4.2 standard deviations.

  11. Model for the Operation of a Monolayer MoS2 Thin-Film Transistor with Charges Trapped near the Channel Interface

    NASA Astrophysics Data System (ADS)

    Hur, Ji-Hyun; Park, Junghak; Kim, Deok-kee; Jeon, Sanghun

    2017-04-01

    We propose a model that describes the operation characteristics of a two-dimensional electron gas (2DEG) in a monolayer transition-metal dichalcogenide thin-film transistor (TFT) having trapped charges near the channel interface. We calculate the drift mobility of the carriers scattered by charged defects located in the channel or near the channel interfaces. The calculated drift mobility is a function of the 2DEG areal density of interface traps. Finally, we calculate the model transfer (ID-VG S ) and output (ID-VS D ) characteristics and verify them by comparing with the experimental results performed with monolayer MoS2 TFTs. We find the modeled results to be excellently consistent with the experiments. This proposed model can be utilized for measuring the interface-trapped charge and trap site densities from the measured transfer curves directly, avoiding more complicated and expensive measurement methods.

  12. 33 CFR 334.783 - Arlington Channel, U.S. Coast Guard Base Mobile, Mobile, Alabama, Coast Guard restricted area.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Guard Base Mobile, Mobile, Alabama, Coast Guard restricted area. 334.783 Section 334.783 Navigation and... RESTRICTED AREA REGULATIONS § 334.783 Arlington Channel, U.S. Coast Guard Base Mobile, Mobile, Alabama, Coast... without prior approval from the Commanding Officer, U.S. Coast Guard Group Mobile or his designated...

  13. 12.5 Gb/s multi-channel broadcasting transmission for free-space optical communication based on the optical frequency comb module.

    PubMed

    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.

  14. Protein-directed synthesis of Mn-doped ZnS quantum dots: a dual-channel biosensor for two proteins.

    PubMed

    Wu, Peng; Zhao, Ting; Tian, Yunfei; Wu, Lan; Hou, Xiandeng

    2013-06-03

    Proteins typically have nanoscale dimensions and multiple binding sites with inorganic ions, which facilitates the templated synthesis of nanoparticles to yield nanoparticle-protein hybrids with tailored functionality, water solubility, and tunable frameworks with well-defined structure. In this work, we report a protein-templated synthesis of Mn-doped ZnS quantum dots (QDs) by exploring bovine serum albumin (BSA) as the template. The obtained Mn-doped ZnS QDs give phosphorescence emission centered at 590 nm, with a decay time of about 1.9 ms. A dual-channel sensing system for two different proteins was developed through integration of the optical responses (phosphorescence emission and resonant light scattering (RLS)) of Mn-doped ZnS QDs and recognition of them by surface BSA phosphorescent sensing of trypsin and RLS sensing of lysozyme. Trypsin can digest BSA and remove BSA from the surface of Mn-doped ZnS QDs, thus quenching the phosphorescence of QDs, whereas lysozyme can assemble with BSA to lead to aggregation of QDs and enhanced RLS intensity. The detection limits for trypsin and lysozyme were 40 and 3 nM, respectively. The selectivity of the respective channel for trypsin and lysozyme was evaluated with a series of other proteins. Unlike other protein sensors based on nanobioconjugates, the proposed dual-channel sensor employs only one type of QDs but can detect two different proteins. Further, we found the RLS of QDs can also be useful for studying the BSA-lysozyme binding stoichiometry, which has not been reported in the literature. These successful biosensor applications clearly demonstrate that BSA not only serves as a template for growth of Mn-doped ZnS QDs, but also impacts the QDs for selective recognition of analyte proteins. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Cross-channel variability in benthic habitat

    USGS Publications Warehouse

    Vayssieres, Marc; Peterson, Heather

    2003-01-01

    The Interagency Ecological Program’s Environmental Monitoring Program (EMP) has monitored benthic invertebrates since the mid-1970s. A recent review of the EMP found that the spatial study design of the benthos monitoring element was in need of a thorough reexamination through intense special studies and extensive historic data analyses. This article reports the results of preliminary analyses of historical EMP data focusing on cross-channel variability. Specific questions are: (1) do benthic habitats and community assemblages vary between positions across a river channel? (2) Are benthic samples taken at a single channel position sufficiently representative of benthos assemblages across the channel to characterize long term changes in the benthos community of a particular section of a river?

  16. Blueberry juice causes potent relaxation of rat aortic rings via the activation of potassium channels and the H₂S pathway.

    PubMed

    Horrigan, Louise A; Holohan, Catherine A; Lawless, Gráinne A; Murtagh, Melissa A; Williams, Carmel T; Webster, Christina M

    2013-02-26

    The objective of this study was to investigate the in vitro effects of blueberry juice on healthy rat aortic rings, and to explore the roles of potassium channels and of the hydrogen sulphide (H(2)S) pathway in mediating the effects of blueberry juice. Firstly, the antioxidant capacity of blueberry juice was compared to other popular juice drinks using the Folin-Ciocalteu and the DPPH assays. Blueberry juice had significantly higher total polyphenol content than any of the other drinks studied (p < 0.01). The effect of blueberry juice on noradrenaline-contracted aortic rings was then observed, and the juice caused significant inhibition of noradrenaline-induced contractions (p < 0.01). Voltage-gated potassium channel (Kv) blockers 4-aminopyridine (1 mM) and 3,4-diaminopyridine (1 mM), as well as the cystathionine γ-lysase (CSE) inhibitor d,l-propargylglycine (2 mM) were then utilised to elucidate the role of Kv channels and the CSE/H(2)S pathway. Kv channel blocker 3,4-diaminopyridine caused significant blockade at 1/100 and 1/50 dilutions of juice (p < 0.01), whilst 4-aminopyridine caused significant blockade of the 1/100 dilution of blueberry juice (p < 0.05). In addition, d,l-propargylglycine potently inhibited the effect of 1/100 and 1/50 dilutions of blueberry juice (p < 0.01). This study indicates that blueberry juice has potent vasorelaxing properties, and thus may be a useful dietary agent for the prevention and treatment of hypertension. This study also provides strong evidence that Kv channels and the CSE/H(2)S pathway may be responsible, at least in part, for mediating the effects of blueberry juice.

  17. Bovine chromaffin cells possess FTX-sensitive calcium channels.

    PubMed

    Gandía, L; Albillos, A; García, A G

    1993-07-30

    The effects of the synthetic analogue of the toxin from the venom of the funnel-web spider Agenelopsis aperta (sFTX) on whole-cell Ba2+ currents through Ca2+ channels were studied in cultured bovine chromaffin cells. sFTX selectively and reversibly blocked a significant component (55 +/- 3%) of the whole-cell IBa. Effects of sFTX were additive to those of omega-conotoxin GVIA, a selective blocker of N-type Ca2+ channels, and those of furnidipine, a novel dihydropyridine L-type Ca2+ channel blocker. We conclude that the cultured bovine chromaffin cells, in addition to N- and L-type Ca2+ channels, possess a P-type component in their whole-cell currents through their Ca2+ channels.

  18. Plasma-assisted quadruple-channel optosensing of proteins and cells with Mn-doped ZnS quantum dots.

    PubMed

    Li, Chenghui; Wu, Peng; Hou, Xiandeng

    2016-02-21

    Information extraction from nano-bio-systems is crucial for understanding their inner molecular level interactions and can help in the development of multidimensional/multimodal sensing devices to realize novel or expanded functionalities. The intrinsic fluorescence (IF) of proteins has long been considered as an effective tool for studying protein structures and dynamics, but not for protein recognition analysis partially because it generally contributes to the fluorescence background in bioanalysis. Here we explored the use of IF as the fourth channel optical input for a multidimensional optosensing device, together with the triple-channel optical output of Mn-doped ZnS QDs (fluorescence from ZnS host, phosphorescence from Mn(2+) dopant, and Rayleigh light scattering from the QDs), to dramatically improve the protein recognition and discrimination resolution. To further increase the cross-reactivity of the multidimensional optosensing device, plasma modification of proteins was explored to enhance the IF difference as well as their interactions with Mn-doped ZnS QDs. Such a sensor device was demonstrated for highly discriminative and precise identification of proteins in human serum and urine samples, and for cancer and normal cells as well.

  19. Construction dynamics of a lava channel

    NASA Astrophysics Data System (ADS)

    Harris, Andrew J. L.; Favalli, Massimiliano; Mazzarini, Francesco; Hamilton, Christopher W.

    2009-05-01

    We use a kinematic GPS and laser range finder survey of a 200 m-long section of the Muliwai a Pele lava channel (Mauna Ulu, Kilauea) to examine the construction processes and flow dynamics responsible for the channel-levee structure. The levees comprise three packages. The basal package comprises an 80-150 m wide 'a'a flow in which a ˜2 m deep and ˜11 m wide channel became centred. This is capped by a second package of thin (<45 cm thick) sheets of pahoehoe extending no more than 50 m from the channel. The upper-most package comprises localised 'a'a overflows. The channel itself contains two blockages located 130 m apart and composed of levee chunks veneered with overflow lava. The channel was emplaced over 50 h, spanning 30 May-2 June, 1974, with the flow front arriving at our section (4.4 km from the vent) 8 h after the eruption began. The basal 'a'a flow thickness yields effusion rates of 35 m3 s-1 for the opening phase, with the initial flow advancing across the mapped section at ˜10 m/min. Short-lived overflows of fluid pahoehoe then built the levee cap, increasing the apparent channel depth to 4.8 m. There were at least six pulses at 90-420 m3 s-1, causing overflow of limited extent lasting no more than 5 min. Brim-full flow conditions were thus extremely short-lived. During a dominant period of below-bank flow, flow depth was ˜2 m with an effusion rate of ˜35 m3 s-1, consistent with the mean output rate (obtained from the total flow bulk volume) of 23-54 m3 s-1. During pulses, levee chunks were plucked and floated down channel to form blockages. In a final low effusion rate phase, lava ponded behind the lower blockage to form a syn-channel pond that fed 'a'a overflow. After the end of the eruption the roofed-over pond continued to drain through the lower blockage, causing the roof to founder. Drainage emplaced inflated flows on the channel floor below the lower blockage for a further ˜10 h. The complex processes involved in levee-channel construction

  20. Macroscopic kinetics of pentameric ligand gated ion channels: comparisons between two prokaryotic channels and one eukaryotic channel.

    PubMed

    Laha, Kurt T; Ghosh, Borna; Czajkowski, Cynthia

    2013-01-01

    Electrochemical signaling in the brain depends on pentameric ligand-gated ion channels (pLGICs). Recently, crystal structures of prokaryotic pLGIC homologues from Erwinia chrysanthemi (ELIC) and Gloeobacter violaceus (GLIC) in presumed closed and open channel states have been solved, which provide insight into the structural mechanisms underlying channel activation. Although structural studies involving both ELIC and GLIC have become numerous, thorough functional characterizations of these channels are still needed to establish a reliable foundation for comparing kinetic properties. Here, we examined the kinetics of ELIC and GLIC current activation, desensitization, and deactivation and compared them to the GABAA receptor, a prototypic eukaryotic pLGIC. Outside-out patch-clamp recordings were performed with HEK-293T cells expressing ELIC, GLIC, or α1β2γ2L GABAA receptors, and ultra-fast ligand application was used. In response to saturating agonist concentrations, we found both ELIC and GLIC current activation were two to three orders of magnitude slower than GABAA receptor current activation. The prokaryotic channels also had slower current desensitization on a timescale of seconds. ELIC and GLIC current deactivation following 25 s pulses of agonist (cysteamine and pH 4.0 buffer, respectively) were relatively fast with time constants of 24.9 ± 5.1 ms and 1.2 ± 0.2 ms, respectively. Surprisingly, ELIC currents evoked by GABA activated very slowly with a time constant of 1.3 ± 0.3 s and deactivated even slower with a time constant of 4.6 ± 1.2 s. We conclude that the prokaryotic pLGICs undergo similar agonist-mediated gating transitions to open and desensitized states as eukaryotic pLGICs, supporting their use as experimental models. Their uncharacteristic slow activation, slow desensitization and rapid deactivation time courses are likely due to differences in specific structural elements, whose future identification may help uncover mechanisms underlying p

  1. Voltage-Dependent Gating of hERG Potassium Channels

    PubMed Central

    Cheng, Yen May; Claydon, Tom W.

    2012-01-01

    The mechanisms by which voltage-gated channels sense changes in membrane voltage and energetically couple this with opening of the ion conducting pore has been the source of significant interest. In voltage-gated potassium (Kv) channels, much of our knowledge in this area comes from Shaker-type channels, for which voltage-dependent gating is quite rapid. In these channels, activation and deactivation are associated with rapid reconfiguration of the voltage-sensing domain unit that is electromechanically coupled, via the S4–S5 linker helix, to the rate-limiting opening of an intracellular pore gate. However, fast voltage-dependent gating kinetics are not typical of all Kv channels, such as Kv11.1 (human ether-à-go-go related gene, hERG), which activates and deactivates very slowly. Compared to Shaker channels, our understanding of the mechanisms underlying slow hERG gating is much poorer. Here, we present a comparative review of the structure–function relationships underlying activation and deactivation gating in Shaker and hERG channels, with a focus on the roles of the voltage-sensing domain and the S4–S5 linker that couples voltage sensor movements to the pore. Measurements of gating current kinetics and fluorimetric analysis of voltage sensor movement are consistent with models suggesting that the hERG activation pathway contains a voltage independent step, which limits voltage sensor transitions. Constraints upon hERG voltage sensor movement may result from loose packing of the S4 helices and additional intra-voltage sensor counter-charge interactions. More recent data suggest that key amino acid differences in the hERG voltage-sensing unit and S4–S5 linker, relative to fast activating Shaker-type Kv channels, may also contribute to the increased stability of the resting state of the voltage sensor. PMID:22586397

  2. The L‐type Ca2+ channel facilitates abnormal metabolic activity in the cTnI‐G203S mouse model of hypertrophic cardiomyopathy

    PubMed Central

    Viola, Helena; Johnstone, Victoria; Cserne Szappanos, Henrietta; Richman, Tara; Tsoutsman, Tatiana; Filipovska, Aleksandra; Semsarian, Christopher

    2016-01-01

    Key points Genetic mutations in cardiac troponin I (cTnI) are associated with development of hypertrophic cardiomyopathy characterized by myocyte remodelling, disorganization of cytoskeletal proteins and altered energy metabolism.The L‐type Ca2+ channel is the main route for calcium influx and is crucial to cardiac excitation and contraction. The channel also regulates mitochondrial function in the heart by a functional communication between the channel and mitochondria via the cytoskeletal network.We find that L‐type Ca2+ channel kinetics are altered in cTnI‐G203S cardiac myocytes and that activation of the channel causes a significantly greater increase in mitochondrial membrane potential and metabolic activity in cTnI‐G203S cardiac myocytes.These responses occur as a result of impaired communication between the L‐type Ca2+ channel and cytoskeletal protein F‐actin, involving decreased movement of actin–myosin and block of the mitochondrial voltage‐dependent anion channel, resulting in a ‘hypermetabolic’ mitochondrial state.We propose that L‐type Ca2+ channel antagonists, such as diltiazem, might be effective in reducing the cardiomyopathy by normalizing mitochondrial metabolic activity. Abstract Genetic mutations in cardiac troponin I (cTnI) account for 5% of families with hypertrophic cardiomyopathy. Hypertrophic cardiomyopathy is associated with disorganization of cytoskeletal proteins and altered energy metabolism. The L‐type Ca2+ channel (ICa‐L) plays an important role in regulating mitochondrial function. This involves a functional communication between the channel and mitochondria via the cytoskeletal network. We investigate the role of ICa‐L in regulating mitochondrial function in 25‐ to 30‐week‐old cardiomyopathic mice expressing the human disease‐causing mutation Gly203Ser in cTnI (cTnI‐G203S). The inactivation rate of ICa‐L is significantly faster in cTnI‐G203S myocytes [cTnI‐G203S: τ1 = 40.68 ± 3.22, n

  3. Man-induced channel adjustment in Tennessee streams

    USGS Publications Warehouse

    Robbins, C.H.; Simon, Andrew

    1983-01-01

    Channel modifications in Tennessee, particularly in the western part, have led to large-scale instabilities in the channelized rivers and may have contributed to several bridge failures. These modifications, together with land-use practices, led to downcutting, headward erosion, downstream aggradation, accelerated scour, and bank instabilities. Changes in gradient by channel straightening caused more severe channel response than did dredging or clearing. Large-scale changes continue to occur in all the channelized rivers: the Obion River, its forks, and the South Fork Forked Deer River. However, the non-channelized Hatchie River in west Tennessee not only withstood the natural stresses imposed by the wet years of 1973 to 1975 but continues to exhibit characteristics of stability. Water-surface slope, the primary dependent variable, proved to be a sensitive and descriptive parameter useful in determining channel adjustment. Adjustments to man-induced increases in channel-slope are described by inverse exponential functions of the basic form S=ae(-b(t)); where ' S ' is some function describing channel-slope, ' t ' is the number of years since completion of channel work, and ' a ' and ' b ' are coefficients. Response times for the attainment of ' equilibrium ' channel slopes are a function of the magnitude and extent of the imposed modifications. The adjusted profile gradients attained by the streams following channelization are similar to the predisturbed profile gradients, where no alteration to channel length was made. Where the channels were straightened by constructing cut-offs, thus shortening channel length, then slope adjustments (reduction) proceed past the predisturbed profile gradients, to new profiles with lower gradients. (USGS)

  4. Stream Channel Stability.

    DTIC Science & Technology

    1981-04-01

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

  5. 4 channel × 10 Gb/s bidirectional optical subassembly using silicon optical bench with precise passive optical alignment.

    PubMed

    Kang, Eun Kyu; Lee, Yong Woo; Ravindran, Sooraj; Lee, Jun Ki; Choi, Hee Ju; Ju, Gun Wu; Min, Jung Wook; Song, Young Min; Sohn, Ik-Bu; Lee, Yong Tak

    2016-05-16

    We demonstrate an advanced structure for optical interconnect consisting of 4 channel × 10 Gb/s bidirectional optical subassembly (BOSA) formed using silicon optical bench (SiOB) with tapered fiber guiding holes (TFGHs) for precise and passive optical alignment of vertical-cavity surface-emitting laser (VCSEL)-to-multi mode fiber (MMF) and MMF-to-photodiode (PD). The co-planar waveguide (CPW) transmission line (Tline) was formed on the backside of silicon substrate to reduce the insertion loss of electrical data signal. The 4 channel VCSEL and PD array are attached at the end of CPW Tline using a flip-chip bonder and solder pad. The 12-channel ribbon fiber is simply inserted into the TFGHs of SiOB and is passively aligned to the VCSEL and PD in which no additional coupling optics are required. The fabricated BOSA shows high coupling efficiency and good performance with the clearly open eye patterns and a very low bit error rate of less than 10-12 order at a data rate of 10 Gb/s with a PRBS pattern of 231-1.

  6. Recommendations on presenting LHC searches for missing transverse energy signals using simplified s-channel models of dark matter

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Boveia, Antonio; Buchmueller, Oliver; Busoni, Giorgio

    2016-03-14

    This document summarises the proposal of the LHC Dark Matter Working Group on how to present LHC results on s-channel simplified dark matter models and to compare them to direct (indirect) detection experiments.

  7. $$B^{0}_{s}$$ Lifetime Measurement in the CP-odd Decay Channel $$B^{0}_{s} \\to J/\\psi\\mbox{ }f_{0}(980)$$

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Abazov, V. M.

    Here, the lifetime of the B s 0 meson is measured in the decay channel B s 0→J/ψπ +π - with 880 ≤ M π+π- ≤ 1080 MeV/c 2, which is mainly a CP-odd state and dominated by the f 0(980) resonance. In 10.4 fb -1 of data collected with the D0 detector in Run II of the Tevatron, the lifetime of the B s 0 meson is measured to be τ(B s 0) = 1.70 ± 0.14(stat) ± 0.05(syst) ps. Neglecting CP violation in B s 0/more » $$\\bar{B}$$ 0 s mixing, the measurement can be translated into the width of the heavy mass eigenstate of the B s 0, Γ H = 0.59 ± 0.05(stat) ± 0.02(syst) ps -1.« less

  8. $$B^{0}_{s}$$ Lifetime Measurement in the CP-odd Decay Channel $$B^{0}_{s} \\to J/\\psi\\mbox{ }f_{0}(980)$$

    DOE PAGES

    Abazov, V. M.

    2016-07-06

    Here, the lifetime of the B s 0 meson is measured in the decay channel B s 0→J/ψπ +π - with 880 ≤ M π+π- ≤ 1080 MeV/c 2, which is mainly a CP-odd state and dominated by the f 0(980) resonance. In 10.4 fb -1 of data collected with the D0 detector in Run II of the Tevatron, the lifetime of the B s 0 meson is measured to be τ(B s 0) = 1.70 ± 0.14(stat) ± 0.05(syst) ps. Neglecting CP violation in B s 0/more » $$\\bar{B}$$ 0 s mixing, the measurement can be translated into the width of the heavy mass eigenstate of the B s 0, Γ H = 0.59 ± 0.05(stat) ± 0.02(syst) ps -1.« less

  9. B s 0 lifetime measurement in the C P -odd decay channel B s 0 → J / ψ f 0 ( 980 )

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Abazov, V. M.; Abbott, B.; Acharya, B. S.

    2016-07-01

    Here, the lifetime of the Bmore » $$0\\atop{S}$$ meson is measured in the decay channel B$$0\\atop{S}$$→J/ψπ +π - with 880 ≤ M π+π- ≤ 1080 MeV/c 2, which is mainly a CP-odd state and dominated by the f 0(980) resonance. In 10.4 fb -1 of data collected with the D0 detector in Run II of the Tevatron, the lifetime of the B$$0\\atop{S}$$ meson is measured to be τ(B$$0\\atop{S}$$) = 1.70 ± 0.14(stat) ± 0.05(syst) ps. Neglecting CP violation in B$$0\\atop{S}/$$\\bar{B}$ 0 s mixing, the measurement can be translated into the width of the heavy mass eigenstate of the B$$0\\atop{S}$$, Γ H = 0.59 ± 0.05(stat) ± 0.02(syst) ps -1.« less

  10. Channel Protein Engineering: A Novel Approach Towards the Molecular Dissection Determinants in Ligand-Regulated Channels

    DTIC Science & Technology

    1991-01-23

    lidocaine , within the lumen of the pore. Specific predictions for possible experimental mutations are made which can serve to test both the proposed...to the protein from the bilayer interior. 2. Synthesis of tetrameric synthetic channel proteins and demonstration of channel blockade by a local...Congress, Vancouver, Canada. S9.4, p. 2 4 (1990). Grove, A., J. M. Tomich and M. Montal. Design, synthesis and single channel characterization of d

  11. Amyloid pore-channel hypothesis: effect of ethanol on aggregation state using frog oocytes for an Alzheimer’s disease study

    PubMed Central

    Parodi, Jorge; Ormeño, David; la Paz, Lenin D. Ochoa-de

    2015-01-01

    Alzheimer's disease severely compromises cognitive function. One of the mechanisms to explain the pathology of Alzheimer’s disease has been the hypotheses of amyloid-pore/channel formation by complex Aβ-aggregates. Clinical studies suggested the moderate alcohol consumption can reduces probability developing neurodegenerative pathologies. A recent report explored the ability of ethanol to disrupt the generation of complex Aβ in vitro and reduce the toxicity in two cell lines. Molecular dynamics simulations were applied to understand how ethanol blocks the aggregation of amyloid. On the other hand, the in silico modeling showed ethanol effect over the dynamics assembling for complex Aβ-aggregates mediated by break the hydrosaline bridges between Asp 23 and Lys 28, was are key element for amyloid dimerization. The amyloid pore/channel hypothesis has been explored only in neuronal models, however recently experiments suggested the frog oocytes such an excellent model to explore the mechanism of the amyloid pore/channel hypothesis. So, the used of frog oocytes to explored the mechanism of amyloid aggregates is new, mainly for amyloid/pore hypothesis. Therefore, this experimental model is a powerful tool to explore the mechanism implicates in the Alzheimer’s disease pathology and also suggests a model to prevent the Alzheimer’s disease pathology. [BMB Reports 2015; 48(1): 13-18] PMID:25047445

  12. Upgrade of optical WDM transport systems introducing linerates at 40 Gbit/s per channel

    NASA Astrophysics Data System (ADS)

    Schneiders, Malte; Vorbeck, Sascha; Aust, Nora

    2006-10-01

    Driven by high growth rates of internet traffic the question of upgrading existing optical metro-, regio- and long haul transport networks introducing 40 Gbit/s/λ is one of the most important questions today and in the near future. Current WDM Systems in photonic networks are commonly operated at linerates of 2.5 and 10 Gbit/s/λ. Induced by market analyses and the historical development of transport systems some work has already been carried out to evaluate update scenarios from 10 to 40 Gbit/s channel data rates. Due to the inherent quadruplication of the bandwidth per channel, limitations due to linear and non-linear transmission impairments become stronger resulting in a highly increased complexity of link engineering, potentially increasing the capital and operational expenditures. A lot of work is therefore in progress, which targets at the relaxation of constraints for 40 Gbit/s transmission to find the most efficient upgrade strategies. One approach towards an increased robustness against signal distortions is the introduction of more advanced modulation formats. Different modulation schemes show strongly different optical WDM transmission characteristics. The choice of the appropriate format does not only depend on the technical requirements, but also on economical considerations as an increased transmitter- and receiver-complexity will drive the transponder price. This article presents investigations on different modulation formats for the upgrade of existing metro-/ regio and long haul transport networks. Tolerances and robustness against the main degrading effects dispersion, noise and nonlinearities are considered together with mitigation strategies like the adaptation of dispersion maps. Results from numerical simulations are provided for some of the most promising modulation formats like NRZ, RZ, CS-RZ, Optical Duobinary and DPSK.

  13. Channel-planform evolution in four rivers of Olympic National Park, Washington, U.S.A.: The roles of physical drivers and trophic cascades

    USGS Publications Warehouse

    East, Amy E.; Jenkins, Kurt J.; Happe, Patricia J.; Bountry, Jennifer A.; Beechie, Timothy J.; Mastin, Mark C.; Sankey, Joel B.; Randle, Timothy J.

    2017-01-01

    Identifying the relative contributions of physical and ecological processes to channel evolution remains a substantial challenge in fluvial geomorphology. We use a 74-year aerial photographic record of the Hoh, Queets, Quinault, and Elwha Rivers, Olympic National Park, Washington, U.S.A., to investigate whether physical or trophic-cascade-driven ecological factors—excessive elk impacts after wolves were extirpated a century ago—are the dominant controls on channel planform of these gravel-bed rivers. We find that channel width and braiding show strong relationships with recent flood history. All four rivers have widened significantly in recent decades, consistent with increased flood activity since the 1970s. Channel planform also reflects sediment-supply changes, evident from landslide response on the Elwha River. We surmise that the Hoh River, which shows a multi-decadal trend toward greater braiding, is adjusting to increased sediment supply associated with rapid glacial retreat. In this sediment-routing system with high connectivity, such climate-driven signals appear to propagate downstream without being buffered substantially by sediment storage. Legacy effects of anthropogenic modification likely also affect the Quinault River planform. We infer no correspondence between channel geomorphic evolution and elk abundance, suggesting that trophic-cascade effects in this setting are subsidiary to physical controls on channel morphology. Our findings differ from previous interpretations of Olympic National Park fluvial dynamics and contrast with the classic example of Yellowstone National Park, where legacy effects of elk overuse are apparent in channel morphology; we attribute these differences to hydrologic regime and large-wood availability.

  14. Low-frequency 1/f noise in MoS{sub 2} transistors: Relative contributions of the channel and contacts

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Renteria, J.; Jiang, C.; Samnakay, R.

    2014-04-14

    We report on the results of the low-frequency (1/f, where f is frequency) noise measurements in MoS{sub 2} field-effect transistors revealing the relative contributions of the MoS{sub 2} channel and Ti/Au contacts to the overall noise level. The investigation of the 1/f noise was performed for both as fabricated and aged transistors. It was established that the McWhorter model of the carrier number fluctuations describes well the 1/f noise in MoS{sub 2} transistors, in contrast to what is observed in graphene devices. The trap densities extracted from the 1/f noise data for MoS{sub 2} transistors, are 2 × 10{sup 19} eV{sup −1}cm{sup −3}more » and 2.5 × 10{sup 20} eV{sup −1}cm{sup −3} for the as fabricated and aged devices, respectively. It was found that the increase in the noise level of the aged MoS{sub 2} transistors is due to the channel rather than the contact degradation. The obtained results are important for the proposed electronic applications of MoS{sub 2} and other van der Waals materials.« less

  15. One-channel Cell-attached Patch-clamp Recording

    PubMed Central

    Maki, Bruce A.; Cummings, Kirstie A.; Paganelli, Meaghan A.; Murthy, Swetha E.; Popescu, Gabriela K.

    2014-01-01

    Ion channel proteins are universal devices for fast communication across biological membranes. The temporal signature of the ionic flux they generate depends on properties intrinsic to each channel protein as well as the mechanism by which it is generated and controlled and represents an important area of current research. Information about the operational dynamics of ion channel proteins can be obtained by observing long stretches of current produced by a single molecule. Described here is a protocol for obtaining one-channel cell-attached patch-clamp current recordings for a ligand gated ion channel, the NMDA receptor, expressed heterologously in HEK293 cells or natively in cortical neurons. Also provided are instructions on how to adapt the method to other ion channels of interest by presenting the example of the mechano-sensitive channel PIEZO1. This method can provide data regarding the channel’s conductance properties and the temporal sequence of open-closed conformations that make up the channel’s activation mechanism, thus helping to understand their functions in health and disease. PMID:24961614

  16. The gating mechanism of the large mechanosensitive channel MscL

    NASA Technical Reports Server (NTRS)

    Sukharev, S.; Betanzos, M.; Chiang, C. S.; Guy, H. R.

    2001-01-01

    The mechanosensitive channel of large conductance, MscL, is a ubiquitous membrane-embedded valve involved in turgor regulation in bacteria. The crystal structure of MscL from Mycobacterium tuberculosis provides a starting point for analysing molecular mechanisms of tension-dependent channel gating. Here we develop structural models in which a cytoplasmic gate is formed by a bundle of five amino-terminal helices (S1), previously unresolved in the crystal structure. When membrane tension is applied, the transmembrane barrel expands and pulls the gate apart through the S1-M1 linker. We tested these models by substituting cysteines for residues predicted to be near each other only in either the closed or open conformation. Our results demonstrate that S1 segments form the bundle when the channel is closed, and crosslinking between S1 segments prevents opening. S1 segments interact with M2 when the channel is open, and crosslinking of S1 to M2 impedes channel closing. Gating is affected by the length of the S1-M1 linker in a manner consistent with the model, revealing critical spatial relationships between the domains that transmit force from the lipid bilayer to the channel gate.

  17. Search for s -Channel Single-Top-Quark Production in Events with Missing Energy Plus Jets in p p ¯ Collisions at s = 1.96 TeV

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Aaltonen, T.; Amerio, S.; Amidei, D.

    2014-06-09

    The first search for single-top-quark production from the exchange of an s -channel virtual W boson using events with an imbalance in the total transverse energy, b -tagged jets, and no identified leptons is presented. Assuming the electroweak production of top quarks of mass 172.5 GeV / c 2 in the s channel, a cross section of 1.1 2more » $$+ 0.61\\atop{- 0.57}$$ ( stat + syst ) pb with a significance of 1.9 standard deviations is measured. This measurement is combined with the result obtained from events with an imbalance in total transverse momentum, b -tagged jets, and exactly one identified lepton, yielding a cross section of 1.3 6$$+ 0.37\\atop{- 0.32}$$ ( stat + syst ) pb, with a significance of 4.2 standard deviations.« less

  18. Channel CAT: A Tactical Link Analysis Tool

    DTIC Science & Technology

    1997-09-01

    NAVAL POSTGRADUATE SCHOOL Monterey, California THESIS CHANNEL CAT : A TACTICAL LINK ANALYSIS TOOL by Michael Glenn Coleman September 1997 Thesis...REPORT TYPE AND DATES COVERED September 1997 Master’s Thesis 4. TITLE AND SUBTITLE CHANNEL CAT : A TACTICAL LINK ANALYSIS TOOL 5. FUNDING NUMBERS 6...tool, the Channel Capacity Analysis Tool (Channel CAT ), designed to provide an automated tool for the anlysis of design decisions in developing client

  19. Enlargement and contracture of C2-ceramide channels.

    PubMed

    Siskind, Leah J; Davoody, Amirparviz; Lewin, Naomi; Marshall, Stephanie; Colombini, Marco

    2003-09-01

    Ceramides are known to play a major regulatory role in apoptosis by inducing cytochrome c release from mitochondria. We have previously reported that ceramide, but not dihydroceramide, forms large and stable channels in phospholipid membranes and outer membranes of isolated mitochondria. C(2)-ceramide channel formation is characterized by conductance increments ranging from <1 to >200 nS. These conductance increments often represent the enlargement and contracture of channels rather than the opening and closure of independent channels. Enlargement is supported by the observation that many small conductance increments can lead to a large decrement. Also the initial conductances favor cations, but this selectivity drops dramatically with increasing total conductance. La(+3) causes rapid ceramide channel disassembly in a manner indicative of large conducting structures. These channels have a propensity to contract by a defined size (often multiples of 4 nS) indicating the formation of cylindrical channels with preferred diameters rather than a continuum of sizes. The results are consistent with ceramides forming barrel-stave channels whose size can change by loss or insertion of multiple ceramide columns.

  20. Enlargement and Contracture of C2-Ceramide Channels

    PubMed Central

    Siskind, Leah J.; Davoody, Amirparviz; Lewin, Naomi; Marshall, Stephanie; Colombini, Marco

    2003-01-01

    Ceramides are known to play a major regulatory role in apoptosis by inducing cytochrome c release from mitochondria. We have previously reported that ceramide, but not dihydroceramide, forms large and stable channels in phospholipid membranes and outer membranes of isolated mitochondria. C2-ceramide channel formation is characterized by conductance increments ranging from <1 to >200 nS. These conductance increments often represent the enlargement and contracture of channels rather than the opening and closure of independent channels. Enlargement is supported by the observation that many small conductance increments can lead to a large decrement. Also the initial conductances favor cations, but this selectivity drops dramatically with increasing total conductance. La+3 causes rapid ceramide channel disassembly in a manner indicative of large conducting structures. These channels have a propensity to contract by a defined size (often multiples of 4 nS) indicating the formation of cylindrical channels with preferred diameters rather than a continuum of sizes. The results are consistent with ceramides forming barrel-stave channels whose size can change by loss or insertion of multiple ceramide columns. PMID:12944273

  1. Characterisation of the LMS propagation channel at L- and S-bands: Narrowband experimental data and channel modelling

    NASA Technical Reports Server (NTRS)

    Sforza, Mario; Buonomo, Sergio

    1993-01-01

    During the period 1983-1992 the European Space Agency (ESA) carried out several experimental campaigns to investigate the propagation impairments of the Land Mobile Satellite (LMS) communication channel. A substantial amount of data covering quite a large range of elevation angles, environments, and frequencies was obtained. Results from the data analyses are currently used for system planning and design applications within the framework of the future ESA LMS projects. This comprehensive experimental data base is presently utilized also for channel modeling purposes and preliminary results are given. Cumulative Distribution Functions (PDF) and Duration of Fades (DoF) statistics at different elevation angles and environments were also included.

  2. Channel evolution of the Hatchie River near the U.S. Highway 51 crossing in Lauderdale and Tipton counties, West Tennessee

    USGS Publications Warehouse

    Bryan, B.A.

    1989-01-01

    An investigation was conducted to describe the channel cross-section evolution near the bridge crossing of the Hatchie River at U.S. Highway 51 in Lauderdale and Tipton Counties, in West Tennessee. The study also included velocity and discharge distributions near the bridge crossing, and definition of streamflow duration and flood frequencies at the bridge site and comparison of these statistics with flows prior to the bridge collapse. Cross-section measurements at the site indicated that the channel was widening at a rate of 0.8 ft/year from 1931 through about 1975. The channel bed was stable at an elevation of about 235 ft. Construction of a south bound bridge in 1974 and 1975 reduced the effective flow width from about 4,000 to about 1,000 ft. Data collected from 1975 to 1981 indicated that the channel bed degraded to an elevation of about 230 ft and the widening rate increased to about 4.5 ft/year. The channel bed returned to approximately the pre-construction elevation of 235 ft as channel width increased. The widening rate decreased to about 1.8 ft/year from 1981 through 1989. Channel-geometry data indicated that recent channel morphology changes along the toe of the right bank have resulted in continued bank undercutting and bank failure. Cross-section geometry and flow-velocity distributions from measurements made from April 6 through 10, 1989, indicate that there is a high-flow meander pattern through this river reach and that the bridges are located at the point where the current strikes the right bank. (USGS)

  3. The still uncertain identity of the channel-forming unit(s) of the mitochondrial permeability transition pore.

    PubMed

    Baines, Christopher P; Gutiérrez-Aguilar, Manuel

    2018-07-01

    Mitochondria from different organisms can undergo a sudden process of inner membrane unselective leakiness to molecules known as the mitochondrial permeability transition (MPT). This process has been studied for nearly four decades and several proteins have been claimed to constitute, or at least regulate the usually inactive pore responsible for this transition. However, no protein candidate proposed as the actual pore-forming unit has passed rigorous gain- or loss-of-function genetic tests. Here we review evidence for -and against- putative channel-forming components of the MPT pore. We conclude that the structure of the MPT pore still remains largely undefined and suggest that future studies should follow established technical considerations to unambiguously consolidate the channel forming constituent(s) of the MPT pore. Copyright © 2018 Elsevier Ltd. All rights reserved.

  4. Landscape assessment of side channel plugs and associated cumulative side channel attrition across a large river floodplain.

    PubMed

    Reinhold, Ann Marie; Poole, Geoffrey C; Bramblett, Robert G; Zale, Alexander V; Roberts, David W

    2018-04-24

    Determining the influences of anthropogenic perturbations on side channel dynamics in large rivers is important from both assessment and monitoring perspectives because side channels provide critical habitat to numerous aquatic species. Side channel extents are decreasing in large rivers worldwide. Although riprap and other linear structures have been shown to reduce side channel extents in large rivers, we hypothesized that small "anthropogenic plugs" (flow obstructions such as dikes or berms) across side channels modify whole-river geomorphology via accelerating side channel senescence. To test this hypothesis, we conducted a geospatial assessment, comparing digitized side channel areas from aerial photographs taken during the 1950s and 2001 along 512 km of the Yellowstone River floodplain. We identified longitudinal patterns of side channel recruitment (created/enlarged side channels) and side channel attrition (destroyed/senesced side channels) across n = 17 river sections within which channels were actively migrating. We related areal measures of recruitment and attrition to the density of anthropogenic side channel plugs across river sections. Consistent with our hypothesis, a positive spatial relationship existed between the density of anthropogenic plugs and side channel attrition, but no relationship existed between plug density and side channel recruitment. Our work highlights important linkages among side channel plugs and the persistence and restoration of side channels across floodplain landscapes. Specifically, management of small plugs represents a low-cost, high-benefit restoration opportunity to facilitate scouring flows in side channels to enable the persistence of these habitats over time.

  5. Landscape assessment of side channel plugs and associated cumulative side channel attrition across a large river floodplain

    USGS Publications Warehouse

    Reinhold, Ann Marie; Poole, Geoffrey C.; Bramblett, Robert G.; Zale, Alexander V.; Roberts, David W.

    2018-01-01

    Determining the influences of anthropogenic perturbations on side channel dynamics in large rivers is important from both assessment and monitoring perspectives because side channels provide critical habitat to numerous aquatic species. Side channel extents are decreasing in large rivers worldwide. Although riprap and other linear structures have been shown to reduce side channel extents in large rivers, we hypothesized that small “anthropogenic plugs” (flow obstructions such as dikes or berms) across side channels modify whole-river geomorphology via accelerating side channel senescence. To test this hypothesis, we conducted a geospatial assessment, comparing digitized side channel areas from aerial photographs taken during the 1950s and 2001 along 512 km of the Yellowstone River floodplain. We identified longitudinal patterns of side channel recruitment (created/enlarged side channels) and side channel attrition (destroyed/senesced side channels) across n = 17 river sections within which channels were actively migrating. We related areal measures of recruitment and attrition to the density of anthropogenic side channel plugs across river sections. Consistent with our hypothesis, a positive spatial relationship existed between the density of anthropogenic plugs and side channel attrition, but no relationship existed between plug density and side channel recruitment. Our work highlights important linkages among side channel plugs and the persistence and restoration of side channels across floodplain landscapes. Specifically, management of small plugs represents a low-cost, high-benefit restoration opportunity to facilitate scouring flows in side channels to enable the persistence of these habitats over time.

  6. Erythorbic acid promoted formation of CdS QDs in a tube-in-tube micro-channel reactor

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Liang, Yan; Tan, Jiawei; Wang, Jiexin

    2014-12-15

    Erythorbic acid assistant synthesis of CdS quantum dots (QDs) was conducted by homogeneous mixing of two continuous liquids in a high-throughput microporous tube-in-tube micro-channel reactor (MTMCR) at room temperature. The effects of the micropore size of the MTMCR, liquid flow rate, mixing time and reactant concentration on the size and size distribution of CdS QDs were investigated. It was found that the size and size distribution of CdS QDs could be tuned in the MTMCR. A combination of erythorbic acid promoted formation technique with the MTMCR may be a promising pathway for controllable mass production of QDs.

  7. Components of gating charge movement and S4 voltage-sensor exposure during activation of hERG channels.

    PubMed

    Wang, Zhuren; Dou, Ying; Goodchild, Samuel J; Es-Salah-Lamoureux, Zeineb; Fedida, David

    2013-04-01

    The human ether-á-go-go-related gene (hERG) K(+) channel encodes the pore-forming α subunit of the rapid delayed rectifier current, IKr, and has unique activation gating kinetics, in that the α subunit of the channel activates and deactivates very slowly, which focuses the role of IKr current to a critical period during action potential repolarization in the heart. Despite its physiological importance, fundamental mechanistic properties of hERG channel activation gating remain unclear, including how voltage-sensor movement rate limits pore opening. Here, we study this directly by recording voltage-sensor domain currents in mammalian cells for the first time and measuring the rates of voltage-sensor modification by [2-(trimethylammonium)ethyl] methanethiosulfonate chloride (MTSET). Gating currents recorded from hERG channels expressed in mammalian tsA201 cells using low resistance pipettes show two charge systems, defined as Q(1) and Q(2), with V(1/2)'s of -55.7 (equivalent charge, z = 1.60) and -54.2 mV (z = 1.30), respectively, with the Q(2) charge system carrying approximately two thirds of the overall gating charge. The time constants for charge movement at 0 mV were 2.5 and 36.2 ms for Q(1) and Q(2), decreasing to 4.3 ms for Q(2) at +60 mV, an order of magnitude faster than the time constants of ionic current appearance at these potentials. The voltage and time dependence of Q2 movement closely correlated with the rate of MTSET modification of I521C in the outermost region of the S4 segment, which had a V(1/2) of -64 mV and time constants of 36 ± 8.5 ms and 11.6 ± 6.3 ms at 0 and +60 mV, respectively. Modeling of Q(1) and Q(2) charge systems showed that a minimal scheme of three transitions is sufficient to account for the experimental findings. These data point to activation steps further downstream of voltage-sensor movement that provide the major delays to pore opening in hERG channels.

  8. Differential regulation of a CLC anion channel by SPAK kinase ortholog-mediated multisite phosphorylation

    PubMed Central

    Miyazaki, Hiroaki

    2012-01-01

    Shrinkage-induced inhibition of the Caenorhabditis elegans cell volume and cell cycle-dependent CLC anion channel CLH-3b occurs by concomitant phosphorylation of S742 and S747, which are located on a 175 amino acid linker domain between cystathionine-β-synthase 1 (CBS1) and CBS2. Phosphorylation is mediated by the SPAK kinase homolog GCK-3 and is mimicked by substituting serine residues with glutamate. Type 1 serine/threonine protein phosphatases mediate swelling-induced channel dephosphorylation. S742E/S747E double mutant channels are constitutively inactive and cannot be activated by cell swelling. S742E and S747E mutant channels were fully active in the absence of GCK-3 and were inactive when coexpressed with the kinase. Both channels responded to cell volume changes. However, the S747E mutant channel activated and inactivated in response to cell swelling and shrinkage, respectively, much more slowly than either wild-type or S742E mutant channels. Slower activation and inactivation of S747E was not due to altered rates of dephosphorylation or dephosphorylation-dependent conformational changes. GCK-3 binds to the 175 amino acid inter-CBS linker domain. Coexpression of wild-type CLH-3b and GCK-3 with either wild-type or S742E linkers gave rise to similar channel activity and regulation. In contrast, coexpression with the S747E linker greatly enhanced basal channel activity and increased the rate of shrinkage-induced channel inactivation. Our findings suggest the intriguing possibility that the phosphorylation state of S742 in S747E mutant channels modulates GCK-3/channel interaction and hence channel phosphorylation. These results provide a foundation for further detailed studies of the role of multisite phosphorylation in regulating CLH-3b and GCK-3 activity. PMID:22357738

  9. Reconfigurable virtual electrowetting channels.

    PubMed

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

    2012-02-21

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

  10. Methylene blue counteracts H2S toxicity-induced cardiac depression by restoring L-type Ca channel activity

    PubMed Central

    Zhang, Xue-Qian; Sonobe, Takashi; Song, Jianliang; Rannals, Matthew D.; Wang, JuFang; Tubbs, Nicole; Cheung, Joseph Y.; Haouzi, Philippe

    2016-01-01

    We have previously reported that methylene blue (MB) can counteract hydrogen sulfide (H2S) intoxication-induced circulatory failure. Because of the multifarious effects of high concentrations of H2S on cardiac function, as well as the numerous properties of MB, the nature of this interaction, if any, remains uncertain. The aim of this study was to clarify 1) the effects of MB on H2S-induced cardiac toxicity and 2) whether L-type Ca2+ channels, one of the targets of H2S, could transduce some of the counteracting effects of MB. In sedated rats, H2S infused at a rate that would be lethal within 5 min (24 μM·kg−1·min−1), produced a rapid fall in left ventricle ejection fraction, determined by echocardiography, leading to a pulseless electrical activity. Blood concentrations of gaseous H2S reached 7.09 ± 3.53 μM when cardiac contractility started to decrease. Two to three injections of MB (4 mg/kg) transiently restored cardiac contractility, blood pressure, and V̇o2, allowing the animals to stay alive until the end of H2S infusion. MB also delayed PEA by several minutes following H2S-induced coma and shock in unsedated rats. Applying a solution containing lethal levels of H2S (100 μM) on isolated mouse cardiomyocytes significantly reduced cell contractility, intracellular calcium concentration ([Ca2+]i) transient amplitudes, and L-type Ca2+ currents (ICa) within 3 min of exposure. MB (20 mg/l) restored the cardiomyocyte function, ([Ca2+]i) transient, and ICa. The present results offer a new approach for counteracting H2S toxicity and potentially other conditions associated with acute inhibition of L-type Ca2+ channels. PMID:26962024

  11. Molecular mechanism of pharmacological activation of BK channels

    PubMed Central

    Gessner, Guido; Cui, Yong-Mei; Otani, Yuko; Ohwada, Tomohiko; Soom, Malle; Hoshi, Toshinori; Heinemann, Stefan H.

    2012-01-01

    Large-conductance voltage- and Ca2+-activated K+ (Slo1 BK) channels serve numerous cellular functions, and their dysregulation is implicated in various diseases. Drugs activating BK channels therefore bear substantial therapeutic potential, but their deployment has been hindered in part because the mode of action remains obscure. Here we provide mechanistic insight into how the dehydroabietic acid derivative Cym04 activates BK channels. As a representative of NS1619-like BK openers, Cym04 reversibly left-shifts the half-activation voltage of Slo1 BK channels. Using an established allosteric BK gating model, the Cym04 effect can be simulated by a shift of the voltage sensor and the ion conduction gate equilibria toward the activated and open state, respectively. BK activation by Cym04 occurs in a splice variant-specific manner; it does not occur in such Slo1 BK channels using an alternative neuronal exon 9, which codes for the linker connecting the transmembrane segment S6 and the cytosolic RCK1 domain—the S6/RCK linker. In addition, Cym04 does not affect Slo1 BK channels with a two-residue deletion within this linker. Mutagenesis and model-based gating analysis revealed that BK openers, such as Cym04 and NS1619 but not mallotoxin, activate BK channels by functionally interacting with the S6/RCK linker, mimicking site-specific shortening of this purported passive spring, which transmits force from the cytosolic gating ring structure to open the channel's gate. PMID:22331907

  12. The ELIXIR channel in F1000Research

    PubMed Central

    Blomberg, Niklas; Oliveira, Arlindo; Mons, Barend; Persson, Bengt; Jonassen, Inge

    2016-01-01

    ELIXIR, the European life science infrastructure for biological information, is a unique initiative to consolidate Europe’s national centres, services, and core bioinformatics resources into a single, coordinated infrastructure. ELIXIR brings together Europe’s major life-science data archives and connects these with national bioinformatics infrastructures  - the ELIXIR Nodes. This editorial introduces the ELIXIR channel in F1000Research; the aim of the channel is to collect and present ELIXIR’s scientific and operational output, engage with the broad life science community and encourage discussion on proposed infrastructure solutions. Submissions will be assessed by the ELIXIR channel Advisory Board to ensure they are relevant to ELIXIR community, and subjected to F1000Research open peer review process. PMID:26913192

  13. Water transport by the bacterial channel alpha-hemolysin

    NASA Technical Reports Server (NTRS)

    Paula, S.; Akeson, M.; Deamer, D.

    1999-01-01

    This study is an investigation of the ability of the bacterial channel alpha-hemolysin to facilitate water permeation across biological membranes. alpha-Hemolysin channels were incorporated into rabbit erythrocyte ghosts at varying concentrations, and water permeation was induced by mixing the ghosts with hypertonic sucrose solutions. The resulting volume decrease of the ghosts was followed by time-resolved optical absorption at pH 5, 6, and 7. The average single-channel permeability coefficient of alpha-hemolysin for water ranged between 1.3x10-12 cm/s and 1.5x10-12 cm/s, depending on pH. The slightly increased single-channel permeability coefficient at lower pH-values was attributed to an increase in the effective pore size. The activation energy of water transport through the channel was low (Ea=5.4 kcal/mol), suggesting that the properties of water inside the alpha-hemolysin channel resemble those of bulk water. This conclusion was supported by calculations based on macroscopic hydrodynamic laws of laminar water flow. Using the known three-dimensional structure of the channel, the calculations accurately predicted the rate of water flow through the channel. The latter finding also indicated that water permeation data can provide a good estimate of the pore size for large channels.

  14. Ternary Kv4.2 channels recapitulate voltage-dependent inactivation kinetics of A-type K+ channels in cerebellar granule neurons.

    PubMed

    Amarillo, Yimy; De Santiago-Castillo, Jose A; Dougherty, Kevin; Maffie, Jonathon; Kwon, Elaine; Covarrubias, Manuel; Rudy, Bernardo

    2008-04-15

    Kv4 channels mediate most of the somatodendritic subthreshold operating A-type current (I(SA)) in neurons. This current plays essential roles in the regulation of spike timing, repetitive firing, dendritic integration and plasticity. Neuronal Kv4 channels are thought to be ternary complexes of Kv4 pore-forming subunits and two types of accessory proteins, Kv channel interacting proteins (KChIPs) and the dipeptidyl-peptidase-like proteins (DPPLs) DPPX (DPP6) and DPP10. In heterologous cells, ternary Kv4 channels exhibit inactivation that slows down with increasing depolarization. Here, we compared the voltage dependence of the inactivation rate of channels expressed in heterologous mammalian cells by Kv4.2 proteins with that of channels containing Kv4.2 and KChIP1, Kv4.2 and DPPX-S, or Kv4.2, KChIP1 and DPPX-S, and found that the relation between inactivation rate and membrane potential is distinct for these four conditions. Moreover, recordings from native neurons showed that the inactivation kinetics of the I(SA) in cerebellar granule neurons has voltage dependence that is remarkably similar to that of ternary Kv4 channels containing KChIP1 and DPPX-S proteins in heterologous cells. The fact that this complex and unique behaviour (among A-type K(+) currents) is observed in both the native current and the current expressed in heterologous cells by the ternary complex containing Kv4, DPPX and KChIP proteins supports the hypothesis that somatically recorded native Kv4 channels in neurons include both types of accessory protein. Furthermore, quantitative global kinetic modelling showed that preferential closed-state inactivation and a weakly voltage-dependent opening step can explain the slowing of the inactivation rate with increasing depolarization. Therefore, it is likely that preferential closed-state inactivation is the physiological mechanism that regulates the activity of both ternary Kv4 channel complexes and native I(SA)-mediating channels.

  15. Spark channel propagation in a microbubble liquid

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Panov, V. A.; Vasilyak, L. M., E-mail: vasilyak@ihed.ras.ru; Vetchinin, S. P.

    Experimental study on the development of the spark channel from the anode needle under pulsed electrical breakdown of isopropyl alcohol solution in water with air microbubbles has been performed. The presence of the microbubbles increases the velocity of the spark channel propagation and increases the current in the discharge gap circuit. The observed rate of spark channel propagation in microbubble liquid ranges from 4 to 12 m/s, indicating the thermal mechanism of the spark channel development in a microbubble liquid.

  16. The isolated voltage sensing domain of the Shaker potassium channel forms a voltage-gated cation channel.

    PubMed

    Zhao, Juan; Blunck, Rikard

    2016-10-06

    Domains in macromolecular complexes are often considered structurally and functionally conserved while energetically coupled to each other. In the modular voltage-gated ion channels the central ion-conducting pore is surrounded by four voltage sensing domains (VSDs). Here, the energetic coupling is mediated by interactions between the S4-S5 linker, covalently linking the domains, and the proximal C-terminus. In order to characterize the intrinsic gating of the voltage sensing domain in the absence of the pore domain, the Shaker Kv channel was truncated after the fourth transmembrane helix S4 (Shaker-iVSD). Shaker-iVSD showed significantly altered gating kinetics and formed a cation-selective ion channel with a strong preference for protons. Ion conduction in Shaker-iVSD developed despite identical primary sequence, indicating an allosteric influence of the pore domain. Shaker-iVSD also displays pronounced 'relaxation'. Closing of the pore correlates with entry into relaxation suggesting that the two processes are energetically related.

  17. Kv7 (KCNQ) channel openers induce hypothermia in the mouse.

    PubMed

    Kristensen, Line V; Sandager-Nielsen, Karin; Hansen, Henrik H

    2011-01-20

    Kv7 channels, encoded by corresponding kcnq genes, are expressed both centrally and peripherally where they serve to dampen neuronal activity. While Kv7 channel openers have shown efficacy in neurological and neuropsychiatric disease models, the impact of Kv7 channel activation on physiological endpoint markers have not been addressed in detail. In this study we assessed the effect of a range of Kv7 channel openers with different affinity for neuronal Kv7.2-5 channel subunits on body temperature regulation in mice. Female NMRI mice were acutely exposed to vehicle (10% Tween-80, i.p.), retigabine (3-30 mg/kg, i.p., pan-Kv7 channel opener), (S)BMS-204352 (60-240 mg/kg, i.p., Kv7.4/5 channel-preferring opener), ICA-27243 (1-10mg/kg, i.p., Kv7.2/3 channel-preferring opener), or S-(1) (10-60 mg/kg, i.p., Kv7.2/3 channel-preferring opener), and rectal body temperature was measured 15-120 min post-injection. Retigabine (>10mg/kg), ICA-27243 (≥ 10 mg/kg), and S-(1) (≥ 30 mg/kg) dose-dependently lowered rectal body temperature with maximal doses of each Kv7 channel opener inducing a marked drop (>4°C) in rectal temperature. The Kv7 channel openers showed differential temporal pharmacodynamics, which likely reflects their different pharmacokinetic profiles. Pretreatment with the pan-Kv7 channel blocker XE-991 (1.0mg/kg, i.p.) completely reversed the hypothermic effect of the pan-Kv7 opener, retigabine (15 mg/kg), whereas ICA-27243-induced hypothermia (10mg/kg) could only be partially prevented by XE-991. Because ICA-27743 and S-(1) are Kv7.2/3 channel subunit-preferring compounds, this suggests that the Kv7.2/3 channel isoform is the predominant substrate for Kv7 channel opener-evoked hypothermia. These data indicate the physiological relevance of Kv7 channel function on body temperature regulation which may potentially reside from central inhibitory Kv7 channel activity. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  18. Ionic Channels as Natural Nanodevices

    DTIC Science & Technology

    2006-05-01

    introduce the numerical techniques required to simulate charge transport in ion channels. [1] Using Poisson- Nernst -Planck-type (PNP) equations ...Eisenberg. 2003. Ionic diffusion through protein channels: from molecular description to continuum equations . Nanotech 2003, 3: 439-442. 4...Nadler, B., Schuss, Z., Singer, A., and R. S. Eisenberg. 2004. Ionic diffusion through confined geometries: from Langevin equations to partial

  19. Efficient syntheses of polyamine and polyamine amide voltage-sensitive calcium channel blockers: FTX-3.3 and sFTX-3.3.

    PubMed

    Moya, E; Blagbrough, I S

    1996-02-01

    Efficient syntheses of FTX-3.3 and sFTX-3.3, voltage-sensitive calcium channel blockers are described. These modified polyamines were prepared from selectively protected polyamines and purified on a practical scale.

  20. Divergent actions of the pyrethroid insecticides S-bioallethrin, tefluthrin, and deltamethrin on rat Na{sub v}1.6 sodium channels

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Tan Jianguo; Soderlund, David M., E-mail: dms6@cornell.ed

    2010-09-15

    We expressed rat Na{sub v}1.6 sodium channels in combination with the rat {beta}{sub 1} and {beta}{sub 2} auxiliary subunits in Xenopus laevis oocytes and evaluated the effects of the pyrethroid insecticides S-bioallethrin, deltamethrin, and tefluthrin on expressed sodium currents using the two-electrode voltage clamp technique. S-Bioallethrin, a type I structure, produced transient modification evident in the induction of rapidly decaying sodium tail currents, weak resting modification (5.7% modification at 100 {mu}M), and no further enhancement of modification upon repetitive activation by high-frequency trains of depolarizing pulses. By contrast deltamethrin, a type II structure, produced sodium tail currents that were {approx}more » 9-fold more persistent than those caused by S-bioallethrin, barely detectable resting modification (2.5% modification at 100 {mu}M), and 3.7-fold enhancement of modification upon repetitive activation. Tefluthrin, a type I structure with high mammalian toxicity, exhibited properties intermediate between S-bioallethrin and deltamethrin: intermediate tail current decay kinetics, much greater resting modification (14.1% at 100 {mu}M), and 2.8-fold enhancement of resting modification upon repetitive activation. Comparison of concentration-effect data showed that repetitive depolarization increased the potency of tefluthrin {approx} 15-fold and that tefluthrin was {approx} 10-fold more potent than deltamethrin as a use-dependent modifier of Na{sub v}1.6 sodium channels. Concentration-effect data from parallel experiments with the rat Na{sub v}1.2 sodium channel coexpressed with the rat {beta}{sub 1} and {beta}{sub 2} subunits in oocytes showed that the Na{sub v}1.6 isoform was at least 15-fold more sensitive to tefluthrin and deltamethrin than the Na{sub v}1.2 isoform. These results implicate sodium channels containing the Na{sub v}1.6 isoform as potential targets for the central neurotoxic effects of pyrethroids.« less

  1. 2 Tbit/s free-space data transmission on two orthogonal orbital-angular-momentum beams each carrying 25 WDM channels.

    PubMed

    Fazal, Irfan M; Ahmed, Nisar; Wang, Jian; Yang, Jeng-Yuan; Yan, Yan; Shamee, Bishara; Huang, Hao; Yue, Yang; Dolinar, Sam; Tur, Moshe; Willner, Alan E

    2012-11-15

    We demonstrate a 2 Tbit/s free-space data link using two orthogonal orbital angular momentum beams each carrying 25 different wavelength-division-multiplexing channels. We measure the performance for different modulation formats, including directly detected 40 Gbit/s nonreturn-to-zero (NRZ) differential phase-shift keying, 40 Gbit/s NRZ on-off keying, and coherently-detected 10 Gbaud NRZ quadrature phase-shift keying, and achieve low bit error rates with penalties less than 5 dB.

  2. Coupled-channel approach to strangeness S = -2 baryon-bayron interactions in lattice QCD

    NASA Astrophysics Data System (ADS)

    Sasaki, Kenji; Aoki, Sinya; Doi, Takumi; Hatsuda, Tetsuo; Ikeda, Yoichi; Inoue, Takashi; Ishii, Noriyoshi; Murano, Keiko

    2015-11-01

    Baryon-baryon interactions with strangeness S=-2 with flavor SU(3) breaking are calculated for the first time by using the HAL QCD method extended to the coupled-channel system in lattice QCD. The potential matrices are extracted from the Nambu-Bethe-Salpeter wave functions obtained by the 2+1-flavor gauge configurations of the CP-PACS/JLQCD Collaborations with a physical volume of (1.93 fm)^3 and with m_{π }/m_K=0.96, 0.90, 0.86. The spatial structure and the quark mass dependence of the potential matrix in the baryon basis and in the SU(3) basis are investigated.

  3. Roughness coefficients for stream channels in Arizona

    USGS Publications Warehouse

    Aldridge, B.N.; Garrett, J.M.

    1973-01-01

           n in which V = mean cross-sectional velocity of flow, in feet per second; R = hydraulic radius at a cross section, which is the cross-sectional area divided by the wetter perimeter, in feet; Se = energy slope; and n = coefficient of roughness. Many research studies have been made to determine "n" values for open-channel flow (Carter and others, 1963). Guidelines for selecting coefficient of roughness for stream channels are given in most of the literature of stream-channel hydraulics, but few of the data relate directly to streams of Arizona, The U.S> Geological Survey, at the request of the Arizona Highway Department, assembled the color photographs and tables of the Manning "n" values in this report to aid highway engineers in the selection of roughness coefficients for Arizona streams. Most of the photographs show channel reaches for which values of "n" have been assigned by experienced Survey personnel; a few photographs are included for reaches where "n" values have been verified. Verified "n" values are computed from a known discharge and measured channel geometry. Selected photographs of stream channels for which "n" values have been verified are included in U.S. Geological Survey Water-Supply Paper 1849 (Barnes, 1967); stereoscopic slides of Barnes' (1967) photographs and additional photographs can be inspected at U.S> Geological Survey offices in: 2555 E. First Street, Tucson; and 5017 Federal Building, 230 N. First Avenue, Phoenix.

  4. Pacemaker channels produce an instantaneous current.

    PubMed

    Proenza, Catherine; Angoli, Damiano; Agranovich, Eugene; Macri, Vincenzo; Accili, Eric A

    2002-02-15

    Spontaneous rhythmic activity in mammalian heart and brain depends on pacemaker currents (I(h)), which are produced by hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. Here, we report that the mouse HCN2 pacemaker channel isoform also produced a large instantaneous current (I(inst(HCN2))) in addition to the well characterized, slowly activating I(h). I(inst(HCN2)) was specific to expression of HCN2 on the plasma membrane and its amplitude was correlated with that of I(h). The two currents had similar reversal potentials, and both were modulated by changes in intracellular Cl(-) and cAMP. A mutation in the S4 domain of HCN2 (S306Q) decreased I(h) but did not alter I(inst(HCN2)), and instantaneous currents in cells expressing either wild type HCN2 or mutant S306Q channels were insensitive to block by Cs(+). Co-expression of HCN2 with the accessory subunit, MiRP1, decreased I(h) and increased I(inst(HCN2)), suggesting a mechanism for modulation of both currents in vivo. These data suggest that expression of HCN channels may be accompanied by a background conductance in native tissues and are consistent with at least two open states of HCN channels: I(inst(HCN2)) is produced by a Cs(+)-open state; hyperpolarization produces an additional Cs(+)-sensitive open state, which results in I(h).

  5. Pool spacing, channel morphology, and the restoration of tidal forested wetlands of the Columbia River, U.S.A.

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Diefenderfer, Heida L.; Montgomery, David R.

    2008-10-09

    Tidal forested wetlands have sustained substantial areal losses, and restoration practitioners lack a description of many ecosystem structures associated with these late-successional systems in which surface water is a significant controlling factor on the flora and fauna. The roles of large woody debris in terrestrial and riverine ecosystems have been well described compared to functions in tidal areas. This study documents the role of large wood in forcing channel morphology in Picea-sitchensis (Sitka spruce) dominated freshwater tidal wetlands in the floodplain of the Columbia River, U.S.A. near the Pacific coast. The average pool spacing documented in channel surveys of threemore » freshwater tidal forested wetlands near Grays Bay were 2.2 ± 1.3, 2.3 ± 1.2, and 2.5 ± 1.5. There were significantly greater numbers of pools on tidal forested wetland channels than on a nearby restoration site. On the basis of pool spacing and the observed sequences of log jams and pools, the tidal forested wetland channels were classified consistent with a forced step-pool class. Tidal systems, with bidirectional flow, have not previously been classified in this way. The classification provides a useful basis for restoration project design and planning in historically forested tidal freshwater areas, particularly in regard to the use of large wood in restoration actions and the development of pool habitats for aquatic species. Significant modifications by beaver on these sites warrant further investigation to explore the interactions between these animals and restoration actions affecting hydraulics and channel structure in tidal areas.« less

  6. Effects of natural and synthetic isothiocyanate-based H2S-releasers against chemotherapy-induced neuropathic pain: Role of Kv7 potassium channels.

    PubMed

    Di Cesare Mannelli, Lorenzo; Lucarini, Elena; Micheli, Laura; Mosca, Ilaria; Ambrosino, Paolo; Soldovieri, Maria Virginia; Martelli, Alma; Testai, Lara; Taglialatela, Maurizio; Calderone, Vincenzo; Ghelardini, Carla

    2017-07-15

    Hydrogen sulfide (H 2 S) is a crucial signaling molecule involved in several physiological and pathological processes. Nonetheless, the role of this gasotransmitter in the pathogenesis and treatment of neuropathic pain is controversial. The aim of the present study was to investigate the pain relieving profile of a series of slow releasing H 2 S donors (the natural allyl-isothiocyanate and the synthetics phenyl- and carboxyphenyl-isothiocyanate) in animal models of neuropathic pain induced by paclitaxel or oxaliplatin, anticancer drugs characterized by a dose-limiting neurotoxicity. The potential contribution of Kv7 potassium channels modulation was also studied. Mice were treated with paclitaxel (2.0 mg kg -1 ) i.p. on days 1, 3, 5 and 7; oxaliplatin (2.4 mg kg -1 ) was administered i.p. on days 1-2, 5-9, 12-14. Behavioral tests were performed on day 15. In both models, single subcutaneous administrations of H 2 S donors (1.33, 4.43, 13.31 μmol kg -1 ) reduced the hypersensitivity to cold non-noxious stimuli (allodynia-related measurement). The prototypical H 2 S donor NaHS was also effective. Activity was maintained after i.c.v. administrations. On the contrary, the S-lacking molecule allyl-isocyanate did not increase pain threshold; the H 2 S-binding molecule hemoglobin abolished the pain-relieving effects of isothiocyanates and NaHS. The anti-neuropathic properties of H 2 S donors were reverted by the Kv7 potassium channel blocker XE991. Currents carried by Kv7.2 homomers and Kv7.2/Kv7.3 heteromers expressed in CHO cells were potentiated by H 2 S donors. Sistemically- or centrally-administered isothiocyanates reduced chemotherapy-induced neuropathic pain by releasing H 2 S. Activation of Kv7 channels largely mediate the anti-neuropathic effect. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. A computer program for analyzing channel geometry

    USGS Publications Warehouse

    Regan, R.S.; Schaffranek, R.W.

    1985-01-01

    The Channel Geometry Analysis Program (CGAP) provides the capability to process, analyze, and format cross-sectional data for input to flow/transport simulation models or other computational programs. CGAP allows for a variety of cross-sectional data input formats through use of variable format specification. The program accepts data from various computer media and provides for modification of machine-stored parameter values. CGAP has been devised to provide a rapid and efficient means of computing and analyzing the physical properties of an open-channel reach defined by a sequence of cross sections. CGAP 's 16 options provide a wide range of methods by which to analyze and depict a channel reach and its individual cross-sectional properties. The primary function of the program is to compute the area, width, wetted perimeter, and hydraulic radius of cross sections at successive increments of water surface elevation (stage) from data that consist of coordinate pairs of cross-channel distances and land surface or channel bottom elevations. Longitudinal rates-of-change of cross-sectional properties are also computed, as are the mean properties of a channel reach. Output products include tabular lists of cross-sectional area, channel width, wetted perimeter, hydraulic radius, average depth, and cross-sectional symmetry computed as functions of stage; plots of cross sections; plots of cross-sectional area and (or) channel width as functions of stage; tabular lists of cross-sectional area and channel width computed as functions of stage for subdivisions of a cross section; plots of cross sections in isometric projection; and plots of cross-sectional area at a fixed stage as a function of longitudinal distance along an open-channel reach. A Command Procedure Language program and Job Control Language procedure exist to facilitate program execution on the U.S. Geological Survey Prime and Amdahl computer systems respectively. (Lantz-PTT)

  8. The isolated voltage sensing domain of the Shaker potassium channel forms a voltage-gated cation channel

    PubMed Central

    Zhao, Juan; Blunck, Rikard

    2016-01-01

    Domains in macromolecular complexes are often considered structurally and functionally conserved while energetically coupled to each other. In the modular voltage-gated ion channels the central ion-conducting pore is surrounded by four voltage sensing domains (VSDs). Here, the energetic coupling is mediated by interactions between the S4-S5 linker, covalently linking the domains, and the proximal C-terminus. In order to characterize the intrinsic gating of the voltage sensing domain in the absence of the pore domain, the Shaker Kv channel was truncated after the fourth transmembrane helix S4 (Shaker-iVSD). Shaker-iVSD showed significantly altered gating kinetics and formed a cation-selective ion channel with a strong preference for protons. Ion conduction in Shaker-iVSD developed despite identical primary sequence, indicating an allosteric influence of the pore domain. Shaker-iVSD also displays pronounced 'relaxation'. Closing of the pore correlates with entry into relaxation suggesting that the two processes are energetically related. DOI: http://dx.doi.org/10.7554/eLife.18130.001 PMID:27710769

  9. Lightning energetics: Estimates of energy dissipation in channels, channel radii, and channel-heating risetimes

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Borovsky, J.E.

    1998-05-01

    In this report, several lightning-channel parameters are calculated with the aid of an electrodynamic model of lightning. The electrodynamic model describes dart leaders and return strokes as electromagnetic waves that are guided along conducting lightning channels. According to the model, electrostatic energy is delivered to the channel by a leader, where it is stored around the outside of the channel; subsequently, the return stroke dissipates this locally stored energy. In this report this lightning-energy-flow scenario is developed further. Then the energy dissipated per unit length in lightning channels is calculated, where this quantity is now related to the linear chargemore » density on the channel, not to the cloud-to-ground electrostatic potential difference. Energy conservation is then used to calculate the radii of lightning channels: their initial radii at the onset of return strokes and their final radii after the channels have pressure expanded. Finally, the risetimes for channel heating during return strokes are calculated by defining an energy-storage radius around the channel and by estimating the radial velocity of energy flow toward the channel during a return stroke. In three appendices, values for the linear charge densities on lightning channels are calculated, estimates of the total length of branch channels are obtained, and values for the cloud-to-ground electrostatic potential difference are estimated. {copyright} 1998 American Geophysical Union« less

  10. Multi-channel imaging cytometry with a single detector

    NASA Astrophysics Data System (ADS)

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

    2018-02-01

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

  11. Highly permeable artificial water channels that can self-assemble into two-dimensional arrays

    PubMed Central

    Shen, Yue-xiao; Si, Wen; Erbakan, Mustafa; Decker, Karl; De Zorzi, Rita; Saboe, Patrick O.; Kang, You Jung; Majd, Sheereen; Butler, Peter J.; Walz, Thomas; Aksimentiev, Aleksei; Hou, Jun-li; Kumar, Manish

    2015-01-01

    Bioinspired artificial water channels aim to combine the high permeability and selectivity of biological aquaporin (AQP) water channels with chemical stability. Here, we carefully characterized a class of artificial water channels, peptide-appended pillar[5]arenes (PAPs). The average single-channel osmotic water permeability for PAPs is 1.0(±0.3) × 10−14 cm3/s or 3.5(±1.0) × 108 water molecules per s, which is in the range of AQPs (3.4∼40.3 × 108 water molecules per s) and their current synthetic analogs, carbon nanotubes (CNTs, 9.0 × 108 water molecules per s). This permeability is an order of magnitude higher than first-generation artificial water channels (20 to ∼107 water molecules per s). Furthermore, within lipid bilayers, PAP channels can self-assemble into 2D arrays. Relevant to permeable membrane design, the pore density of PAP channel arrays (∼2.6 × 105 pores per μm2) is two orders of magnitude higher than that of CNT membranes (0.1∼2.5 × 103 pores per μm2). PAP channels thus combine the advantages of biological channels and CNTs and improve upon them through their relatively simple synthesis, chemical stability, and propensity to form arrays. PMID:26216964

  12. Hydrophobic interaction between contiguous residues in the S6 transmembrane segment acts as a stimuli integration node in the BK channel

    PubMed Central

    Carrasquel-Ursulaez, Willy; Contreras, Gustavo F.; Sepúlveda, Romina V.; Aguayo, Daniel; González-Nilo, Fernando

    2015-01-01

    Large-conductance Ca2+- and voltage-activated K+ channel (BK) open probability is enhanced by depolarization, increasing Ca2+ concentration, or both. These stimuli activate modular voltage and Ca2+ sensors that are allosterically coupled to channel gating. Here, we report a point mutation of a phenylalanine (F380A) in the S6 transmembrane helix that, in the absence of internal Ca2+, profoundly hinders channel opening while showing only minor effects on the voltage sensor active–resting equilibrium. Interpretation of these results using an allosteric model suggests that the F380A mutation greatly increases the free energy difference between open and closed states and uncouples Ca2+ binding from voltage sensor activation and voltage sensor activation from channel opening. However, the presence of a bulky and more hydrophobic amino acid in the F380 position (F380W) increases the intrinsic open–closed equilibrium, weakening the coupling between both sensors with the pore domain. Based on these functional experiments and molecular dynamics simulations, we propose that F380 interacts with another S6 hydrophobic residue (L377) in contiguous subunits. This pair forms a hydrophobic ring important in determining the open–closed equilibrium and, like an integration node, participates in the communication between sensors and between the sensors and pore. Moreover, because of its effects on open probabilities, the F380A mutant can be used for detailed voltage sensor experiments in the presence of permeant cations. PMID:25548136

  13. Electrical spin injection and detection in molybdenum disulfide multilayer channel

    PubMed Central

    Liang, Shiheng; Yang, Huaiwen; Renucci, Pierre; Tao, Bingshan; Laczkowski, Piotr; Mc-Murtry, Stefan; Wang, Gang; Marie, Xavier; George, Jean-Marie; Petit-Watelot, Sébastien; Djeffal, Abdelhak; Mangin, Stéphane; Jaffrès, Henri; Lu, Yuan

    2017-01-01

    Molybdenum disulfide has recently emerged as a promising two-dimensional semiconducting material for nano-electronic, opto-electronic and spintronic applications. However, the demonstration of an electron spin transport through a semiconducting MoS2 channel remains challenging. Here we show the evidence of the electrical spin injection and detection in the conduction band of a multilayer MoS2 semiconducting channel using a two-terminal spin-valve configuration geometry. A magnetoresistance around 1% has been observed through a 450 nm long, 6 monolayer thick MoS2 channel with a Co/MgO tunnelling spin injector and detector. It is found that keeping a good balance between the interface resistance and channel resistance is mandatory for the observation of the two-terminal magnetoresistance. Moreover, the electron spin-relaxation is found to be greatly suppressed in the multilayer MoS2 channel with an in-plane spin polarization. The long spin diffusion length (approximately ∼235 nm) could open a new avenue for spintronic applications using multilayer transition metal dichalcogenides. PMID:28387252

  14. Effects of S(+)-efonidipine on the rabbit sinus node action potential and calcium channel subunits Ca(V)1.2, Ca(V)1.3 and Ca(V)3.1.

    PubMed

    Tanaka, Hikaru; Namekata, Iyuki; Ogawa, Toru; Tsuneoka, Yayoi; Komikado, Chisa; Takahara, Akira; Iida-Tanaka, Naoko; Izumi-Nakaseko, Hiroko; Tsuru, Hiromichi; Adachi-Akahane, Satomi

    2010-12-15

    The effect of S(+)-efonidipine on sinus node action potential and calcium channel α-subunits was examined. The slope of the phase 4 depolarization of isolated rabbit sinus node tissue was significantly reduced by S(+)-efonidipine (1 μM), slightly reduced by nifedipine (1 μM), but was not affected by R(-)-efonidipine. S(+)-efonidipine (1 μM), inhibited the expressed Ca(V)1.2, Ca(V)1.3 and Ca(V)3.1 channel currents by 75.7%, 75.3% and 94.0%, nifedipine 84.0%, 43.2% and 14.9%, and R(-)-efonidipine 30.0%, 19.6% and 92.8%, respectively. Thus, the prolongation of the phase 4 depolarization of the rabbit sinus node by S(+)-efonidipine may be explained by blockade of the Ca(V)1.3 channel current. Copyright © 2010 Elsevier B.V. All rights reserved.

  15. The orientation and molecular movement of a k(+) channel voltage-sensing domain.

    PubMed

    Gandhi, Chris S; Clark, Eliana; Loots, Eli; Pralle, Arnd; Isacoff, Ehud Y

    2003-10-30

    Voltage-gated channels operate through the action of a voltage-sensing domain (membrane segments S1-S4) that controls the conformation of gates located in the pore domain (membrane segments S5-S6). Recent structural studies on the bacterial K(v)AP potassium channel have led to a new model of voltage sensing in which S4 lies in the lipid at the channel periphery and moves through the membrane as a unit with a portion of S3. Here we describe accessibility probing and disulfide scanning experiments aimed at determining how well the K(v)AP model describes the Drosophila Shaker potassium channel. We find that the S1-S3 helices have one end that is externally exposed, S3 does not undergo a transmembrane motion, and S4 lies in close apposition to the pore domain in the resting and activated state.

  16. TRP channels: sensors and transducers of gasotransmitter signals

    PubMed Central

    Takahashi, Nobuaki; Kozai, Daisuke; Mori, Yasuo

    2012-01-01

    The transient receptor potential (trp) gene superfamily encodes cation channels that act as multimodal sensors for a wide variety of stimuli from outside and inside the cell. Upon sensing, they transduce electrical and Ca2+ signals via their cation channel activities. These functional features of TRP channels allow the body to react and adapt to different forms of environmental changes. Indeed, members of one class of TRP channels have emerged as sensors of gaseous messenger molecules that control various cellular processes. Nitric oxide (NO), a vasoactive gaseous molecule, regulates TRP channels directly via cysteine (Cys) S-nitrosylation or indirectly via cyclic GMP (cGMP)/protein kinase G (PKG)-dependent phosphorylation. Recent studies have revealed that changes in the availability of molecular oxygen (O2) also control the activation of TRP channels. Anoxia induced by O2-glucose deprivation and severe hypoxia (1% O2) activates TRPM7 and TRPC6, respectively, whereas TRPA1 has recently been identified as a novel sensor of hyperoxia and mild hypoxia (15% O2) in vagal and sensory neurons. TRPA1 also detects other gaseous molecules such as hydrogen sulfide (H2S) and carbon dioxide (CO2). In this review, we focus on how signaling by gaseous molecules is sensed and integrated by TRP channels. PMID:22934072

  17. Co-Channel Interference Mitigation Using Satellite Based Receivers

    DTIC Science & Technology

    2014-12-01

    NAVAL POSTGRADUATE SCHOOL MONTEREY, CALIFORNIA THESIS CO-CHANNEL INTERFERENCE MITIGATION USING SATELLITE BASED RECEIVERS by John E. Patterson...07-02-2012 to 12-19-2014 4. TITLE AND SUBTITLE CO-CHANNEL INTERFERENCE MITIGATION USING SATELLITE BASED RE- CEIVERS 5. FUNDING NUMBERS 6. AUTHOR(S...Approved for public release; distribution is unlimited CO-CHANNEL INTERFERENCE MITIGATION USING SATELLITE BASED RECEIVERS John E. Patterson Commander

  18. Human-induced stream channel abandonment/capture and filling of floodplain channels within the Atchafalaya River Basin, Louisiana

    USGS Publications Warehouse

    Kroes, Daniel E.; Kraemer, Thomas F.

    2013-01-01

    The Atchafalaya River Basin is a distributary system of the Mississippi River containing the largest riparian area in the lower Mississippi River Valley and the largest remaining forested bottomland in North America. Reductions in the area of open water in the Atchafalaya have been occurring over the last 100 years, and many historical waterways are increasingly filled by sediment. This study examines two cases of swamp channels (3/s) that are filling and becoming unnavigable as a result of high sediment loads and slow water velocities. The water velocities in natural bayous are further reduced because of flow capture by channels constructed for access. Bathymetry, flow, suspended sediment, deposited bottom-material, isotopes, and photointerpretation were used to characterize the channel fill. On average, water flowing through these two channels lost 23% of the suspended sediment load in the studied reaches. Along one of the studied reaches, two constructed access channels diverted significant flow out of the primary channel and into the adjacent swamp. Immediately downstream of each of the two access channels, the cross-sectional area of the studied channel was reduced. Isotopic analyses of bottom-material cores indicate that bed filling has been rapid and occurred after detectable levels of Cesium-137 were no longer being deposited. Interpretation of aerial photography indicates that water is bypassing the primary channels in favor of the more hydraulically efficient access channels, resulting in low or no-velocity flow conditions in the primary channel. These swamp channel conditions are typical in the Atchafalaya River Basin where relict large channel dimensions result in flow velocities that are normally too low to carry fine-grained sediment. Constructed channels increase the rate of natural channel avulsion and abandonment as a result of flow capture.

  19. Functional characterization of Kv11.1 (hERG) potassium channels split in the voltage-sensing domain.

    PubMed

    de la Peña, Pilar; Domínguez, Pedro; Barros, Francisco

    2018-03-23

    Voltage-dependent KCNH family potassium channel functionality can be reconstructed using non-covalently linked voltage-sensing domain (VSD) and pore modules (split channels). However, the necessity of a covalent continuity for channel function has not been evaluated at other points within the two functionally independent channel modules. We find here that by cutting Kv11.1 (hERG, KCNH2) channels at the different loops linking the transmembrane spans of the channel core, not only channels split at the S4-S5 linker level, but also those split at the intracellular S2-S3 and the extracellular S3-S4 loops, yield fully functional channel proteins. Our data indicate that albeit less markedly, channels split after residue 482 in the S2-S3 linker resemble the uncoupled gating phenotype of those split at the C-terminal end of the VSD S4 transmembrane segment. Channels split after residues 514 and 518 in the S3-S4 linker show gating characteristics similar to those of the continuous wild-type channel. However, breaking the covalent link at this level strongly accelerates the voltage-dependent accessibility of a membrane impermeable methanethiosulfonate reagent to an engineered cysteine at the N-terminal region of the S4 transmembrane helix. Thus, besides that of the S4-S5 linker, structural integrity of the intracellular S2-S3 linker seems to constitute an important factor for proper transduction of VSD rearrangements to opening and closing the cytoplasmic gate. Furthermore, our data suggest that the short and probably rigid characteristics of the extracellular S3-S4 linker are not an essential component of the Kv11.1 voltage sensing machinery.

  20. IP3-gated channels and their occurrence relative to CNG channels in the soma and dendritic knob of rat olfactory receptor neurons.

    PubMed

    Kaur, R; Zhu, X O; Moorhouse, A J; Barry, P H

    2001-05-15

    Olfactory receptor neurons respond to odorants with G protein-mediated increases in the concentrations of cyclic adenosine 3',5'-monophosphate (cAMP) and/or inositol-1,4,5-trisphosphate (IP3). This study provides evidence that both second messengers can directly activate distinct ion channels in excised inside-out patches from the dendritic knob and soma membrane of rat olfactory receptor neurons (ORNs). The IP3-gated channels in the dendritic knob and soma membranes could be classified into two types, with conductances of 40 +/- 7 pS (n = 5) and 14 +/- 3 pS (n = 4), with the former having longer open dwell times. Estimated values of the densities of both channels from the same inside-out membrane patches were very much smaller for IP3-gated than for CNG channels. For example, in the dendritic knob membrane there were about 1000 CNG channels x microm(-2) compared to about 85 IP3-gated channels x microm(-2). Furthermore, only about 36% of the dendritic knob patches responded to IP3, whereas 83% of the same patches responded to cAMP. In the soma, both channel densities were lower, with the CNG channel density again being larger ( approximately 57 channels x microm(-2)) than that of the IP3-gated channels ( approximately 13 channels x microm(-2)), with again a much smaller fraction of patches responding to IP3 than to cAMP. These results were consistent with other evidence suggesting that the cAMP-pathway dominates the IP3 pathway in mammalian olfactory transduction.

  1. Chloride channels mediate sodium sulphide-induced relaxation in rat uteri

    PubMed Central

    Mijušković, Ana; Kokić, Aleksandra Nikolić; Dušić, Zorana Oreščanin; Slavić, Marija; Spasić, Mihajlo B; Blagojević, Duško

    2015-01-01

    Background and Purpose Hydrogen sulphide reduces uterine contractility and is of potential interest as a treatment for uterine disorders. The aim of this study was to explore the mechanism of sodium sulphide (Na2S)-induced relaxation of rat uterus, investigate the importance of redox effects and ion channel-mediated mechanisms, and any interactions between these two mechanisms. Experimental Approach Organ bath studies were employed to assess the pharmacological effects of Na2S in uterine strips by exposing them to Na2S with or without Cl− channel blockers (DIDS, NFA, IAA-94, T16Ainh-A01, TA), raised KCl (15 and 75 mM), K+ channel inhibitors (glibenclamide, TEA, 4-AP), L-type Ca2+ channel activator (S-Bay K 8644), propranolol and methylene blue. The activities of antioxidant enzymes were measured in homogenates of treated uteri. The expression of bestrophin channel 1 (BEST-1) was determined by Western blotting and RT-PCR. Key Results Na2S caused concentration-dependent reversible relaxation of spontaneously active and calcium-treated uteri, affecting both amplitude and frequency of contractions. Uteri exposed to 75 mM KCl were less sensitive to Na2S compared with uteri in 15 mM KCl. Na2S-induced relaxations were abolished by DIDS, but unaffected by other modulators or by the absence of extracellular HCO3−, suggesting the involvement of chloride ion channels. Na2S in combination with different modulators provoked specific changes in the anti-oxidant profiles of uteri. The expression of BEST-1, both mRNA and protein, was demonstrated in rat uteri. Conclusions and Implications The relaxant effects of Na2S in rat uteri are mediated mainly via a DIDS-sensitive Cl−-pathway. Components of the relaxation are redox- and Ca2+-dependent. PMID:25857480

  2. Chloride channels mediate sodium sulphide-induced relaxation in rat uteri.

    PubMed

    Mijušković, Ana; Kokić, Aleksandra Nikolić; Dušić, Zorana Oreščanin; Slavić, Marija; Spasić, Mihajlo B; Blagojević, Duško

    2015-07-01

    Hydrogen sulphide reduces uterine contractility and is of potential interest as a treatment for uterine disorders. The aim of this study was to explore the mechanism of sodium sulphide (Na2 S)-induced relaxation of rat uterus, investigate the importance of redox effects and ion channel-mediated mechanisms, and any interactions between these two mechanisms. Organ bath studies were employed to assess the pharmacological effects of Na2 S in uterine strips by exposing them to Na2 S with or without Cl(-) channel blockers (DIDS, NFA, IAA-94, T16Ainh-A01, TA), raised KCl (15 and 75 mM), K(+) channel inhibitors (glibenclamide, TEA, 4-AP), L-type Ca(2+) channel activator (S-Bay K 8644), propranolol and methylene blue. The activities of antioxidant enzymes were measured in homogenates of treated uteri. The expression of bestrophin channel 1 (BEST-1) was determined by Western blotting and RT-PCR. Na2 S caused concentration-dependent reversible relaxation of spontaneously active and calcium-treated uteri, affecting both amplitude and frequency of contractions. Uteri exposed to 75 mM KCl were less sensitive to Na2 S compared with uteri in 15 mM KCl. Na2 S-induced relaxations were abolished by DIDS, but unaffected by other modulators or by the absence of extracellular HCO3 (-) , suggesting the involvement of chloride ion channels. Na2 S in combination with different modulators provoked specific changes in the anti-oxidant profiles of uteri. The expression of BEST-1, both mRNA and protein, was demonstrated in rat uteri. The relaxant effects of Na2 S in rat uteri are mediated mainly via a DIDS-sensitive Cl(-) -pathway. Components of the relaxation are redox- and Ca(2+) -dependent. © 2015 The British Pharmacological Society.

  3. Appearance of Saturn’s F ring azimuthal channels for the anti-alignment configuration between the ring and Prometheus

    NASA Astrophysics Data System (ADS)

    Chavez, Carlos E.

    2009-09-01

    In this article we explore the aspect of the F ring with respect to the anti-alignment configuration between the ring and Prometheus. We focus our attention on the shape of the F ring's azimuthal channels which were first reported by Porco et al. (Porco, C.C., Baker, E., Barbara, J., Beurle, K., Brahic, A., Burns, J.A., Charnoz, S., Cooper, N., Dawson, D.D., Del Genio, A.D., Denk, T., Dones, L., Dyudina, U., Evans, M.W., Giese, B., Grazier, K., Helfenstein, P., Ingersoll, A.P., Jacobson, R.A., Johnson, T.V., McEwen, A., Murray, C.D., Neukum, G., Owen, W.M., Perry, J., Roatsch, T., Spitale, J., Squyres, S., Thomas, P., Tiscareno, M., Turtle, E., Vasavada, A.R., Veverka, J., Wagner, R., West, R. [2005] Science, 307, 1226-1236) and numerically explored by Murray et al. (Murray, C.D., Chavez, C., Beurle, K., Cooper, N., Evans, M.W., Burns, J.A., Porco, C.C. [2005] Nature 437, 1326-1329) who found excellent agreement between Cassini's ISS reprojected images and their numerical model via a direct comparison. We find that for anti-alignment the channels are wider and go deeper inside the ring material. From our numerical model we find a new feature, an island in the middle of the channel. This island is made up of the particles that have been perturbed the most by Prometheus and only appears when this satellite is close to apoapsis. In addition, plots of the anti-alignment configuration for different orbital stages of Prometheus are obtained and discussed here.

  4. 428-Gb/s single-channel coherent optical OFDM transmission over 960-km SSMF with constellation expansion and LDPC coding.

    PubMed

    Yang, Qi; Al Amin, Abdullah; Chen, Xi; Ma, Yiran; Chen, Simin; Shieh, William

    2010-08-02

    High-order modulation formats and advanced error correcting codes (ECC) are two promising techniques for improving the performance of ultrahigh-speed optical transport networks. In this paper, we present record receiver sensitivity for 107 Gb/s CO-OFDM transmission via constellation expansion to 16-QAM and rate-1/2 LDPC coding. We also show the single-channel transmission of a 428-Gb/s CO-OFDM signal over 960-km standard-single-mode-fiber (SSMF) without Raman amplification.

  5. Two-pore channels (TPCs): Novel voltage-gated ion channels with pleiotropic functions

    PubMed Central

    Feijóo-Bandín, Sandra; García-Vence, María; García-Rúa, Vanessa; Roselló-Lletí, Esther; Portolés, Manuel; Rivera, Miguel; González-Juanatey, José Ramón; Lago, Francisca

    2017-01-01

    ABSTRACT Two-pore channels (TPC1-3) comprise a subfamily of the eukaryotic voltage-gated ion channels (VGICs) superfamily that are mainly expressed in acidic stores in plants and animals. TPCS are widespread across the animal kingdom, with primates, mice and rats lacking TPC3, and mainly act as Ca+ and Na+ channels, although it was also suggested that they could be permeable to other ions. Nowadays, TPCs have been related to the development of different diseases, including Parkinson´s disease, obesity or myocardial ischemia. Due to this, their study has raised the interest of the scientific community to try to understand their mechanism of action in order to be able to develop an efficient drug that could regulate TPCs activity. In this review, we will provide an updated view regarding TPCs structure, function and activation, as well as their role in different pathophysiological processes. PMID:27440385

  6. 47 CFR 76.701 - Leased access channels.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 47 Telecommunication 4 2013-10-01 2013-10-01 false Leased access channels. 76.701 Section 76.701... CABLE TELEVISION SERVICE Cable Television Access § 76.701 Leased access channels. (a) Notwithstanding 47 U.S.C. 532(b)(2) (Communications Act of 1934, as amended, section 612), a cable operator, in...

  7. Two NIRCam Channels are Better than One: How JWST Can Do More Science with NIRCam’s Short-wavelength Dispersed Hartmann Sensor

    NASA Astrophysics Data System (ADS)

    Schlawin, E.; Rieke, M.; Leisenring, J.; Walker, L. M.; Fraine, J.; Kelly, D.; Misselt, K.; Greene, T.; Line, M.; Lewis, N.; Stansberry, J.

    2017-01-01

    The James Webb Space Telescope (JWST) offers unprecedented sensitivity, stability, and wavelength coverage for transiting exoplanet studies, opening up new avenues for measuring atmospheric abundances, structure, and temperature profiles. Taking full advantage of JWST spectroscopy of planets from 0.6 to 28 μm, however, will require many observations with a combination of the NIRISS, NIRCam, NIRSpec, and MIRI instruments. In this white paper, we discuss a new NIRCam mode (not yet approved or implemented) that can reduce the number of necessary observations to cover the 1.0-5.0 μm wavelength range. Even though NIRCam was designed primarily as an imager, it also includes several grisms for phasing and aligning JWST’s 18 hexagonal mirror segments. NIRCam’s long-wavelength channel includes grisms that cover 2.4-5.0 μm with a resolving power of R = 1200-1550 using two separate configurations. The long-wavelength grisms have already been approved for science operations, including wide field and single object (time series) slitless spectroscopy. We propose a new mode that will simultaneously measure spectra for science targets in the 1.0-2.0 μm range using NIRCam’s short-wavelength channel. This mode, if approved, would take advantage of NIRCam’s Dispersed Hartmann Sensor (DHS), which produces 10 spatially separated spectra per source at R ˜ 300. We discuss the added benefit of the DHS in constraining abundances in exoplanet atmospheres as well as its ability to observe the brightest systems. The DHS essentially comes for free (at no time cost) with any NIRCam long-wavelength grism observation, but the detector integration parameters have to be selected to ensure that the long-wavelength grism observations do not saturate and that JWST data volume downlink constraints are not violated. Combining both of NIRCam’s channels will maximize the science potential of JWST, which is a limited life observatory.

  8. Performance, Stability, and Plume Characterization of the HERMeS Thruster with Boron Nitride Silica Composite Discharge Channel

    NASA Technical Reports Server (NTRS)

    Kamhawi, Hani; Huang, Wensheng; Gilland, James H.; Haag, Thomas W.; Mackey, Jonathan; Yim, John; Pinero, Luis; Williams, George; Peterson, Peter; Herman, Daniel

    2017-01-01

    NASA's Hall Effect Rocket with Magnetic Shielding (HERMeS) 12.5kW Technology Demonstration Unit-3 (TDU-3) has been the subject of extensive technology maturation in preparation for flight system development. Detailed performance, stability, and plume characterization tests of the thruster were performed at NASA GRC's Vacuum Facility 5 (VF-5). The TDU-3 thruster implements a magnetic topology that is identical to TDU-1. The TDU-3 boron nitride silica composite discharge channel material is different than the TDU-1 heritage boron nitride discharge channel material. Performance and stability characterization of the TDU-3 thruster was performed at discharge voltages between 300V and 600V and at discharge currents between 5A and 21.8A. The thruster performance and stability were assessed for varying magnetic field strength, cathode flow fractions between 5% and 9%, varying harness inductance, and for reverse magnet polarity. Performance characterization test results indicate that the TDU-3 thruster performance is in family with the TDU-1 levels. TDU-3's thrust efficiency of 65% and specific impulse of 2,800sec at 600V and 12.5kW exceed performance levels of SOA Hall thrusters. Thruster stability regimes were characterized with respect to the thruster discharge current oscillations (discharge current peak-to-peak and root mean square magnitudes), discharge current waveform power spectral density analysis, and maps of the current-voltage-magnetic field. Stability characterization test results indicate a stability profile similar to TDU-1. Finally, comparison of the TDU-1 and TDU-3 plume profiles found that there were negligible differences in the plasma plume characteristics between the TDU with heritage boron nitride versus the boron nitride silica composite discharge channel.

  9. Structure of the TRPV1 ion channel determined by electron cryo-microscopy.

    PubMed

    Liao, Maofu; Cao, Erhu; Julius, David; Cheng, Yifan

    2013-12-05

    Transient receptor potential (TRP) channels are sensors for a wide range of cellular and environmental signals, but elucidating how these channels respond to physical and chemical stimuli has been hampered by a lack of detailed structural information. Here we exploit advances in electron cryo-microscopy to determine the structure of a mammalian TRP channel, TRPV1, at 3.4 Å resolution, breaking the side-chain resolution barrier for membrane proteins without crystallization. Like voltage-gated channels, TRPV1 exhibits four-fold symmetry around a central ion pathway formed by transmembrane segments 5-6 (S5-S6) and the intervening pore loop, which is flanked by S1-S4 voltage-sensor-like domains. TRPV1 has a wide extracellular 'mouth' with a short selectivity filter. The conserved 'TRP domain' interacts with the S4-S5 linker, consistent with its contribution to allosteric modulation. Subunit organization is facilitated by interactions among cytoplasmic domains, including amino-terminal ankyrin repeats. These observations provide a structural blueprint for understanding unique aspects of TRP channel function.

  10. Structure of the TRPV1 ion channel determined by electron cryo-microscopy

    PubMed Central

    Liao, Maofu; Cao, Erhu; Julius, David; Cheng, Yifan

    2014-01-01

    Transient receptor potential (TRP) channels are sensors for a wide range of cellular and environmental signals, but elucidating how these channels respond to physical and chemical stimuli has been hampered by a lack of detailed structural information. Here, we exploit advances in electron cryo-microscopy to determine the structure of a mammalian TRP channel, TRPV1, at 3.4Å resolution, breaking the side-chain resolution barrier for membrane proteins without crystallization. Like voltage-gated channels, TRPV1 exhibits four-fold symmetry around a central ion pathway formed by transmembrane helices S5–S6 and the intervening pore loop, which is flanked by S1–S4 voltage sensor-like domains. TRPV1 has a wide extracellular ‘mouth’ with short selectivity filter. The conserved ‘TRP domain’ interacts with the S4–S5 linker, consistent with its contribution to allosteric modulation. Subunit organization is facilitated by interactions among cytoplasmic domains, including N-terminal ankyrin repeats. These observations provide a structural blueprint for understanding unique aspects of TRP channel function. PMID:24305160

  11. Channels of Propaganda.

    ERIC Educational Resources Information Center

    Sproule, J. Michael

    Defining propaganda as "efforts by special interests to win over the public covertly by infiltrating messages into various channels of public expression ordinarily viewed as politically neutral," this book argues that propaganda has become pervasive in American life. Pointing out that the 1990s society is inundated with propaganda from…

  12. Structural Determinants of the Closed KCa3.1 Channel Pore in Relation to Channel Gating: Results from a Substituted Cysteine Accessibility Analysis

    PubMed Central

    Klein, Hélène; Garneau, Line; Banderali, Umberto; Simoes, Manuel; Parent, Lucie; Sauvé, Rémy

    2007-01-01

    In this work we address the question of the KCa3.1 channel pore structure in the closed configuration in relation to the contribution of the C-terminal end of the S6 segments to the Ca2+-dependent gating process. Our results based on SCAM (substituted cysteine accessibility method) experiments first demonstrate that the S6 transmembrane segment of the open KCa3.1 channel contains two distinct functional domains delimited by V282 with MTSEA and MTSET binding leading to a total channel inhibition at positions V275, T278, and V282 and to a steep channel activation at positions A283 and A286. The rates of modification by MTSEA (diameter 4.6 Å) of the 275C (central cavity) and 286C residues (S6 C-terminal end) for the closed channel configuration were found to differ by less than sevenfold, whereas experiments performed with the larger MTSET reagent (diameter 5.8 Å) resulted in modification rates 103–104 faster for cysteines at 286 compared with 275. Consistent with these results, the modification rates of the cavity lining 275C residue by MTSEA, Et-Hg+, and Ag+ appeared poorly state dependent, whereas modification rates by MTSET were 103 faster for the open than the closed configuration. A SCAM analysis of the channel inner vestibule in the closed state revealed in addition that cysteine residues at 286 were accessible to MTS reagents as large as MTS-PtrEA, a result supported by the observation that binding of MTSET to cysteines at positions 283 or 286 could neither sterically nor electrostatically block the access of MTSEA to the closed channel cavity (275C). It follows that the closed KCa3.1 structure can hardly be accountable by an inverted teepee-like structure as described for KcsA, but is better represented by a narrow passage centered at V282 (equivalent to V474 in Shaker) connecting the channel central cavity to the cytosolic medium. This passage would not be however restrictive to the diffusion of small reagents such as MTSEA, Et-Hg+, and Ag+, arguing

  13. 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

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Gui, Ping

    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 candidatemore » for the Versatile Link PLUS (VL+) project, offering flexibility in configuring multiple Transmitters and receivers.« less

  14. KCNE1 constrains the voltage sensor of Kv7.1 K+ channels.

    PubMed

    Shamgar, Liora; Haitin, Yoni; Yisharel, Ilanit; Malka, Eti; Schottelndreier, Hella; Peretz, Asher; Paas, Yoav; Attali, Bernard

    2008-04-09

    Kv7 potassium channels whose mutations cause cardiovascular and neurological disorders are members of the superfamily of voltage-gated K(+) channels, comprising a central pore enclosed by four voltage-sensing domains (VSDs) and sharing a homologous S4 sensor sequence. The Kv7.1 pore-forming subunit can interact with various KCNE auxiliary subunits to form K(+) channels with very different gating behaviors. In an attempt to characterize the nature of the promiscuous gating of Kv7.1 channels, we performed a tryptophan-scanning mutagenesis of the S4 sensor and analyzed the mutation-induced perturbations in gating free energy. Perturbing the gating energetics of Kv7.1 bias most of the mutant channels towards the closed state, while fewer mutations stabilize the open state or the inactivated state. In the absence of auxiliary subunits, mutations of specific S4 residues mimic the gating phenotypes produced by co-assembly of Kv7.1 with either KCNE1 or KCNE3. Many S4 perturbations compromise the ability of KCNE1 to properly regulate Kv7.1 channel gating. The tryptophan-induced packing perturbations and cysteine engineering studies in S4 suggest that KCNE1 lodges at the inter-VSD S4-S1 interface between two adjacent subunits, a strategic location to exert its striking action on Kv7.1 gating functions.

  15. KCNE1 Constrains the Voltage Sensor of Kv7.1 K+ Channels

    PubMed Central

    Yisharel, Ilanit; Malka, Eti; Schottelndreier, Hella; Peretz, Asher; Paas, Yoav; Attali, Bernard

    2008-01-01

    Kv7 potassium channels whose mutations cause cardiovascular and neurological disorders are members of the superfamily of voltage-gated K+ channels, comprising a central pore enclosed by four voltage-sensing domains (VSDs) and sharing a homologous S4 sensor sequence. The Kv7.1 pore-forming subunit can interact with various KCNE auxiliary subunits to form K+ channels with very different gating behaviors. In an attempt to characterize the nature of the promiscuous gating of Kv7.1 channels, we performed a tryptophan-scanning mutagenesis of the S4 sensor and analyzed the mutation-induced perturbations in gating free energy. Perturbing the gating energetics of Kv7.1 bias most of the mutant channels towards the closed state, while fewer mutations stabilize the open state or the inactivated state. In the absence of auxiliary subunits, mutations of specific S4 residues mimic the gating phenotypes produced by co-assembly of Kv7.1 with either KCNE1 or KCNE3. Many S4 perturbations compromise the ability of KCNE1 to properly regulate Kv7.1 channel gating. The tryptophan-induced packing perturbations and cysteine engineering studies in S4 suggest that KCNE1 lodges at the inter-VSD S4-S1 interface between two adjacent subunits, a strategic location to exert its striking action on Kv7.1 gating functions. PMID:18398469

  16. Higher-order QCD predictions for dark matter production at the LHC in simplified models with s-channel mediators.

    PubMed

    Backović, Mihailo; Krämer, Michael; Maltoni, Fabio; Martini, Antony; Mawatari, Kentarou; Pellen, Mathieu

    Weakly interacting dark matter particles can be pair-produced at colliders and detected through signatures featuring missing energy in association with either QCD/EW radiation or heavy quarks. In order to constrain the mass and the couplings to standard model particles, accurate and precise predictions for production cross sections and distributions are of prime importance. In this work, we consider various simplified models with s -channel mediators. We implement such models in the FeynRules/MadGraph5_aMC@NLO framework, which allows to include higher-order QCD corrections in realistic simulations and to study their effect systematically. As a first phenomenological application, we present predictions for dark matter production in association with jets and with a top-quark pair at the LHC, at next-to-leading order accuracy in QCD, including matching/merging to parton showers. Our study shows that higher-order QCD corrections to dark matter production via s -channel mediators have a significant impact not only on total production rates, but also on shapes of distributions. We also show that the inclusion of next-to-leading order effects results in a sizeable reduction of the theoretical uncertainties.

  17. Channel degradation in southeastern Nebraska Rivers

    USGS Publications Warehouse

    Wahl, Kenneth L.; Weiss, Linda S.; ,

    1995-01-01

    Many stream channels in southeastern Nebraska were dredged and straightened during 1904-15. The resulting channels were both shorter and steeper than the original channels. Tests for time trends were conducted using the nonparametric Kendall tau test to see if the channels have responded to these changes. Tests were conducted on the stages associated with specific discharges and on measurement characteristics at gaging stations. Tests also were conducted on hydrologic forcing variables (annual mean precipitation, annual peak discharges, annual mean discharge, and annual mean base flows). The null hypothesis (that the data were free from trend) was rejected for stages associated with the mean of the annual discharges for 6 of 7 gaging stations in the study area, but was accepted for all 3 gages on the main stem of the Missouri River. The trends at the 6 streamflow gaging stations were for decreasing stages (degrading channels) for specific discharges. The rates of change ranged from about 0.2 to 0.5 m per decade. Mean stream bed elevations computed for individual discharge measurements at these streamflow gaging stations confirmed that the channels are degrading. However, neither the precipitation nor flow variables show evidence of trends. The tendency for the channels to degrade thus cannot be attributed to changes in runoff characteristics and are assumed to be a response to the channel modifications in the early 1900's. Indications are that the channels presently are continuing to degrade.

  18. Planar Superconducting Millimeter-Wave/Terahertz Channelizing Filter

    NASA Technical Reports Server (NTRS)

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

    2013-01-01

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

  19. Integrative Approach with Electrophysiological and Theoretical Methods Reveals a New Role of S4 Positively Charged Residues in PKD2L1 Channel Voltage-Sensing.

    PubMed

    Numata, Tomohiro; Tsumoto, Kunichika; Yamada, Kazunori; Kurokawa, Tatsuki; Hirose, Shinichi; Nomura, Hideki; Kawano, Mitsuhiro; Kurachi, Yoshihisa; Inoue, Ryuji; Mori, Yasuo

    2017-08-29

    Numerical model-based simulations provide important insights into ion channel gating when experimental limitations exist. Here, a novel strategy combining numerical simulations with patch clamp experiments was used to investigate the net positive charges in the putative transmembrane segment 4 (S4) of the atypical, positively-shifted voltage-dependence of polycystic kidney disease 2-like 1 (PKD2L1) channel. Charge-neutralising mutations (K452Q, K455Q and K461Q) in S4 reduced gating charges, positively shifted the Boltzmann-type activation curve [i.e., open probability (P open )-V curve] and altered the time-courses of activation/deactivation of PKD2L1, indicating that this region constitutes part of a voltage sensor. Numerical reconstruction of wild-type (WT) and mutant PKD2L1-mediated currents necessitated, besides their voltage-dependent gating parameters, a scaling factor that describes the voltage-dependence of maximal conductance, G max . Subsequent single-channel conductance (γ) measurements revealed that voltage-dependence of G max in WT can be explained by the inward-rectifying property of γ, which is greatly changed in PKD2L1 mutants. Homology modelling based on PKD2 and Na V Ab structures suggest that such voltage dependence of P open and γ in PKD2L1 could both reflect the charged state of the S4 domain. The present conjunctive experimental and theoretical approaches provide a framework to explore the undetermined mechanism(s) regulating TRP channels that possess non-classical voltage-dependent properties.

  20. Biophysical Properties of ATP-sensitive Potassium Channels in CA3 Hippocampal Neurons

    NASA Astrophysics Data System (ADS)

    Obregón-Herrera, Armando; Márquez-Gamiño, Sergio; Onetti, Carlos G.

    2004-09-01

    Single-channel activity of glucose-sensitive channels from CA3 neurons of the rat hippocampus, was studied in cell-attached membrane patches. Single-channel activity was totally abolished at 20 mM external glucose. Glucose-sensitive channels were selective to K+ ions; the unitary conductance was 170 pS in 140 mM K+, and the K+ permeability was 3.86×10-13 cmṡs-1. The open-state probability (PO) increased with membrane depolarization as a result of mean open time enhancement and shortening of the closure periods. The activation midpoint was -79 mV. Glucose-sensitive K+ channel of CA3 neurons could be considered as an ATP-sensitive potassium channel.

  1. Molecular Dynamics Simulation of the Antiamoebin Ion Channel: Linking Structure and Conductance

    NASA Technical Reports Server (NTRS)

    Wilson, Michael A.; Wei, Chenyu; Bjelkmar, Paer; Wallace, B. A.; Pohorille, Andrew

    2011-01-01

    Molecular dynamics simulations were carried out in order to ascertain which of the potential multimeric forms of the transmembrane peptaibol channel, antiamoebin, is consistant with its measured conductance. Estimates of the conductance obtained through counting ions that cross the channel and by solving the Nernst-Planck equation yield consistent results, indicating that the motion of ions inside the channel can be satisfactorily described as diffusive.The calculated conductance of octameric channels is markedly higher than the conductance measured in single channel recordings, whereas the tetramer appears to be non-conducting. The conductance of the hexamer was estimated to be 115+/-34 pS and 74+/-20 pS, at 150 mV and 75 mV, respectively, in satisfactory agreement with the value of 90 pS measured at 75 mV. On this basis we propose that the antiamoebin channel consists of six monomers. Its pore is large enough to accommodate K(+) and Cl(-) with their first solvation shells intact. The free energy barrier encountered by K(+) is only 2.2 kcal/mol whereas Cl(-) encounters a substantially higher barrier of nearly 5 kcal/mol. This difference makes the channel selective for cations. Ion crossing events are shown to be uncorrelated and follow Poisson statistics. keywords: ion channels, peptaibols, channel conductance, molecular dynamics

  2. Evolutionarily conserved intracellular gate of voltage-dependent sodium channels

    NASA Astrophysics Data System (ADS)

    Oelstrom, Kevin; Goldschen-Ohm, Marcel P.; Holmgren, Miguel; Chanda, Baron

    2014-03-01

    Members of the voltage-gated ion channel superfamily (VGIC) regulate ion flux and generate electrical signals in excitable cells by opening and closing pore gates. The location of the gate in voltage-gated sodium channels, a founding member of this superfamily, remains unresolved. Here we explore the chemical modification rates of introduced cysteines along the S6 helix of domain IV in an inactivation-removed background. We find that state-dependent accessibility is demarcated by an S6 hydrophobic residue; substituted cysteines above this site are not modified by charged thiol reagents when the channel is closed. These accessibilities are consistent with those inferred from open- and closed-state structures of prokaryotic sodium channels. Our findings suggest that an intracellular gate composed of a ring of hydrophobic residues is not only responsible for regulating access to the pore of sodium channels, but is also a conserved feature within canonical members of the VGIC superfamily.

  3. Mechanism of Electromechanical Coupling in Voltage-Gated Potassium Channels

    PubMed Central

    Blunck, Rikard; Batulan, Zarah

    2012-01-01

    Voltage-gated ion channels play a central role in the generation of action potentials in the nervous system. They are selective for one type of ion – sodium, calcium, or potassium. Voltage-gated ion channels are composed of a central pore that allows ions to pass through the membrane and four peripheral voltage sensing domains that respond to changes in the membrane potential. Upon depolarization, voltage sensors in voltage-gated potassium channels (Kv) undergo conformational changes driven by positive charges in the S4 segment and aided by pairwise electrostatic interactions with the surrounding voltage sensor. Structure-function relations of Kv channels have been investigated in detail, and the resulting models on the movement of the voltage sensors now converge to a consensus; the S4 segment undergoes a combined movement of rotation, tilt, and vertical displacement in order to bring 3–4e+ each through the electric field focused in this region. Nevertheless, the mechanism by which the voltage sensor movement leads to pore opening, the electromechanical coupling, is still not fully understood. Thus, recently, electromechanical coupling in different Kv channels has been investigated with a multitude of techniques including electrophysiology, 3D crystal structures, fluorescence spectroscopy, and molecular dynamics simulations. Evidently, the S4–S5 linker, the covalent link between the voltage sensor and pore, plays a crucial role. The linker transfers the energy from the voltage sensor movement to the pore domain via an interaction with the S6 C-termini, which are pulled open during gating. In addition, other contact regions have been proposed. This review aims to provide (i) an in-depth comparison of the molecular mechanisms of electromechanical coupling in different Kv channels; (ii) insight as to how the voltage sensor and pore domain influence one another; and (iii) theoretical predictions on the movement of the cytosolic face of the Kv channels during

  4. Channel stability of Turkey Creek, Nebraska

    USGS Publications Warehouse

    Rus, David L.; Soenksen, Philip J.

    1998-01-01

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

  5. Functional ion channels in human pulmonary artery smooth muscle cells: Voltage-dependent cation channels

    PubMed Central

    Firth, Amy L.; Remillard, Carmelle V.; Platoshyn, Oleksandr; Fantozzi, Ivana; Ko, Eun A.; Yuan, Jason X.-J.

    2011-01-01

    The activity of voltage-gated ion channels is critical for the maintenance of cellular membrane potential and generation of action potentials. In turn, membrane potential regulates cellular ion homeostasis, triggering the opening and closing of ion channels in the plasma membrane and, thus, enabling ion transport across the membrane. Such transmembrane ion fluxes are important for excitation–contraction coupling in pulmonary artery smooth muscle cells (PASMC). Families of voltage-dependent cation channels known to be present in PASMC include voltage-gated K+ (Kv) channels, voltage-dependent Ca2+-activated K+ (Kca) channels, L- and T- type voltage-dependent Ca2+ channels, voltage-gated Na+ channels and voltage-gated proton channels. When cells are dialyzed with Ca2+-free K+- solutions, depolarization elicits four components of 4-aminopyridine (4-AP)-sensitive Kvcurrents based on the kinetics of current activation and inactivation. In cell-attached membrane patches, depolarization elicits a wide range of single-channel K+ currents, with conductances ranging between 6 and 290 pS. Macroscopic 4-AP-sensitive Kv currents and iberiotoxin-sensitive Kca currents are also observed. Transcripts of (a) two Na+ channel α-subunit genes (SCN5A and SCN6A), (b) six Ca2+ channel α–subunit genes (α1A, α1B, α1X, α1D, α1Eand α1G) and many regulatory subunits (α2δ1, β1-4, and γ6), (c) 22 Kv channel α–subunit genes (Kv1.1 - Kv1.7, Kv1.10, Kv2.1, Kv3.1, Kv3.3, Kv3.4, Kv4.1, Kv4.2, Kv5.1, Kv 6.1-Kv6.3, Kv9.1, Kv9.3, Kv10.1 and Kv11.1) and three Kv channel β-subunit genes (Kvβ1-3) and (d) four Kca channel α–subunit genes (Sloα1 and SK2-SK4) and four Kca channel β-subunit genes (Kcaβ1-4) have been detected in PASMC. Tetrodotoxin-sensitive and rapidly inactivating Na+ currents have been recorded with properties similar to those in cardiac myocytes. In the presence of 20 mM external Ca2+, membrane depolarization from a holding potential of -100 mV elicits a rapidly

  6. Metaflumizone is a novel sodium channel blocker insecticide.

    PubMed

    Salgado, V L; Hayashi, J H

    2007-12-15

    Metaflumizone is a novel semicarbazone insecticide, derived chemically from the pyrazoline sodium channel blocker insecticides (SCBIs) discovered at Philips-Duphar in the early 1970s, but with greatly improved mammalian safety. This paper describes studies confirming that the insecticidal action of metaflumizone is due to the state-dependent blockage of sodium channels. Larvae of the moth Spodoptera eridania injected with metaflumizone became paralyzed, concomitant with blockage of all nerve activity. Furthermore, tonic firing of abdominal stretch receptor organs from Spodoptera frugiperda was blocked by metaflumizone applied in the bath, consistent with the block of voltage-dependent sodium channels. Studies on native sodium channels, in primary-cultured neurons isolated from the CNS of the larvae of the moth Manduca sexta and on Para/TipE sodium channels heterologously expressed in Xenopus (African clawed frog) oocytes, confirmed that metaflumizone blocks sodium channels by binding selectively to the slow-inactivated state, which is characteristic of the SCBIs. The results confirm that metaflumizone is a novel sodium channel blocker insecticide.

  7. Evidence for single top-quark production in the s-channel in proton–proton collisions at √s = 8TeV with the ATLAS detector using the Matrix Element Method

    DOE PAGES

    Aad, G.

    2016-03-08

    This Letter presents evidence for single top-quark production in the s-channel using proton–proton collisions at a centre-of-mass energy of 8 TeV with the ATLAS detector at the CERN Large Hadron Collider. The analysis is performed on events containing one isolated electron or muon, large missing transverse momentum and exactly two b-tagged jets in the final state. The analysed data set corresponds to an integrated luminosity of 20.3 fb -1. The signal is extracted using a maximum-likelihood fit of a discriminant which is based on the matrix element method and optimized in order to separate single-top-quark s-channel events from the mainmore » background contributions, which are top-quark pair production and W boson production in association with heavy-flavour jets. The measurement leads to an observed signal significance of 3.2 standard deviations and a measured cross-section of σ s = 4.8 ± 0.8(stat.) -1.3 +1.6(syst.) pb, which is consistent with the Standard Model expectation. As a result, the expected significance for the analysis is 3.9 standard deviations.« less

  8. Enhanced Handoff Scheme for Downlink-Uplink Asymmetric Channels in Cellular Systems

    PubMed Central

    2013-01-01

    In the latest cellular networks, data services like SNS and UCC can create asymmetric packet generation rates over the downlink and uplink channels. This asymmetry can lead to a downlink-uplink asymmetric channel condition being experienced by cell edge users. This paper proposes a handoff scheme to cope effectively with downlink-uplink asymmetric channels. The proposed handoff scheme exploits the uplink channel quality as well as the downlink channel quality to determine the appropriate timing and direction of handoff. We first introduce downlink and uplink channel models that consider the intercell interference, to verify the downlink-uplink channel asymmetry. Based on these results, we propose an enhanced handoff scheme that exploits both the uplink and downlink channel qualities to reduce the handoff-call dropping probability and the service interruption time. The simulation results show that the proposed handoff scheme reduces the handoff-call dropping probability about 30% and increases the satisfaction of the service interruption time requirement about 7% under high-offered load, compared to conventional mobile-assisted handoff. Especially, the proposed handoff scheme is more efficient when the uplink QoS requirement is much stricter than the downlink QoS requirement or uplink channel quality is worse than downlink channel quality. PMID:24501576

  9. The first transmembrane domain (TM1) of β2-subunit binds to the transmembrane domain S1 of α-subunit in BK potassium channels

    PubMed Central

    Morera, Francisco J.; Alioua, Abderrahmane; Kundu, Pallob; Salazar, Marcelo; Gonzalez, Carlos; Martinez, Agustin D.; Stefani, Enrico; Toro, Ligia; Latorre, Ramon

    2012-01-01

    The BK channel is one of the most broadly expressed ion channels in mammals. In many tissues, the BK channel pore-forming α-subunit is associated to an auxiliary β-subunit that modulates the voltage- and Ca2+-dependent activation of the channel. Structural components present in β-subunits that are important for the physical association with the α-subunit are yet unknown. Here, we show through co-immunoprecipitation that the intracellular C-terminus, the second transmembrane domain (TM2) and the extracellular loop of the β2-subunit are dispensable for association with the α-subunit pointing transmembrane domain 1 (TM1) as responsible for the interaction. Indeed, the TOXCAT assay for transmembrane protein–protein interactions demonstrated for the first time that TM1 of the β2-subunit physically binds to the transmembrane S1 domain of the α-subunit. PMID:22710124

  10. Characterization of cocaine-induced block of cardiac sodium channels.

    PubMed

    Crumb, W J; Clarkson, C W

    1990-03-01

    Recent evidence suggests that cocaine can produce marked cardiac arrhythmias and sudden death. A possible mechanism for this effect is slowing of impulse conduction due to block of cardiac Na channels. We therefore investigated its effects on Na channels in isolated guinea pig ventricular myocytes using the whole-cell variant of the patch clamp technique. Cocaine (10-50 microM) was found to reduce Na current in a use-dependent manner. The time course for block development and recovery were characterized. At 30 microM cocaine, two phases of block development were defined: a rapid phase (tau = 5.7 +/- 4.9 ms) and a slower phase (tau = 2.3 +/- 0.7 s). Recovery from block at -140 mV was also defined by two phases: (tau f = 136 +/- 61 ms, tau s = 8.5 +/- 1.7 s) (n = 6). To further clarify the molecular mechanisms of cocaine action on cardiac Na channels, we characterized its effects using the guarded receptor model, obtaining estimated Kd values of 328, 19, and 8 microM for channels predominantly in the rested, activated, and inactivated states. These data indicate that cocaine can block cardiac Na channels in a use-dependent manner and provides a possible cellular explanation for its cardiotoxic effects.

  11. 33 CFR 117.753 - Ship Channel, Great Egg Harbor Bay.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 33 Navigation and Navigable Waters 1 2012-07-01 2012-07-01 false Ship Channel, Great Egg Harbor... SECURITY BRIDGES DRAWBRIDGE OPERATION REGULATIONS Specific Requirements New Jersey § 117.753 Ship Channel, Great Egg Harbor Bay. The draw of the S52 (Ship Channel) bridge, mile 0.5 between Somers Point and Ocean...

  12. 33 CFR 117.753 - Ship Channel, Great Egg Harbor Bay.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 33 Navigation and Navigable Waters 1 2013-07-01 2013-07-01 false Ship Channel, Great Egg Harbor... SECURITY BRIDGES DRAWBRIDGE OPERATION REGULATIONS Specific Requirements New Jersey § 117.753 Ship Channel, Great Egg Harbor Bay. The draw of the S52 (Ship Channel) bridge, mile 0.5 between Somers Point and Ocean...

  13. Physical Hydraulic Model of Side-Channel Spillway of Lambuk DAM, Bali

    NASA Astrophysics Data System (ADS)

    Harifa, A. C.; Sholichin, M.; Othman, F. B.

    2013-12-01

    The spillway is among the most important structures of a dam project. A spillway is designed to prevent overtopping of a dam at a place that is not designed for overtopping. Side-channel spillways are commonly used to release water flow from a reservoir in places where the sides are steep and have a considerable height above the dam. Experimental results were collected with a hydraulic model of the side-channel spillway for releasing the peak overflow of Lambuk Dam. This dam is, located on the Lambuk River, which is a tributary of the Yeh Hoo River ~ 34.6 km north of Denpasar on the island of Bali. The bituminous geomembrane faced dam is 24 m in height, with a 35-m wide spillway. The length of the side channel is 35 m long, with 58 m of transition channel, 67.37 m of chuteway channel and 22.71 m of stilling basin. The capacity of the spillway is 231.91 m3/s and the outlet works capacity is 165.28 m3/s. The reservoir is designed for irrigation and water supply. The purpose of this study was to optimize the designed of the structure and to ensure its safe operation. In hydraulic model may help the decision-makers to visualize the flow field before selecting a ';suitable' design. The hydraulic model study was performed to ensure passage of the maximum discharge at maximum reservoir capacity; to study the spillway approach conditions, water surface profiles, and flow patterns in the chuteway; and to reveal potential demerits of the proposed hydraulic design of various structures and explore solutions. The model was constructed at 1 : 40 scale, Reservoir topography was modeled using concrete, the river bed using sand and some gravel, the river berm using concrete, and the spillway and channel using Plexiglas. Water was measured using Rectangular contracted weir. Design floods (with return period in year) were Q2 = 111.40 m3/s, Q5 = 136.84 m3/s, Q10 = 159.32 m3/s, Q25 = 174.61 m3/s, Q50 = 185.13 m3/s, Q100 = 198.08 m3/s, Q200 = 210.55 m3/s, Q1000 = 231.91 m3/s and the

  14. Thirty-Four Megabit Four-Channel Multiplexer

    DTIC Science & Technology

    1985-10-01

    person or conveying any rights or permis- sion to manufacture , use, or sell any patented invention thai ma> in any way be related thereto. WARNING...System (DCS) in Europe. The system is evolving from frequency division multiplex ( FDM ) to time division multiplex (TDM) equipment. The bulk of the...channel multi- plexer permits expansion by providing the spare MBS and 2.048~Mb/s data channels, and will do so with no additional cost

  15. The Distribution of Lightning Channel Lengths in Northern Alabama Thunderstorms

    NASA Technical Reports Server (NTRS)

    Peterson, H. S.; Koshak, W. J.

    2010-01-01

    Lightning is well known to be a major source of tropospheric NOx, and in most cases is the dominant natural source (Huntreiser et al 1998, Jourdain and Hauglustaine 2001). Production of NOx by a segment of a lightning channel is a function of channel segment energy density and channel segment altitude. A first estimate of NOx production by a lightning flash can be found by multiplying production per segment [typically 104 J/m; Hill (1979)] by the total length of the flash s channel. The purpose of this study is to determine average channel length for lightning flashes near NALMA in 2008, and to compare average channel length of ground flashes to the average channel length of cloud flashes.

  16. Characteristics of camel-gate structures with active doping channel profiles

    NASA Astrophysics Data System (ADS)

    Tsai, Jung-Hui; Lour, Wen-Shiung; Laih, Lih-Wen; Liu, Rong-Chau; Liu, Wen-Chau

    1996-03-01

    In this paper, we demonstrate the influence of channel doping profile on the performances of camel-gate field effect transistors (CAMFETs). For comparison, single and tri-step doping channel structures with identical doping thickness products are employed, while other parameters are kept unchanged. The results of a theoretical analysis show that the single doping channel FET with lightly doping active layer has higher barrier height and drain-source saturation current. However, the transconductance is decreased. For a tri-step doping channel structure, it is found that the output drain-source saturation current and the barrier height are enhanced. Furthermore, the relatively voltage independent performances are improved. Two CAMFETs with single and tri-step doping channel structures have been fabricated and discussed. The devices exhibit nearly voltage independent transconductances of 144 mS mm -1 and 222 mS mm -1 for single and tri-step doping channel CAMFETs, respectively. The operation gate voltage may extend to ± 1.5 V for a tri-step doping channel CAMFET. In addition, the drain current densities of > 750 and 405 mA mm -1 are obtained for the tri-step and single doping CAMFETs. These experimental results are inconsistent with theoretical analysis.

  17. High-current discharge channel contraction in high density gas

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Rutberg, Ph. G.; Bogomaz, A. A.; Pinchuk, M. E.

    Research results for discharges at current amplitudes of 0.5-1.6 MA and current rise rate of {approx}10{sup 10} A/s are presented. The discharge is performed in the hydrogen environment at the initial pressure of 5-35 MPa. Initiation is implemented by a wire explosion. The time length of the first half-period of the discharge current is 70-150 {mu}s. Under such conditions, discharge channel contraction is observed; the contraction is followed by soft x-ray radiation. The phenomena are discussed, which are determined by high density of the gas surrounding the discharge channel. These phenomena are increase of the current critical value, where themore » channel contraction begins and growth of temperature in the axis region of the channel, where the initial density of the gas increases.« less

  18. [Data collection of signals in the multi-channel sEMG system of masticatory muscles and development and preliminary clinical application of an analytic system].

    PubMed

    Du, Hongliang; Li, Xin; Li, Shan; Zhang, Rui; Song, Rong; Li, Lan; Wang, Wei; Kang, Hong

    2014-02-01

    The aim of this study was to design a simple, economic, with high Common Mode Rejection Ratio (CMRR), preamplifier and multi-channel masticatory muscle surface electromyography (sEMG) signal acquisition system assisting to diagnose temporomandibular disorders (TMD). We used the USB interface technology in the EMG data with the aid of the windows to operate system and graphical interface. Eight patients with TMD and eight controls were analyzed separately using this system. In this system, we analyzed sEMG by an optional combination of time domain, frequency domain, time-frequency, several spectral analysis, wavelets and other special algorithms under multi-parameter. Multi-channel sEMG System of Masticatory Muscles is a simple, economic system. It has high sensitivity and specificity. The sEMG signals were changed in patients with TMD. The system would pave the way for diagnosis TMD and help us to assess the treatment effect. A novel and objective method is provided for diagnosis and treatment of oral-maxillofacial disease and functional reconstruction.

  19. Transmembrane S1 mutations in CNGA3 from achromatopsia 2 patients cause loss of function and impaired cellular trafficking of the cone CNG channel.

    PubMed

    Patel, Kirti A; Bartoli, Kristen M; Fandino, Richard A; Ngatchou, Anita N; Woch, Gustaw; Carey, Jannette; Tanaka, Jacqueline C

    2005-07-01

    Achromatopsia 2, an inherited retinal disorder resulting in attenuation or loss of cone function, is caused by mutations in the alpha subunit of the cone cyclic nucleotide-gated (CNG) channel gene CNGA3. Examination of mutations that cluster in the first transmembrane segment of the protein may provide insight into its role in CNG channel structure, function, biogenesis, and pathophysiology. The human CNGA3 gene was tagged at the C terminus with green fluorescent protein. Four mutations, Y181C, N182Y, L186F, and C191Y, were expressed in human embryonic kidney cells. Protein expression was evaluated with immunoblot analysis and cellular localization was determined by immunocytochemistry. Channel function was evaluated by patch-clamp electrophysiology. All the mutations result in loss of channel function, as determined by the failure of cGMP to activate wild-type currents in excised patches. Full-length mutant proteins were synthesized but retained in the endoplasmic reticulum. Glycerol treatment did not rescue channel function nor did coexpression with CNGB3, a subunit of native hetero-tetrameric cone channels. A control mutant, C191S, exhibited cGMP current activation with significantly reduced cooperativity, suggesting that mutations in the first transmembrane domain alter in inter- or intrasubunit communication. The results implicate the first transmembrane segment in both maturation and function of CNG channels. The defects are not reversed with glycerol, a chemical chaperone that rescues channel function in some channelopathies. Molecular analysis of achromatopsia 2 mutations may be useful in evaluating potential therapeutic approaches for treatment of this channelopathy.

  20. Conformational dynamics of the inner pore helix of voltage-gated potassium channels

    NASA Astrophysics Data System (ADS)

    Choe, Seungho; Grabe, Michael

    2009-06-01

    Voltage-gated potassium (Kv) channels control the electrical excitability of neurons and muscles. Despite this key role, how these channels open and close or gate is not fully understood. Gating is usually attributed to the bending and straightening of pore-lining helices at glycine and proline residues. In this work we focused on the role of proline in the Pro-Val-Pro (PVP) motif of the inner S6 helix in the Kv1.2 channel. We started by developing a simple hinged-rod model to fully explore the configurational space of bent helices and we related these configurations to the degree of pore opening. We then carried out fully atomistic simulations of the S6 helices and compared these simulations to the hinged-rod model. Both methods suggest that Kv1 channels are not tightly closed when the inner helices are straight, unlike what is seen in the non-PVP containing channels KcsA and KirBac. These results invite the possibility that the S6 helices may be kinked when Kv1 channels are closed. Our simulations indicate that the wild-type helix adopts multiple spatially distinct configurations, which is consistent with its role in adopting a closed state and an open state. The two most dominant configurational basins correspond to a 6 Å movement of the helix tail accompanied by the PVP region undergoing a local α-helix to 310-helix transition. We explored how single point mutations affect the propensity of the S6 helix to adopt particular configurations. Interestingly, mutating the first proline, P405 (P473 in Shaker), to alanine completely removed the bistable nature of the S6 helix possibly explaining why this mutation compromises the channel. Next, we considered four other mutations in the area known to affect channel gating and we saw similarly dramatic changes to the helix's dynamics and range of motion. Our results suggest a possible mechanism of helix pore closure and they suggest differences in the closed state of glycine-only channels, like KcsA, and PVP containing

  1. Shadow poles in coupled-channel problems calculated with the Berggren basis

    NASA Astrophysics Data System (ADS)

    Id Betan, R. M.; Kruppa, A. T.; Vertse, T.

    2018-02-01

    Background: In coupled-channels models the poles of the scattering S matrix are located on different Riemann sheets. Physical observables are affected mainly by poles closest to the physical region but sometimes shadow poles have considerable effect too. Purpose: The purpose of this paper is to show that in coupled-channels problems all poles of the S matrix can be located by an expansion in terms of a properly constructed complex-energy basis. Method: The Berggren basis is used for expanding the coupled-channels solutions. Results: The locations of the poles of the S matrix for the Cox potential, constructed for coupled-channels problems, were numerically calculated and compared with the exact ones. In a nuclear physics application the Jπ=3 /2+ resonant poles of 5He were calculated in a phenomenological two-channel model. The properties of both the normal and shadow resonances agree with previous findings. Conclusions: We have shown that, with an appropriately chosen Berggren basis, all poles of the S matrix including the shadow poles can be determined. We have found that the shadow pole of 5He migrates between Riemann sheets if the coupling strength is varied.

  2. Molecular Interactions between Tarantula Toxins and Low-Voltage-Activated Calcium Channels

    PubMed Central

    Salari, Autoosa; Vega, Benjamin S.; Milescu, Lorin S.; Milescu, Mirela

    2016-01-01

    Few gating-modifier toxins have been reported to target low-voltage-activated (LVA) calcium channels, and the structural basis of toxin sensitivity remains incompletely understood. Studies of voltage-gated potassium (Kv) channels have identified the S3b–S4 “paddle motif,” which moves at the protein-lipid interface to drive channel opening, as the target for these amphipathic neurotoxins. Voltage-gated calcium (Cav) channels contain four homologous voltage sensor domains, suggesting multiple toxin binding sites. We show here that the S3–S4 segments within Cav3.1 can be transplanted into Kv2.1 to examine their individual contributions to voltage sensing and pharmacology. With these results, we now have a more complete picture of the conserved nature of the paddle motif in all three major voltage-gated ion channel types (Kv, Nav, and Cav). When screened with tarantula toxins, the four paddle sequences display distinct toxin binding properties, demonstrating that gating-modifier toxins can bind to Cav channels in a domain specific fashion. Domain III was the most commonly and strongly targeted, and mutagenesis revealed an acidic residue that is important for toxin binding. We also measured the lipid partitioning strength of all toxins tested and observed a positive correlation with their inhibition of Cav3.1, suggesting a key role for membrane partitioning. PMID:27045173

  3. Design of boron carbide-shielded irradiation channel of the outer irradiation channel of the Ghana Research Reactor-1 using MCNP.

    PubMed

    Abrefah, R G; Sogbadji, R B M; Ampomah-Amoako, E; Birikorang, S A; Odoi, H C; Nyarko, B J B

    2011-01-01

    The MCNP model for the Ghana Research Reactor-1 was redesigned to incorporate a boron carbide-shielded irradiation channel in one of the outer irradiation channels. Extensive investigations were made before arriving at the final design of only one boron carbide covered outer irradiation channel; as all the other designs that were considered did not give desirable results of neutronic performance. The concept of redesigning a new MCNP model, which has a boron carbide-shielded channel is to equip the Ghana Research Reactor-1 with the means of performing efficient epithermal neutron activation analysis. After the simulation, a comparison of the results from the original MCNP model for the Ghana Research Reactor-1 and the new redesigned model of the boron carbide shielded channel was made. The final effective criticality of the original MCNP model for the GHARR-1 was recorded as 1.00402 while that of the new boron carbide designed model was recorded as 1.00282. Also, a final prompt neutron lifetime of 1.5245 × 10(-4)s was recorded for the new boron carbide designed model while a value of 1.5571 × 10(-7)s was recorded for the original MCNP design of the GHARR-1. Copyright © 2010 Elsevier Ltd. All rights reserved.

  4. IKs channels open slowly because KCNE1 accessory subunits slow the movement of S4 voltage sensors in KCNQ1 pore-forming subunits

    PubMed Central

    Ruscic, Katarina J.; Miceli, Francesco; Villalba-Galea, Carlos A.; Dai, Hui; Mishina, Yukiko; Bezanilla, Francisco; Goldstein, Steve A. N.

    2013-01-01

    Human IKs channels activate slowly with the onset of cardiac action potentials to repolarize the myocardium. IKs channels are composed of KCNQ1 (Q1) pore-forming subunits that carry S4 voltage-sensor segments and KCNE1 (E1) accessory subunits. Together, Q1 and E1 subunits recapitulate the conductive and kinetic properties of IKs. How E1 modulates Q1 has been unclear. Investigators have variously posited that E1 slows the movement of S4 segments, slows opening and closing of the conduction pore, or modifies both aspects of electromechanical coupling. Here, we show that Q1 gating current can be resolved in the absence of E1, but not in its presence, consistent with slowed movement of the voltage sensor. E1 was directly demonstrated to slow S4 movement with a fluorescent probe on the Q1 voltage sensor. Direct correlation of the kinetics of S4 motion and ionic current indicated that slowing of sensor movement by E1 was both necessary and sufficient to determine the slow-activation time course of IKs. PMID:23359697

  5. Dark-matter production through loop-induced processes at the LHC: the s-channel mediator case.

    PubMed

    Mattelaer, Olivier; Vryonidou, Eleni

    We show how studies relevant for mono-X searches at the LHC in simplified models featuring a dark-matter candidate and an s -channel mediator can be performed within the MadGraph5_aMC@NLO framework. We focus on gluon-initiated loop-induced processes, mostly relevant to the case where the mediator couples preferentially to third generation quarks and in particular to the top quark. Our implementation allows us to study signatures at hadron colliders involving missing transverse energy plus jets or plus neutral bosons ([Formula: see text]), possibly including the effects of extra radiation by multi-parton merging and matching to the parton shower.

  6. Martian channels and valleys: Their characteristics, distribution, and age

    USGS Publications Warehouse

    Carr, M.H.; Clow, G.D.

    1981-01-01

    All Martian channels and valleys visible at a resolution of 125 to 300 meters between 65??N and 65??S were mapped at a scale of 1:5,000,000 and the maps then digitized. Correlations of valley presence with other surface features show that almost all valleys are in the old cratered terrain. preferentially in areas of low albedo, low violet/red ratios, and high elevation. The networks are open, the individual drainage basins are small relative to Earth, and large distances separate the basins, features which all suggest an immature drainage system. The simplest explanation of the correlations and the restriction of valley networks to old terrain is that the channels themselves are old, and that the climatic conditions necessary for their formation did not prevail for long after the decline in the cratering rate around 3.9 billion years ago. Two types of outflow channel are distinguished: unconfined, in which broad swaths of terrain are scoured, and confined, in which flow is restricted to discrete channels. The outflow channels have a wide range of ages and may form under present climatic conditions. Fretted channels are largely restrited to two latitude belts centered on 40??N and 45??S, where relatively rapid erosion along escarpments results from mass wasting. They probably form by enlargement of preexisting channels by escarpment retreat. ?? 1981.

  7. Single or Multiple Access Channels to the CYP450s Active Site? An Answer from Free Energy Simulations of the Human Aromatase Enzyme.

    PubMed

    Magistrato, Alessandra; Sgrignani, Jacopo; Krause, Rolf; Cavalli, Andrea

    2017-05-04

    Cytochromes P450 (CYP450s), in particular, CYP19A1 and CYP17A1, are key clinical targets of breast and prostate anticancer therapies, critical players in drug metabolism, and their overexpression in tumors is associated with drug resistance. In these enzymes, ligand (substrates, drugs) metabolism occurs in deeply buried active sites accessible only via several grueling channels, whose exact biological role remains unclear. Gaining direct insights on the mechanism by which ligands travel in and out is becoming increasingly important given that channels are involved in the modulation of binding/dissociation kinetics and the specificity of ligands toward a CYP450. This has profound implications for enzymatic efficiency and drug efficacy/toxicity. Here, by applying free energy methods, for a cumulative simulation time of 20 μs, we provide detailed atomistic characterization and free energy profiles of the entry/exit routes preferentially followed by a substrate (androstenedione) and a last-generation inhibitor (letrozole) to/from the catalytic site of CYP19A1 (the human aromatase (HA) enzyme), a key clinical target against breast cancer, studied here as prototypical CYP450. Despite the remarkably different size/shape/hydrophobicity of the ligands, two channels appear accessible to their entrance, while only one exit route appears to be preferential. Our study shows that the preferential paths may be conserved among different CYP450s. Moreover, our results highlight that, at least in the case of HA, ligand channeling is associated with large enzyme structural rearrangements. A wise choice of the computational method and very long simulations are, thus, required to obtain fully converged quantitative free energy profiles, which might be used to design novel biocatalysts or next-generation cytochrome inhibitors with an in silico tuned K m .

  8. DFT studies on the multi-channel reaction of CH3S+NO2

    NASA Astrophysics Data System (ADS)

    Tang, Yi-Zhen; Sun, Hao; Pan, Ya-Ru; Pan, Xiu-Mei; Wang, Rong-Shun

    The mechanisms for the reaction of CH3S with NO2 are investigated at the QCISD(T)/6-311++G(d,p)//B3LYP/6-311++G(d,p) on both single and triple potential energy surfaces (PESs). The geometries, vibrational frequencies, and zero-point energy (ZPE) correction of all stationary points involved in the title reaction are calculated at the B3LYP/6-311++G(d,p) level. More accurate energies are obtained at the QCISD(T)/6-311++G(d,p). The results show that 5 intermediates and 14 transition states are found. The reaction is more predominant on the single PES, while it is negligible on the triple PES. Without any barrier height for the whole process, the main channel of the reaction is to form CH3SONO and then dissociate to CH3SO+NO.

  9. United in Diversity: Mechanosensitive Ion Channels in Plants

    PubMed Central

    Hamilton, Eric S.; Schlegel, Angela M.; Haswell, Elizabeth S.

    2015-01-01

    Mechanosensitive (MS) ion channels are a common mechanism for perceiving and responding to mechanical force. This class of mechanoreceptors is capable of transducing membrane tension directly into ion flux. In plant systems, MS ion channels have been proposed to play a wide array of roles, from the perception of touch and gravity to the osmotic homeostasis of intracellular organelles. Three families of plant MS ion channels have been identified: the MscS-like (MSL), Mid1-complementing activity (MCA), and two-pore potassium (TPK) families. Channels from these families vary widely in structure and function, localize to multiple cellular compartments, and conduct chloride, calcium, and/or potassium ions. However, they are still likely to represent only a fraction of the MS ion channel diversity in plant systems. PMID:25494462

  10. Modeling of Single Noninactivating Na+ Channels: Evidence for Two Open and Several Fast Inactivated States

    PubMed Central

    The, Yu-Kai; Fernandes, Jacqueline; Popa, M. Oana; Alekov, Alexi K.; Timmer, Jens; Lerche, Holger

    2006-01-01

    Voltage-gated Na+ channels play a fundamental role in the excitability of nerve and muscle cells. Defects in fast Na+ channel inactivation can cause hereditary muscle diseases with hyper- or hypoexcitability of the sarcolemma. To explore the kinetics and gating mechanisms of noninactivating muscle Na+ channels on a molecular level, we analyzed single channel currents from wild-type and five mutant Na+ channels. The mutations were localized in different protein regions which have been previously shown to be important for fast inactivation (D3-D4-linker, D3/S4-S5, D4/S4-S5, D4/S6) and exhibited distinct grades of defective fast inactivation with varying levels of persistent Na+ currents caused by late channel reopenings. Different gating schemes were fitted to the data using hidden Markov models with a correction for time interval omission and compared statistically. For all investigated channels including the wild-type, two open states were necessary to describe our data. Whereas one inactivated state was sufficient to fit the single channel behavior of wild-type channels, modeling the mutants with impaired fast inactivation revealed evidence for several inactivated states. We propose a single gating scheme with two open and three inactivated states to describe the behavior of all five examined mutants. This scheme provides a biological interpretation of the collected data, based on previous investigations in voltage-gated Na+ and K+ channels. PMID:16513781

  11. TRP Channels

    NASA Astrophysics Data System (ADS)

    Voets, Thomas; Owsianik, Grzegorz; Nilius, Bernd

    The TRP superfamily represents a highly diverse group of cation-permeable ion channels related to the product of the Drosophila trp (transient receptor potential) gene. The cloning and characterization of members of this cation channel family has experienced a remarkable growth during the last decade, uncovering a wealth of information concerning the role of TRP channels in a variety of cell types, tissues, and species. Initially, TRP channels were mainly considered as phospholipase C (PLC)-dependent and/or store-operated Ca2+-permeable cation channels. More recent research has highlighted the sensitivity of TRP channels to a broad array of chemical and physical stimuli, allowing them to function as dedicated biological sensors involved in processes ranging from vision to taste, tactile sensation, and hearing. Moreover, the tailored selectivity of certain TRP channels enables them to play key roles in the cellular uptake and/or transepithelial transport of Ca2+, Mg2+, and trace metal ions. In this chapter we give a brief overview of the TRP channel superfamily followed by a survey of current knowledge concerning their structure and activation mechanisms.

  12. 12-bit 32 channel 500 MS/s low-latency ADC for particle accelerators real-time control

    NASA Astrophysics Data System (ADS)

    Karnitski, Anton; Baranauskas, Dalius; Zelenin, Denis; Baranauskas, Gytis; Zhankevich, Alexander; Gill, Chris

    2017-09-01

    Particle beam control systems require real-time low latency digital feedback with high linearity and dynamic range. Densely packed electronic systems employ high performance multichannel digitizers causing excessive heat dissipation. Therefore, low power dissipation is another critical requirement for these digitizers. A described 12-bit 500 MS/s ADC employs a sub-ranging architecture based on a merged sample & hold circuit, a residue C-DAC and a shared 6-bit flash core ADC. The core ADC provides a sequential coarse and fine digitization featuring a latency of two clock cycles. The ADC is implemented in a 28 nm CMOS process and consumes 4 mW of power per channel from a 0.9 V supply (interfacing and peripheral circuits are excluded). Reduced power consumption and small on-chip area permits the implementation of 32 ADC channels on a 10.7 mm2 chip. The ADC includes a JESD204B standard compliant output data interface operated at the 7.5 Gbps/ch rate. To minimize the data interface related time latency, a special feature permitting to bypass the JESD204B interface is built in. DoE Phase I Award Number: DE-SC0017213.

  13. Blind Equalization and Fading Channel Signal Recovery of OFDM Modulation

    DTIC Science & Technology

    2011-03-01

    Square LTI Linear Time Invariant MIMO Multiple-Input Multiple-Output OFDM Orthogonal Frequency-Division Multiplexing QPSK Quadrature Phase-Shift...AND FADING CHANNEL SIGNAL RECOVERY OF OFDM MODULATION by Anthony G. Stranges March 2011 Thesis Co-Advisors: Roberto Cristi Frank Kragh...Master’s Thesis 4. TITLE AND SUBTITLE Blind Equalization and Fading Channel Signal Recovery of OFDM Modulation 6. AUTHOR(S) Anthony G. Stranges

  14. NPPB structure-specifically activates TRPA1 channels.

    PubMed

    Liu, Kun; Samuel, Manoj; Ho, Melisa; Harrison, Richard K; Paslay, Jeff W

    2010-07-01

    TRPA1 channels have been found to play an important role in mammalian pain sensation, especially when the pain is caused by chemicals on site of inflammation. A large number of structurally diverse chemicals are found to activate TRPA1 channels, implicating a potential chemosensor in neuronal nociception. Identification of the channel activation by cysteine modification through covalent chemical reaction provides arguments for the diversity of the agonist structures. However, it is largely unknown how nonreactive compounds activate TRPA1 channels. Here, we report that NPPB, a classic Cl(-) channel blocker, potently activated human TRPA1 channels overexpressed in mammalian HEK-293 cells. This effect was confirmed in Ca(2+) imaging assay, patch clamp whole cell and single channel recordings. The NPPB response was quick, fully reversible and replicable, contrary to the effect of covalent modification by AITC. The mutagenesis studies revealed a refreshed look at several mutations known to be critical for the actions of AITC and menthol. The blocking profile of NPPB on these mutants showed that the NPPB activation was similar to that of FTS and different from AITC and menthol. The results indicated a possible close interaction between S5 and N-terminal domains of the channel. We also tested a group of NPPB analogs on TRPA1 channel activities. The results demonstrated that NPPB activation was tightly associated with chemical structure. None of the single chemical group was sufficient to activate the channel, indicating that NPPB activated TRPA1 through a structure-specific mechanism. (c) 2010 Elsevier Inc. All rights reserved.

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

    PubMed Central

    Geng, Yanyan; Magleby, Karl L.

    2014-01-01

    Single-channel kinetics has proven a powerful tool to reveal information about the gating mechanisms that control the opening and closing of ion channels. This introductory review focuses on the gating of large conductance Ca2+- and voltage-activated K+ (BK or Slo1) channels at the single-channel level. It starts with single-channel current records and progresses to presentation and analysis of single-channel data and the development of gating mechanisms in terms of discrete state Markov (DSM) models. The DSM models are formulated in terms of the tetrameric modular structure of BK channels, consisting of a central transmembrane pore-gate domain (PGD) attached to four surrounding transmembrane voltage sensing domains (VSD) and a large intracellular cytosolic domain (CTD), also referred to as the gating ring. The modular structure and data analysis shows that the Ca2+ and voltage dependent gating considered separately can each be approximated by 10-state two-tiered models with five closed states on the upper tier and five open states on the lower tier. The modular structure and joint Ca2+ and voltage dependent gating are consistent with a 50 state two-tiered model with 25 closed states on the upper tier and 25 open states on the lower tier. Adding an additional tier of brief closed (flicker states) to the 10-state or 50-state models improved the description of the gating. For fixed experimental conditions a channel would gate in only a subset of the potential number of states. The detected number of states and the correlations between adjacent interval durations are consistent with the tiered models. The examined models can account for the single-channel kinetics and the bursting behavior of gating. Ca2+ and voltage activate BK channels by predominantly increasing the effective opening rate of the channel with a smaller decrease in the effective closing rate. Ca2+ and depolarization thus activate by mainly destabilizing the closed states. PMID:25653620

  16. The neutron channeling phenomenon.

    PubMed

    Khanouchi, A; Sabir, A; Boulkheir, M; Ichaoui, R; Ghassoun, J; Jehouani, A

    1997-01-01

    Shields, used for protection against radiation, are often pierced with vacuum channels for passing cables and other instruments for measurements. The neutron transmission through these shields is an unavoidable phenomenon. In this work we study and discuss the effect of channels on neutron transmission through shields. We consider an infinite homogeneous slab, with a fixed thickness (20 lambda, with lambda the mean free path of the neutron in the slab), which contains a vacuum channel. This slab is irradiated with an infinite source of neutrons on the left side and on the other side (right side) many detectors with windows equal to 2 lambda are placed in order to evaluate the neutron transmission probabilities (Khanouchi, A., Aboubekr, A., Ghassoun, J. and Jehouani, A. (1994) Rencontre Nationale des Jeunes Chercheurs en Physique. Casa Blanca Maroc; Khanouchi, A., Sabir, A., Ghassoun, J. and Jehouani, A. (1995) Premier Congré International des Intéractions Rayonnements Matière. Eljadida Maroc). The neutron history within the slab is simulated by the Monte Carlo method (Booth, T. E. and Hendricks, J. S. (1994) Nuclear Technology 5) and using the exponential biasing technique in order to improve the Monte Carlo calculation (Levitt, L. B. (1968) Nuclear Science and Engineering 31, 500-504; Jehouani, A., Ghassoun, J. and Aboubker, A. (1994) In Proceedings of the 6th International Symposium on Radiation Physics, Rabat, Morocco). Then different geometries of the vacuum channel have been studied. For each geometry we have determined the detector response and calculated the neutron transmission probability for different detector positions. This neutron transmission probability presents a peak for the detectors placed in front of the vacuum channel. This study allowed us to clearly identify the neutron channeling phenomenon. One application of our study is to detect vacuum defects in materials.

  17. Streambed adjustment and channel widening in eastern Nebraska

    USGS Publications Warehouse

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

    2003-01-01

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

  18. Structure of a eukaryotic cyclic nucleotide-gated channel

    PubMed Central

    Li, Minghui; Zhou, Xiaoyuan; Wang, Shu; Michailidis, Ioannis; Gong, Ye; Su, Deyuan; Li, Huan; Li, Xueming; Yang, Jian

    2018-01-01

    Summary Cyclic nucleotide-gated (CNG) channels are essential for vision and olfaction. They belong to the voltage-gated ion channel superfamily but their activities are controlled by intracellular cyclic nucleotides instead of transmembrane voltage. Here we report a 3.5 Å-resolution single-particle electron cryomicroscopy structure of a CNG channel from C. elegans in the cGMP-bound open state. The channel has an unusual voltage-sensor-like domain (VSLD), accounting for its deficient voltage dependence. A C-terminal linker connecting S6 and the cyclic nucleotide-binding domain interacts directly with both the VSLD and pore domain, forming a gating ring that couples conformational changes triggered by cyclic nucleotide binding to the gate. The selectivity filter is lined by the carboxylate side chains of a functionally important glutamate and three rings of backbone carbonyls. This structure provides a new framework for understanding mechanisms of ion permeation, gating and channelopathy of CNG channels and cyclic nucleotide modulation of related channels. PMID:28099415

  19. Tension-activated channels in the mechanism of osmotic fitness in Pseudomonas aeruginosa

    PubMed Central

    Rowe, Ian; Schams, Anthony; Mayhew, Christina

    2017-01-01

    Pseudomonas aeruginosa (PA) is an opportunistic pathogen with an exceptional ability to adapt to a range of environments. Part of its adaptive potential is the ability to survive drastic osmolarity changes. Upon a sudden dilution of external medium, such as during exposure to rain, bacteria evade mechanical rupture by engaging tension-activated channels that act as osmolyte release valves. In this study, we compare fast osmotic permeability responses in suspensions of wild-type PA and Escherichia coli (EC) strains in stopped-flow experiments and provide electrophysiological descriptions of osmotic-release channels in PA. Using osmotic dilution experiments, we first show that PA tolerates a broader range of shocks than EC. We record the kinetics of cell equilibration reported by light scattering responses to osmotic up- and down-shocks. PA exhibits a lower water permeability and faster osmolyte release rates during large osmotic dilutions than EC, which correlates with better survival. To directly characterize the PA tension-activated channels, we generate giant spheroplasts from this microorganism and record current responses in excised patches. Unlike EC, which relies primarily on two types of channels, EcMscS and EcMscL, to generate a distinctive two-wave pressure ramp response, PA exhibits a more gradual response that is dominated by MscL-type channels. Genome analysis, cloning, and expression reveal that PA possesses one MscL-type (PaMscL) and two MscS-type (PaMscS-1 and 2) proteins. In EC spheroplasts, both PaMscS channels exhibit a slightly earlier activation by pressure compared with EcMscS. Unitary currents reveal that PaMscS-2 has a smaller conductance, higher anionic preference, stronger inactivation, and slower recovery compared with PaMscS-1. We conclude that PA relies on MscL as the major valve defining a high rate of osmolyte release sufficient to curb osmotic swelling under extreme shocks, but it still requires MscS-type channels with a strong

  20. Identification and Analysis of Putative Homologues of Mechanosensitive Channels in Pathogenic Protozoa

    PubMed Central

    Prole, David L.; Taylor, Colin W.

    2013-01-01

    Mechanosensitive channels play important roles in the physiology of many organisms, and their dysfunction can affect cell survival. This suggests that they might be therapeutic targets in pathogenic organisms. Pathogenic protozoa lead to diseases such as malaria, dysentery, leishmaniasis and trypanosomiasis that are responsible for millions of deaths each year worldwide. We analyzed the genomes of pathogenic protozoa and show the existence within them of genes encoding putative homologues of mechanosensitive channels. Entamoeba histolytica, Leishmania spp., Trypanosoma cruzi and Trichomonas vaginalis have genes encoding homologues of Piezo channels, while most pathogenic protozoa have genes encoding homologues of mechanosensitive small-conductance (MscS) and K+-dependent (MscK) channels. In contrast, all parasites examined lack genes encoding mechanosensitive large-conductance (MscL), mini-conductance (MscM) and degenerin/epithelial Na+ (DEG/ENaC) channels. Multiple sequence alignments of evolutionarily distant protozoan, amoeban, plant, insect and vertebrate Piezo channel subunits define an absolutely conserved motif that may be involved in channel conductance or gating. MscS channels are not present in humans, and the sequences of protozoan and human homologues of Piezo channels differ substantially. This suggests the possibility for specific targeting of mechanosensitive channels of pathogens by therapeutic drugs. PMID:23785469

  1. Models of Voltage-Dependent Conformational Changes in NaChBac Channels

    PubMed Central

    Shafrir, Yinon; Durell, Stewart R.; Guy, H. Robert

    2008-01-01

    Models of the transmembrane region of the NaChBac channel were developed in two open/inactivated and several closed conformations. Homology models of NaChBac were developed using crystal structures of Kv1.2 and a Kv1.2/2.1 chimera as templates for open conformations, and MlotiK and KcsA channels as templates for closed conformations. Multiple molecular-dynamic simulations were performed to refine and evaluate these models. A striking difference between the S4 structures of the Kv1.2-like open models and MlotiK-like closed models is the secondary structure. In the open model, the first part of S4 forms an α-helix, and the last part forms a 310 helix, whereas in the closed model, the first part of S4 forms a 310 helix, and the last part forms an α-helix. A conformational change that involves this type of transition in secondary structure should be voltage-dependent. However, this transition alone is not sufficient to account for the large gating charge movement reported for NaChBac channels and for experimental results in other voltage-gated channels. To increase the magnitude of the motion of S4, we developed another model of an open/inactivated conformation, in which S4 is displaced farther outward, and a number of closed models in which S4 is displaced farther inward. A helical screw motion for the α-helical part of S4 and a simple axial translation for the 310 portion were used to develop models of these additional conformations. In our models, four positively charged residues of S4 moved outwardly during activation, across a transition barrier formed by highly conserved hydrophobic residues on S1, S2, and S3. The S4 movement was coupled to an opening of the activation gate formed by S6 through interactions with the segment linking S4 to S5. Consistencies of our models with experimental studies of NaChBac and Kv channels are discussed. PMID:18641074

  2. The Ketogenic Diet and Potassium Channel Function

    DTIC Science & Technology

    2015-11-01

    1 AWARD NUMBER: W81XWH-13-1-0463 TITLE: The Ketogenic Diet and Potassium Channel Function PRINCIPAL INVESTIGATOR: Dr. Geoffrey Murphy...NUMBER The Ketogenic Diet and Potassium Channel Function 5b. GRANT NUMBER W81XWH-13-1-0463 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Geoffrey Murphy...The overall objective of this Discovery Award was to explore the hypothesis the ketogenic diet (KD) regulates neuronal excitability by influencing

  3. Structure-function study on a de novo synthetic hydrophobic ion channel.

    PubMed Central

    Qi, Z; Sokabe, M; Donowaki, K; Ishida, H

    1999-01-01

    Ion conduction properties of a de novo synthesized channel, formed from cyclic octa-peptides consisting of four alternate L-alanine (Ala) and N'-acylated 3-aminobenzoic acid (Aba) moieties, were studied in bilayer membranes. The single-channel conductance was 9 pS in symmetrical 500 mM KCl. The channel favored permeation of cations over anions with a permeability ratio (PCl-/PK+) of 0.15. The selectivity sequence among monovalent cations based on permeability ratio (PX+/PK+) fell into an order: NH4+(1.4) > Cs+(1. 1) >/= K+(1.0) > Na+(0.4) >> Li+(0). The conductance-activity relationship of the channel in K+ solutions followed simple Michaelis-Menten kinetics with a half-maximal saturating activity of 8 mM and a maximal conductance of 9 pS. The permeability ratio PNa+/PK+ remained constant ( approximately 0.40) under biionic concentrations from 10 to 500 mM. These results suggests that the channel is a one-ion channel. The pore diameter probed by a set of organic cations was approximately 6 A. The single-channel current was blocked by Ca2+ in a dose-dependent manner that followed a single-site titration curve with a voltage-dependent dissociation constant of 0.6 mM at 100 mV. The electric distance of the binding site for Ca2+ was 0.07 from both entrances of the channel, indicating the presence of two symmetrical binding sites in each vicinity of the channel entrance. Correlations between conduction properties and structural aspects of the channel are discussed in terms of a three-barrier and two-binding-site (3B2S) model of Eyring rate theory. All available structural information supported an idea that the channel was formed from a tail-to-tail associated dimer of the molecule, the pore of which was lined with hydrophobic acyl chains. This is the first report to have made a systematic analysis of ion permeation through a hydrophobic pore. PMID:9929469

  4. CryoEM structure of a prokaryotic cyclic nucleotide-gated ion channel

    PubMed Central

    James, Zachary M.; Borst, Andrew J.; Haitin, Yoni; Frenz, Brandon; DiMaio, Frank; Zagotta, William N.; Veesler, David

    2017-01-01

    Cyclic nucleotide-gated (CNG) and hyperpolarization-activated cyclic nucleotide-regulated (HCN) ion channels play crucial physiological roles in phototransduction, olfaction, and cardiac pace making. These channels are characterized by the presence of a carboxyl-terminal cyclic nucleotide-binding domain (CNBD) that connects to the channel pore via a C-linker domain. Although cyclic nucleotide binding has been shown to promote CNG and HCN channel opening, the precise mechanism underlying gating remains poorly understood. Here we used cryoEM to determine the structure of the intact LliK CNG channel isolated from Leptospira licerasiae—which shares sequence similarity to eukaryotic CNG and HCN channels—in the presence of a saturating concentration of cAMP. A short S4–S5 linker connects nearby voltage-sensing and pore domains to produce a non–domain-swapped transmembrane architecture, which appears to be a hallmark of this channel family. We also observe major conformational changes of the LliK C-linkers and CNBDs relative to the crystal structures of isolated C-linker/CNBD fragments and the cryoEM structures of related CNG, HCN, and KCNH channels. The conformation of our LliK structure may represent a functional state of this channel family not captured in previous studies. PMID:28396445

  5. Protons stabilize the closed conformation of gain-of-function mutants of the TRPV1 channel.

    PubMed

    Boukalova, Stepana; Teisinger, Jan; Vlachova, Viktorie

    2013-03-01

    The vanilloid transient receptor potential channel TRPV1 is a molecular integrator of noxious stimuli, including capsaicin, heat and protons. Despite clear similarities between the overall architecture of TRPV1 and voltage-dependent potassium (Kv) channels, the extent of conservation in the molecular logic for gating is unknown. In Kv channels, a small contact surface between S1 and the pore-helix is required for channel functioning. To explore the function of S1 in TRPV1, we used tryptophan-scanning mutagenesis and characterized the responses to capsaicin and protons. Wild-type-like currents were generated in 9 out of 17 mutants; three mutants (M445W, A452W, R455W) were non-functional. The conservative mutation R455K in the extracellular extent of S1 slowed down capsaicin-induced activation and prevented normal channel closure. This mutant was neither activated nor potentiated by protons, on the contrary, protons promoted a rapid deactivation of its currents. Similar phenotypes were found in two other gain-of-function mutants and also in the pore-helix mutant T633A, known to uncouple proton activation. We propose that the S1 domain contains a functionally important region that may be specifically involved in TRPV1 channel gating, and thus be important for the energetic coupling between S1-S4 sensor activation and gate opening. Analogous to Kv channels, the S1-pore interface might serve to stabilize conformations associated with TRPV1 channel gating. Copyright © 2012 Elsevier B.V. All rights reserved.

  6. Fading channel simulator

    DOEpatents

    Argo, Paul E.; Fitzgerald, T. Joseph

    1993-01-01

    Fading channel effects on a transmitted communication signal are simulated with both frequency and time variations using a channel scattering function to affect the transmitted signal. A conventional channel scattering function is converted to a series of channel realizations by multiplying the square root of the channel scattering function by a complex number of which the real and imaginary parts are each independent variables. The two-dimensional inverse-FFT of this complex-valued channel realization yields a matrix of channel coefficients that provide a complete frequency-time description of the channel. The transmitted radio signal is segmented to provide a series of transmitted signal and each segment is subject to FFT to generate a series of signal coefficient matrices. The channel coefficient matrices and signal coefficient matrices are then multiplied and subjected to inverse-FFT to output a signal representing the received affected radio signal. A variety of channel scattering functions can be used to characterize the response of a transmitter-receiver system to such atmospheric effects.

  7. Sumatriptan Inhibits TRPV1 Channels in Trigeminal Neurons

    PubMed Central

    Evans, M. Steven; Cheng, Xiangying; Jeffry, Joseph A.; Disney, Kimberly E.; Premkumar, Louis S.

    2011-01-01

    Objective To understand a possible role for transient potential receptor vanilloid 1 (TRPV1) ion channels in sumatriptan relief of pain mediated by trigeminal nociceptors. Background TRPV1 channels are expressed in small nociceptive sensory neurons. In dorsal root ganglia (DRG), TRPV1-containing nociceptors mediate certain types of inflammatory pain. Neurogenic inflammation of cerebral dura and blood vessels in the trigeminal nociceptive system is thought to be important in migraine pain, but the ion channels important in transducing migraine pain are not known. Sumatriptan is an agent effective in treatment of migraine and cluster headache. We hypothesized that sumatriptan might modulate activity of TRPV1 channels found in the trigeminal nociceptive system. Methods We used immunohistochemistry to detect the presence of TRPV1 channel protein, whole cell recording in acutely dissociated trigeminal ganglia (TG) to detect functionality of TRPV1 channels, and whole cell recording in trigeminal nucleus caudalis (TNC) to detect effects on release of neurotransmitters from trigeminal neurons onto second order sensory neurons. Effects specifically on TG neurons that project to cerebral dura were assessed by labeling dural nociceptors with DiI. Results Immunohistochemistry demonstrated that TRPV1 channels are present in cerebral dura, trigeminal ganglion, and in the trigeminal nucleus caudalis. Capsaicin, a TRPV1 agonist, produced depolarization and repetitive action potential firing in current clamp recordings and large inward currents in voltage clamp recordings from acutely dissociated TG neurons, demonstrating that TRPV1 channels are functional in trigeminal neurons. Capsaicin increased spontaneous excitatory postsynaptic currents (sEPSCs) in neurons of layer II in TNC slices, showing that these channels have a physiological effect on central synaptic transmission. Sumatriptan (10 μM), a selective anti-migraine drug inhibited TRPV1-mediated inward currents in TG. and

  8. Amazon floodplain channels regulate channel-floodplain water exchange

    NASA Astrophysics Data System (ADS)

    Bates, P. D.; Baugh, C.; Trigg, M.

    2017-12-01

    We examine the role of floodplain channels in regulating the exchange of water between the Amazon main stem and its extensive floodplains using a combination of field survey, remote sensing and numerical modelling for a 30,000 km2 area around the confluence of the Solimões and Purus rivers. From Landsat imagery we identified 1762 individual floodplain channel reaches with total length of nearly 9300 line km that range in width from 900m to 20m. Using a boat survey we measured width and depth along 509 line km of floodplain channels in 45 separate reaches and used these data to develop geomorphic relationships between width and depth. This enabled reconstruction of the depth of all other channels in the Landsat survey to an RMSE of 2.5m. We then constructed a 2D hydraulic model of this site which included all 9300km of floodplain channels as sub-grid scale features using a recently developed version of the LISFLOOD-FP code. The DEM for the model was derived from a version of the SRTM Digital Elevation Model that was processed to remove vegetation artefacts. The model was run at 270m resolution over the entire 30,000 km2 domain for the period from 2002-2009. Simulations were run with and without floodplain channels to examine the impact of these features on floodplain flow dynamics and storage. Simulated floodplain channel hydraulics were validated against a combination of in-situ and remotely sensed data. Our results show that approximately 100 km3 of water is exchanged between the channel and the floodplain during a typical annual cycle, and 8.5±2.1% of mainstem flows is routed through the floodplain. The overall effect of floodplains channels was to increase the duration of connections between the Amazon River and the floodplain. Inclusion of floodplain channels in the model increased inundation volume by 7.3% - 11.3% at high water, and decreased it at low water by 4.0% - 16.6%, with the range in these estimates due to potential errors in floodplain channel

  9. Coffee-Ring Defined Short Channels for Inkjet-Printed Metal Oxide Thin-Film Transistors.

    PubMed

    Li, Yuzhi; Lan, Linfeng; Xiao, Peng; Sun, Sheng; Lin, Zhenguo; Song, Wei; Song, Erlong; Gao, Peixiong; Wu, Weijing; Peng, Junbiao

    2016-08-03

    Short-channel electronic devices several micrometers in length are difficult to implement by direct inkjet printing due to the limitation of position accuracy of the common inkjet printer system and the spread of functional ink on substrates. In this report, metal oxide thin-film transistors (TFTs) with channel lengths of 3.5 ± 0.7 μm were successfully fabricated with a common inkjet printer without any photolithography steps. Hydrophobic CYTOP coffee stripes, made by inkjet-printing and plasma-treating processes, were utilized to define the channel area of TFTs with channel lengths as short as ∼3.5 μm by dewetting the inks of the source/drain (S/D) precursors. Furthermore, by introduction of an ultrathin layer of PVA to modify the S/D surfaces, the spreading of precursor ink of the InOx semiconductor layer was well-controlled. The inkjet-printed short-channel TFTs exhibited a maximum mobility of 4.9 cm(2) V(-1) s(-1) and an on/off ratio of larger than 10(9). This approach of fabricating short-channel TFTs by inkjet printing will promote the large-area fabrication of short-channel TFTs in a cost-effective manner.

  10. Subconductance states of mitochondrial chloride channels: implication for functionally-coupled tetramers.

    PubMed

    Tomasek, Milan; Misak, Anton; Grman, Marian; Tomaskova, Zuzana

    2017-08-01

    Recently, it has been discovered that isoforms of intracellular chloride channels (CLIC) are present in cardiac mitochondria. By reconstituting rat cardiac mitochondrial chloride channels into bilayer lipid membranes, we detected three equally separated subconductance states with conductance increment of 45 pS and < 2% occupancy. The observed rare events of channel decomposition into substates, accompanied by disrupted gating, provide an insight into channel quaternary structure. Our findings suggest that the observed channels work as four functionally coupled subunits with synchronized gating. We discuss the putative connection of channel activity from native mitochondria with the recombinant CLIC channels. However, conclusive evidence is needed to prove this connection. © 2017 Federation of European Biochemical Societies.

  11. Molecular Basis of Cardiac Delayed Rectifier Potassium Channel Function and Pharmacology.

    PubMed

    Wu, Wei; Sanguinetti, Michael C

    2016-06-01

    Human cardiomyocytes express 3 distinct types of delayed rectifier potassium channels. Human ether-a-go-go-related gene (hERG) channels conduct the rapidly activating current IKr; KCNQ1/KCNE1 channels conduct the slowly activating current IKs; and Kv1.5 channels conduct an ultrarapid activating current IKur. Here the authors provide a general overview of the mechanistic and structural basis of ion selectivity, gating, and pharmacology of the 3 types of cardiac delayed rectifier potassium ion channels. Most blockers bind to S6 residues that line the central cavity of the channel, whereas activators interact with the channel at 4 symmetric binding sites outside the cavity. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Basolateral K channels in an insect epithelium. Channel density, conductance, and block by barium

    PubMed Central

    Hanrahan, JW; Wills, NK; Phillips, JE; Lewis, SA

    1986-01-01

    K channels in the basolateral membrane of insect hindgut were studied using current fluctuation analysis and microelectrodes. Locust recta were mounted in Ussing-type chambers containing Cl-free saline and cyclic AMP (cAMP). A transepithelial K current was induced by raising serosal [K] under short-circuit conditions. Adding Ba to the mucosal (luminal) side under these conditions had no effect; however, serosal Ba reversibly inhibited the short-circuit current (Isc), increased transepithelial resistance (Rt), and added a Lorentzian component to power density spectra of the Isc. A nonlinear relationship between corner frequency and serosal [Ba] was observed, which suggests that the rate constant for Ba association with basolateral channels increased as [Ba] was elevated. Microelectrode experiments revealed that the basolateral membrane hyperpolarized when Ba was added: this change in membrane potential could explain the nonlinearity of the 2 pi fc vs. [Ba] relationship if external Ba sensed about three-quarters of the basolateral membrane field. Conventional microelectrodes were used to determine the correspondence between transepithelially measured current noise and basolateral membrane conductance fluctuations, and ion-sensitive microelectrodes were used to measure intracellular K activity (acK). From the relationship between the net electrochemical potential for K across the basolateral membrane and the single channel current calculated from noise analysis, we estimate that the conductance of basolateral K channels is approximately 60 pS, and that there are approximately 180 million channels per square centimeter of tissue area. PMID:2420918

  13. Molecular mechanism of voltage sensing in voltage-gated proton channels

    PubMed Central

    Rebolledo, Santiago; Perez, Marta E.

    2013-01-01

    Voltage-gated proton (Hv) channels play an essential role in phagocytic cells by generating a hyperpolarizing proton current that electrically compensates for the depolarizing current generated by the NADPH oxidase during the respiratory burst, thereby ensuring a sustained production of reactive oxygen species by the NADPH oxidase in phagocytes to neutralize engulfed bacteria. Despite the importance of the voltage-dependent Hv current, it is at present unclear which residues in Hv channels are responsible for the voltage activation. Here we show that individual neutralizations of three charged residues in the fourth transmembrane domain, S4, all reduce the voltage dependence of activation. In addition, we show that the middle S4 charged residue moves from a position accessible from the cytosolic solution to a position accessible from the extracellular solution, suggesting that this residue moves across most of the membrane electric field during voltage activation of Hv channels. Our results show for the first time that the charge movement of these three S4 charges accounts for almost all of the measured gating charge in Hv channels. PMID:23401575

  14. Measurement of the top quark mass in the t t bar →dilepton channel from √{ s} = 8 TeV ATLAS data

    NASA Astrophysics Data System (ADS)

    Aaboud, M.; Aad, G.; Abbott, B.; Abdallah, J.; Abdinov, O.; Abeloos, B.; Aben, R.; Abouzeid, O. S.; Abraham, N. L.; Abramowicz, H.; Abreu, H.; Abreu, R.; Abulaiti, Y.; Acharya, B. S.; Adamczyk, L.; Adams, D. L.; Adelman, J.; Adomeit, S.; Adye, T.; Affolder, A. A.; Agatonovic-Jovin, T.; Agricola, J.; Aguilar-Saavedra, J. A.; Ahlen, S. P.; Ahmadov, F.; Aielli, G.; Akerstedt, H.; Åkesson, T. P. A.; Akimov, A. V.; Alberghi, G. L.; Albert, J.; Albrand, S.; Alconada Verzini, M. J.; Aleksa, M.; Aleksandrov, I. N.; Alexa, C.; Alexander, G.; Alexopoulos, T.; Alhroob, M.; Ali, B.; Aliev, M.; Alimonti, G.; Alison, J.; Alkire, S. P.; Allbrooke, B. M. M.; Allen, B. W.; Allport, P. P.; Aloisio, A.; Alonso, A.; Alonso, F.; Alpigiani, C.; Alstaty, M.; Alvarez Gonzalez, B.; Álvarez Piqueras, D.; Alviggi, M. G.; Amadio, B. T.; Amako, K.; Amaral Coutinho, Y.; Amelung, C.; Amidei, D.; Amor Dos Santos, S. P.; Amorim, A.; Amoroso, S.; Amundsen, G.; Anastopoulos, C.; Ancu, L. S.; Andari, N.; Andeen, T.; Anders, C. F.; Anders, G.; Anders, J. K.; Anderson, K. J.; Andreazza, A.; Andrei, V.; Angelidakis, S.; Angelozzi, I.; Anger, P.; Angerami, A.; Anghinolfi, F.; Anisenkov, A. V.; Anjos, N.; Annovi, A.; Antel, C.; Antonelli, M.; Antonov, A.; Anulli, F.; Aoki, M.; Aperio Bella, L.; Arabidze, G.; Arai, Y.; Araque, J. P.; Arce, A. T. H.; Arduh, F. A.; Arguin, J.-F.; Argyropoulos, S.; Arik, M.; Armbruster, A. J.; Armitage, L. J.; Arnaez, O.; Arnold, H.; Arratia, M.; Arslan, O.; Artamonov, A.; Artoni, G.; Artz, S.; Asai, S.; Asbah, N.; Ashkenazi, A.; Åsman, B.; Asquith, L.; Assamagan, K.; Astalos, R.; Atkinson, M.; Atlay, N. B.; Augsten, K.; Avolio, G.; Axen, B.; Ayoub, M. K.; Azuelos, G.; Baak, M. A.; Baas, A. E.; Baca, M. J.; Bachacou, H.; Bachas, K.; Backes, M.; Backhaus, M.; Bagiacchi, P.; Bagnaia, P.; Bai, Y.; Baines, J. T.; Baker, O. K.; Baldin, E. M.; Balek, P.; Balestri, T.; Balli, F.; Balunas, W. K.; Banas, E.; Banerjee, Sw.; Bannoura, A. A. E.; Barak, L.; Barberio, E. L.; Barberis, D.; Barbero, M.; Barillari, T.; Barisits, M.-S.; Barklow, T.; Barlow, N.; Barnes, S. L.; Barnett, B. M.; Barnett, R. M.; Barnovska, Z.; Baroncelli, A.; Barone, G.; Barr, A. J.; Barranco Navarro, L.; Barreiro, F.; Barreiro Guimarães da Costa, J.; Bartoldus, R.; Barton, A. E.; Bartos, P.; Basalaev, A.; Bassalat, A.; Bates, R. L.; Batista, S. J.; Batley, J. R.; Battaglia, M.; Bauce, M.; Bauer, F.; Bawa, H. S.; Beacham, J. B.; Beattie, M. D.; Beau, T.; Beauchemin, P. H.; Bechtle, P.; Beck, H. P.; Becker, K.; Becker, M.; Beckingham, M.; Becot, C.; Beddall, A. J.; Beddall, A.; Bednyakov, V. A.; Bedognetti, M.; Bee, C. P.; Beemster, L. J.; Beermann, T. A.; Begel, M.; Behr, J. K.; Belanger-Champagne, C.; Bell, A. S.; Bella, G.; Bellagamba, L.; Bellerive, A.; Bellomo, M.; Belotskiy, K.; Beltramello, O.; Belyaev, N. L.; Benary, O.; Benchekroun, D.; Bender, M.; Bendtz, K.; Benekos, N.; Benhammou, Y.; Benhar Noccioli, E.; Benitez, J.; Benjamin, D. P.; Bensinger, J. R.; Bentvelsen, S.; Beresford, L.; Beretta, M.; Berge, D.; Bergeaas Kuutmann, E.; Berger, N.; Beringer, J.; Berlendis, S.; Bernard, N. R.; Bernius, C.; Bernlochner, F. U.; Berry, T.; Berta, P.; Bertella, C.; Bertoli, G.; Bertolucci, F.; Bertram, I. A.; Bertsche, C.; Bertsche, D.; Besjes, G. J.; Bessidskaia Bylund, O.; Bessner, M.; Besson, N.; Betancourt, C.; Bethani, A.; Bethke, S.; Bevan, A. J.; Bianchi, R. M.; Bianchini, L.; Bianco, M.; Biebel, O.; Biedermann, D.; Bielski, R.; Biesuz, N. V.; Biglietti, M.; Bilbao de Mendizabal, J.; Billoud, T. R. V.; Bilokon, H.; Bindi, M.; Binet, S.; Bingul, A.; Bini, C.; Biondi, S.; Bjergaard, D. M.; Black, C. W.; Black, J. E.; Black, K. M.; Blackburn, D.; Blair, R. E.; Blanchard, J.-B.; Blazek, T.; Bloch, I.; Blocker, C.; Blum, W.; Blumenschein, U.; Blunier, S.; Bobbink, G. J.; Bobrovnikov, V. S.; Bocchetta, S. S.; Bocci, A.; Bock, C.; Boehler, M.; Boerner, D.; Bogaerts, J. A.; Bogavac, D.; Bogdanchikov, A. G.; Bohm, C.; Boisvert, V.; Bokan, P.; Bold, T.; Boldyrev, A. S.; Bomben, M.; Bona, M.; Boonekamp, M.; Borisov, A.; Borissov, G.; Bortfeldt, J.; Bortoletto, D.; Bortolotto, V.; Bos, K.; Boscherini, D.; Bosman, M.; Bossio Sola, J. D.; Boudreau, J.; Bouffard, J.; Bouhova-Thacker, E. V.; Boumediene, D.; Bourdarios, C.; Boutle, S. K.; Boveia, A.; Boyd, J.; Boyko, I. R.; Bracinik, J.; Brandt, A.; Brandt, G.; Brandt, O.; Bratzler, U.; Brau, B.; Brau, J. E.; Braun, H. M.; Breaden Madden, W. D.; Brendlinger, K.; Brennan, A. J.; Brenner, L.; Brenner, R.; Bressler, S.; Bristow, T. M.; Britton, D.; Britzger, D.; Brochu, F. M.; Brock, I.; Brock, R.; Brooijmans, G.; Brooks, T.; Brooks, W. K.; Brosamer, J.; Brost, E.; Broughton, J. H.; Bruckman de Renstrom, P. A.; Bruncko, D.; Bruneliere, R.; Bruni, A.; Bruni, G.; Bruni, L. S.; Brunt, Bh; Bruschi, M.; Bruscino, N.; Bryant, P.; Bryngemark, L.; Buanes, T.; Buat, Q.; Buchholz, P.; Buckley, A. G.; Budagov, I. A.; Buehrer, F.; Bugge, M. K.; Bulekov, O.; Bullock, D.; Burckhart, H.; Burdin, S.; Burgard, C. D.; Burghgrave, B.; Burka, K.; Burke, S.; Burmeister, I.; Burr, J. T. P.; Busato, E.; Büscher, D.; Büscher, V.; Bussey, P.; Butler, J. M.; Buttar, C. M.; Butterworth, J. M.; Butti, P.; Buttinger, W.; Buzatu, A.; Buzykaev, A. R.; Cabrera Urbán, S.; Caforio, D.; Cairo, V. M.; Cakir, O.; Calace, N.; Calafiura, P.; Calandri, A.; Calderini, G.; Calfayan, P.; Callea, G.; Caloba, L. P.; Calvente Lopez, S.; Calvet, D.; Calvet, S.; Calvet, T. P.; Camacho Toro, R.; Camarda, S.; Camarri, P.; Cameron, D.; Caminal Armadans, R.; Camincher, C.; Campana, S.; Campanelli, M.; Camplani, A.; Campoverde, A.; Canale, V.; Canepa, A.; Cano Bret, M.; Cantero, J.; Cantrill, R.; Cao, T.; Capeans Garrido, M. D. M.; Caprini, I.; Caprini, M.; Capua, M.; Caputo, R.; Carbone, R. M.; Cardarelli, R.; Cardillo, F.; Carli, I.; Carli, T.; Carlino, G.; Carminati, L.; Caron, S.; Carquin, E.; Carrillo-Montoya, G. D.; Carter, J. 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M.; Tyndel, M.; Ucchielli, G.; Ueda, I.; Ughetto, M.; Ukegawa, F.; Unal, G.; Undrus, A.; Unel, G.; Ungaro, F. C.; Unno, Y.; Unverdorben, C.; Urban, J.; Urquijo, P.; Urrejola, P.; Usai, G.; Usanova, A.; Vacavant, L.; Vacek, V.; Vachon, B.; Valderanis, C.; Valdes Santurio, E.; Valencic, N.; Valentinetti, S.; Valero, A.; Valery, L.; Valkar, S.; Valls Ferrer, J. A.; van den Wollenberg, W.; van der Deijl, P. C.; van der Graaf, H.; van Eldik, N.; van Gemmeren, P.; van Nieuwkoop, J.; van Vulpen, I.; van Woerden, M. C.; Vanadia, M.; Vandelli, W.; Vanguri, R.; Vaniachine, A.; Vankov, P.; Vardanyan, G.; Vari, R.; Varnes, E. W.; Varol, T.; Varouchas, D.; Vartapetian, A.; Varvell, K. E.; Vasquez, J. G.; Vazeille, F.; Vazquez Schroeder, T.; Veatch, J.; Veeraraghavan, V.; Veloce, L. M.; Veloso, F.; Veneziano, S.; Ventura, A.; Venturi, M.; Venturi, N.; Venturini, A.; Vercesi, V.; Verducci, M.; Verkerke, W.; Vermeulen, J. C.; Vest, A.; Vetterli, M. C.; Viazlo, O.; Vichou, I.; Vickey, T.; Vickey Boeriu, O. E.; Viehhauser, G. H. A.; Viel, S.; Vigani, L.; Villa, M.; Villaplana Perez, M.; Vilucchi, E.; Vincter, M. G.; Vinogradov, V. B.; Vittori, C.; Vivarelli, I.; Vlachos, S.; Vlasak, M.; Vogel, M.; Vokac, P.; Volpi, G.; Volpi, M.; von der Schmitt, H.; von Toerne, E.; Vorobel, V.; Vorobev, K.; Vos, M.; Voss, R.; Vossebeld, J. H.; Vranjes, N.; Vranjes Milosavljevic, M.; Vrba, V.; Vreeswijk, M.; Vuillermet, R.; Vukotic, I.; Vykydal, Z.; Wagner, P.; Wagner, W.; Wahlberg, H.; Wahrmund, S.; Wakabayashi, J.; Walder, J.; Walker, R.; Walkowiak, W.; Wallangen, V.; Wang, C.; Wang, C.; Wang, F.; Wang, H.; Wang, H.; Wang, J.; Wang, J.; Wang, K.; Wang, R.; Wang, S. M.; Wang, T.; Wang, T.; Wang, W.; Wang, X.; Wanotayaroj, C.; Warburton, A.; Ward, C. P.; Wardrope, D. R.; Washbrook, A.; Watkins, P. M.; Watson, A. T.; Watson, M. F.; Watts, G.; Watts, S.; Waugh, B. M.; Webb, S.; Weber, M. S.; Weber, S. W.; Webster, J. S.; Weidberg, A. R.; Weinert, B.; Weingarten, J.; Weiser, C.; Weits, H.; Wells, P. S.; Wenaus, T.; Wengler, T.; Wenig, S.; Wermes, N.; Werner, M.; Werner, M. D.; Werner, P.; Wessels, M.; Wetter, J.; Whalen, K.; Whallon, N. L.; Wharton, A. M.; White, A.; White, M. J.; White, R.; Whiteson, D.; Wickens, F. J.; Wiedenmann, W.; Wielers, M.; Wienemann, P.; Wiglesworth, C.; Wiik-Fuchs, L. A. M.; Wildauer, A.; Wilk, F.; Wilkens, H. G.; Williams, H. H.; Williams, S.; Willis, C.; Willocq, S.; Wilson, J. A.; Wingerter-Seez, I.; Winklmeier, F.; Winston, O. J.; Winter, B. T.; Wittgen, M.; Wittkowski, J.; Wolf, T. M. H.; Wolter, M. W.; Wolters, H.; Worm, S. D.; Wosiek, B. K.; Wotschack, J.; Woudstra, M. J.; Wozniak, K. W.; Wu, M.; Wu, M.; Wu, S. L.; Wu, X.; Wu, Y.; Wyatt, T. R.; Wynne, B. M.; Xella, S.; Xu, D.; Xu, L.; Yabsley, B.; Yacoob, S.; Yamaguchi, D.; Yamaguchi, Y.; Yamamoto, A.; Yamamoto, S.; Yamanaka, T.; Yamauchi, K.; Yamazaki, Y.; Yan, Z.; Yang, H.; Yang, H.; Yang, Y.; Yang, Z.; Yao, W.-M.; Yap, Y. C.; Yasu, Y.; Yatsenko, E.; Yau Wong, K. H.; Ye, J.; Ye, S.; Yeletskikh, I.; Yen, A. L.; Yildirim, E.; Yorita, K.; Yoshida, R.; Yoshihara, K.; Young, C.; Young, C. J. S.; Youssef, S.; Yu, D. R.; Yu, J.; Yu, J. M.; Yu, J.; Yuan, L.; Yuen, S. P. Y.; Yusuff, I.; Zabinski, B.; Zaidan, R.; Zaitsev, A. M.; Zakharchuk, N.; Zalieckas, J.; Zaman, A.; Zambito, S.; Zanello, L.; Zanzi, D.; Zeitnitz, C.; Zeman, M.; Zemla, A.; Zeng, J. C.; Zeng, Q.; Zengel, K.; Zenin, O.; Ženiš, T.; Zerwas, D.; Zhang, D.; Zhang, F.; Zhang, G.; Zhang, H.; Zhang, J.; Zhang, L.; Zhang, R.; Zhang, R.; Zhang, X.; Zhang, Z.; Zhao, X.; Zhao, Y.; Zhao, Z.; Zhemchugov, A.; Zhong, J.; Zhou, B.; Zhou, C.; Zhou, L.; Zhou, L.; Zhou, M.; Zhou, N.; Zhu, C. G.; Zhu, H.; Zhu, J.; Zhu, Y.; Zhuang, X.; Zhukov, K.; Zibell, A.; Zieminska, D.; Zimine, N. I.; Zimmermann, C.; Zimmermann, S.; Zinonos, Z.; Zinser, M.; Ziolkowski, M.; Živković, L.; Zobernig, G.; Zoccoli, A.; Zur Nedden, M.; Zwalinski, L.; Atlas Collaboration

    2016-10-01

    The top quark mass is measured in the t t bar →dilepton channel (lepton = e , μ) using ATLAS data recorded in the year 2012 at the LHC. The data were taken at a proton-proton centre-of-mass energy of √{ s} = 8 TeV and correspond to an integrated luminosity of about 20.2 fb-1. Exploiting the template method, and using the distribution of invariant masses of lepton- b-jet pairs, the top quark mass is measured to be mtop = 172.99 ± 0.41 (stat) ± 0.74 (syst) GeV, with a total uncertainty of 0.84 GeV. Finally, a combination with previous ATLAS mtop measurements from √{ s} = 7 TeV data in the t t bar →dilepton and t t bar →lepton +jets channels results in mtop = 172.84 ± 0.34 (stat) ± 0.61 (syst) GeV, with a total uncertainty of 0.70 GeV.

  15. Inactivation gating determines nicotine blockade of human HERG channels.

    PubMed

    Wang, H Z; Shi, H; Liao, S J; Wang, Z

    1999-09-01

    We have previously found that nicotine blocked multiple K+ currents, including the rapid component of delayed rectifier K+ currents (IKr), by interacting directly with the channels. To shed some light on the mechanisms of interaction between nicotine and channels, we performed detailed analysis on the human ether-à-go-go-related gene (HERG) channels, which are believed to be equivalent to the native I(Kr) when expressed in Xenopus oocytes. Nicotine suppressed the HERG channels in a concentration-dependent manner with greater potency with voltage protocols, which favor channel inactivation. Nicotine caused dramatic shifts of the voltage-dependent inactivation curve to more negative potentials and accelerated the inactivation process. Conversely, maneuvers that weakened the channel inactivation gating considerably relieved the blockade. Elevating the extracellular K+ concentration from 5 to 20 mM increased the nicotine concentration (by approximately 100-fold) needed to achieve the same degree of inhibition. Moreover, nicotine lost its ability to block the HERG channels when a single mutation was introduced to a residue located after transmembrane domain 6 (S631A) to remove the rapid channel inactivation. Our data suggest that the inactivation gating determines nicotine blockade of the HERG channels.

  16. Location of the β4 transmembrane helices in the BK potassium channel

    PubMed Central

    Wu, Roland S.; Chudasama, Neelesh; Zakharov, Sergey I.; Doshi, Darshan; Motoike, Howard; Liu, Guoxia; Yao, Yongneng; Niu, Xiaowei; Deng, Shi-Xian; Landry, Donald W.; Karlin, Arthur; Marx, Steven O.

    2009-01-01

    Large-conductance, voltage- and Ca2+-gated potassium (BK) channels control excitability in a number of cell types. BK channels are composed of α subunits, which contain the voltage-sensor domains and the Ca2+- sensor domains, and form the pore, and often one of four types of β subunits, which modulate the channel in a cell-specific manner. β4 is expressed in neurons throughout the brain. Deletion of β4 in mice causes temporal lobe epilepsy. Compared to channels composed of α alone, channels composed of α and β4 activate and deactivate more slowly. We inferred the locations of the two β4 transmembrane (TM) helices, TM1 and TM2, relative to the seven αTM helices, S0-S6, from the extent of disulfide bond formation between cysteines substituted in the extracellular flanks of these TM helices. We found that β4 TM2 is close to α S0 and that β4 TM1 is close to both α S1 and S2. At least at their extracellular ends, TM1 and TM2 are not close to S3 through S6. In six of eight of the most highly crosslinked cysteine pairs, four crosslinks from TM2 to S0 and one each from TM1 to S1 and S2 had small effects on the V50 and on the rates of activation and deactivation. That disulfide crosslinking caused only small functional perturbations is consistent with the proximity of the extracellular ends of TM2 to S0 and of TM1 to S1 and to S2, in both the open and closed states. PMID:19571123

  17. Cortisone Dissociates the Shaker Family K Channels from their Beta Subunit

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Pan, Y.; Weng, J; Kabaleeswaran, V

    2008-01-01

    The Shaker family voltage-dependent potassium channels (Kv1) are expressed in a wide variety of cells and are essential for cellular excitability. In humans, loss-of-function mutations of Kv1 channels lead to hyperexcitability and are directly linked to episodic ataxia and atrial fibrillation. All Kv1 channels assemble with {Beta} subunits (Kv{Beta}s), and certain Kv{Beta}s, for example Kv{Beta}1, have an N-terminal segment that closes the channel by the N-type inactivation mechanism. In principle, dissociation of Kv{Beta}1, although never reported, should eliminate inactivation and thus potentiate Kv1 current. We found that cortisone increases rat Kv1 channel activity by binding to Kv{Beta}1. A crystal structuremore » of the K{Beta}v-cortisone complex was solved to 1.82-{angstrom}resolution and revealed novel cortisone binding sites. Further studies demonstrated that cortisone promotes dissociation of Kv{Beta}. The new mode of channel modulation may be explored by native or synthetic ligands to fine-tune cellular excitability.« less

  18. Cysteine residues in the nucleotide binding domains regulate the conductance state of CFTR channels.

    PubMed Central

    Harrington, Melissa A; Kopito, Ron R

    2002-01-01

    Gating of cystic fibrosis transmembrane conductance regulator (CFTR) channels requires intermolecular or interdomain interactions, but the exact nature and physiological significance of those interactions remains uncertain. Subconductance states of the channel may result from alterations in interactions among domains, and studying mutant channels enriched for a single conductance type may elucidate those interactions. Analysis of CFTR channels in inside-out patches revealed that mutation of cysteine residues in NBD1 and NBD2 affects the frequency of channel opening to the full-size versus a 3-pS subconductance. Mutating cysteines in NBD1 resulted in channels that open almost exclusively to the 3-pS subconductance, while mutations of cysteines in NBD2 decreased the frequency of subconductance openings. Wild-type channels open to both size conductances and make fast transitions between them within a single open burst. Full-size and subconductance openings of both mutant and wild-type channels are similarly activated by ATP and phosphorylation. However, the different size conductances open very differently in the presence of a nonhydrolyzable ATP analog, with subconductance openings significantly shortened by ATPgammaS, while full-size channels are locked open. In wild-type channels, reducing conditions increase the frequency and decrease the open time of subconductance channels, while oxidizing conditions decrease the frequency of subconductance openings. In contrast, in the cysteine mutants studied, altering redox potential has little effect on gating of the subconductance. PMID:11867445

  19. Self-consistent Dark Matter simplified models with an s-channel scalar mediator

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Bell, Nicole F.; Busoni, Giorgio; Sanderson, Isaac W., E-mail: n.bell@unimelb.edu.au, E-mail: giorgio.busoni@unimelb.edu.au, E-mail: isanderson@student.unimelb.edu.au

    We examine Simplified Models in which fermionic DM interacts with Standard Model (SM) fermions via the exchange of an s -channel scalar mediator. The single-mediator version of this model is not gauge invariant, and instead we must consider models with two scalar mediators which mix and interfere. The minimal gauge invariant scenario involves the mixing of a new singlet scalar with the Standard Model Higgs boson, and is tightly constrained. We construct two Higgs doublet model (2HDM) extensions of this scenario, where the singlet mixes with the 2nd Higgs doublet. Compared with the one doublet model, this provides greater freedommore » for the masses and mixing angle of the scalar mediators, and their coupling to SM fermions. We outline constraints on these models, and discuss Yukawa structures that allow enhanced couplings, yet keep potentially dangerous flavour violating processes under control. We examine the direct detection phenomenology of these models, accounting for interference of the scalar mediators, and interference of different quarks in the nucleus. Regions of parameter space consistent with direct detection measurements are determined.« less

  20. Functional role of hCngb3 in regulation of human cone cng channel: effect of rod monochromacy-associated mutations in hCNGB3 on channel function.

    PubMed

    Okada, Akira; Ueyama, Hisao; Toyoda, Futoshi; Oda, Sanae; Ding, Wei-Guang; Tanabe, Shoko; Yamade, Shinichi; Matsuura, Hiroshi; Ohkubo, Iwao; Kani, Kazutaka

    2004-07-01

    The human cone photoreceptor cyclic nucleotide-gated (CNG) channel comprises alpha- and beta-subunits, which are respectively encoded by hCNGA3 and hCNGB3. The purpose was to examine the functional role of hCNGB3 in modulation of human cone CNG channels and to characterize functional consequences of rod monochromacy-associated mutations in hCNGB3 (S435F and D633G). Macroscopic patch currents were recorded from human embryonic kidney (HEK) 293 cells expressing homomeric (hCNGA3 and hCNGB3) and heteromeric (hCNGA3/hCNGB3, hCNGA3/hCNGB3-S435F, and hCNGA3/hCNGB3-D633G) channels using inside-out patch-clamp technique. Both hCNGA3 homomeric and hCNGA3/hCNGB3 heteromeric channels were activated by cGMP, with half-maximally activating concentration (K(1/2)) of 11.1 +/- 1.0 and 26.2 +/- 1.9 micro M, respectively. The hCNGA3 channels appeared to be more sensitive to inhibition by extracellular Ca(2+) compared with hCNGA3/hCNGB3 channels, when assessed by the degree of outward rectification. Coexpression of either of rod monochromacy-associated mutants of hCNGB3 with hCNGA3 significantly reduced K(1/2) value for cGMP but little affected the sensitivity to extracellular Ca(2+), compared with wild-type heteromeric channels. The selectivity of hCNGA3, hCNGA3/hCNGB3, hCNGA3/hCNGB3-S435F, and hCNGA3/hCNGB3-D633G channels for monovalent cations were largely similar. Immunoprecipitation experiments showed association of hCNGA3 subunit with both of wild-type and mutant hCNGB3 subunits. The hCNGB3 plays an important modulatory role in the function of human cone CNG channels with respect to cGMP and extracellular Ca(2+) sensitivities. The rod monochromacy-associated S435F and D633G mutations in hCNGB3 evokes a significant increase in the apparent affinity for cGMP, which should alter cone function and thereby contribute at least partly to pathogenesis of the disease.

  1. Detection of New Dissociative Electron Attachment Channels in NO

    NASA Technical Reports Server (NTRS)

    Orient, O. J.; Chutjian, A.

    1995-01-01

    Three dissociative electron attachment channels have been detected and identified in NO via measurement of the O minus (exp 2)P fragment energy. In addition to the known N((exp 2 D(exp 0)) + O minus (exp 2)P channel, two new channels N((exp 1 S(exp 0)) + 0 (2 P) and N(exp 2)P(exp 0) + O(exp 2)P were detected. Cross sections for each of the channels are reported by normalizing the scattering intensities to previously measured total cross sections. The experimental approach uses solenoidal magnetic confinement of the electrons and ions, and trochoidal energy analysis of the low-energy ions.

  2. Water Channel Facility for Fluid Dynamics Experiments

    NASA Astrophysics Data System (ADS)

    Eslam-Panah, Azar; Sabatino, Daniel

    2016-11-01

    This study presents the design, assembly, and verification process of the circulating water channel constructed by undergraduate students at the Penn State University at Berks. This work was significantly inspired from the closed-loop free-surface water channel at Lafayette College (Sabatino and Maharjan, 2015) and employed for experiments in fluid dynamics. The channel has a 11 ft length, 2.5 ft width, and 2 ft height glass test section with a maximum velocity of 3.3 ft/s. First, the investigation justifies the needs of a water channel in an undergraduate institute and its potential applications in the whole field of engineering. Then, the design procedures applied to find the geometry and material of some elements of the channel, especially the contraction, the test section, the inlet and end tanks, and the pump system are described. The optimization of the contraction design, including the maintenance of uniform exit flow and avoidance of flow separation, is also included. Finally, the discussion concludes by identifying the problems with the undergraduate education through this capstone project and suggesting some new investigations to improve flow quality.

  3. Mechanosensitive Channel MscS in the Open State: Modeling of the Transition, Explicit Simulations, and Experimental Measurements of Conductance

    PubMed Central

    Anishkin, Andriy; Kamaraju, Kishore; Sukharev, Sergei

    2008-01-01

    Mechanosensitive channels of small conductance (MscS) are ubiquitous turgor pressure regulators found in many walled cells and some intracellular organelles. Escherichia coli MscS acting as a tension-activated osmolyte release valve shows a nonsaturable conductance (1.2 nS in a 39 mS/cm electrolyte) and weak preference for anions. Pursuing the transition pathways in this channel, we applied the extrapolated motion protocol (cycles of displacements, minimizations, and short simulations) to the previously generated compact resting conformation of MscS. We observed tilting and straightening of the kinked pore-forming TM3 helices during the barrel expansion. Extended all-atom simulations confirmed the stability of the open conformation in the bilayer. A 53° spontaneous axial rotation of TM3s observed after equilibration increased the width and polarity of the pore allowing for stable voltage-independent hydration and presence of both cations and anions throughout the pore. The resultant open state, characterized by a pore 1.6 nm wide, satisfied the experimental conductance and in-plane expansion. Applied transmembrane electric field (±100 to ±200 mV) in simulations produced a flow of both K+ and Cl−, with Cl− current dominating at higher voltages. Electroosmotic water flux strongly correlated with the chloride current (∼8 waters per Cl−). The selectivity and rectification were in agreement with the experimental measurements performed in the same range of voltages. Among the charged residues surrounding the pore, only K169 was found to contribute noticeably in the rectification. We conclude that (a) the barrel expansion involving tilting, straightening, and rotation of TM3s provides the geometry and electrostatics that accounts for the conductive properties of the open pore; (b) the observed regimen of ion passage through the pore is similar to electrodiffusion, thus macroscopic estimations closely approximate the experimental and molecular dynamics

  4. A unique modulation system for two channel data transmission

    NASA Technical Reports Server (NTRS)

    Melrose, B. T.

    1972-01-01

    A simple low cost system is reported for the telemetry of information from meteorological rocket payloads including parachute borne systems. It uses S- or L-band microwave links with low cost oscillator type transmitters. An extension of this system to transmit two channels of data simultaneously by standard time and frequency multiplexing techniques as a sampled pulse is described. One channel is represented by the pulse repetition rate while the other channel is represented by the instantaneous duty cycle of the pulse train.

  5. Anion channels in the sea urchin sperm plasma membrane.

    PubMed

    Morales, E; de la Torre, L; Moy, G W; Vacquier, V D; Darszon, A

    1993-10-01

    Ionic fluxes in sea urchin sperm plasma membrane regulate cell motility and the acrosome reaction (AR). Although cationic channels mediate some of the ionic movements, little is known about anion channels in these cells. The fusion of sperm plasma membranes into lipid bilayers allowed identification of a 150 pS anion channel. This anion channel was enriched from detergent-solubilized sperm plasma membranes using a wheat germ agglutinin Sepharose column. Vesicles formed from this preparation were fused into black lipid membranes (BLM), yielding single channel anion-selective activity with the properties of those found in the sperm membranes. The following anion selectivity sequence was found: NO3- > CNS- > Br- > Cl-. This anion channel has a high open probability at the holding potentials tested, it is partially blocked by 4,4'-diisothiocyano-2,2'-stilbendisulfonic acid (DIDS), and it often displays substates. The sperm AR was also inhibited by DIDS.

  6. Channel characteristics and coordination in three-echelon dual-channel supply chain

    NASA Astrophysics Data System (ADS)

    Saha, Subrata

    2016-02-01

    We explore the impact of channel structure on the manufacturer, the distributer, the retailer and the entire supply chain by considering three different channel structures in radiance of with and without coordination. These structures include a traditional retail channel and two manufacturer direct channels with and without consistent pricing. By comparing the performance of the manufacturer, the distributer and the retailer, and the entire supply chain in three different supply chain structures, it is established analytically that, under some conditions, a dual channel can outperform a single retail channel; as a consequence, a coordination mechanism is developed that not only coordinates the dual channel but also outperforms the non-cooperative single retail channel. All the analytical results are further analysed through numerical examples.

  7. Voltage-dependent gating of KCNH potassium channels lacking a covalent link between voltage-sensing and pore domains

    PubMed Central

    Lörinczi, Éva; Gómez-Posada, Juan Camilo; de la Peña, Pilar; Tomczak, Adam P.; Fernández-Trillo, Jorge; Leipscher, Ulrike; Stühmer, Walter; Barros, Francisco; Pardo, Luis A.

    2015-01-01

    Voltage-gated channels open paths for ion permeation upon changes in membrane potential, but how voltage changes are coupled to gating is not entirely understood. Two modules can be recognized in voltage-gated potassium channels, one responsible for voltage sensing (transmembrane segments S1 to S4), the other for permeation (S5 and S6). It is generally assumed that the conversion of a conformational change in the voltage sensor into channel gating occurs through the intracellular S4–S5 linker that provides physical continuity between the two regions. Using the pathophysiologically relevant KCNH family, we show that truncated proteins interrupted at, or lacking the S4–S5 linker produce voltage-gated channels in a heterologous model that recapitulate both the voltage-sensing and permeation properties of the complete protein. These observations indicate that voltage sensing by the S4 segment is transduced to the channel gate in the absence of physical continuity between the modules. PMID:25818916

  8. Voltage-dependent gating of KCNH potassium channels lacking a covalent link between voltage-sensing and pore domains.

    PubMed

    Lörinczi, Éva; Gómez-Posada, Juan Camilo; de la Peña, Pilar; Tomczak, Adam P; Fernández-Trillo, Jorge; Leipscher, Ulrike; Stühmer, Walter; Barros, Francisco; Pardo, Luis A

    2015-03-30

    Voltage-gated channels open paths for ion permeation upon changes in membrane potential, but how voltage changes are coupled to gating is not entirely understood. Two modules can be recognized in voltage-gated potassium channels, one responsible for voltage sensing (transmembrane segments S1 to S4), the other for permeation (S5 and S6). It is generally assumed that the conversion of a conformational change in the voltage sensor into channel gating occurs through the intracellular S4-S5 linker that provides physical continuity between the two regions. Using the pathophysiologically relevant KCNH family, we show that truncated proteins interrupted at, or lacking the S4-S5 linker produce voltage-gated channels in a heterologous model that recapitulate both the voltage-sensing and permeation properties of the complete protein. These observations indicate that voltage sensing by the S4 segment is transduced to the channel gate in the absence of physical continuity between the modules.

  9. Voltage-dependent gating of KCNH potassium channels lacking a covalent link between voltage-sensing and pore domains

    NASA Astrophysics Data System (ADS)

    Lörinczi, Éva; Gómez-Posada, Juan Camilo; de La Peña, Pilar; Tomczak, Adam P.; Fernández-Trillo, Jorge; Leipscher, Ulrike; Stühmer, Walter; Barros, Francisco; Pardo, Luis A.

    2015-03-01

    Voltage-gated channels open paths for ion permeation upon changes in membrane potential, but how voltage changes are coupled to gating is not entirely understood. Two modules can be recognized in voltage-gated potassium channels, one responsible for voltage sensing (transmembrane segments S1 to S4), the other for permeation (S5 and S6). It is generally assumed that the conversion of a conformational change in the voltage sensor into channel gating occurs through the intracellular S4-S5 linker that provides physical continuity between the two regions. Using the pathophysiologically relevant KCNH family, we show that truncated proteins interrupted at, or lacking the S4-S5 linker produce voltage-gated channels in a heterologous model that recapitulate both the voltage-sensing and permeation properties of the complete protein. These observations indicate that voltage sensing by the S4 segment is transduced to the channel gate in the absence of physical continuity between the modules.

  10. Chryse Outflow Channel

    NASA Image and Video Library

    1998-06-08

    A color image of the south Chryse basin Valles Marineris outflow channels on Mars; north toward top. The scene shows on the southwest corner the chaotic terrain of the east part of Valles Marineris and two of its related canyons: Eos and Capri Chasmata (south to north). Ganges Chasma lies directly north. The chaos in the southern part of the image gives rise to several outflow channels, Shalbatana, Simud, Tiu, and Ares Valles (left to right), that drained north into the Chryse basin. The mouth of Ares Valles is the site of the Mars Pathfinder lander. This image is a composite of NASA's Viking medium-resolution images in black and white and low-resolution images in color. The image extends from latitude 20 degrees S. to 20 degrees N. and from longitude 15 degrees to 53 degrees; Mercator projection. http://photojournal.jpl.nasa.gov/catalog/PIA00418

  11. Single-channel measurements of an N-acetylneuraminic acid-inducible outer membrane channel in Escherichia coli

    PubMed Central

    Giri, Janhavi; Tang, John M.; Wirth, Christophe; Peneff, Caroline M.

    2012-01-01

    NanC is an Escherichia coli outer membrane protein involved in sialic acid (Neu5Ac, i.e., N-acetylneuraminic acid) uptake. Expression of the NanC gene is induced and controlled by Neu5Ac. The transport mechanism of Neu5Ac is not known. The structure of NanC was recently solved (PDB code: 2WJQ) and includes a unique arrangement of positively charged (basic) side chains consistent with a role in acidic sugar transport. However, initial functional measurements of NanC failed to find its role in the transport of sialic acids, perhaps because of the ionic conditions used in the experiments. We show here that the ionic conditions generally preferred for measuring the function of outer-membrane porins are not appropriate for NanC. Single channels of NanC at pH 7.0 have: (1) conductance 100 pS to 800 pS in 100 mM KCl to 3 M KCl), (2) anion over cation selectivity (Vreversal = +16 mV in 250 mM KCl || 1 M KCl), and (3) two forms of voltage-dependent gating (channel closures above ±200 mV). Single-channel conductance decreases by 50% when HEPES concentration is increased from 100 μM to 100 mM in 250 mM KCl at pH 7.4, consistent with the two HEPES binding sites observed in the crystal structure. Studying alternative buffers, we find that phosphate interferes with the channel conductance. Single-channel conductance decreases by 19% when phosphate concentration is increased from 0 mM to 5 mM in 250 mM KCl at pH 8.0. Surprisingly, TRIS in the baths reacts with Ag|AgCl electrodes, producing artifacts even when the electrodes are on the far side of agar–KCl bridges. A suitable baseline solution for NanC is 250 mM KCl adjusted to pH 7.0 without buffer. PMID:22246445

  12. Volcanic or Fluvial Channels on Ascraeus Mons: Focus on the Source Area of Sinuous Channels on the Southeast Rift Apron

    NASA Technical Reports Server (NTRS)

    Signorella, Julia D.; deWet, A.; Bleacher, J. E.; Collins, A.; Schierl, Z. P.; Schwans, B.

    2012-01-01

    Deciphering the Mars water history is important to understanding the planet's geological evolution and whether it could have sustained life. Channel features on Mars, such as the features documented in Kasei Valles, are generally accepted as evidence for water flowing over the Mars surface in the past [1]. However, not all channels are the product of fluvial processes and many can be interpreted as having a volcanic origin [2]. This research involves studying channel features on the flanks of the Ascraeus Mons volcano, which is a part of the Tharsis province. Numerous sinuous channels exist on the rift apron of Ascraeus Mons and they have been interpreted as either fluvial [3] or volcanic [4,5]. The channels originate from pits and linear depressions and extend for many 100 s of km downslope. Mapping the proximal to distal morphology of the complete channel and determining its relationship with other features on the apron provides evidence for the processes of formation and their relative temporal relationships. This study focused on sinuous channels located on the south-east part of the Ascraeus rift apron (Fig. 1). Observations of possible analogous features on Hawaii are used to provide insights into the processes of formation of the Mars features.

  13. Atlantic water flow through the Faroese Channels

    NASA Astrophysics Data System (ADS)

    Hansen, Bogi; Poulsen, Turið; Margretha Húsgarð Larsen, Karin; Hátún, Hjálmar; Østerhus, Svein; Darelius, Elin; Berx, Barbara; Quadfasel, Detlef; Jochumsen, Kerstin

    2017-11-01

    Through the Faroese Channels - the collective name for a system of channels linking the Faroe-Shetland Channel, Wyville Thomson Basin, and Faroe Bank Channel - there is a deep flow of cold waters from Arctic regions that exit the system as overflow through the Faroe Bank Channel and across the Wyville Thomson Ridge. The upper layers, in contrast, are dominated by warm, saline water masses from the southwest, termed Atlantic water. In spite of intensive research over more than a century, there are still open questions on the passage of these waters through the system with conflicting views in recent literature. Of special note is the suggestion that there is a flow of Atlantic water from the Faroe-Shetland Channel through the Faroe Bank Channel, which circles the Faroes over the slope region in a clockwise direction. Here, we combine the observational evidence from ship-borne hydrography, moored current measurements, surface drifter tracks, and satellite altimetry to address these questions and propose a general scheme for the Atlantic water flow through this channel system. We find no evidence for a continuous flow of Atlantic water from the Faroe-Shetland Channel to the Faroe Bank Channel over the Faroese slope. Rather, the southwestward-flowing water over the Faroese slope of the Faroe-Shetland Channel is totally recirculated within the combined area of the Faroe-Shetland Channel and Wyville Thomson Basin, except possibly for a small release in the form of eddies. This does not exclude a possible westward flow over the southern tip of the Faroe Shelf, but even including that, we estimate that the average volume transport of a Circum-Faroe Current does not exceed 0.5 Sv (1 Sv = 106 m3 s-1). Also, there seems to be a persistent flow of Atlantic water from the western part of the Faroe Bank Channel into the Faroe-Shetland Channel that joins the Slope Current over the Scottish slope. These conclusions will affect potential impacts from offshore activities in the

  14. The human red cell voltage-regulated cation channel. The interplay with the chloride conductance, the Ca(2+)-activated K(+) channel and the Ca(2+) pump.

    PubMed

    Bennekou, P; Kristensen, B I; Christophersen, P

    2003-09-01

    The activation/deactivation kinetics of the human erythrocyte voltage-dependent cation channel was characterized at the single-channel level using inside-out patches. It was found that the time dependence for voltage activation after steps to positive membrane potentials was slow ( t(1/2) about 30 s), whereas the deactivation was fast ( t(1/2) about 15 ms). Both activation and deactivation of this channel were also demonstrated in intact red cells in suspension. At very positive membrane potentials generated by suspension in extracellular low Cl(-) concentrations, the cation conductance switched on with a time constant of about 2 min. Deactivation of the cation channel was clearly demonstrated during transient activation of the Gárdos channel elicited by Ca(2+) influx via the cation channel and ensuing efflux via the Ca(2+) pump. Thus, the voltage-dependent cation channel, the Gárdos channel and the Ca(2+) pump constitute a coupled feedback-regulated system that may become operative under physiological conditions.

  15. Proper horizontal photospheric flows in a filament channel

    NASA Astrophysics Data System (ADS)

    Schmieder, B.; Roudier, T.; Mein, N.; Mein, P.; Malherbe, J. M.; Chandra, R.

    2014-04-01

    Context. An extended filament in the central part of the active region NOAA 11106 crossed the central meridian on Sept. 17, 2010 in the southern hemisphere. It has been observed in Hα with the THEMIS telescope in the Canary Islands and in 304 Å with the EUV imager (AIA) onboard the Solar Dynamic Observatory (SDO). Counterstreaming along the Hα threads and bright moving blobs (jets) along the 304 Å filament channel were observed during 10 h before the filament erupted at 17:03 UT. Aims: The aim of the paper is to understand the coupling between magnetic field and convection in filament channels and relate the horizontal photospheric motions to the activity of the filament. Methods: An analysis of the proper photospheric motions using SDO/HMI continuum images with the new version of the coherent structure tracking (CST) algorithm developed to track granules, as well as the large scale photospheric flows, was performed for three hours. Using corks, we derived the passive scalar points and produced a map of the cork distribution in the filament channel. Averaging the velocity vectors in the southern hemisphere in each latitude in steps of 3.5 arcsec, we defined a profile of the differential rotation. Results: Supergranules are clearly identified in the filament channel. Diverging flows inside the supergranules are similar in and out of the filament channel. Converging flows corresponding to the accumulation of corks are identified well around the Hα filament feet and at the edges of the EUV filament channel. At these convergence points, the horizontal photospheric velocity may reach 1 km s-1, but with a mean velocity of 0.35 km s-1. In some locations, horizontal flows crossing the channel are detected, indicating eventually large scale vorticity. Conclusions: The coupling between convection and magnetic field in the photosphere is relatively strong. The filament experienced the convection motions through its anchorage points with the photosphere, which are

  16. TRIC-B channels display labile gating: evidence from the TRIC-A knockout mouse model.

    PubMed

    Venturi, Elisa; Matyjaszkiewicz, Antoni; Pitt, Samantha J; Tsaneva-Atanasova, Krasimira; Nishi, Miyuki; Yamazaki, Daiju; Takeshima, Hiroshi; Sitsapesan, Rebecca

    2013-08-01

    Sarcoplasmic/endoplasmic reticulum (SR) and nuclear membranes contain two related cation channels named TRIC-A and TRIC-B. In many tissues, both subtypes are co-expressed, making it impossible to distinguish the distinct single-channel properties of each subtype. We therefore incorporated skeletal muscle SR vesicles derived from Tric-a-knockout mice into bilayers in order to characterise the biophysical properties of native TRIC-B without possible misclassification of the channels as TRIC-A, and without potential distortion of functional properties by detergent purification protocols. The native TRIC-B channels were ideally selective for cations. In symmetrical 210 mM K(+), the maximum (full) open channel level (199 pS) was equivalent to that observed when wild-type SR vesicles were incorporated into bilayers. Analysis of TRIC-B gating revealed complex and variable behaviour. Four main sub-conductance levels were observed at approximately 80 % (161 pS), 60 % (123 pS), 46 % (93 pS), and 30 % (60 pS) of the full open state. Seventy-five percent of the channels were voltage sensitive with Po being markedly reduced at negative holding potentials. The frequent, rapid transitions between TRIC-B sub-conductance states prevented development of reliable gating models using conventional single-channel analysis. Instead, we used mean-variance plots to highlight key features of TRIC-B gating in a more accurate and visually useful manner. Our study provides the first biophysical characterisation of native TRIC-B channels and indicates that this channel would be suited to provide counter current in response to Ca(2+) release from the SR. Further experiments are required to distinguish the distinct functional properties of TRIC-A and TRIC-B and understand their individual but complementary physiological roles.

  17. Solvent-programmed microchip open-channel electrochromatography.

    PubMed

    Kutter, J P; Jacobson, S C; Matsubara, N; Ramsey, J M

    1998-08-01

    Open-channel electrochromatography in combination with solvent programming is demonstrated using a microchip device. Channel walls were coated with octadecylsilanes at ambient temperatures, yielding stationary phases for chromatographic separations of neutral dyes. The electroosmotic flow after coating was sufficient to ensure transport of all species and on-chip mixing of isocratic and gradient elution conditions with acetonitrile-buffer mixtures. Chips having different channel depths between 10.2 and 2.9 μm were evaluated for performance, and van Deemter plots were established. Channel depths of about 5 μm were found to be a good compromise between efficiency and ease of operation. Isocratic and gradient elution conditions were easily established and manipulated by computer-controlled application of voltages to the terminals of the microchip. Linear gradients with different slopes, start times, duration times, and start percentages of organic modifier proved to be powerful tools to tune selectivity and analysis time for the separation of a test mixture. Even very steep gradients still produced excellent efficiencies. Together with fast reconditioning times, complete runs could be finished in under 60 s.

  18. Optical Design of the WFIRST Phase-A Integral Field Channel

    NASA Technical Reports Server (NTRS)

    Gao, Guangjun; Pasquale, Bert A.; Marx, Catherine T.; Chambers, Victor

    2017-01-01

    WFIRST is one of NASA's Decadal Survey Missions and is currently in Phase-A development. The optical design of the WFIRST Integral Field Channel (IFC), one of three main optical channels of WFIRST, is presented, and the evolution of the IFC channel since Mission Concept Review (MCR, end of Pre-Phase A) is discussed. The IFC has two sub-channels: Supernova (IFC-S) and Galaxy (IFC-G) channels, with Fields of View of 3"x4.5" and 4.2"x9" respectively, and approximately R 75 spectral analysis over waveband 0.42 approximately 2.0 micrometers. The Phase-A IFC optical design meets image quality requirements over the FOV areas while balancing cost and volume constraints.

  19. The cooperative voltage sensor motion that gates a potassium channel.

    PubMed

    Pathak, Medha; Kurtz, Lisa; Tombola, Francesco; Isacoff, Ehud

    2005-01-01

    The four arginine-rich S4 helices of a voltage-gated channel move outward through the membrane in response to depolarization, opening and closing gates to generate a transient ionic current. Coupling of voltage sensing to gating was originally thought to operate with the S4s moving independently from an inward/resting to an outward/activated conformation, so that when all four S4s are activated, the gates are driven to open or closed. However, S4 has also been found to influence the cooperative opening step (Smith-Maxwell et al., 1998a), suggesting a more complex mechanism of coupling. Using fluorescence to monitor structural rearrangements in a Shaker channel mutant, the ILT channel (Ledwell and Aldrich, 1999), that energetically isolates the steps of activation from the cooperative opening step, we find that opening is accompanied by a previously unknown and cooperative movement of S4. This gating motion of S4 appears to be coupled to the internal S6 gate and to two forms of slow inactivation. Our results suggest that S4 plays a direct role in gating. While large transmembrane rearrangements of S4 may be required to unlock the gating machinery, as proposed before, it appears to be the gating motion of S4 that drives the gates to open and close.

  20. The Cooperative Voltage Sensor Motion that Gates a Potassium Channel

    PubMed Central

    Pathak, Medha; Kurtz, Lisa; Tombola, Francesco; Isacoff, Ehud

    2005-01-01

    The four arginine-rich S4 helices of a voltage-gated channel move outward through the membrane in response to depolarization, opening and closing gates to generate a transient ionic current. Coupling of voltage sensing to gating was originally thought to operate with the S4s moving independently from an inward/resting to an outward/activated conformation, so that when all four S4s are activated, the gates are driven to open or closed. However, S4 has also been found to influence the cooperative opening step (Smith-Maxwell et al., 1998a), suggesting a more complex mechanism of coupling. Using fluorescence to monitor structural rearrangements in a Shaker channel mutant, the ILT channel (Ledwell and Aldrich, 1999), that energetically isolates the steps of activation from the cooperative opening step, we find that opening is accompanied by a previously unknown and cooperative movement of S4. This gating motion of S4 appears to be coupled to the internal S6 gate and to two forms of slow inactivation. Our results suggest that S4 plays a direct role in gating. While large transmembrane rearrangements of S4 may be required to unlock the gating machinery, as proposed before, it appears to be the gating motion of S4 that drives the gates to open and close. PMID:15623895

  1. High-resolution orientation and depth of insertion of the voltage-sensing S4 helix of a potassium channel in lipid bilayers.

    PubMed

    Doherty, Tim; Su, Yongchao; Hong, Mei

    2010-08-27

    The opening and closing of voltage-gated potassium (Kv) channels are controlled by several conserved Arg residues in the S4 helix of the voltage-sensing domain. The interaction of these positively charged Arg residues with the lipid membrane has been of intense interest for understanding how membrane proteins fold to allow charged residues to insert into lipid bilayers against free-energy barriers. Using solid-state NMR, we have now determined the orientation and insertion depth of the S4 peptide of the KvAP channel in lipid bilayers. Two-dimensional (15)N correlation experiments of macroscopically oriented S4 peptide in phospholipid bilayers revealed a tilt angle of 40 degrees and two possible rotation angles differing by 180 degrees around the helix axis. Remarkably, the tilt angle and one of the two rotation angles are identical to those of the S4 helix in the intact voltage-sensing domain, suggesting that interactions between the S4 segment and other helices of the voltage-sensing domain are not essential for the membrane topology of the S4 helix. (13)C-(31)P distances between the S4 backbone and the lipid (31)P indicate a approximately 9 A local thinning and 2 A average thinning of the DMPC (1,2-dimyristoyl-sn-glycero-3-phosphochloline)/DMPG (1,2-dimyristoyl-sn-glycero-3-phosphatidylglycerol) bilayer, consistent with neutron diffraction data. Moreover, a short distance of 4.6 A from the guanidinium C(zeta) of the second Arg to (31)P indicates the existence of guanidinium phosphate hydrogen bonding and salt bridges. These data suggest that the structure of the Kv gating helix is mainly determined by protein-lipid interactions instead of interhelical protein-protein interactions, and the S4 amino acid sequence encodes sufficient information for the membrane topology of this crucial gating helix. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

  2. Measurement of the single-top-quark t-channel cross section in pp collisions at $$ \\sqrt{s}=7 $$ TeV

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Chatrchyan, S.; Khachatryan, V.; Sirunyan, A. M.

    A measurement of the single-top-quark t-channel production cross section in pp collisions at sqrt(s) = 7 TeV with the CMS detector at the LHC is presented. Two different and complementary approaches have been followed. The first approach exploits the distributions of the pseudorapidity of the recoil jet and reconstructed top-quark mass using background estimates determined from control samples in data. The second approach is based on multivariate analysis techniques that probe the compatibility of the candidate events with the signal. Data have been collected for the muon and electron final states, corresponding to integrated luminosities of 1.17 and 1.56 inversemore » femtobarns, respectively. The single-top-quark production cross section in the t-channel is measured to be 67.2 +/- 6.1 pb, in agreement with the approximate next-to-next-to-leading-order standard model prediction. Using the standard model electroweak couplings, the CKM matrix element abs(V[tb

  3. Channel nut tool

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Olson, Marvin

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

  4. Inclusion flotation-driven channel segregation in solidifying steels

    PubMed Central

    Li, Dianzhong; Chen, Xing-Qiu; Fu, Paixian; Ma, Xiaoping; Liu, Hongwei; Chen, Yun; Cao, Yanfei; Luan, Yikun; Li, Yiyi

    2014-01-01

    Channel segregation, which is featured by the strip-like shape with compositional variation in cast materials due to density contrast-induced flow during solidification, frequently causes the severe destruction of homogeneity and some fatal damage. An investigation of its mechanism sheds light on the understanding and control of the channel segregation formation in solidifying metals, such as steels. Until now, it still remains controversial what composes the density contrasts and, to what extent, how it affects channel segregation. Here we discover a new force of inclusion flotation that drives the occurrence of channel segregation. It originates from oxide-based inclusions (Al2O3/MnS) and their sufficient volume fraction-driven flotation becomes stronger than the traditionally recognized inter-dendritic thermosolutal buoyancy, inducing the destabilization of the mushy zone and dominating the formation of channels. This study uncovers the mystery of oxygen in steels, extends the classical macro-segregation theory and highlights a significant technological breakthrough to control macrosegregation. PMID:25422943

  5. Nonsensing residues in S3-S4 linker's C terminus affect the voltage sensor set point in K+ channels.

    PubMed

    Carvalho-de-Souza, Joao L; Bezanilla, Francisco

    2018-02-05

    Voltage sensitivity in ion channels is a function of highly conserved arginine residues in their voltage-sensing domains (VSDs), but this conservation does not explain the diversity in voltage dependence among different K + channels. Here we study the non-voltage-sensing residues 353 to 361 in Shaker K + channels and find that residues 358 and 361 strongly modulate the voltage dependence of the channel. We mutate these two residues into all possible remaining amino acids (AAs) and obtain Q-V and G-V curves. We introduced the nonconducting W434F mutation to record sensing currents in all mutants except L361R, which requires K + depletion because it is affected by W434F. By fitting Q-Vs with a sequential three-state model for two voltage dependence-related parameters ( V 0 , the voltage-dependent transition from the resting to intermediate state and V 1 , from the latter to the active state) and G-Vs with a two-state model for the voltage dependence of the pore domain parameter ( V 1/2 ), Spearman's coefficients denoting variable relationships with hydrophobicity, available area, length, width, and volume of the AAs in 358 and 361 positions could be calculated. We find that mutations in residue 358 shift Q-Vs and G-Vs along the voltage axis by affecting V 0 , V 1 , and V 1/2 according to the hydrophobicity of the AA. Mutations in residue 361 also shift both curves, but V 0 is affected by the hydrophobicity of the AA in position 361, whereas V 1 and V 1/2 are affected by size-related AA indices. Small-to-tiny AAs have opposite effects on V 1 and V 1/2 in position 358 compared with 361. We hypothesize possible coordination points in the protein that residues 358 and 361 would temporarily and differently interact with in an intermediate state of VSD activation. Our data contribute to the accumulating knowledge of voltage-dependent ion channel activation by adding functional information about the effects of so-called non-voltage-sensing residues on VSD dynamics. © 2018

  6. Multi-carrier Communications over Time-varying Acoustic Channels

    NASA Astrophysics Data System (ADS)

    Aval, Yashar M.

    Acoustic communication is an enabling technology for many autonomous undersea systems, such as those used for ocean monitoring, offshore oil and gas industry, aquaculture, or port security. There are three main challenges in achieving reliable high-rate underwater communication: the bandwidth of acoustic channels is extremely limited, the propagation delays are long, and the Doppler distortions are more pronounced than those found in wireless radio channels. In this dissertation we focus on assessing the fundamental limitations of acoustic communication, and designing efficient signal processing methods that cam overcome these limitations. We address the fundamental question of acoustic channel capacity (achievable rate) for single-input-multi-output (SIMO) acoustic channels using a per-path Rician fading model, and focusing on two scenarios: narrowband channels where the channel statistics can be approximated as frequency- independent, and wideband channels where the nominal path loss is frequency-dependent. In each scenario, we compare several candidate power allocation techniques, and show that assigning uniform power across all frequencies for the first scenario, and assigning uniform power across a selected frequency-band for the second scenario, are the best practical choices in most cases, because the long propagation delay renders the feedback information outdated for power allocation based on the estimated channel response. We quantify our results using the channel information extracted form the 2010 Mobile Acoustic Communications Experiment (MACE'10). Next, we focus on achieving reliable high-rate communication over underwater acoustic channels. Specifically, we investigate orthogonal frequency division multiplexing (OFDM) as the state-of-the-art technique for dealing with frequency-selective multipath channels, and propose a class of methods that compensate for the time-variation of the underwater acoustic channel. These methods are based on multiple

  7. Identification and characterization of a bacterial hydrosulphide ion channel

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Czyzewski, Bryan K.; Wang, Da-Neng

    2012-10-26

    The hydrosulphide ion (HS{sup -}) and its undissociated form, hydrogen sulphide (H{sub 2}S), which are believed to have been critical to the origin of life on Earth, remain important in physiology and cellular signalling. As a major metabolite in anaerobic bacterial growth, hydrogen sulphide is a product of both assimilatory and dissimilatory sulphate reduction. These pathways can reduce various oxidized sulphur compounds including sulphate, sulphite and thiosulphate. The dissimilatory sulphate reduction pathway uses this molecule as the terminal electron acceptor for anaerobic respiration, in which process it produces excess amounts of H{sub 2}S. The reduction of sulphite is a keymore » intermediate step in all sulphate reduction pathways. In Clostridium and Salmonella, an inducible sulphite reductase is directly linked to the regeneration of NAD{sup +}, which has been suggested to have a role in energy production and growth, as well as in the detoxification of sulphite. Above a certain concentration threshold, both H{sub 2}S and HS{sup -} inhibit cell growth by binding the metal centres of enzymes and cytochrome oxidase, necessitating a release mechanism for the export of this toxic metabolite from the cell. Here we report the identification of a hydrosulphide ion channel in the pathogen Clostridium difficile through a combination of genetic, biochemical and functional approaches. The HS{sup -} channel is a member of the formate/nitrite transport family, in which about 50 hydrosulphide ion channels form a third subfamily alongside those for formate (FocA) and for nitrite (NirC). The hydrosulphide ion channel is permeable to formate and nitrite as well as to HS{sup -} ions. Such polyspecificity can be explained by the conserved ion selectivity filter observed in the channel's crystal structure. The channel has a low open probability and is tightly regulated, to avoid decoupling of the membrane proton gradient.« less

  8. Atypical pharmacology of schistosome TRPA1-like ion channels.

    PubMed

    Bais, Swarna; Berry, Corbett T; Liu, Xiaohong; Ruthel, Gordon; Freedman, Bruce D; Greenberg, Robert M

    2018-05-01

    Parasitic flatworms of the genus Schistosoma cause schistosomiasis, a neglected tropical disease estimated to affect over 200 million people worldwide. Praziquantel is the only antischistosomal currently available for treatment, and there is an urgent need for new therapeutics. Ion channels play key roles in physiology and are targets for many anthelmintics, yet only a few representatives have been characterized in any detail in schistosomes and other parasitic helminths. The transient receptor potential (TRP) channel superfamily comprises a diverse family of non-selective cation channels that play key roles in sensory transduction and a wide range of other functions. TRP channels fall into several subfamilies. Members of both the TRPA and TRPV subfamilies transduce nociceptive and inflammatory signals in mammals, and often also respond to chemical and thermal signals. We previously showed that although schistosomes contain no genes predicted to encode TRPV channels, TRPV1-selective activators such as capsaicin and resiniferatoxin elicit dramatic hyperactivity in adult worms and schistosomula. Surprisingly, this response requires expression of a S. mansoni TRPA1-like orthologue (SmTRPA). Here, we show that capsaicin induces a rise in intracellular Ca2+ in mammalian cells expressing either SmTRPA or a S. haematobium TRPA1 orthologue (ShTRPA). We also test SmTRPA and ShTRPA responses to various TRPV1 and TRPA1 modulators. Interestingly, in contrast to SmTRPA, ShTRPA is not activated by the TRPA1 activator AITC (allyl isothiocyanate), nor do S. haematobium adult worms respond to this compound, a potentially intriguing species difference. Notably, 4-hydroxynonenal (4-HNE), a host-derived, inflammatory product that directly activates mammalian TRPA1, also activates both SmTRPA and ShTRPA. Our results point to parasite TRPA1-like channels which exhibit atypical, mixed TRPA1/TRPV1-like pharmacology, and which may also function to transduce endogenous host signals.

  9. Contribution of voltage-dependent K+ channels to metabolic control of coronary blood flow

    PubMed Central

    Berwick, Zachary C.; Dick, Gregory M.; Moberly, Steven P.; Kohr, Meredith C.; Sturek, Michael; Tune, Johnathan D.

    2011-01-01

    The purpose of this investigation was to test the hypothesis that KV channels contribute to metabolic control of coronary blood flow and that decreases in KV channel function and/or expression significantly attenuate myocardial oxygen supply-demand balance in the metabolic syndrome (MetS). Experiments were conducted in conscious, chronically instrumented Ossabaw swine fed either a normal maintenance diet or an excess calorie atherogenic diet that produces the clinical phenotype of early MetS. Data were obtained under resting conditions and during graded treadmill exercise before and after inhibition of KV channels with 4-aminopyridine (4-AP, 0.3 mg/kg, i.v.). In lean-control swine, 4-AP reduced coronary blood flow ~15% at rest and ~20% during exercise. Inhibition of KV channels also increased aortic pressure (P < 0.01) while reducing coronary venous Po2 (P < 0.01) at a given level of myocardial oxygen consumption (MVo2). Administration of 4-AP had no effect on coronary blood flow, aortic pressure, or coronary venous Po2 in swine with MetS. The lack of response to 4-AP in MetS swine was associated with a ~20% reduction in coronary KV current (P < 0.01) and decreased expression of KV1.5 channels in coronary arteries (P < 0.01). Together, these data demonstrate that KV channels play an important role in balancing myocardial oxygen delivery with metabolism at rest and during exercise-induced increases in MVo2. Our findings also indicate that decreases in KV channel current and expression contribute to impaired control of coronary blood flow in the MetS. PMID:21771599

  10. Mitochondrial benzodiazepine receptor linked to inner membrane ion channels by nanomolar actions of ligands.

    PubMed Central

    Kinnally, K W; Zorov, D B; Antonenko, Y N; Snyder, S H; McEnery, M W; Tedeschi, H

    1993-01-01

    The mitochrondrial benzodiazepine receptor (mBzR) binds a subset of benzodiazepines and isoquinoline carboxamides with nanomolar affinity and consists of the voltage-dependent anion channel, the adenine nucleotide translocator, and an 18-kDa protein. The effect of ligands of the mBzR on two inner mitochondrial membrane channel activities was determined with patch-clamp techniques. The relative inhibitory potencies of the drugs resemble their binding affinities for the mBzR. Ro5-4864 and protoporphyrin IX inhibit activity of the multiple conductance channel (MCC) and the mitochondrial centum-picosiemen (mCtS) channel activities at nanomolar concentrations. PK11195 inhibits mCtS activity at similar levels. Higher concentrations of protoporphyrin IX induce MCC but possibly not mCtS activity. Clonazepam, which has low affinity for mBzR, is at least 500 times less potent at both channel activities. Ro15-1788, which also has a low mBzR affinity, inhibits MCC at very high concentrations (16 microM). The findings indicate an association of these two channel activities with the proteins forming the mBzR complex and are consistent with an interaction of inner and outer membrane channels. PMID:7679505

  11. Saving Moore’s Law Down To 1 nm Channels With Anisotropic Effective Mass

    NASA Astrophysics Data System (ADS)

    Ilatikhameneh, Hesameddin; Ameen, Tarek; Novakovic, Bozidar; Tan, Yaohua; Klimeck, Gerhard; Rahman, Rajib

    2016-08-01

    Scaling transistors’ dimensions has been the thrust for the semiconductor industry in the last four decades. However, scaling channel lengths beyond 10 nm has become exceptionally challenging due to the direct tunneling between source and drain which degrades gate control, switching functionality, and worsens power dissipation. Fortunately, the emergence of novel classes of materials with exotic properties in recent times has opened up new avenues in device design. Here, we show that by using channel materials with an anisotropic effective mass, the channel can be scaled down to 1 nm and still provide an excellent switching performance in phosphorene nanoribbon MOSFETs. To solve power consumption challenge besides dimension scaling in conventional transistors, a novel tunnel transistor is proposed which takes advantage of anisotropic mass in both ON- and OFF-state of the operation. Full-band atomistic quantum transport simulations of phosphorene nanoribbon MOSFETs and TFETs based on the new design have been performed as a proof.

  12. An S-Type Anion Channel SLAC1 Is Involved in Cryptogein-Induced Ion Fluxes and Modulates Hypersensitive Responses in Tobacco BY-2 Cells

    PubMed Central

    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. PMID:23950973

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

    PubMed

    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.

  14. Nutrient channels and stirring enhanced the composition and stiffness of large cartilage constructs.

    PubMed

    Cigan, Alexander D; Nims, Robert J; Albro, Michael B; Vunjak-Novakovic, Gordana; Hung, Clark T; Ateshian, Gerard A

    2014-12-18

    A significant challenge in cartilage tissue engineering is to successfully culture functional tissues that are sufficiently large to treat osteoarthritic joints. Transport limitations due to nutrient consumption by peripheral cells produce heterogeneous constructs with matrix-deficient centers. Incorporation of nutrient channels into large constructs is a promising technique for alleviating transport limitations, in conjunction with simple yet effective methods for enhancing media flow through channels. Cultivation of cylindrical channeled constructs flat in culture dishes, with or without orbital shaking, produced asymmetric constructs with poor tissue properties. We therefore explored a method for exposing the entire construct surface to the culture media, while promoting flow through the channels. To this end, chondrocyte-seeded agarose constructs (∅10mm, 2.34mm thick), with zero or three nutrient channels (∅1mm), were suspended on their sides in custom culture racks and subjected to three media stirring modes for 56 days: uniaxial rocking, orbital shaking, or static control. Orbital shaking led to the highest construct EY, sulfated glycosaminoglycan (sGAG), and collagen contents, whereas rocking had detrimental effects on sGAG and collagen versus static control. Nutrient channels increased EY as well as sGAG homogeneity, and the beneficial effects of channels were most marked in orbitally shaken samples. Under these conditions, the constructs developed symmetrically and reached or exceeded native levels of EY (~400kPa) and sGAG (~9%/ww). These results suggest that the cultivation of channeled constructs in culture racks with orbital shaking is a promising method for engineering mechanically competent large cartilage constructs. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

    PubMed

    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.

  16. Single Nisoldipine-Sensitive Calcium Channels in Smooth Muscle Cells Isolated from Rabbit Mesenteric Artery

    NASA Astrophysics Data System (ADS)

    Worley, Jennings F.; Deitmer, Joachim W.; Nelson, Mark T.

    1986-08-01

    Single smooth muscle cells were enzymatically isolated from the rabbit mesenteric artery. At physiological levels of external Ca, these cells were relaxed and contracted on exposure to norepinephrine, caffeine, or high levels of potassium. The patch-clamp technique was used to measure unitary currents through single channels in the isolated cells. Single channels were selective for divalent cations and exhibited two conductance levels, 8 pS and 15 pS. Both types of channels were voltage-dependent, and channel activity occurred at potentials positive to -40 mV. The activity of both channel types was almost completely inhibited by 50 nM nisoldipine. These channels appear to be the pathways for voltage-dependent Ca influx in vascular smooth muscle and may be the targets of the clinically used dihydropyridines.

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

    PubMed

    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.

  18. The Gárdos channel: a review of the Ca2+-activated K+ channel in human erythrocytes.

    PubMed

    Maher, Anthony D; Kuchel, Philip W

    2003-08-01

    Ca(2+)-dependent K(+) efflux from human erythrocytes was first described in the 1950s. Subsequent studies revealed that a K(+)-specific membrane protein (the Gárdos channel) was responsible for this phenomenon (the Gárdos effect). In recent years several types of Ca-activated K(+) channel have been identified and studied in a wide range of cells, with the erythrocyte Gárdos channel serving as both a model for a broader physiological perspective, and an intriguing component of erythrocyte function. The existence of this channel has raised a number of questions. For example, what is its role in the establishment and maintenance of ionic distribution across the red cell membrane? What role might it play in erythrocyte development? To what extent is it active in circulating erythrocytes? What are the cell-physiological implications of its dysfunction?This review summarises current knowledge of this membrane protein with respect to its function and structure, its physiological roles (some putative) and its contribution to various disease states, and it provides an introduction to adaptable NMR methods, which is our own area of technical expertise, for such ion transport analysis.

  19. A Direct Demonstration of Closed-State Inactivation of K+ Channels at Low pH

    PubMed Central

    Claydon, Thomas W.; Vaid, Moni; Rezazadeh, Saman; Kwan, Daniel C.H.; Kehl, Steven J.; Fedida, David

    2007-01-01

    Lowering external pH reduces peak current and enhances current decay in Kv and Shaker-IR channels. Using voltage-clamp fluorimetry we directly determined the fate of Shaker-IR channels at low pH by measuring fluorescence emission from tetramethylrhodamine-5-maleimide attached to substituted cysteine residues in the voltage sensor domain (M356C to R362C) or S5-P linker (S424C). One aspect of the distal S3-S4 linker α-helix (A359C and R362C) reported a pH-induced acceleration of the slow phase of fluorescence quenching that represents P/C-type inactivation, but neither site reported a change in the total charge movement at low pH. Shaker S424C fluorescence demonstrated slow unquenching that also reflects channel inactivation and this too was accelerated at low pH. In addition, however, acidic pH caused a reversible loss of the fluorescence signal (pKa = 5.1) that paralleled the reduction of peak current amplitude (pKa = 5.2). Protons decreased single channel open probability, suggesting that the loss of fluorescence at low pH reflects a decreased channel availability that is responsible for the reduced macroscopic conductance. Inhibition of inactivation in Shaker S424C (by raising external K+ or the mutation T449V) prevented fluorescence loss at low pH, and the fluorescence report from closed Shaker ILT S424C channels implied that protons stabilized a W434F-like inactivated state. Furthermore, acidic pH changed the fluorescence amplitude (pKa = 5.9) in channels held continuously at −80 mV. This suggests that low pH stabilizes closed-inactivated states. Thus, fluorescence experiments suggest the major mechanism of pH-induced peak current reduction is inactivation of channels from closed states from which they can activate, but not open; this occurs in addition to acceleration of P/C-type inactivation from the open state. PMID:17470663

  20. The Discovery of Water Channels (Aquaporins).

    PubMed

    Brown, Dennis

    2017-01-01

    The movement of water into and out of cells is a fundamental biological process that is essential for life. Such water movement not only regulates the activity of individual cells but also is responsible for the functioning of many organ systems and for maintaining whole body water balance. It had long been suspected that water movement across biological cell membranes was in some way enhanced or facilitated by pores or channels, but the search to identify these channels was long and tedious. As is often the case in science, the secret of the water channel was eventually discovered by chance in 1992 by Peter Agre and his colleagues at the Johns Hopkins University in Baltimore, who were working on red blood cell membrane proteins. This "first" water channel was originally named CHIP28 and is now known as aquaporin 1. Agre received the Nobel Prize in Chemistry in 2003 for this discovery. There are currently 13 known aquaporins in mammals, distributed in most tissues, but many more have been identified in lower organisms and in the plant kingdom. The involvement of aquaporins in processes such as urinary concentration and body fluid homeostasis, brain function, glandular secretion, skin hydration, male fertility, hearing, vision, and most important body functions that can be imagined are now all under intense scientific scrutiny. Moreover, defects in aquaporin function have been related to various disease conditions and pathological states. This brief review will discuss their background, discovery, and function in selected bodily processes, especially focusing on hydration. © 2017 The Author(s) Published by S. Karger AG, Basel.

  1. Miniaturized Ka-Band Dual-Channel Radar

    NASA Technical Reports Server (NTRS)

    Hoffman, James P.; Moussessian, Alina; Jenabi, Masud; Custodero, Brian

    2011-01-01

    Smaller (volume, mass, power) electronics for a Ka-band (36 GHz) radar interferometer were required. To reduce size and achieve better control over RFphase versus temperature, fully hybrid electronics were developed for the RF portion of the radar s two-channel receiver and single-channel transmitter. In this context, fully hybrid means that every active RF device was an open die, and all passives were directly attached to the subcarrier. Attachments were made using wire and ribbon bonding. In this way, every component, even small passives, was selected for the fabrication of the two radar receivers, and the devices were mounted relative to each other in order to make complementary components isothermal and to isolate other components from potential temperature gradients. This is critical for developing receivers that can track each other s phase over temperature, which is a key mission driver for obtaining ocean surface height. Fully hybrid, Ka-band (36 GHz) radar transmitter and dual-channel receiver were developed for spaceborne radar interferometry. The fully hybrid fabrication enables control over every aspect of the component selection, placement, and connection. Since the two receiver channels must track each other to better than 100 millidegrees of RF phase over several minutes, the hardware in the two receivers must be "identical," routed the same (same line lengths), and as isothermal as possible. This level of design freedom is not possible with packaged components, which include many internal passive, unknown internal connection lengths/types, and often a single orientation of inputs and outputs.

  2. Tunable Electron and Hole Injection Enabled by Atomically Thin Tunneling Layer for Improved Contact Resistance and Dual Channel Transport in MoS2/WSe2 van der Waals Heterostructure.

    PubMed

    Khan, Muhammad Atif; Rathi, Servin; Lee, Changhee; Lim, Dongsuk; Kim, Yunseob; Yun, Sun Jin; Youn, Doo Hyeb; Kim, Gil-Ho

    2018-06-25

    Two-dimensional (2D) materials based heterostructures provide a unique platform where interaction between stacked 2D layers can enhance the electrical and opto-electrical properties as well as give rise to interesting new phenomena. Here, operation of a van der Waals heterostructure device comprising of vertically stacked bi-layer MoS 2 and few layered WSe 2 has been demonstrated in which atomically thin MoS 2 layer has been employed as a tunneling layer to the underlying WSe 2 layer. In this way, simultaneous contacts to both MoS 2 and WSe 2 2D layers have been established by forming direct MS (metal semiconductor) to MoS 2 and tunneling based MIS (metal insulator semiconductor) contacts to WSe 2 , respectively. The use of MoS 2 as a dielectric tunneling layer results in improved contact resistance (80 kΩ-µm) for WSe 2 contact, which is attributed to reduction in effective Schottky barrier height and is also confirmed from the temperature dependent measurement. Further, this unique contact engineering and type II band alignment between MoS 2 and WSe 2 enables a selective and independent carrier transport across the respective layers. This contact engineered dual channel heterostructure exhibits an excellent gate control and both channel current and carrier types can be modulated by the vertical electric field of the gate electrode, which is also reflected in on/off ratio of 10 4 for both electrons (MoS 2 ) and holes (WSe 2 ) channels. Moreover, the charge transfer at the heterointerface is studied quantitatively from the shift in the threshold voltage of the pristine MoS 2 and heterostructure device, which agrees with the carrier recombination induced optical quenching as observed in the Raman spectra of the pristine and heterostructure layers. This observation of dual channel ambipolar transport enabled by the hybrid tunneling contacts and strong interlayer coupling can be utilized for high performance opto-electrical devices and applications.

  3. UWB channel estimation using new generating TR transceivers

    DOEpatents

    Nekoogar, Faranak [San Ramon, CA; Dowla, Farid U [Castro Valley, CA; Spiridon, Alex [Palo Alto, CA; Haugen, Peter C [Livermore, CA; Benzel, Dave M [Livermore, CA

    2011-06-28

    The present invention presents a simple and novel channel estimation scheme for UWB communication systems. As disclosed herein, the present invention maximizes the extraction of information by incorporating a new generation of transmitted-reference (Tr) transceivers that utilize a single reference pulse(s) or a preamble of reference pulses to provide improved channel estimation while offering higher Bit Error Rate (BER) performance and data rates without diluting the transmitter power.

  4. Amortized entanglement of a quantum channel and approximately teleportation-simulable channels

    NASA Astrophysics Data System (ADS)

    Kaur, Eneet; Wilde, Mark M.

    2018-01-01

    This paper defines the amortized entanglement of a quantum channel as the largest difference in entanglement between the output and the input of the channel, where entanglement is quantified by an arbitrary entanglement measure. We prove that the amortized entanglement of a channel obeys several desirable properties, and we also consider special cases such as the amortized relative entropy of entanglement and the amortized Rains relative entropy. These latter quantities are shown to be single-letter upper bounds on the secret-key-agreement and PPT-assisted quantum capacities of a quantum channel, respectively. Of especial interest is a uniform continuity bound for these latter two special cases of amortized entanglement, in which the deviation between the amortized entanglement of two channels is bounded from above by a simple function of the diamond norm of their difference and the output dimension of the channels. We then define approximately teleportation- and positive-partial-transpose-simulable (PPT-simulable) channels as those that are close in diamond norm to a channel which is either exactly teleportation- or PPT-simulable, respectively. These results then lead to single-letter upper bounds on the secret-key-agreement and PPT-assisted quantum capacities of channels that are approximately teleportation- or PPT-simulable, respectively. Finally, we generalize many of the concepts in the paper to the setting of general resource theories, defining the amortized resourcefulness of a channel and the notion of ν-freely-simulable channels, connecting these concepts in an operational way as well.

  5. Coupling between the Voltage-sensing and Pore Domains in a Voltage-gated Potassium Channel

    PubMed Central

    Schow, Eric V.; Freites, J. Alfredo; Nizkorodov, Alex; White, Stephen H.; Tobias, Douglas J.

    2012-01-01

    Voltage-dependent potassium (Kv), sodium (Nav), and calcium channels open and close in response to changes in transmembrane (TM) potential, thus regulating cell excitability by controlling ion flow across the membrane. An outstanding question concerning voltage gating is how voltage-induced conformational changes of the channel voltage-sensing domains (VSDs) are coupled through the S4-S5 interfacial linking helices to the opening and closing of the pore domain (PD). To investigate the coupling between the VSDs and the PD, we generated a closed Kv channel configuration from Aeropyrum pernix (KvAP) using atomistic simulations with experiment-based restraints on the VSDs. Full closure of the channel required, in addition to the experimentally determined TM displacement, that the VSDs be displaced both inwardly and laterally around the PD. This twisting motion generates a tight hydrophobic interface between the S4-S5 linkers and the C-terminal ends of the pore domain S6 helices in agreement with available experimental evidence. PMID:22425907

  6. Coupling between the voltage-sensing and pore domains in a voltage-gated potassium channel.

    PubMed

    Schow, Eric V; Freites, J Alfredo; Nizkorodov, Alex; White, Stephen H; Tobias, Douglas J

    2012-07-01

    Voltage-dependent potassium (Kv), sodium (Nav), and calcium channels open and close in response to changes in transmembrane (TM) potential, thus regulating cell excitability by controlling ion flow across the membrane. An outstanding question concerning voltage gating is how voltage-induced conformational changes of the channel voltage-sensing domains (VSDs) are coupled through the S4-S5 interfacial linking helices to the opening and closing of the pore domain (PD). To investigate the coupling between the VSDs and the PD, we generated a closed Kv channel configuration from Aeropyrum pernix (KvAP) using atomistic simulations with experiment-based restraints on the VSDs. Full closure of the channel required, in addition to the experimentally determined TM displacement, that the VSDs be displaced both inwardly and laterally around the PD. This twisting motion generates a tight hydrophobic interface between the S4-S5 linkers and the C-terminal ends of the pore domain S6 helices in agreement with available experimental evidence.

  7. Activation of KV7 channels stimulates vasodilatation of human placental chorionic plate arteries.

    PubMed

    Mills, T A; Greenwood, S L; Devlin, G; Shweikh, Y; Robinson, M; Cowley, E; Hayward, C E; Cottrell, E C; Tropea, T; Brereton, M F; Dalby-Brown, W; Wareing, M

    2015-06-01

    Potassium (K(+)) channels are key regulators of vascular smooth muscle cell (VSMC) excitability. In systemic small arteries, Kv7 channel expression/activity has been noted and a role in vascular tone regulation demonstrated. We aimed to demonstrate functional Kv7 channels in human fetoplacental small arteries. Human placental chorionic plate arteries (CPAs) were obtained at term. CPA responses to Kv7 channel modulators was determined by wire myography. Presence of Kv7 channel mRNA (encoded by KCNQ1-5) and protein expression were assessed by RT-PCR and immunohistochemistry/immunofluorescence, respectively. Kv7 channel blockade with linopirdine increased CPA basal tone and AVP-induced contraction. Pre-contracted CPAs (AVP; 80 mM K(+) depolarization solution) exhibited significant relaxation to flupirtine, retigabine, the acrylamide (S)-1, and (S) BMS-204352, differential activators of Kv7.1 - Kv7.5 channels. All CPAs assessed expressed KCNQ1 and KCNQ3-5 mRNA; KCNQ2 was expressed only in a subset of CPAs. Kv7 protein expression was confirmed in intact CPAs and isolated VSMCs. Kv7 channels are present and active in fetoplacental vessels, contributing to vascular tone regulation in normal pregnancy. Targeting these channels may represent a therapeutic intervention in pregnancies complicated by increased vascular resistance. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. A human intermediate conductance calcium-activated potassium channel.

    PubMed

    Ishii, T M; Silvia, C; Hirschberg, B; Bond, C T; Adelman, J P; Maylie, J

    1997-10-14

    An intermediate conductance calcium-activated potassium channel, hIK1, was cloned from human pancreas. The predicted amino acid sequence is related to, but distinct from, the small conductance calcium-activated potassium channel subfamily, which is approximately 50% conserved. hIK1 mRNA was detected in peripheral tissues but not in brain. Expression of hIK1 in Xenopus oocytes gave rise to inwardly rectifying potassium currents, which were activated by submicromolar concentrations of intracellular calcium (K0.5 = 0.3 microM). Although the K0.5 for calcium was similar to that of small conductance calcium-activated potassium channels, the slope factor derived from the Hill equation was significantly reduced (1.7 vs. 3. 5). Single-channel current amplitudes reflected the macroscopic inward rectification and revealed a conductance level of 39 pS in the inward direction. hIK1 currents were reversibly blocked by charybdotoxin (Ki = 2.5 nM) and clotrimazole (Ki = 24.8 nM) but were minimally affected by apamin (100 nM), iberiotoxin (50 nM), or ketoconazole (10 microM). These biophysical and pharmacological properties are consistent with native intermediate conductance calcium-activated potassium channels, including the erythrocyte Gardos channel.

  9. High-resolution swath interferometric data collected within Muskeget Channel, Massachusetts

    USGS Publications Warehouse

    Pendleton, Elizabeth A.; Denny, Jane F.; Danforth, William W.; Baldwin, Wayne E.; Irwin, Barry J.

    2014-01-01

    Swath interferometric bathymetery data were collected within and around Muskeget Channel and along select nearshore areas south and east of Martha's Vineyard, Massachusetts. Data were collected aboard the U.S. Geological Survey research vessel Rafael in October and November 2010 in a collaborative effort between the U.S. Geological Survey and the Woods Hole Oceanographic Institution. This report describes the data-collection methods and -processing steps and releases the data in geospatial format. These data were collected to support an assessment of the effect on sediment transport that a tidal instream energy conversion facility would have within Muskeget Channel. Baseline bathymetry data were obtained for the Muskeget Channel area, and surveys in select areas were repeated after one month to monitor sediment transport and bedform migration.

  10. Measurement of the top quark mass in the t t ¯ → dilepton channel from s = 8  TeV ATLAS data

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Aaboud, M.

    Here, the top quark mass is measured in the tt¯→ dilepton channel (lepton=e,μ) using ATLAS data recorded in the year 2012 at the LHC. The data were taken at a proton–proton centre-of-mass energy of √s=8 TeV and correspond to an integrated luminosity of about 20.2 fb –1. Exploiting the template method, and using the distribution of invariant masses of lepton–b-jetb-jet pairs, the top quark mass is measured to be m top = 172.99 ± 0.41 (stat) ± 0.74 (syst) GeV, with a total uncertainty of 0.84 GeV0.84 GeV. Lastly, a combination with previous ATLAS m top measurements from √s=7 TeVmore » data in the tt¯→ dilepton and tt¯→ lepton + jets channels results in m top = 172.84 ± 0.34 (stat) ± 0.61 (syst) GeV with a total uncertainty of 0.70 GeV.« less

  11. Measurement of the top quark mass in the t t ¯ → dilepton channel from s = 8  TeV ATLAS data

    DOE PAGES

    Aaboud, M.

    2016-08-24

    Here, the top quark mass is measured in the tt¯→ dilepton channel (lepton=e,μ) using ATLAS data recorded in the year 2012 at the LHC. The data were taken at a proton–proton centre-of-mass energy of √s=8 TeV and correspond to an integrated luminosity of about 20.2 fb –1. Exploiting the template method, and using the distribution of invariant masses of lepton–b-jetb-jet pairs, the top quark mass is measured to be m top = 172.99 ± 0.41 (stat) ± 0.74 (syst) GeV, with a total uncertainty of 0.84 GeV0.84 GeV. Lastly, a combination with previous ATLAS m top measurements from √s=7 TeVmore » data in the tt¯→ dilepton and tt¯→ lepton + jets channels results in m top = 172.84 ± 0.34 (stat) ± 0.61 (syst) GeV with a total uncertainty of 0.70 GeV.« less

  12. Ion channel stabilization of synthetic alamethicin analogs by rings of inter-helix H-bonds.

    PubMed Central

    Molle, G; Dugast, J Y; Spach, G; Duclohier, H

    1996-01-01

    Rings of inter-helix H-bonds due to Gln at position 7, a highly conserved residue in all pore-forming peptaibols, have been suggested to play an important role in the stabilization of alamethicin channels. In an attempt to test this hypothesis, experimental studies have been undertaken on four synthetic alamethicin non-Aib analogs (Alm-dUL) in which the Gln at position 7 (Q7) is substituted by Ala, Asn, or Ser (Q7A, Q7N, or Q7S). Voltage-dependent pore formation by these analogs in planar lipid bilayers is compared at the macroscopic and single-channel conductance levels. As anticipated, the Q7A substitution abolished all channel-forming activity. The voltage dependence of macroscopic current-voltage curves was conserved with the Q7N substitution but reduced in the Q7S analog. Normalized single-channel conductance ratios between substates follow the same pattern, with the Q7S analog yielding the highest unit conductances. Channel lifetimes were the most significantly modulated parameter with markedly faster kinetics when Gln or Asn was replaced by Ser. The effect of the Q7S substitution on channel lifetimes may be explained through a reduced stabilization of bundles by inter-helix H-bonds. PMID:8785325

  13. Antisense oligodeoxynucleotide inhibition of a swelling-activated cation channel in osteoblast-like osteosarcoma cells

    NASA Technical Reports Server (NTRS)

    Duncan, R. L.; Kizer, N.; Barry, E. L.; Friedman, P. A.; Hruska, K. A.

    1996-01-01

    By patch-clamp analysis, we have shown that chronic, intermittent mechanical strain (CMS) increases the activity of stretch-activated cation channels of osteoblast-like UMR-106.01 cells. CMS also produces a swelling-activated whole-cell conductance (Gm) regulated by varying strain levels. We questioned whether the swelling-activated conductance was produced by stretch-activated cation channel activity. We have identified a gene involved in the increase in conductance by using antisense oligodeoxynucleotides (ODN) derived from the alpha 1-subunit genes of calcium channels found in UMR-106.01 cells (alpha1S, alpha1C, and alpha1D). We demonstrate that alpha 1C antisense ODNs abolish the increase in Gm in response to hypotonic swelling following CMS. Antisense ODNs to alpha1S and alpha1D, sense ODNs to alpha1C, and sham permeabilization had no effect on the conductance increase. In addition, during cell-attached patch-clamp studies, antisense ODNs to alpha1c completely blocked the swelling-activated and stretch-activated nonselective cation channel response to strain. Antisense ODNs to alpha1S treatment produced no effect on either swelling-activated or stretch-activated cation channel activity. There were differences in the stretch-activated and swelling-activated cation channel activity, but whether they represent different channels could not be determined from our data. Our data indicate that the alpha1C gene product is involved in the Gm and the activation of the swelling-activated cation channels induced by CMS. The possibility that swelling-activated cation channel genes are members of the calcium channel superfamily exists, but if alpha1c is not the swelling-activated cation channel itself, then its expression is required for induction of swelling-activated cation channel activity by CMS.

  14. BCI`S domestic automotive replacement battery shipments by channel of distribution

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    NONE

    1995-07-01

    Thirteen manufacturing members, of Battery Council International, supplied the shipment figures contained in this report. This Channel of Distribution continues to account for an estimated 97% of the domestic replacement battery industry. This report indicates solely domestic replacement battery shipments for the following battery classifications: passenger car & light commercial; heavy duty commercial; special tractor; marine; general utility and golf car.

  15. Ca2+ and Mn2+ Influx Through Receptor-Mediated Activation of Nonspecific Cation Channels in Mast Cells

    NASA Astrophysics Data System (ADS)

    Fasolato, Cristina; Hoth, Markus; Matthews, Gary; Penner, Reinhold

    1993-04-01

    Whole-cell patch-clamp recordings of membrane currents and Fura-2 measurements of free intracellular calcium concentration ([Ca2+]_i) were used to study calcium influx through receptor-activated cation channels in rat peritoneal mast cells. Cation channels were activated by the secretagogue compound 48/80, whereas a possible concomitant Ca2+ entry through pathways activated by depletion of calcium stores was blocked by dialyzing cells with heparin. Heparin effectively suppressed the transient Ca2+ release induced by 48/80 and abrogated inositol 1,4,5-trisphosphate-induced calcium influx without affecting activation of 50-pS cation channels. There was a clear correlation between changes in [Ca2+]_i and the activity of 50-pS channels. The changes in [Ca2+]_i increased with elevation of extracellular Ca2+. At the same time, inward currents through 50-pS channels were diminished as more Ca2+ permeated. This effect was due to a decrease in slope conductance and a reduction in the open probability of the cation channels. In physiological solutions, 3.6% of the total current was carried by Ca2+. The cation channels were not only permeable to Ca2+ but also to Mn2+, as evidenced by the quench of Fura-2 fluorescence. Mn2+ current through 50-pS channels could not be resolved at the single-channel level. Our results suggest that 50-pS cation channels partially contribute to sustained increases of [Ca2+]_i in mast cells following receptor activation.

  16. Connexin channels and phospholipids: association and modulation

    PubMed Central

    Locke, Darren; Harris, Andrew L

    2009-01-01

    Background For membrane proteins, lipids provide a structural framework and means to modulate function. Paired connexin hemichannels form the intercellular channels that compose gap junction plaques while unpaired hemichannels have regulated functions in non-junctional plasma membrane. The importance of interactions between connexin channels and phospholipids is poorly understood. Results Endogenous phospholipids most tightly associated with purified connexin26 or connexin32 hemichannels or with junctional plaques in cell membranes, those likely to have structural and/or modulatory effects, were identified by tandem electrospray ionization-mass spectrometry using class-specific interpretative methods. Phospholipids were characterized by headgroup class, charge, glycerol-alkyl chain linkage and by acyl chain length and saturation. The results indicate that specific endogenous phospholipids are uniquely associated with either connexin26 or connexin32 channels, and some phospholipids are associated with both. Functional effects of the major phospholipid classes on connexin channel activity were assessed by molecular permeability of hemichannels reconstituted into liposomes. Changes to phospholipid composition(s) of the liposome membrane altered the activity of connexin channels in a manner reflecting changes to the surface charge/potential of the membrane and, secondarily, to cholesterol content. Together, the data show that connexin26 and connexin32 channels have a preference for tight association with unique anionic phospholipids, and that these, independent of headgroup, have a positive effect on the activity of both connexin26 and connexin32 channels. Additionally, the data suggest that the likely in vivo phospholipid modulators of connexin channel structure-function that are connexin isoform-specific are found in the cytoplasmic leaflet. A modulatory role for phospholipids that promote negative curvature is also inferred. Conclusion This study is the first to

  17. Octanol reduces end-plate channel lifetime

    PubMed Central

    Gage, Peter W.; McBurney, Robert N.; Van Helden, Dirk

    1978-01-01

    1. Post-synaptic effects of n-octanol at concentrations of 0·1-1 mM were examined in toad sartorius muscles by use of extracellular and voltage-clamp techniques. 2. Octanol depressed the amplitude and duration of miniature end-plate currents and hence depressed neuromuscular transmission. 3. The decay of miniature end-plate currents remained exponential in octanol solutions even when the time constant of decay (τD) was decreased by 80-90%. 4. The lifetime of end-plate channels, obtained by analysis of acetylcholine noise, was also decreased by octanol. The average lifetime measured from noise spectra agreed reasonably well with the time constant of decay of miniature end-plate currents, both in control solution and in octanol solutions. 5. Octanol caused a reduction in the conductance of end-plate channels. Single channel conductance was on average about 25 pS in control solution and 20 pS in octanol. 6. In most cells the normal voltage sensitivity of the decay of miniature end-plate currents was retained in octanol solutions. The lifetime of end-plate channels measured from acetylcholine noise also remained voltage-sensitive in octanol solutions. In some experiments in which channel lifetime was exceptionally reduced the voltage sensitivity was less than normal. 7. In octanol solutions, τD was still very sensitive to temperature changes in most cells although in some the temperature sensitivity of τD was clearly reduced. Changes in τD with temperature could generally be fitted by the Arrhenius equation suggesting that a single step reaction controlled the decay of currents both in control and in octanol solutions. In some cells in which τD became less than 0·3 ms, the relationship between τD and temperature became inconsistent with the Arrhenius equation. 8. As the decay of end-plate currents in octanol solutions remains exponential, and the voltage and temperature sensitivity can be unchanged even when τD is significantly reduced, it seems likely that

  18. Molecular basis of proton block of L-type Ca2+ channels.

    PubMed

    Chen, X H; Bezprozvanny, I; Tsien, R W

    1996-11-01

    Hydrogen ions are important regulators of ion flux through voltage-gated Ca2+ channels but their site of action has been controversial. To identify molecular determinants of proton block of L-type Ca2+ channels, we combined site-directed mutagenesis and unitary current recordings from wild-type (WT) and mutant L-type Ca2+ channels expressed in Xenopus oocytes. WT channels in 150 mM K+ displayed two conductance states, deprotonated (140 pS) and protonated (45 pS), as found previously in native L-type Ca2+ channels. Proton block was altered in a unique fashion by mutation of each of the four P-region glutamates (EI-EIV) that form the locus of high affinity Ca2+ interaction. Glu(E)-->Gln(Q) substitution in either repeats I or III abolished the high-conductance state, as if the titration site had become permanently protonated. While the EIQ mutant displayed only an approximately 40 pS conductance, the EIIIQ mutant showed the approximately 40 pS conductance plus additional pH-sensitive transitions to an even lower conductance level. The EIVQ mutant exhibited the same deprotonated and protonated conductance states as WT, but with an accelerated rate of deprotonation. The EIIQ mutant was unusual in exhibiting three conductance states (approximately 145, 102, 50 pS, respectively). Occupancy of the low conductance state increased with external acidification, albeit much higher proton concentration was required than for WT. In contrast, the equilibrium between medium and high conductance levels was apparently pH-insensitive. We concluded that the protonation site in L-type Ca2+ channels lies within the pore and is formed by a combination of conserved P-region glutamates in repeats I, II, and III, acting in concert. EIV lies to the cytoplasmic side of the site but exerts an additional stabilizing influence on protonation, most likely via electrostatic interaction. These findings are likely to hold for all voltage-gated Ca2+ channels and provide a simple molecular explanation

  19. Comparative sequence analysis suggests a conserved gating mechanism for TRP channels

    PubMed Central

    Palovcak, Eugene; Delemotte, Lucie; Klein, Michael L.

    2015-01-01

    The transient receptor potential (TRP) channel superfamily plays a central role in transducing diverse sensory stimuli in eukaryotes. Although dissimilar in sequence and domain organization, all known TRP channels act as polymodal cellular sensors and form tetrameric assemblies similar to those of their distant relatives, the voltage-gated potassium (Kv) channels. Here, we investigated the related questions of whether the allosteric mechanism underlying polymodal gating is common to all TRP channels, and how this mechanism differs from that underpinning Kv channel voltage sensitivity. To provide insight into these questions, we performed comparative sequence analysis on large, comprehensive ensembles of TRP and Kv channel sequences, contextualizing the patterns of conservation and correlation observed in the TRP channel sequences in light of the well-studied Kv channels. We report sequence features that are specific to TRP channels and, based on insight from recent TRPV1 structures, we suggest a model of TRP channel gating that differs substantially from the one mediating voltage sensitivity in Kv channels. The common mechanism underlying polymodal gating involves the displacement of a defect in the H-bond network of S6 that changes the orientation of the pore-lining residues at the hydrophobic gate. PMID:26078053

  20. Historical Channel Changes in Cache Creek, Capay Valley, California

    NASA Astrophysics Data System (ADS)

    Higgins, S. A.; Kamman, G. R.

    2009-12-01

    Historical channel changes were assessed for the 21-mile segment of Cache Creek through Capay Valley in order to evaluate temporal changes in stream channel morphology. The Capay Valley segment of Cache Creek is primarily a low-gradient channel with a gravel/cobble substrate. Hydrologic conditions have been affected by dam operations that store runoff during the wet season and deliver water during the dry season for downstream irrigation uses. Widespread distribution of invasive plant species has altered the condition of the riparian corridor. The assessment evaluated a hypothesis that historical changes in hydrology and vegetation cover have triggered changes in geomorphic conditions. Historic channel alignments were digitized to assess planform channel adjustments. Results illustrate a dynamic system with frequent channel movements throughout the historic period. Evaluation of longitudinal channel adjustments revealed a relatively stable bed surface elevation since the 1930’s. Comparisons of cross-sectional channel geometry for topographic profiles surveyed in 1984 were compared to equivalent features in a LiDAR survey from 2008. The comparisons show a relatively consistent channel geometry that has maintained a similar form despite rather large planform adjustments with areas of bank retreat in excess of 500 feet. Results suggest that the study reach has maintained a relatively stable morphology through a series of dynamic planform adjustments during the historic period.

  1. [Study of changes in Chinese herbal medicine distribution channel].

    PubMed

    Lv, Hua; Yang, Guang; Huang, Lu-Qi

    2014-07-01

    Distribution channel of Chinese herbal medicines has been changing. From Han to Ming Dynasty, Chinese herbal medicine were mainly trafficked to urban by dealers or farmers; From the Ming Dynasty to the foundation of new China, distribution channels are primarily intermediated with township "bazaar" and national distribution center with fixed place and regularly trading hours. In the planned economy period, the state-owned herbal medicine company was the sole medium with monopoly nature. From the mid1980s to the end of last century, planned economy and market economy have been co-existing. Stepping into 21st century, producing area highlighted in the distribution channels. Presence or absence and rise or fall of different types of distribution market went throughout the changing process of distribution channels, which became an important clue. Changes were motivated by economical consideration of channel subject, which originated from commodity characteristic and social environment changes.

  2. Recovering endemic plants of the Channel Islands

    USGS Publications Warehouse

    McEachern, A. Kathryn

    2008-01-01

    At the California Channel Islands, off the state’s southern coast, cold waters from the north mix with warmer waters from the south. Each of the eight Channel Islands, which were never connected to the mainland, developed unique floras as colonizing plants adapted to their new island homes. This part of California is one of only five Mediterranean climate regions in the world, characterized by hot, dry summers and cool, wet winters. Thus, the islands support a truly unusual assemblage of plants and animals found nowhere else.

  3. Interactions of Pannexin1 channels with purinergic and NMDA receptor channels.

    PubMed

    Li, Shuo; Bjelobaba, Ivana; Stojilkovic, Stanko S

    2018-01-01

    Pannexins are a three-member family of vertebrate plasma membrane spanning molecules that have homology to the invertebrate gap junction forming proteins, the innexins. However, pannexins do not form gap junctions but operate as plasma membrane channels. The best-characterized member of these proteins, Pannexin1 (Panx1) was suggested to be functionally associated with purinergic P2X and N-methyl-D-aspartate (NMDA) receptor channels. Activation of these receptor channels by their endogenous ligands leads to cross-activation of Panx1 channels. This in turn potentiates P2X and NMDA receptor channel signaling. Two potentiation concepts have been suggested: enhancement of the current responses and/or sustained receptor channel activation by ATP released through Panx1 pore and adenosine generated by ectonucleotidase-dependent dephosphorylation of ATP. Here we summarize the current knowledge and hypotheses about interactions of Panx1 channels with P2X and NMDA receptor channels. This article is part of a Special Issue entitled: Gap Junction Proteins edited by Jean Claude Herve. Published by Elsevier B.V.

  4. Visualization investigation on flowing condensation in horizontal small channels with liquid separator

    NASA Astrophysics Data System (ADS)

    Zhang, Xuan; Jia, Li; Dang, Chao; Peng, Qi

    2018-02-01

    A simultaneous visualization and measurement experiment was carried out to investigate condensation flow patterns and condensing heat transfer characteristics of refrigerant R141b in parallel horizontal multi-channels with liquid-vapor separator. The hydraulic diameter of each channel was 1.5 mm and the channel length was 100 mm. The refrigerant vapor flowing in the small channels was cooled by cooling water. The parallel horizontal multi- channels were covered with a transparent silica glass for visualization of flow patterns. Experiments were performed at different inlet superheat temperatures (ranging from 3°C to 7°C). Mass velocity was in the range of 82.37 kg m-2s-1 to 35.56 kg m-2s-1. It was found that there were three different flow patterns through the multi- channels with the increase of mass velocity. The flow patterns in each channel pass almost tended to be same and all of them were annular flows. The efficiency of the liquid-vapor separator with U-type was related to vapor mass velocity and the pressure in the small channels. It was also found that the heat transfer coefficient increased with the increase of the mass velocity while the cooling water mass flow rate increased. It increased to a top point and then decreased. It increased with the increase of superheat in the low superheat temperature region.

  5. Inhalational anaesthetics and n-alcohols share a site of action in the neuronal Shaw2 Kv channel

    PubMed Central

    Bhattacharji, Aditya; Klett, Nathan; Go, Ramon Christopher V; Covarrubias, Manuel

    2010-01-01

    Background and purpose: Neuronal ion channels are key targets of general anaesthetics and alcohol, and binding of these drugs to pre-existing and relatively specific sites is thought to alter channel gating. However, the underlying molecular mechanisms of this action are still poorly understood. Here, we investigated the neuronal Shaw2 voltage-gated K+ (Kv) channel to ask whether the inhalational anaesthetic halothane and n-alcohols share a binding site near the activation gate of the channel. Experimental approach: Focusing on activation gate mutations that affect channel modulation by n-alcohols, we investigated n-alcohol-sensitive and n-alcohol-resistant Kv channels heterologously expressed in Xenopus oocytes to probe the functional modulation by externally applied halothane using two-electrode voltage clamping and a gas-tight perfusion system. Key results: Shaw2 Kv channels are reversibly inhibited by halothane in a dose-dependent and saturable manner (K0.5= 400 µM; nH= 1.2). Also, discrete mutations in the channel's S4S5 linker are sufficient to reduce or confer inhibition by halothane (Shaw2-T330L and Kv3.4-G371I/T378A respectively). Furthermore, a point mutation in the S6 segment of Shaw2 (P410A) converted the halothane-induced inhibition into halothane-induced potentiation. Lastly, the inhibition resulting from the co-application of n-butanol and halothane is consistent with the presence of overlapping binding sites for these drugs and weak binding cooperativity. Conclusions and implications: These observations strongly support a molecular model of a general anaesthetic binding site in the Shaw2 Kv channel. This site may involve the amphiphilic interface between the S4S5 linker and the S6 segment, which plays a pivotal role in Kv channel activation. PMID:20136839

  6. CNG channel subunit glycosylation regulates MMP-dependent changes in channel gating

    PubMed Central

    Meighan, Starla E.; Meighan, Peter C.; Rich, Elizabeth D.; Brown, R. Lane; Varnum, Michael D.

    2013-01-01

    Cyclic-nucleotide gated (CNG) channels are essential for phototransduction within retinal photoreceptors. We have demonstrated previously that enzymatic activity of matrix metalloproteinase-2 and -9, members of the MMP family of extracellular, Ca+2- and Zn+2-dependent proteases, enhances the ligand sensitivity of both rod (CNGA1 + CNGB1) and cone CNGA3 + CNGB3) CNG channels. Additionally, we have observed a decrease in maximal CNG channel current (IMAX) that begins late during MMP-directed gating changes. Here we demonstrate that CNG channels become non-conductive after prolonged MMP exposure. Concurrent with the loss of conductive channels is the increased relative contribution of channels exhibiting non-modified gating properties, suggesting the presence of a subpopulation of channels that are protected from MMP-induced gating effects. CNGA subunits are known to possess one extracellular core glycosylation site, located at one of two possible positions within the turret loop near the pore-forming region. Our results indicate that CNGA glycosylation can impede MMP-dependent modification of CNG channels. Furthermore, the relative position of the glycosylation site within the pore turret influences the extent of MMP-dependent proteolysis. Glycosylation at the site found in CNGA3 subunits was found to be protective, while glycosylation at the bovine CNGA1 site was not. Relocating the glycosylation site in CNGA1 to the position found in CNGA3 recapitulated CNGA3-like protection from MMP-dependent processing. Taken together, these data indicate that CNGA glycosylation may protect CNG channels from MMP-dependent proteolysis, consistent with MMP modification of channel function having a requirement for physical access to the extracellular face of the channel. PMID:24164424

  7. 47 CFR 73.201 - Numerical designation of FM broadcast channels.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 47 Telecommunication 4 2014-10-01 2014-10-01 false Numerical designation of FM broadcast channels... SERVICES RADIO BROADCAST SERVICES FM Broadcast Stations § 73.201 Numerical designation of FM broadcast... numerical designations which are shown in the table below: Frequency (Mc/s) Channel No. 88.1 201 88.3 202 88...

  8. 47 CFR 73.201 - Numerical designation of FM broadcast channels.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 47 Telecommunication 4 2012-10-01 2012-10-01 false Numerical designation of FM broadcast channels... SERVICES RADIO BROADCAST SERVICES FM Broadcast Stations § 73.201 Numerical designation of FM broadcast... numerical designations which are shown in the table below: Frequency (Mc/s) Channel No. 88.1 201 88.3 202 88...

  9. 47 CFR 73.201 - Numerical designation of FM broadcast channels.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 47 Telecommunication 4 2013-10-01 2013-10-01 false Numerical designation of FM broadcast channels... SERVICES RADIO BROADCAST SERVICES FM Broadcast Stations § 73.201 Numerical designation of FM broadcast... numerical designations which are shown in the table below: Frequency (Mc/s) Channel No. 88.1 201 88.3 202 88...

  10. Communication Channel Estimation and Waveform Design: Time Delay Estimation on Parallel, Flat Fading Channels

    DTIC Science & Technology

    2010-02-01

    channels, so the channel gain is known on each realization and used in a coherent matched filter; and (c) Rayleigh channels with noncoherent matched...gain is known on each realization and used in a coherent matched filter (channel model 1A); and (c) Rayleigh channels with noncoherent matched filters...filters, averaged over Rayleigh channel realizations (channel model 1A). (b) Noncoherent matched filters with Rayleigh fading (channel model 3). MSEs are

  11. Cardiac ion channels

    PubMed Central

    Priest, Birgit T; McDermott, Jeff S

    2015-01-01

    Ion channels are critical for all aspects of cardiac function, including rhythmicity and contractility. Consequently, ion channels are key targets for therapeutics aimed at cardiac pathophysiologies such as atrial fibrillation or angina. At the same time, off-target interactions of drugs with cardiac ion channels can be the cause of unwanted side effects. This manuscript aims to review the physiology and pharmacology of key cardiac ion channels. The intent is to highlight recent developments for therapeutic development, as well as elucidate potential mechanisms for drug-induced cardiac side effects, rather than present an in-depth review of each channel subtype. PMID:26556552

  12. Connecting and disconnecting nematic disclination lines in microfluidic channels.

    PubMed

    Agha, Hakam; Bahr, Christian

    2016-05-14

    Disclination lines in nematic liquid crystals can be used as "soft rails" for the transport of colloids or droplets through microfluidic channels [A. Sengupta, C. Bahr and S. Herminghaus, Soft Matter, 2013, 9, 7251]. In the present study we report on a method to connect and disconnect disclination lines in microfluidic channels using the interplay between anchoring, flow, and electric field. We show that the application of an electric field establishes a continuous disclination that spans across a channel region in which a disclination usually would not exist (because of different anchoring conditions), demonstrating an interruptible and reconnectable soft rail for colloidal transport.

  13. The Berlin oil channel for drag reduction research

    NASA Astrophysics Data System (ADS)

    Bechert, D. W.; Hoppe, G.; van der Hoeven, J. G. Th.; Makris, R.

    1992-03-01

    For drag reduction research an oil channel has been designed and built. It is also well suited for investigations on turbulent flow and in particular on the dynamics of the viscous sublayer near the wall. The thickness of the viscous sublayer ( y += 5) can be varied between 1 and 4 mm. Surfaces with longitudinal ribs (“riblets”), which are known to reduce drag, can have fairly large dimensions. The lateral spacing of the ribs can lie between 3 and 10 mm, as compared to about 0.5 mm spacing for conventional wind tunnels. It has been proved by appropriate tests that the oil channel data are completely equivalent to data from other facilities and with other mean flow geometries. However, the shear stress data from the new oil channel are much more accurate than previous data due to a novel differential shear force balance with an accuracy of ±0.2%. In addition to shear stress measurements, velocity fluctuation measurements can be carried out with hot wire or hot film probes. In order to calibrate these probes, a moving sled permits to emulate the flow velocities with the fluid in the channel at rest. A number of additional innovations contribute to the improvement of the measurements, such as, e.g., (i) novel adjustable turbulators to maintain equilibrium turbulence in the channel, (ii) a “bubble trap” to avoid bubbles in the channel at high flow velocities, (iii) a simple method for the precision calibration of manometers, and (iv) the elimination of (Coulomb) friction in ball bearings. This latter fairly general invention is used for the wheels of the calibration unit of the balance. The channel has a cross section of 25 × 85 cm and is 11 m long. It is filled with about 4.5 metric tons of baby oil (white paraffine oil), which is transparent and odorless like water. The kinematic viscosity of the oil is v = 1.2×10-5 m2/s, and the highest (average) velocity is 1.29 m/s. Thus, the Reynolds number range (calculated with the channel width, 0.25 m) lies between

  14. Interactive communication channel

    NASA Astrophysics Data System (ADS)

    Chan, R. H.; Mann, M. R.; Ciarrocchi, J. A.

    1985-10-01

    Discussed is an interactive communications channel (ICC) for providing a digital computer with high-performance multi-channel interfaces. Sixteen full duplex channels can be serviced in the ICC with the sequence or scan pattern being programmable and dependent upon the number or channels and their speed. A channel buffer system is used for line interface, and character exchange. The channel buffer system is on a byte basis. The ICC performs frame start and frame end functions, bit stripping and bit stuffing. Data is stored in a memory in block format (256 bytes maximum) by a program control and the ICC maintains byte address information and a block byte count. Data exchange with a memory is made by cycle steals. Error detection is also provided for using a cyclic redundancy check technique.

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

    PubMed Central

    Oiki, Shigetoshi

    2015-01-01

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

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

    PubMed

    Oiki, Shigetoshi

    2015-06-15

    The most essential properties of ion channels for their physiologically relevant functions are ion-selective permeation and gating. Among the channel species, the potassium channel is primordial and the most ubiquitous in the biological world, and knowledge of this channel underlies the understanding of features of other ion channels. The strategy applied to studying channels changed dramatically after the crystal structure of the potassium channel was resolved. Given the abundant structural information available, we exploited the bacterial KcsA potassium channel as a simple model channel. In the postcrystal age, there are two effective frameworks with which to decipher the functional codes present in the channel structure, namely reconstitution and re-animation. Complex channel proteins are decomposed into essential functional components, and well-examined parts are rebuilt for integrating channel function in the membrane (reconstitution). Permeation and gating are dynamic operations, and one imagines the active channel by breathing life into the 'frozen' crystal (re-animation). Capturing the motion of channels at the single-molecule level is necessary to characterize the behaviour of functioning channels. Advanced techniques, including diffracted X-ray tracking, lipid bilayer methods and high-speed atomic force microscopy, have been used. Here, I present dynamic pictures of the KcsA potassium channel from the submolecular conformational changes to the supramolecular collective behaviour of channels in the membrane. These results form an integrated picture of the active channel and offer insights into the processes underlying the physiological function of the channel in the cell membrane. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

  17. Microphase separation and the formation of ion conductivity channels in poly(ionic liquid)s: A coarse-grained molecular dynamics study

    NASA Astrophysics Data System (ADS)

    Weyman, Alexander; Bier, Markus; Holm, Christian; Smiatek, Jens

    2018-05-01

    We study generic properties of poly(ionic liquid)s (PILs) via coarse-grained molecular dynamics simulations in bulk solution and under confinement. The influence of different side chain lengths on the spatial properties of the PIL systems and on the ionic transport mechanism is investigated in detail. Our results reveal the formation of apolar and polar nanodomains with increasing side chain length in good agreement with previous results for molecular ionic liquids. The ion transport numbers are unaffected by the occurrence of these domains, and the corresponding values highlight the potential role of PILs as single-ion conductors in electrochemical devices. In contrast to bulk behavior, a pronounced formation of ion conductivity channels in confined systems is initiated in close vicinity to the boundaries. We observe higher ion conductivities in these channels for increasing PIL side chain lengths in comparison with bulk values and provide an explanation for this effect. The appearance of these domains points to an improved application of PILs in modern polymer electrolyte batteries.

  18. The dynamics of a channel-fed lava flow on Pico Partido volcano, Lanzarote

    NASA Astrophysics Data System (ADS)

    Woodcock, Duncan; Harris, Andrew

    2006-09-01

    A short length of channel on Pico Partido volcano, Lanzarote, provides us the opportunity to examine the dynamics of lava flowing in a channel that extends over a sudden break in slope. The 1 2-m-wide, 0.5 2-m-deep channel was built during the 1730 1736 eruptions on Lanzarote and exhibits a sinuous, well-formed channel over a steep (11° slope) 100-m-long proximal section. Over-flow units comprising smooth pahoehoe sheet flow, as well as evidence on the inner channel walls for multiple (at least 11) flow levels, attest to unsteady flow in the channel. In addition, superelevation is apparent at each of the six bends along the proximal channel section. Superelevation results from banking of the lava as it moves around the bend thus causing preferential construction of the outer bank. As a result, the channel profile at each bend is asymmetric with an outer bank that is higher than the inner bank. Analysis of superelevation indicates flow velocities of ~8 m s 1. Our analysis of the superelevation features is based on an inertia-gravity balance, which we show is appropriate, even though the down-channel flow is in laminar flow. We use a viscosity-gravity balance model, together with the velocities calculated from superelevation, to obtain viscosities in the range 25 60 Pa s (assuming that the lava behaved as a Newtonian liquid). Estimated volume fluxes are in the range 7 12 m3 s 1. An apparent down-flow increase in derived volume flux may have resulted from variable supply or bulking up of the flow due to vesiculation. Where the channel moves over a sharp break in slope and onto slopes of ~6°, the channel becomes less well defined and widens considerably. At the break of slope, an elongate ridge extends across the channel. We speculate that this ridge was formed as a result of a reduction in velocity immediately below the break of slope to allow deposition of entrained material or accretion of lava to the channel bed as a result of a change in flow regime or depth.

  19. Microfluidic channel fabrication method

    DOEpatents

    Arnold, Don W.; Schoeniger, Joseph S.; Cardinale, Gregory F.

    2001-01-01

    A new channel structure for microfluidic systems and process for fabricating this structure. In contrast to the conventional practice of fabricating fluid channels as trenches or grooves in a substrate, fluid channels are fabricated as thin walled raised structures on a substrate. Microfluidic devices produced in accordance with the invention are a hybrid assembly generally consisting of three layers: 1) a substrate that can or cannot be an electrical insulator; 2) a middle layer, that is an electrically conducting material and preferably silicon, forms the channel walls whose height defines the channel height, joined to and extending from the substrate; and 3) a top layer, joined to the top of the channels, that forms a cover for the channels. The channels can be defined by photolithographic techniques and are produced by etching away the material around the channel walls.

  20. Inactivation of Gating Currents of L-Type Calcium Channels

    PubMed Central

    Shirokov, Roman; Ferreira, Gonzalo; Yi, Jianxun; Ríos, Eduardo

    1998-01-01

    In studies of gating currents of rabbit cardiac Ca channels expressed as α1C/β2a or α1C/β2a/α2δ subunit combinations in tsA201 cells, we found that long-lasting depolarization shifted the distribution of mobile charge to very negative potentials. The phenomenon has been termed charge interconversion in native skeletal muscle (Brum, G., and E. Ríos. 1987. J. Physiol. (Camb.). 387:489–517) and cardiac Ca channels (Shirokov, R., R. Levis, N. Shirokova, and E. Ríos. 1992. J. Gen. Physiol. 99:863–895). Charge 1 (voltage of half-maximal transfer, V1/2 ≃ 0 mV) gates noninactivated channels, while charge 2 (V1/2 ≃ −90 mV) is generated in inactivated channels. In α1C/β2a cells, the available charge 1 decreased upon inactivating depolarization with a time constant τ ≃ 8, while the available charge 2 decreased upon recovery from inactivation (at −200 mV) with τ ≃ 0.3 s. These processes therefore are much slower than charge movement, which takes <50 ms. This separation between the time scale of measurable charge movement and that of changes in their availability, which was even wider in the presence of α2δ, implies that charges 1 and 2 originate from separate channel modes. Because clear modal separation characterizes slow (C-type) inactivation of Na and K channels, this observation establishes the nature of voltage-dependent inactivation of L-type Ca channels as slow or C-type. The presence of the α2δ subunit did not change the V1/2 of charge 2, but sped up the reduction of charge 1 upon inactivation at 40 mV (to τ ≃ 2 s), while slowing the reduction of charge 2 upon recovery (τ ≃ 2 s). The observations were well simulated with a model that describes activation as continuous electrodiffusion (Levitt, D. 1989. Biophys. J. 55:489–498) and inactivation as discrete modal change. The effects of α2δ are reproduced assuming that the subunit lowers the free energy of the inactivated mode. PMID:9607938

  1. Rational design and validation of a vanilloid-sensitive TRPV2 ion channel.

    PubMed

    Yang, Fan; Vu, Simon; Yarov-Yarovoy, Vladimir; Zheng, Jie

    2016-06-28

    Vanilloids activation of TRPV1 represents an excellent model system of ligand-gated ion channels. Recent studies using cryo-electron microcopy (cryo-EM), computational analysis, and functional quantification revealed the location of capsaicin-binding site and critical residues mediating ligand-binding and channel activation. Based on these new findings, here we have successfully introduced high-affinity binding of capsaicin and resiniferatoxin to the vanilloid-insensitive TRPV2 channel, using a rationally designed minimal set of four point mutations (F467S-S498F-L505T-Q525E, termed TRPV2_Quad). We found that binding of resiniferatoxin activates TRPV2_Quad but the ligand-induced open state is relatively unstable, whereas binding of capsaicin to TRPV2_Quad antagonizes resiniferatoxin-induced activation likely through competition for the same binding sites. Using Rosetta-based molecular docking, we observed a common structural mechanism underlying vanilloids activation of TRPV1 and TRPV2_Quad, where the ligand serves as molecular "glue" that bridges the S4-S5 linker to the S1-S4 domain to open these channels. Our analysis revealed that capsaicin failed to activate TRPV2_Quad likely due to structural constraints preventing such bridge formation. These results not only validate our current working model for capsaicin activation of TRPV1 but also should help guide the design of drug candidate compounds for this important pain sensor.

  2. A new pH-sensitive rectifying potassium channel in mitochondria from the embryonic rat hippocampus.

    PubMed

    Kajma, Anna; Szewczyk, Adam

    2012-10-01

    Patch-clamp single-channel studies on mitochondria isolated from embryonic rat hippocampus revealed the presence of two different potassium ion channels: a large-conductance (288±4pS) calcium-activated potassium channel and second potassium channel with outwardly rectifying activity under symmetric conditions (150/150mM KCl). At positive voltages, this channel displayed a conductance of 67.84pS and a strong voltage dependence at holding potentials from -80mV to +80mV. The open probability was higher at positive than at negative voltages. Patch-clamp studies at the mitoplast-attached mode showed that the channel was not sensitive to activators and inhibitors of mitochondrial potassium channels but was regulated by pH. Moreover, we demonstrated that the channel activity was not affected by the application of lidocaine, an inhibitor of two-pore domain potassium channels, or by tertiapin, an inhibitor of inwardly rectifying potassium channels. In summary, based on the single-channel recordings, we characterised for the first time mitochondrial pH-sensitive ion channel that is selective for cations, permeable to potassium ions, displays voltage sensitivity and does not correspond to any previously described potassium ion channels in the inner mitochondrial membrane. This article is part of a Special Issue entitled: 17th European Bioenergetics Conference (EBEC 2012). Copyright © 2012 Elsevier B.V. All rights reserved.

  3. Note: optical receiver system for 152-channel magnetoencephalography.

    PubMed

    Kim, Jin-Mok; Kwon, Hyukchan; Yu, Kwon-kyu; Lee, Yong-Ho; Kim, Kiwoong

    2014-11-01

    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.

  4. The Molecular Basis of Polyunsaturated Fatty Acid Interactions with the Shaker Voltage-Gated Potassium Channel

    PubMed Central

    Yazdi, Samira; Stein, Matthias; Elinder, Fredrik; Andersson, Magnus; Lindahl, Erik

    2016-01-01

    Voltage-gated potassium (KV) channels are membrane proteins that respond to changes in membrane potential by enabling K+ ion flux across the membrane. Polyunsaturated fatty acids (PUFAs) induce channel opening by modulating the voltage-sensitivity, which can provide effective treatment against refractory epilepsy by means of a ketogenic diet. While PUFAs have been reported to influence the gating mechanism by electrostatic interactions to the voltage-sensor domain (VSD), the exact PUFA-protein interactions are still elusive. In this study, we report on the interactions between the Shaker KV channel in open and closed states and a PUFA-enriched lipid bilayer using microsecond molecular dynamics simulations. We determined a putative PUFA binding site in the open state of the channel located at the protein-lipid interface in the vicinity of the extracellular halves of the S3 and S4 helices of the VSD. In particular, the lipophilic PUFA tail covered a wide range of non-specific hydrophobic interactions in the hydrophobic central core of the protein-lipid interface, while the carboxylic head group displayed more specific interactions to polar/charged residues at the extracellular regions of the S3 and S4 helices, encompassing the S3-S4 linker. Moreover, by studying the interactions between saturated fatty acids (SFA) and the Shaker KV channel, our study confirmed an increased conformational flexibility in the polyunsaturated carbon tails compared to saturated carbon chains, which may explain the specificity of PUFA action on channel proteins. PMID:26751683

  5. Indirect detection constraints on s- and t-channel simplified models of dark matter

    NASA Astrophysics Data System (ADS)

    Carpenter, Linda M.; Colburn, Russell; Goodman, Jessica; Linden, Tim

    2016-09-01

    Recent Fermi-LAT observations of dwarf spheroidal galaxies in the Milky Way have placed strong limits on the gamma-ray flux from dark matter annihilation. In order to produce the strongest limit on the dark matter annihilation cross section, the observations of each dwarf galaxy have typically been "stacked" in a joint-likelihood analysis, utilizing optical observations to constrain the dark matter density profile in each dwarf. These limits have typically been computed only for singular annihilation final states, such as b b ¯ or τ+τ- . In this paper, we generalize this approach by producing an independent joint-likelihood analysis to set constraints on models where the dark matter particle annihilates to multiple final-state fermions. We interpret these results in the context of the most popular simplified models, including those with s- and t-channel dark matter annihilation through scalar and vector mediators. We present our results as constraints on the minimum dark matter mass and the mediator sector parameters. Additionally, we compare our simplified model results to those of effective field theory contact interactions in the high-mass limit.

  6. Mechanosensitive cation channels in human leukaemia cells: calcium permeation and blocking effect

    PubMed Central

    Staruschenko, Alexandr V; Vedernikova, Elena A

    2002-01-01

    Cell-attached and inside-out patch-clamp methods were employed to identify and characterize mechanosensitive (MS) ionic channels in the plasma membrane of human myeloid leukaemia K562 cells. A reversible activation of gadolinium-blockable mechanogated currents in response to negative pressure application was found in 58 % of stable patches (n = 317). I-V relationships measured with a sodium-containing pipette solution showed slight inward rectification. Data analysis revealed the presence of two different populations of channels that were distinguishable by their conductance properties (17.2 ± 0.3 pS and 24.5 ± 0.5 pS), but were indistinguishable with regard to their selective and pharmacological properties. Ion-substitution experiments indicated that MS channels in leukaemia cells were permeable to cations but not to anions and do not discriminate between Na+ and K+. The channels were fully impermeable to large organic cations such as Tris+ and N-methyl-d-glucamine ions (NMDG+). Ca2+ permeation and blockade of MS channels were examined using pipettes containing different concentrations of Ca2+. In the presence of 2 mm CaCl2, when other cations were impermeant, both outward and inward single-channel currents were observed; the I-V relationship showed a unitary conductance of 7.7 ± 1.0 pS. The relative permeability value, PCa/PK, was equal to 0.75, as estimated at physiological Ca2+ concentrations. Partial or full inhibition of inward Ca2+ currents through MS channels was observed at higher concentrations of external Ca2+ (10 or 20 mm). No MS channels were activated when using a pipette containing 90 mm CaCl2. Monovalent mechanogated currents were not significantly affected by extracellular Ca2+ at concentrations within the physiological range (0-2 mm), and at some higher Ca2+ concentrations. PMID:12015421

  7. Hydrophobic interactions between the voltage sensor and pore mediate inactivation in Kv11.1 channels

    PubMed Central

    Perry, Matthew D.; Wong, Sophia; Ng, Chai Ann

    2013-01-01

    Kv11.1 channels are critical for the maintenance of a normal heart rhythm. The flow of potassium ions through these channels is controlled by two voltage-regulated gates, termed “activation” and “inactivation,” located at opposite ends of the pore. Crucially in Kv11.1 channels, inactivation gating occurs much more rapidly, and over a distinct range of voltages, compared with activation gating. Although it is clear that the fourth transmembrane segments (S4), within each subunit of the tetrameric channel, are important for controlling the opening and closing of the activation gate, their role during inactivation gating is much less clear. Here, we use rate equilibrium free energy relationship (REFER) analysis to probe the contribution of the S4 “voltage-sensor” helix during inactivation of Kv11.1 channels. Contrary to the important role that charged residues play during activation gating, it is the hydrophobic residues (Leu529, Leu530, Leu532, and Val535) that are the key molecular determinants of inactivation gating. Within the context of an interconnected multi-domain model of Kv11.1 inactivation gating, our REFER analysis indicates that the S4 helix and the S4–S5 linker undergo a conformational rearrangement shortly after that of the S5 helix and S5P linker, but before the S6 helix. Combining REFER analysis with double mutant cycle analysis, we provide evidence for a hydrophobic interaction between residues on the S4 and S5 helices. Based on a Kv11.1 channel homology model, we propose that this hydrophobic interaction forms the basis of an intersubunit coupling between the voltage sensor and pore domain that is an important mediator of inactivation gating. PMID:23980196

  8. ZnO-based multiple channel and multiple gate FinMOSFETs

    NASA Astrophysics Data System (ADS)

    Lee, Ching-Ting; Huang, Hung-Lin; Tseng, Chun-Yen; Lee, Hsin-Ying

    2016-02-01

    In recent years, zinc oxide (ZnO)-based metal-oxide-semiconductor field-effect transistors (MOSFETs) have attracted much attention, because ZnO-based semiconductors possess several advantages, including large exciton binding energy, nontoxicity, biocompatibility, low material cost, and wide direct bandgap. Moreover, the ZnO-based MOSFET is one of most potential devices, due to the applications in microwave power amplifiers, logic circuits, large scale integrated circuits, and logic swing. In this study, to enhance the performances of the ZnO-based MOSFETs, the ZnObased multiple channel and multiple gate structured FinMOSFETs were fabricated using the simple laser interference photolithography method and the self-aligned photolithography method. The multiple channel structure possessed the additional sidewall depletion width control ability to improve the channel controllability, because the multiple channel sidewall portions were surrounded by the gate electrode. Furthermore, the multiple gate structure had a shorter distance between source and gate and a shorter gate length between two gates to enhance the gate operating performances. Besides, the shorter distance between source and gate could enhance the electron velocity in the channel fin structure of the multiple gate structure. In this work, ninety one channels and four gates were used in the FinMOSFETs. Consequently, the drain-source saturation current (IDSS) and maximum transconductance (gm) of the ZnO-based multiple channel and multiple gate structured FinFETs operated at a drain-source voltage (VDS) of 10 V and a gate-source voltage (VGS) of 0 V were respectively improved from 11.5 mA/mm to 13.7 mA/mm and from 4.1 mS/mm to 6.9 mS/mm in comparison with that of the conventional ZnO-based single channel and single gate MOSFETs.

  9. 33 CFR 117.753 - Ship Channel, Great Egg Harbor Bay.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Ship Channel, Great Egg Harbor Bay. 117.753 Section 117.753 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND..., Great Egg Harbor Bay. The draw of the S52 (Ship Channel) bridge, mile 0.5 between Somers Point and Ocean...

  10. 33 CFR 117.753 - Ship Channel, Great Egg Harbor Bay.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 1 2011-07-01 2011-07-01 false Ship Channel, Great Egg Harbor Bay. 117.753 Section 117.753 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND..., Great Egg Harbor Bay. The draw of the S52 (Ship Channel) bridge, mile 0.5 between Somers Point and Ocean...

  11. An evolutionarily conserved gene family encodes proton-selective ion channels.

    PubMed

    Tu, Yu-Hsiang; Cooper, Alexander J; Teng, Bochuan; Chang, Rui B; Artiga, Daniel J; Turner, Heather N; Mulhall, Eric M; Ye, Wenlei; Smith, Andrew D; Liman, Emily R

    2018-03-02

    Ion channels form the basis for cellular electrical signaling. Despite the scores of genetically identified ion channels selective for other monatomic ions, only one type of proton-selective ion channel has been found in eukaryotic cells. By comparative transcriptome analysis of mouse taste receptor cells, we identified Otopetrin1 (OTOP1), a protein required for development of gravity-sensing otoconia in the vestibular system, as forming a proton-selective ion channel. We found that murine OTOP1 is enriched in acid-detecting taste receptor cells and is required for their zinc-sensitive proton conductance. Two related murine genes, Otop2 and Otop3 , and a Drosophila ortholog also encode proton channels. Evolutionary conservation of the gene family and its widespread tissue distribution suggest a broad role for proton channels in physiology and pathophysiology. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  12. BAD and KATP channels regulate neuron excitability and epileptiform activity

    PubMed Central

    Fernández-Agüera, María Carmen; Nathwani, Nidhi; Lahmann, Carolina; Burnham, Veronica L

    2018-01-01

    Brain metabolism can profoundly influence neuronal excitability. Mice with genetic deletion or alteration of Bad (BCL-2 agonist of cell death) exhibit altered brain-cell fuel metabolism, accompanied by resistance to acutely induced epileptic seizures; this seizure protection is mediated by ATP-sensitive potassium (KATP) channels. Here we investigated the effect of BAD manipulation on KATP channel activity and excitability in acute brain slices. We found that BAD’s influence on neuronal KATP channels was cell-autonomous and directly affected dentate granule neuron (DGN) excitability. To investigate the role of neuronal KATP channels in the anticonvulsant effects of BAD, we imaged calcium during picrotoxin-induced epileptiform activity in entorhinal-hippocampal slices. BAD knockout reduced epileptiform activity, and this effect was lost upon knockout or pharmacological inhibition of KATP channels. Targeted BAD knockout in DGNs alone was sufficient for the antiseizure effect in slices, consistent with a ‘dentate gate’ function that is reinforced by increased KATP channel activity. PMID:29368690

  13. Molecular dynamics of alamethicin transmembrane channels from open-channel current noise analysis.

    PubMed

    Mak, D O; Webb, W W

    1995-12-01

    Conductance noise measurement of the open states of alamethicin transmembrane channels reveals excess noise attributable to cooperative low-frequency molecular dynamics that can generate fluctuations approximately 1 A rms in the effective channel pore radius. Single-channel currents through both persistent and nonpersistent channels with multiple conductance states formed by purified polypeptide alamethicin in artificial phospholipid bilayers isolated onto micropipettes with gigaohm seals were recorded using a voltage-clamp technique with low background noise (rms noise < 3 pA up to 20 kHz). Current noise power spectra between 100 Hz and 20 kHz of each open channel state showed little frequency dependence. Noise from undetected conductance state transitions was insignificant. Johnson and shot noises were evaluated. Current noise caused by electrolyte concentration fluctuation via diffusion was isolated by its dependence on buffer concentration. After removing these contributions, significant current noise remains in all persistent channel states and increases in higher conductance states. In nonpersistent channels, remaining noise occurs primarily in the lowest two states. These fluctuations of channel conductance are attributed to thermal oscillations of the channel molecular conformation and are modeled as a Langevin translational oscillation of alamethicin molecules moving radially from the channel pore, damped mostly by lipid bilayer viscosity.

  14. Search for s channel single top quark production in pp collisions at √{s}=7 and 8 TeV

    NASA Astrophysics Data System (ADS)

    Khachatryan, V.; Sirunyan, A. M.; Tumasyan, A.; Adam, W.; Asilar, E.; Bergauer, T.; Brandstetter, J.; Brondolin, E.; Dragicevic, M.; Erö, J.; Flechl, M.; Friedl, M.; Frühwirth, R.; Ghete, V. M.; Hartl, C.; Hörmann, N.; Hrubec, J.; Jeitler, M.; Knünz, V.; König, A.; Krammer, M.; Krätschmer, I.; Liko, D.; Matsushita, T.; Mikulec, I.; Rabady, D.; Rad, N.; Rahbaran, B.; Rohringer, H.; Schieck, J.; Schöfbeck, R.; Strauss, J.; Treberer-Treberspurg, W.; Waltenberger, W.; Wulz, C.-E.; Mossolov, V.; Shumeiko, N.; Suarez Gonzalez, J.; Alderweireldt, S.; Cornelis, T.; de Wolf, E. A.; Janssen, X.; Knutsson, A.; Lauwers, J.; Luyckx, S.; van de Klundert, M.; van Haevermaet, H.; van Mechelen, P.; van Remortel, N.; van Spilbeeck, A.; Abu Zeid, S.; Blekman, F.; D'Hondt, J.; Daci, N.; de Bruyn, I.; Deroover, K.; Heracleous, N.; Keaveney, J.; Lowette, S.; Moreels, L.; Olbrechts, A.; Python, Q.; Strom, D.; Tavernier, S.; van Doninck, W.; van Mulders, P.; van Onsem, G. P.; van Parijs, I.; Barria, P.; Brun, H.; Caillol, C.; Clerbaux, B.; de Lentdecker, G.; Fang, W.; Fasanella, G.; Favart, L.; Goldouzian, R.; Grebenyuk, A.; Karapostoli, G.; Lenzi, T.; Léonard, A.; Maerschalk, T.; Marinov, A.; Perniè, L.; Randle-Conde, A.; Seva, T.; Vander Velde, C.; Vanlaer, P.; Yonamine, R.; Zenoni, F.; Zhang, F.; Beernaert, K.; Benucci, L.; Cimmino, A.; Crucy, S.; Dobur, D.; Fagot, A.; Garcia, G.; Gul, M.; McCartin, J.; Ocampo Rios, A. A.; Poyraz, D.; Ryckbosch, D.; Salva, S.; Sigamani, M.; Tytgat, M.; van Driessche, W.; Yazgan, E.; Zaganidis, N.; Basegmez, S.; Beluffi, C.; Bondu, O.; Brochet, S.; Bruno, G.; Caudron, A.; Ceard, L.; Delaere, C.; Favart, D.; Forthomme, L.; Giammanco, A.; Jafari, A.; Jez, P.; Komm, M.; Lemaitre, V.; Mertens, A.; Musich, M.; Nuttens, C.; Perrini, L.; Piotrzkowski, K.; Popov, A.; Quertenmont, L.; Selvaggi, M.; Vidal Marono, M.; Beliy, N.; Hammad, G. H.; Aldá Júnior, W. L.; Alves, F. L.; Alves, G. A.; Brito, L.; Correa Martins Junior, M.; Hamer, M.; Hensel, C.; Moraes, A.; Pol, M. E.; Rebello Teles, P.; Belchior Batista Das Chagas, E.; Carvalho, W.; Chinellato, J.; Custódio, A.; da Costa, E. M.; de Jesus Damiao, D.; de Oliveira Martins, C.; Fonseca de Souza, S.; Huertas Guativa, L. M.; Malbouisson, H.; Matos Figueiredo, D.; Mora Herrera, C.; Mundim, L.; Nogima, H.; Prado da Silva, W. L.; Santoro, A.; Sznajder, A.; Tonelli Manganote, E. J.; Vilela Pereira, A.; Ahuja, S.; Bernardes, C. A.; de Souza Santos, A.; Dogra, S.; Fernandez Perez Tomei, T. R.; Gregores, E. M.; Mercadante, P. G.; Moon, C. S.; Novaes, S. F.; Padula, Sandra S.; Romero Abad, D.; Ruiz Vargas, J. C.; Aleksandrov, A.; Hadjiiska, R.; Iaydjiev, P.; Rodozov, M.; Stoykova, S.; Sultanov, G.; Vutova, M.; Dimitrov, A.; Glushkov, I.; Litov, L.; Pavlov, B.; Petkov, P.; Ahmad, M.; Bian, J. G.; Chen, G. M.; Chen, H. S.; Chen, M.; Cheng, T.; Du, R.; Jiang, C. H.; Leggat, D.; Plestina, R.; Romeo, F.; Shaheen, S. M.; Spiezia, A.; Tao, J.; Wang, C.; Wang, Z.; Zhang, H.; Asawatangtrakuldee, C.; Ban, Y.; Li, Q.; Liu, S.; Mao, Y.; Qian, S. J.; Wang, D.; Xu, Z.; Avila, C.; Cabrera, A.; Chaparro Sierra, L. F.; Florez, C.; Gomez, J. P.; Gomez Moreno, B.; Sanabria, J. C.; Godinovic, N.; Lelas, D.; Puljak, I.; Ribeiro Cipriano, P. M.; Antunovic, Z.; Kovac, M.; Brigljevic, V.; Kadija, K.; Luetic, J.; Micanovic, S.; Sudic, L.; Attikis, A.; Mavromanolakis, G.; Mousa, J.; Nicolaou, C.; Ptochos, F.; Razis, P. A.; Rykaczewski, H.; Bodlak, M.; Finger, M.; Finger, M.; El-Khateeb, E.; Elkafrawy, T.; Mohamed, A.; Salama, E.; Calpas, B.; Kadastik, M.; Murumaa, M.; Raidal, M.; Tiko, A.; Veelken, C.; Eerola, P.; Pekkanen, J.; Voutilainen, M.; Härkönen, J.; Karimäki, V.; Kinnunen, R.; Lampén, T.; Lassila-Perini, K.; Lehti, S.; Lindén, T.; Luukka, P.; Peltola, T.; Tuominiemi, J.; Tuovinen, E.; Wendland, L.; Talvitie, J.; Tuuva, T.; Besancon, M.; Couderc, F.; Dejardin, M.; Denegri, D.; Fabbro, B.; Faure, J. L.; Favaro, C.; Ferri, F.; Ganjour, S.; Givernaud, A.; Gras, P.; Hamel de Monchenault, G.; Jarry, P.; Locci, E.; Machet, M.; Malcles, J.; Rander, J.; Rosowsky, A.; Titov, M.; Zghiche, A.; Abdulsalam, A.; Antropov, I.; Baffioni, S.; Beaudette, F.; Busson, P.; Cadamuro, L.; Chapon, E.; Charlot, C.; Davignon, O.; Filipovic, N.; Granier de Cassagnac, R.; Jo, M.; Lisniak, S.; Mastrolorenzo, L.; Miné, P.; Naranjo, I. N.; Nguyen, M.; Ochando, C.; Ortona, G.; Paganini, P.; Pigard, P.; Regnard, S.; Salerno, R.; Sauvan, J. B.; Sirois, Y.; Strebler, T.; Yilmaz, Y.; Zabi, A.; Agram, J.-L.; Andrea, J.; Aubin, A.; Bloch, D.; Brom, J.-M.; Buttignol, M.; Chabert, E. C.; Chanon, N.; Collard, C.; Conte, E.; Coubez, X.; Fontaine, J.-C.; Gelé, D.; Goerlach, U.; Goetzmann, C.; Le Bihan, A.-C.; Merlin, J. A.; Skovpen, K.; van Hove, P.; Gadrat, S.; Beauceron, S.; Bernet, C.; Boudoul, G.; Bouvier, E.; Carrillo Montoya, C. A.; Chierici, R.; Contardo, D.; Courbon, B.; Depasse, P.; El Mamouni, H.; Fan, J.; Fay, J.; Gascon, S.; Gouzevitch, M.; Ille, B.; Lagarde, F.; Laktineh, I. B.; Lethuillier, M.; Mirabito, L.; Pequegnot, A. L.; Perries, S.; Ruiz Alvarez, J. D.; Sabes, D.; Sgandurra, L.; Sordini, V.; Vander Donckt, M.; Verdier, P.; Viret, S.; Toriashvili, T.; Tsamalaidze, Z.; Autermann, C.; Beranek, S.; Feld, L.; Heister, A.; Kiesel, M. K.; Klein, K.; Lipinski, M.; Ostapchuk, A.; Preuten, M.; Raupach, F.; Schael, S.; Schulte, J. F.; Verlage, T.; Weber, H.; Zhukov, V.; Ata, M.; Brodski, M.; Dietz-Laursonn, E.; Duchardt, D.; Endres, M.; Erdmann, M.; Erdweg, S.; Esch, T.; Fischer, R.; Güth, A.; Hebbeker, T.; Heidemann, C.; Hoepfner, K.; Knutzen, S.; Kreuzer, P.; Merschmeyer, M.; Meyer, A.; Millet, P.; Mukherjee, S.; Olschewski, M.; Padeken, K.; Papacz, P.; Pook, T.; Radziej, M.; Reithler, H.; Rieger, M.; Scheuch, F.; Sonnenschein, L.; Teyssier, D.; Thüer, S.; Cherepanov, V.; Erdogan, Y.; Flügge, G.; Geenen, H.; Geisler, M.; Hoehle, F.; Kargoll, B.; Kress, T.; Künsken, A.; Lingemann, J.; Nehrkorn, A.; Nowack, A.; Nugent, I. M.; Pistone, C.; Pooth, O.; Stahl, A.; Aldaya Martin, M.; Asin, I.; Bartosik, N.; Behnke, O.; Behrens, U.; Borras, K.; Burgmeier, A.; Campbell, A.; Contreras-Campana, C.; Costanza, F.; Diez Pardos, C.; Dolinska, G.; Dooling, S.; Dorland, T.; Eckerlin, G.; Eckstein, D.; Eichhorn, T.; Flucke, G.; Gallo, E.; Garay Garcia, J.; Geiser, A.; Gizhko, A.; Gunnellini, P.; Hauk, J.; Hempel, M.; Jung, H.; Kalogeropoulos, A.; Karacheban, O.; Kasemann, M.; Katsas, P.; Kieseler, J.; Kleinwort, C.; Korol, I.; Lange, W.; Leonard, J.; Lipka, K.; Lobanov, A.; Lohmann, W.; Mankel, R.; Melzer-Pellmann, I.-A.; Meyer, A. B.; Mittag, G.; Mnich, J.; Mussgiller, A.; Naumann-Emme, S.; Nayak, A.; Ntomari, E.; Perrey, H.; Pitzl, D.; Placakyte, R.; Raspereza, A.; Roland, B.; Sahin, M. Ö.; Saxena, P.; Schoerner-Sadenius, T.; Seitz, C.; Spannagel, S.; Stefaniuk, N.; Trippkewitz, K. D.; Walsh, R.; Wissing, C.; Blobel, V.; Centis Vignali, M.; Draeger, A. R.; Erfle, J.; Garutti, E.; Goebel, K.; Gonzalez, D.; Görner, M.; Haller, J.; Hoffmann, M.; Höing, R. S.; Junkes, A.; Klanner, R.; Kogler, R.; Kovalchuk, N.; Lapsien, T.; Lenz, T.; Marchesini, I.; Marconi, D.; Meyer, M.; Nowatschin, D.; Ott, J.; Pantaleo, F.; Peiffer, T.; Perieanu, A.; Pietsch, N.; Poehlsen, J.; Rathjens, D.; Sander, C.; Scharf, C.; Schleper, P.; Schlieckau, E.; Schmidt, A.; Schumann, S.; Schwandt, J.; Sola, V.; Stadie, H.; Steinbrück, G.; Stober, F. M.; Tholen, H.; Troendle, D.; Usai, E.; Vanelderen, L.; Vanhoefer, A.; Vormwald, B.; Barth, C.; Baus, C.; Berger, J.; Böser, C.; Butz, E.; Chwalek, T.; Colombo, F.; de Boer, W.; Descroix, A.; Dierlamm, A.; Fink, S.; Frensch, F.; Friese, R.; Giffels, M.; Gilbert, A.; Haitz, D.; Hartmann, F.; Heindl, S. M.; Husemann, U.; Katkov, I.; Kornmayer, A.; Lobelle Pardo, P.; Maier, B.; Mildner, H.; Mozer, M. U.; Müller, T.; Müller, Th.; Plagge, M.; Quast, G.; Rabbertz, K.; Röcker, S.; Roscher, F.; Schröder, M.; Sieber, G.; Simonis, H. J.; Ulrich, R.; Wagner-Kuhr, J.; Wayand, S.; Weber, M.; Weiler, T.; Williamson, S.; Wöhrmann, C.; Wolf, R.; Anagnostou, G.; Daskalakis, G.; Geralis, T.; Giakoumopoulou, V. A.; Kyriakis, A.; Loukas, D.; Psallidas, A.; Topsis-Giotis, I.; Agapitos, A.; Kesisoglou, S.; Panagiotou, A.; Saoulidou, N.; Tziaferi, E.; Evangelou, I.; Flouris, G.; Foudas, C.; Kokkas, P.; Loukas, N.; Manthos, N.; Papadopoulos, I.; Paradas, E.; Strologas, J.; Bencze, G.; Hajdu, C.; Hazi, A.; Hidas, P.; Horvath, D.; Sikler, F.; Veszpremi, V.; Vesztergombi, G.; Zsigmond, A. J.; Beni, N.; Czellar, S.; Karancsi, J.; Molnar, J.; Szillasi, Z.; Bartók, M.; Makovec, A.; Raics, P.; Trocsanyi, Z. L.; Ujvari, B.; Choudhury, S.; Mal, P.; Mandal, K.; Sahoo, D. K.; Sahoo, N.; Swain, S. K.; Bansal, S.; Beri, S. B.; Bhatnagar, V.; Chawla, R.; Gupta, R.; Bhawandeep, U.; Kalsi, A. K.; Kaur, A.; Kaur, M.; Kumar, R.; Mehta, A.; Mittal, M.; Singh, J. B.; Walia, G.; Kumar, Ashok; Bhardwaj, A.; Choudhary, B. C.; Garg, R. B.; Malhotra, S.; Naimuddin, M.; Nishu, N.; Ranjan, K.; Sharma, R.; Sharma, V.; Bhattacharya, S.; Chatterjee, K.; Dey, S.; Dutta, S.; Majumdar, N.; Modak, A.; Mondal, K.; Mukhopadhyay, S.; Roy, A.; Roy, D.; Roy Chowdhury, S.; Sarkar, S.; Sharan, M.; Chudasama, R.; Dutta, D.; Jha, V.; Kumar, V.; Mohanty, A. K.; Pant, L. M.; Shukla, P.; Topkar, A.; Aziz, T.; Banerjee, S.; Bhowmik, S.; Chatterjee, R. M.; Dewanjee, R. K.; Dugad, S.; Ganguly, S.; Ghosh, S.; Guchait, M.; Gurtu, A.; Jain, Sa.; Kole, G.; Kumar, S.; Mahakud, B.; Maity, M.; Majumder, G.; Mazumdar, K.; Mitra, S.; Mohanty, G. B.; Parida, B.; Sarkar, T.; Sur, N.; Sutar, B.; Wickramage, N.; Chauhan, S.; Dube, S.; Kapoor, A.; Kothekar, K.; Sharma, S.; Bakhshiansohi, H.; Behnamian, H.; Etesami, S. M.; Fahim, A.; Khakzad, M.; Mohammadi Najafabadi, M.; Naseri, M.; Paktinat Mehdiabadi, S.; Rezaei Hosseinabadi, F.; Safarzadeh, B.; Zeinali, M.; Felcini, M.; Grunewald, M.; Abbrescia, M.; Calabria, C.; Caputo, C.; Colaleo, A.; Creanza, D.; Cristella, L.; de Filippis, N.; de Palma, M.; Fiore, L.; Iaselli, G.; Maggi, G.; Maggi, M.; Miniello, G.; My, S.; Nuzzo, S.; Pompili, A.; Pugliese, G.; Radogna, R.; Ranieri, A.; Selvaggi, G.; Silvestris, L.; Venditti, R.; Abbiendi, G.; Battilana, C.; Bonacorsi, D.; Braibant-Giacomelli, S.; Brigliadori, L.; Campanini, R.; Capiluppi, P.; Castro, A.; Cavallo, F. R.; Chhibra, S. S.; Codispoti, G.; Cuffiani, M.; Dallavalle, G. M.; Fabbri, F.; Fanfani, A.; Fasanella, D.; Giacomelli, P.; Grandi, C.; Guiducci, L.; Marcellini, S.; Masetti, G.; Montanari, A.; Navarria, F. L.; Perrotta, A.; Rossi, A. M.; Rovelli, T.; Siroli, G. 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M.; Lanza, G.; Lista, L.; Meola, S.; Merola, M.; Paolucci, P.; Sciacca, C.; Thyssen, F.; Tramontano, F.; Azzi, P.; Bacchetta, N.; Benato, L.; Bisello, D.; Boletti, A.; Branca, A.; Carlin, R.; Checchia, P.; Dall'Osso, M.; Dorigo, T.; Dosselli, U.; Gasparini, F.; Gasparini, U.; Gozzelino, A.; Kanishchev, K.; Lacaprara, S.; Margoni, M.; Meneguzzo, A. T.; Passaseo, M.; Pazzini, J.; Pozzobon, N.; Ronchese, P.; Simonetto, F.; Torassa, E.; Tosi, M.; Zanetti, M.; Zotto, P.; Zucchetta, A.; Zumerle, G.; Braghieri, A.; Magnani, A.; Montagna, P.; Ratti, S. P.; Re, V.; Riccardi, C.; Salvini, P.; Vai, I.; Vitulo, P.; Alunni Solestizi, L.; Bilei, G. M.; Ciangottini, D.; Fanò, L.; Lariccia, P.; Mantovani, G.; Menichelli, M.; Saha, A.; Santocchia, A.; Androsov, K.; Azzurri, P.; Bagliesi, G.; Bernardini, J.; Boccali, T.; Castaldi, R.; Ciocci, M. A.; Dell'Orso, R.; Donato, S.; Fedi, G.; Foà, L.; Giassi, A.; Grippo, M. 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F.; Khatiwada, A.; Prosper, H.; Weinberg, M.; Baarmand, M. M.; Bhopatkar, V.; Colafranceschi, S.; Hohlmann, M.; Kalakhety, H.; Noonan, D.; Roy, T.; Yumiceva, F.; Adams, M. R.; Apanasevich, L.; Berry, D.; Betts, R. R.; Bucinskaite, I.; Cavanaugh, R.; Evdokimov, O.; Gauthier, L.; Gerber, C. E.; Hofman, D. J.; Kurt, P.; O'Brien, C.; Sandoval Gonzalez, I. D.; Turner, P.; Varelas, N.; Wu, Z.; Zakaria, M.; Zhang, J.; Bilki, B.; Clarida, W.; Dilsiz, K.; Durgut, S.; Gandrajula, R. P.; Haytmyradov, M.; Khristenko, V.; Merlo, J.-P.; Mermerkaya, H.; Mestvirishvili, A.; Moeller, A.; Nachtman, J.; Ogul, H.; Onel, Y.; Ozok, F.; Penzo, A.; Snyder, C.; Tiras, E.; Wetzel, J.; Yi, K.; Anderson, I.; Barnett, B. A.; Blumenfeld, B.; Cocoros, A.; Eminizer, N.; Fehling, D.; Feng, L.; Gritsan, A. V.; Maksimovic, P.; Osherson, M.; Roskes, J.; Sarica, U.; Swartz, M.; Xiao, M.; Xin, Y.; You, C.; Baringer, P.; Bean, A.; Bruner, C.; Kenny, R. P.; Majumder, D.; Malek, M.; McBrayer, W.; Murray, M.; Sanders, S.; Stringer, R.; Wang, Q.; Ivanov, A.; Kaadze, K.; Khalil, S.; Makouski, M.; Maravin, Y.; Mohammadi, A.; Saini, L. K.; Skhirtladze, N.; Toda, S.; Lange, D.; Rebassoo, F.; Wright, D.; Anelli, C.; Baden, A.; Baron, O.; Belloni, A.; Calvert, B.; Eno, S. C.; Ferraioli, C.; Gomez, J. A.; Hadley, N. J.; Jabeen, S.; Kellogg, R. G.; Kolberg, T.; Kunkle, J.; Lu, Y.; Mignerey, A. C.; Shin, Y. H.; Skuja, A.; Tonjes, M. B.; Tonwar, S. C.; Apyan, A.; Barbieri, R.; Baty, A.; Bi, R.; Bierwagen, K.; Brandt, S.; Busza, W.; Cali, I. A.; Demiragli, Z.; Di Matteo, L.; Gomez Ceballos, G.; Goncharov, M.; Gulhan, D.; Iiyama, Y.; Innocenti, G. M.; Klute, M.; Kovalskyi, D.; Lai, Y. S.; Lee, Y.-J.; Levin, A.; Luckey, P. D.; Marini, A. C.; McGinn, C.; Mironov, C.; Narayanan, S.; Niu, X.; Paus, C.; Roland, C.; Roland, G.; Salfeld-Nebgen, J.; Stephans, G. S. F.; Sumorok, K.; Tatar, K.; Varma, M.; Velicanu, D.; Veverka, J.; Wang, J.; Wang, T. W.; Wyslouch, B.; Yang, M.; Zhukova, V.; Benvenuti, A. C.; Dahmes, B.; Evans, A.; Finkel, A.; Gude, A.; Hansen, P.; Kalafut, S.; Kao, S. C.; Klapoetke, K.; Kubota, Y.; Lesko, Z.; Mans, J.; Nourbakhsh, S.; Ruckstuhl, N.; Rusack, R.; Tambe, N.; Turkewitz, J.; Acosta, J. G.; Oliveros, S.; Avdeeva, E.; Bartek, R.; Bloom, K.; Bose, S.; Claes, D. R.; Dominguez, A.; Fangmeier, C.; Gonzalez Suarez, R.; Kamalieddin, R.; Knowlton, D.; Kravchenko, I.; Meier, F.; Monroy, J.; Ratnikov, F.; Siado, J. E.; Snow, G. R.; Alyari, M.; Dolen, J.; George, J.; Godshalk, A.; Harrington, C.; Iashvili, I.; Kaisen, J.; Kharchilava, A.; Kumar, A.; Rappoccio, S.; Roozbahani, B.; Alverson, G.; Barberis, E.; Baumgartel, D.; Chasco, M.; Hortiangtham, A.; Massironi, A.; Morse, D. M.; Nash, D.; Orimoto, T.; Teixeira de Lima, R.; Trocino, D.; Wang, R.-J.; Wood, D.; Zhang, J.; Bhattacharya, S.; Hahn, K. A.; Kubik, A.; Low, J. F.; Mucia, N.; Odell, N.; Pollack, B.; Schmitt, M.; Sung, K.; Trovato, M.; Velasco, M.; Dev, N.; Hildreth, M.; Jessop, C.; Karmgard, D. J.; Kellams, N.; Lannon, K.; Marinelli, N.; Meng, F.; Mueller, C.; Musienko, Y.; Planer, M.; Reinsvold, A.; Ruchti, R.; Smith, G.; Taroni, S.; Valls, N.; Wayne, M.; Wolf, M.; Woodard, A.; Antonelli, L.; Brinson, J.; Bylsma, B.; Durkin, L. S.; Flowers, S.; Hart, A.; Hill, C.; Hughes, R.; Ji, W.; Ling, T. Y.; Liu, B.; Luo, W.; Puigh, D.; Rodenburg, M.; Winer, B. L.; Wulsin, H. W.; Driga, O.; Elmer, P.; Hardenbrook, J.; Hebda, P.; Koay, S. A.; Lujan, P.; Marlow, D.; Medvedeva, T.; Mooney, M.; Olsen, J.; Palmer, C.; Piroué, P.; Stickland, D.; Tully, C.; Zuranski, A.; Malik, S.; Barker, A.; Barnes, V. E.; Benedetti, D.; Bortoletto, D.; Gutay, L.; Jha, M. K.; Jones, M.; Jung, A. W.; Jung, K.; Kumar, A.; Miller, D. H.; Neumeister, N.; Radburn-Smith, B. C.; Shi, X.; Shipsey, I.; Silvers, D.; Sun, J.; Svyatkovskiy, A.; Wang, F.; Xie, W.; Xu, L.; Parashar, N.; Stupak, J.; Adair, A.; Akgun, B.; Chen, Z.; Ecklund, K. M.; Geurts, F. J. M.; Guilbaud, M.; Li, W.; Michlin, B.; Northup, M.; Padley, B. P.; Redjimi, R.; Roberts, J.; Rorie, J.; Tu, Z.; Zabel, J.; Betchart, B.; Bodek, A.; de Barbaro, P.; Demina, R.; Eshaq, Y.; Ferbel, T.; Galanti, M.; Garcia-Bellido, A.; Han, J.; Hindrichs, O.; Khukhunaishvili, A.; Lo, K. H.; Tan, P.; Verzetti, M.; Chou, J. P.; Contreras-Campana, E.; Ferencek, D.; Gershtein, Y.; Halkiadakis, E.; Heindl, M.; Hidas, D.; Hughes, E.; Kaplan, S.; Kunnawalkam Elayavalli, R.; Lath, A.; Nash, K.; Saka, H.; Salur, S.; Schnetzer, S.; Sheffield, D.; Somalwar, S.; Stone, R.; Thomas, S.; Thomassen, P.; Walker, M.; Foerster, M.; Riley, G.; Rose, K.; Spanier, S.; Thapa, K.; Bouhali, O.; Castaneda Hernandez, A.; Celik, A.; Dalchenko, M.; de Mattia, M.; Delgado, A.; Dildick, S.; Eusebi, R.; Gilmore, J.; Huang, T.; Kamon, T.; Krutelyov, V.; Mueller, R.; Osipenkov, I.; Pakhotin, Y.; Patel, R.; Perloff, A.; Rose, A.; Safonov, A.; Tatarinov, A.; Ulmer, K. A.; Akchurin, N.; Cowden, C.; Damgov, J.; Dragoiu, C.; Dudero, P. R.; Faulkner, J.; Kunori, S.; Lamichhane, K.; Lee, S. W.; Libeiro, T.; Undleeb, S.; Volobouev, I.; Appelt, E.; Delannoy, A. G.; Greene, S.; Gurrola, A.; Janjam, R.; Johns, W.; Maguire, C.; Mao, Y.; Melo, A.; Ni, H.; Sheldon, P.; Tuo, S.; Velkovska, J.; Xu, Q.; Arenton, M. W.; Cox, B.; Francis, B.; Goodell, J.; Hirosky, R.; Ledovskoy, A.; Li, H.; Lin, C.; Neu, C.; Sinthuprasith, T.; Sun, X.; Wang, Y.; Wolfe, E.; Wood, J.; Xia, F.; Clarke, C.; Harr, R.; Karchin, P. E.; Kottachchi Kankanamge Don, C.; Lamichhane, P.; Sturdy, J.; Belknap, D. A.; Carlsmith, D.; Cepeda, M.; Dasu, S.; Dodd, L.; Duric, S.; Gomber, B.; Grothe, M.; Herndon, M.; Hervé, A.; Klabbers, P.; Lanaro, A.; Levine, A.; Long, K.; Loveless, R.; Mohapatra, A.; Ojalvo, I.; Perry, T.; Pierro, G. A.; Polese, G.; Ruggles, T.; Sarangi, T.; Savin, A.; Sharma, A.; Smith, N.; Smith, W. H.; Taylor, D.; Verwilligen, P.; Woods, N.

    2016-09-01

    A search is presented for single top quark production in the s channel in proton-proton collisions with the CMS detector at the CERN LHC in decay modes of the top quark containing a muon or an electron in the final state. The signal is extracted through a maximum-likelihood fit to the distribution of a multivariate discriminant defined using boosted decision trees to separate the expected signal contribution from background processes. The analysis uses data collected at centre-of-mass energies of 7 and 8 TeV and corresponding to integrated luminosities of 5.1 and 19.7 fb-1, respectively. The measured cross sections of 7.1 ± 8.1 pb (at 7 TeV) and 13.4 ± 7.3 pb (at 8 TeV) result in a best fit value of 2.0 ± 0.9 for the combined ratio of the measured and expected values. The signal significance is 2.5 standard deviations, and the upper limit on the rate relative to the standard model expectation is 4.7 at 95% confidence level. [Figure not available: see fulltext.

  15. A human intermediate conductance calcium-activated potassium channel

    PubMed Central

    Ishii, Takahiro M.; Silvia, Christopher; Hirschberg, Birgit; Bond, Chris T.; Adelman, John P.; Maylie, James

    1997-01-01

    An intermediate conductance calcium-activated potassium channel, hIK1, was cloned from human pancreas. The predicted amino acid sequence is related to, but distinct from, the small conductance calcium-activated potassium channel subfamily, which is ≈50% conserved. hIK1 mRNA was detected in peripheral tissues but not in brain. Expression of hIK1 in Xenopus oocytes gave rise to inwardly rectifying potassium currents, which were activated by submicromolar concentrations of intracellular calcium (K0.5 = 0.3 μM). Although the K0.5 for calcium was similar to that of small conductance calcium-activated potassium channels, the slope factor derived from the Hill equation was significantly reduced (1.7 vs. 3.5). Single-channel current amplitudes reflected the macroscopic inward rectification and revealed a conductance level of 39 pS in the inward direction. hIK1 currents were reversibly blocked by charybdotoxin (Ki = 2.5 nM) and clotrimazole (Ki = 24.8 nM) but were minimally affected by apamin (100 nM), iberiotoxin (50 nM), or ketoconazole (10 μM). These biophysical and pharmacological properties are consistent with native intermediate conductance calcium-activated potassium channels, including the erythrocyte Gardos channel. PMID:9326665

  16. Spectrally Shaped DP-16QAM Super-Channel Transmission with Multi-Channel Digital Back-Propagation

    PubMed Central

    Maher, Robert; Xu, Tianhua; Galdino, Lidia; Sato, Masaki; Alvarado, Alex; Shi, Kai; Savory, Seb J.; Thomsen, Benn C.; Killey, Robert I.; Bayvel, Polina

    2015-01-01

    The achievable transmission capacity of conventional optical fibre communication systems is limited by nonlinear distortions due to the Kerr effect and the difficulty in modulating the optical field to effectively use the available fibre bandwidth. In order to achieve a high information spectral density (ISD), while simultaneously maintaining transmission reach, multi-channel fibre nonlinearity compensation and spectrally efficient data encoding must be utilised. In this work, we use a single coherent super-receiver to simultaneously receive a DP-16QAM super-channel, consisting of seven spectrally shaped 10GBd sub-carriers spaced at the Nyquist frequency. Effective nonlinearity mitigation is achieved using multi-channel digital back-propagation (MC-DBP) and this technique is combined with an optimised forward error correction implementation to demonstrate a record gain in transmission reach of 85%; increasing the maximum transmission distance from 3190 km to 5890 km, with an ISD of 6.60 b/s/Hz. In addition, this report outlines for the first time, the sensitivity of MC-DBP gain to linear transmission line impairments and defines a trade-off between performance and complexity. PMID:25645457

  17. Assembly of the epithelial Na+ channel evaluated using sucrose gradient sedimentation analysis.

    PubMed

    Cheng, C; Prince, L S; Snyder, P M; Welsh, M J

    1998-08-28

    Three subunits, alpha, beta, and gamma, contribute to the formation of the epithelial Na+ channel. To investigate the oligomeric assembly of the channel complex, we used sucrose gradient sedimentation analysis to determine the sedimentation properties of individual subunits and heteromultimers comprised of multiple subunits. When the alpha subunit was expressed alone, it first formed an oligomeric complex with a sedimentation coefficient of 11 S, and then generated a higher order multimer of 25 S. In contrast, individual beta and gamma subunits predominately assembled into 11 S complexes. We obtained similar results with expression in cells and in vitro. When we co-expressed beta with alpha or with alpha plus gamma, the beta subunit assembled into a 25 S complex. Glycosylation of the alpha subunit was not required for assembly into a 25 S complex. We found that the alpha subunit formed intra-chain disulfide bonds. Although such bonds were not required to generate an oligomeric complex, under nonreducing conditions the alpha subunit formed a complex that migrated more homogeneously at 25 S. This suggests that intra-chain disulfide bonds may stabilize the complex. These data suggest that the epithelial Na+ channel subunits form high order oligomeric complexes and that the alpha subunit contains the information that facilitates such formation. Interestingly, the ability of the alpha, but not the beta or gamma, subunit to assemble into a 25 S homomeric complex correlates with the ability of these subunits to generate functional channels when expressed alone.

  18. Coupling interactions between voltage sensors of the sodium channel as revealed by site-specific measurements.

    PubMed

    Chanda, Baron; Asamoah, Osei Kwame; Bezanilla, Francisco

    2004-03-01

    The voltage-sensing S4 segments in the sodium channel undergo conformational rearrangements in response to changes in the electric field. However, it remains unclear whether these structures move independently or in a coordinated manner. Previously, site-directed fluorescence measurements were shown to track S4 transitions in each of the four domains. Here, using a similar technique, we provide direct evidence of coupling interactions between voltage sensors in the sodium channel. Pairwise interactions between S4s were evaluated by comparing site-specific conformational changes in the presence and absence of a gating perturbation in a distal domain. Reciprocity of effect, a fundamental property of thermodynamically coupled systems, was measured by generating converse mutants. The magnitude of a local gating perturbation induced by a remote S4 mutation depends on the coupling strength and the relative equilibrium positions of the two voltage sensors. In general, our data indicates that the movement of all four voltage sensors in the sodium channel are coupled to a varying extent. Moreover, a gating perturbation in S4-DI has the largest effect on the activation of S4-DIV and vice versa, demonstrating an energetic linkage between S4-DI and S4-DIV. This result suggests a physical mechanism by which the activation and inactivation process may be coupled in voltage-gated sodium channels. In addition, we propose that cooperative interactions between voltage sensors may be the mechanistic basis for the fast activation kinetics of the sodium channel.

  19. Mechanisms Responsible for ω-Pore Currents in Cav Calcium Channel Voltage-Sensing Domains.

    PubMed

    Monteleone, Stefania; Lieb, Andreas; Pinggera, Alexandra; Negro, Giulia; Fuchs, Julian E; Hofer, Florian; Striessnig, Jörg; Tuluc, Petronel; Liedl, Klaus R

    2017-10-03

    Mutations of positively charged amino acids in the S4 transmembrane segment of a voltage-gated ion channel form ion-conducting pathways through the voltage-sensing domain, named ω-current. Here, we used structure modeling and MD simulations to predict pathogenic ω-currents in Ca V 1.1 and Ca V 1.3 Ca 2+ channels bearing several S4 charge mutations. Our modeling predicts that mutations of Ca V 1.1-R1 (R528H/G, R897S) or Ca V 1.1-R2 (R900S, R1239H) linked to hypokalemic periodic paralysis type 1 and of Ca V 1.3-R3 (R990H) identified in aldosterone-producing adenomas conducts ω-currents in resting state, but not during voltage-sensing domain activation. The mechanism responsible for the ω-current and its amplitude depend on the number of charges in S4, the position of the mutated S4 charge and countercharges, and the nature of the replacing amino acid. Functional characterization validates the modeling prediction showing that Ca V 1.3-R990H channels conduct ω-currents at hyperpolarizing potentials, but not upon membrane depolarization compared with wild-type channels. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  20. Characterization of Two-Pore Channel 2 by Nuclear Membrane Electrophysiology

    PubMed Central

    Lee, Claire Shuk-Kwan; Tong, Benjamin Chun-Kit; Cheng, Cecily Wing-Hei; Hung, Harry Chun-Hin; Cheung, King-Ho

    2016-01-01

    Lysosomal calcium (Ca2+) release mediated by NAADP triggers signalling cascades that regulate many cellular processes. The identification of two-pore channel 2 (TPC2) as the NAADP receptor advances our understanding of lysosomal Ca2+ signalling, yet the lysosome is not amenable to traditional patch-clamp electrophysiology. Previous attempts to record TPC2 single-channel activity put TPC2 outside its native environment, which not reflect TPC2’s true physiological properties. To test the feasibility of using nuclear membrane electrophysiology for TPC2 channel characterization, we constructed a stable human TPC2-expressing DT40TKO cell line that lacks endogenous InsP3R and RyR (DT40TKO-hTPC2). Immunostaining revealed hTPC2 expression on the ER and nuclear envelope. Intracellular dialysis of NAADP into Fura-2-loaded DT40TKO-hTPC2 cells elicited cytosolic Ca2+ transients, suggesting that hTPC2 was functionally active. Using nuclear membrane electrophysiology, we detected a ~220 pS single-channel current activated by NAADP with K+ as the permeant ion. The detected single-channel recordings displayed a linear current-voltage relationship, were sensitive to Ned-19 inhibition, were biphasically regulated by NAADP concentration, and regulated by PKA phosphorylation. In summary, we developed a cell model for the characterization of the TPC2 channel and the nuclear membrane patch-clamp technique provided an alternative approach to rigorously investigate the electrophysiological properties of TPC2 with minimal manipulation. PMID:26838264

  1. A patch clamp study on reconstituted calcium permeable channels of human sperm plasma membranes.

    PubMed

    Ma, X H; Shi, Y L

    1999-10-01

    Ionic flux is thought to be important in the initiating process of gamete interaction such as acrosome reaction. However, modern electrophysiological methods, intracellular recording and patch-clamping, are difficult to approach the ion channels in mammal sperm membrane of an intact sperm due to its small size. In this work, by reconstituting the channel protein into lipid bilayer, Ca2+ channels in human spermatozoa were investigated with voltage clamp technique. Membrane proteins isolated from human sperm of 12 healthy donors were incorporated into lipid bilayer via fusion. In a cis 50//trans 10 mmol/L CaCl2 solution system, two types of channel events with similar reversal potential near the value of a perfect Ca2+ electrode, and sensitive to nifedipine and verapamil, were observed. Their unit conductance was 40 and 25 pS respectively. Percentage of channel open time was not dependent to holding potential for the former. However, for the channels of 25 pS, the percentage increased when the holding potential was changed from -20 to 100 mV. Ca(2+)-permeable channels were also detected from the spermatozoon samples of two infertile donors. Abnormal open time of these channels indicates that there are some defects in the conformation of the channel protein of infertile sperm membrane.

  2. [Single channel analysis of aconitine blockade of calcium channels in rat myocardiocytes].

    PubMed

    Chen, L; Ma, C; Cai, B C; Lu, Y M; Wu, H

    1995-01-01

    Ventricular myocardiocytes from neonatal Wistar rats were isolated and cultured. Aconitine, Ca2+ channel blocker verapamil or Ca2+ channel activator BAY K8644 were added to the bath solution separately. Using the cell-attached configuration of the patch clamp technique, the single channel activities of L type Ca2+ channel were recorded before and after addition of all three drugs. The results showed the blocking effect of aconitine (50 micrograms.ml-1) on L type Ca2+ channels. Its mechanism may be relevant to the decrease in both open state probability and the mean open time of Ca2+ channel. The difference was statistically significant compared with control group (P < 0.01). The amplitude of Ba2+ currents, which flow through open L type Ca2+ channel was unchanged.

  3. Antibodies to Kv1 potassium channel-complex proteins leucine-rich, glioma inactivated 1 protein and contactin-associated protein-2 in limbic encephalitis, Morvan’s syndrome and acquired neuromyotonia

    PubMed Central

    Irani, Sarosh R.; Alexander, Sian; Waters, Patrick; Kleopa, Kleopas A.; Pettingill, Philippa; Zuliani, Luigi; Peles, Elior; Buckley, Camilla; Lang, Bethan

    2010-01-01

    Antibodies that immunoprecipitate 125I-α-dendrotoxin-labelled voltage-gated potassium channels extracted from mammalian brain tissue have been identified in patients with neuromyotonia, Morvan’s syndrome, limbic encephalitis and a few cases of adult-onset epilepsy. These conditions often improve following immunomodulatory therapies. However, the proportions of the different syndromes, the numbers with associated tumours and the relationships with potassium channel subunit antibody specificities have been unclear. We documented the clinical phenotype and tumour associations in 96 potassium channel antibody positive patients (titres >400 pM). Five had thymomas and one had an endometrial adenocarcinoma. To define the antibody specificities, we looked for binding of serum antibodies and their effects on potassium channel currents using human embryonic kidney cells expressing the potassium channel subunits. Surprisingly, only three of the patients had antibodies directed against the potassium channel subunits. By contrast, we found antibodies to three proteins that are complexed with 125I-α-dendrotoxin-labelled potassium channels in brain extracts: (i) contactin-associated protein-2 that is localized at the juxtaparanodes in myelinated axons; (ii) leucine-rich, glioma inactivated 1 protein that is most strongly expressed in the hippocampus; and (iii) Tag-1/contactin-2 that associates with contactin-associated protein-2. Antibodies to Kv1 subunits were found in three sera, to contactin-associated protein-2 in 19 sera, to leucine-rich, glioma inactivated 1 protein in 55 sera and to contactin-2 in five sera, four of which were also positive for the other antibodies. The remaining 18 sera were negative for potassium channel subunits and associated proteins by the methods employed. Of the 19 patients with contactin-associated protein-antibody-2, 10 had neuromyotonia or Morvan’s syndrome, compared with only 3 of the 55 leucine-rich, glioma inactivated 1 protein

  4. Highly Repeatable and Recoverable Phototransistors Based on Multifunctional Channels of Photoactive CdS, Fast Charge Transporting ZnO, and Chemically Durable Al2O3 Layers.

    PubMed

    Ahn, Cheol Hyoun; Kang, Won Jun; Kim, Ye Kyun; Yun, Myeong Gu; Cho, Hyung Koun

    2016-06-22

    Highly repeatable and recoverable phototransistors were explored using a "multifunctional channels" structure with multistacked chalcogenide and oxide semiconductors. These devices were made of (i) photoactive CdS (with a visible band gap), (ii) fast charge transporting ZnO (with a high field-effect mobility), and (iii) a protection layer of Al2O3 (with high chemical durability). The CdS TFT without the Al2O3 protection layer did not show a transfer curve due to the chemical damage that occurred on the ZnO layer during the chemical bath deposition (CBD) process used for CdS deposition. Alternatively, compared to CdS phototransistors with long recovery time and high hysteresis (ΔVth = 19.5 V), our "multi-functional channels" phototransistors showed an extremely low hysteresis loop (ΔVth = 0.5V) and superior photosensitivity with repeatable high photoresponsivity (52.9 A/W at 400 nm). These improvements are likely caused by the physical isolation of the sensing region and charge transport region by the insertion of the ultrathin Al2O3 layer. This approach successfully addresses some of the existing problems in CdS phototransistors, such as the high gate-interface trap site density and high absorption of molecular oxygen, which originate from the polycrystalline CdS.

  5. Adaptive channel estimation for soft decision decoding over non-Gaussian optical channel

    NASA Astrophysics Data System (ADS)

    Xiang, Jing-song; Miao, Tao-tao; Huang, Sheng; Liu, Huan-lin

    2016-10-01

    An adaptive priori likelihood ratio (LLR) estimation method is proposed over non-Gaussian channel in the intensity modulation/direct detection (IM/DD) optical communication systems. Using the nonparametric histogram and the weighted least square linear fitting in the tail regions, the LLR is estimated and used for the soft decision decoding of the low-density parity-check (LDPC) codes. This method can adapt well to the three main kinds of intensity modulation/direct detection (IM/DD) optical channel, i.e., the chi-square channel, the Webb-Gaussian channel and the additive white Gaussian noise (AWGN) channel. The performance penalty of channel estimation is neglected.

  6. Investigation of InP/In0.65Ga0.35As metamorphic p-channel doped-channel field-effect transistor

    NASA Astrophysics Data System (ADS)

    Tsai, Jung-Hui

    2016-07-01

    In this article, the device mechanism and characteristics of InP/InGaAs metamorphic p-channel field-effect transistor (FET), which has a high indium mole fraction of InGaAs channel, grown on the GaAs substrate is demonstrated. The device was fabricated on the top of the InxGa1-xP graded metamorphic buffer layer, and the In0.65Ga0.35As pseudomorphic channel was employed to elevate the transistor performance. For the p-type FET, due to the considerably large valence band discontinuity at InP/In0.65Ga0.35As heterojunction and a relatively thin as well as heavily doped pseudomorphic In0.65Ga0.35As channel between two undoped InP layers, a maximum extrinsic transconductance of 27.3 mS/mm and a maximum saturation current density of -54.3 mA/mm are obtained. Consequently, the studied metamorphic FET is suitable for the development in signal amplification, integrated circuits, and low supply-voltage complementary logic inverters.

  7. Structure of the voltage-gated K⁺ channel Eag1 reveals an alternative voltage sensing mechanism.

    PubMed

    Whicher, Jonathan R; MacKinnon, Roderick

    2016-08-12

    Voltage-gated potassium (K(v)) channels are gated by the movement of the transmembrane voltage sensor, which is coupled, through the helical S4-S5 linker, to the potassium pore. We determined the single-particle cryo-electron microscopy structure of mammalian K(v)10.1, or Eag1, bound to the channel inhibitor calmodulin, at 3.78 angstrom resolution. Unlike previous K(v) structures, the S4-S5 linker of Eag1 is a five-residue loop and the transmembrane segments are not domain swapped, which suggest an alternative mechanism of voltage-dependent gating. Additionally, the structure and position of the S4-S5 linker allow calmodulin to bind to the intracellular domains and to close the potassium pore, independent of voltage-sensor position. The structure reveals an alternative gating mechanism for K(v) channels and provides a template to further understand the gating properties of Eag1 and related channels. Copyright © 2016, American Association for the Advancement of Science.

  8. Molecular Coupling between Voltage Sensor and Pore Opening in the Arabidopsis Inward Rectifier K+ Channel KAT1

    PubMed Central

    Latorre, Ramon; Olcese, Riccardo; Basso, Claudia; Gonzalez, Carlos; Muñoz, Fabian; Cosmelli, Diego; Alvarez, Osvaldo

    2003-01-01

    Animal and plant voltage-gated ion channels share a common architecture. They are made up of four subunits and the positive charges on helical S4 segments of the protein in animal K+ channels are the main voltage-sensing elements. The KAT1 channel cloned from Arabidopsis thaliana, despite its structural similarity to animal outward rectifier K+ channels is, however, an inward rectifier. Here we detected KAT1-gating currents due to the existence of an intrinsic voltage sensor in this channel. The measured gating currents evoked in response to hyperpolarizing voltage steps consist of a very fast (τ = 318 ± 34 μs at −180 mV) and a slower component (4.5 ± 0.5 ms at −180 mV) representing charge moved when most channels are closed. The observed gating currents precede in time the ionic currents and they are measurable at voltages (less than or equal to −60) at which the channel open probability is negligible (≈10−4). These two observations, together with the fact that there is a delay in the onset of the ionic currents, indicate that gating charge transits between several closed states before the KAT1 channel opens. To gain insight into the molecular mechanisms that give rise to the gating currents and lead to channel opening, we probed external accessibility of S4 domain residues to methanethiosulfonate-ethyltrimethylammonium (MTSET) in both closed and open cysteine-substituted KAT1 channels. The results demonstrate that the putative voltage–sensing charges of S4 move inward when the KAT1 channels open. PMID:14517271

  9. Ion channels in plants.

    PubMed

    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.

  10. Thin walled channel

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Crowther, R.L.; Johansson, E.B.

    1988-06-07

    A fuel assembly is described comprising fuel rods positioned in a spaced array by upper and lower tie-plates, an open ended flow channel surrounding the array for conducting coolant upward about the fuel rods, the open ended channel having a polygon shaped cross section with flat side sections connected between the corner sections; means separate from the channel connecting the upper and lower tie-plates together and maintaining the fuel rods in spaced array independent of the flow channel, improvement in the flow channel comprising: four corners having a first thickness; four sides having a second and reduced thickness from themore » corner thickness, the sides welded to the corner sections.« less

  11. The Blurred Line between Form and Process: A Comparison of Stream Channel Classification Frameworks

    PubMed Central

    Kasprak, Alan; Hough-Snee, Nate

    2016-01-01

    Stream classification provides a means to understand the diversity and distribution of channels and floodplains that occur across a landscape while identifying links between geomorphic form and process. Accordingly, stream classification is frequently employed as a watershed planning, management, and restoration tool. At the same time, there has been intense debate and criticism of particular frameworks, on the grounds that these frameworks classify stream reaches based largely on their physical form, rather than direct measurements of their component hydrogeomorphic processes. Despite this debate surrounding stream classifications, and their ongoing use in watershed management, direct comparisons of channel classification frameworks are rare. Here we implement four stream classification frameworks and explore the degree to which each make inferences about hydrogeomorphic process from channel form within the Middle Fork John Day Basin, a watershed of high conservation interest within the Columbia River Basin, U.S.A. We compare the results of the River Styles Framework, Natural Channel Classification, Rosgen Classification System, and a channel form-based statistical classification at 33 field-monitored sites. We found that the four frameworks consistently classified reach types into similar groups based on each reach or segment’s dominant hydrogeomorphic elements. Where classified channel types diverged, differences could be attributed to the (a) spatial scale of input data used, (b) the requisite metrics and their order in completing a framework’s decision tree and/or, (c) whether the framework attempts to classify current or historic channel form. Divergence in framework agreement was also observed at reaches where channel planform was decoupled from valley setting. Overall, the relative agreement between frameworks indicates that criticism of individual classifications for their use of form in grouping stream channels may be overstated. These form

  12. Channel optimization of high-intensity laser beams in millimeter-scale plasmas

    DOE PAGES

    Ceurvorst, L.; Savin, A.; Ratan, N.; ...

    2018-04-20

    Channeling experiments were performed at the OMEGA EP facility using relativistic intensity (> 10 18 W/cm 2) kilojoule laser pulses through large density scale length (~ 390-570 μm) laser-produced plasmas, demonstrating the effects of the pulse’s focal location and intensity as well as the plasma’s temperature on the resulting channel formation. The results show deeper channeling when focused into hot plasmas and at lower densities as expected. However, contrary to previous large scale particle-in-cell studies, the results also indicate deeper penetration by short (10 ps), intense pulses compared to their longer duration equivalents. To conclude, this new observation has manymore » implications for future laser-plasma research in the relativistic regime.« less

  13. Channel optimization of high-intensity laser beams in millimeter-scale plasmas

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ceurvorst, L.; Savin, A.; Ratan, N.

    Channeling experiments were performed at the OMEGA EP facility using relativistic intensity (> 10 18 W/cm 2) kilojoule laser pulses through large density scale length (~ 390-570 μm) laser-produced plasmas, demonstrating the effects of the pulse’s focal location and intensity as well as the plasma’s temperature on the resulting channel formation. The results show deeper channeling when focused into hot plasmas and at lower densities as expected. However, contrary to previous large scale particle-in-cell studies, the results also indicate deeper penetration by short (10 ps), intense pulses compared to their longer duration equivalents. To conclude, this new observation has manymore » implications for future laser-plasma research in the relativistic regime.« less

  14. Escitalopram block of hERG potassium channels.

    PubMed

    Chae, Yun Ju; Jeon, Ji Hyun; Lee, Hong Joon; Kim, In-Beom; Choi, Jin-Sung; Sung, Ki-Wug; Hahn, Sang June

    2014-01-01

    Escitalopram, a selective serotonin reuptake inhibitor, is the pharmacologically active S-enantiomer of the racemic mixture of RS-citalopram and is widely used in the treatment of depression. The effects of escitalopram and citalopram on the human ether-a-go-go-related gene (hERG) channels expressed in human embryonic kidney cells were investigated using voltage-clamp and Western blot analyses. Both drugs blocked hERG currents in a concentration-dependent manner with an IC50 value of 2.6 μM for escitalopram and an IC50 value of 3.2 μM for citalopram. The blocking of hERG by escitalopram was voltage-dependent, with a steep increase across the voltage range of channel activation. However, voltage independence was observed over the full range of activation. The blocking by escitalopram was frequency dependent. A rapid application of escitalopram induced a rapid and reversible blocking of the tail current of hERG. The extent of the blocking by escitalopram during the depolarizing pulse was less than that during the repolarizing pulse, suggesting that escitalopram has a high affinity for the open state of the hERG channel, with a relatively lower affinity for the inactivated state. Both escitalopram and citalopram produced a reduction of hERG channel protein trafficking to the plasma membrane but did not affect the short-term internalization of the hERG channel. These results suggest that escitalopram blocked hERG currents at a supratherapeutic concentration and that it did so by preferentially binding to both the open and the inactivated states of the channels and by inhibiting the trafficking of hERG channel protein to the plasma membrane.

  15. Analysis of a novel double-barreled anion channel from rat liver rough endoplasmic reticulum.

    PubMed Central

    Morier, N; Sauvé, R

    1994-01-01

    The presence of anionic channels in stripped rough endoplasmic reticulum membranes isolated from rat hepatocytes was investigated by fusing microsomes from these membranes to a planar lipid bilayer. Several types of anion-selective channels were observed including a voltage-gated Cl- channel, the activity of which appeared in bursts characterized by transitions among three distinct conductance levels of 0 pS (0 level), 160 pS (O1 level), and 320 pS (O2 level), respectively, in 450 mM (cis) 50 mM (trans) KCl conditions. A chi 2 analysis on current records where interburst silent periods were omitted showed that the relative probability of current levels 0 (baseline), O1, and O2 followed a binomial statistic. However, measurements of the conditional probabilities W(level 0 at tau/level O2 at 0) and W(level O2 at tau/level 0 at 0) provided clear evidence of direct transitions between the current levels 0 and O2 without any detectable transitions to the intermediate level O1. It was concluded on the basis of these results that the observed channel was controlled by at least two distinct gating processes, namely 1) a voltage-dependent activation mechanism in which the entire system behaves as two independent monomeric channels of 160 pS with each channel characterized by a simple Open-Closed kinetic, and 2) a slow voltage-dependent process that accounts for both the appearance of silent periods between bursts of channel activity and the transitions between the current levels 0 and O2. Finally, an analysis of the relative probability for the system to be in levels 0, O1, and O2 showed that our results are more compatible with a model in which all the states resulting from the superposition of the two independent monomeric channels have access at different rates to a common inactivated state than with a model where a simple Open-Closed main gate either occludes or exposes simultaneously two independent 160-pS monomers. Images FIGURE 2 FIGURE 6 PMID:7524709

  16. Chryse Basin channels: low-gradients and ponded flows.

    USGS Publications Warehouse

    Lucchitta, B.K.; Ferguson, H.M.

    1983-01-01

    Gradients on the floors of the Martian outflow channels that are derived from radar-elevation profiles across Lunae Planum and Chryse Basin have much lower values than those obtained from the U.S. Geological Survey's topographic map. Whereas the gradients of Maja and Ares Valles are similar to those of the catastrophic flood channels in the Scablands of Washington State, the gradients of Simud and Tiu Valles are essentially level, and the movement of fluids to the N poses problems. It is proposed that ponding may have formed lakes in depressions associated with the Valles Marineris grabens, ancient craters in the chaotic terrain area, and possibly even the regional low where most chaotic terrains occur. It is envisaged that lakes eventually overflowed, forming the present channels. When dams broke, floods were released catastrophically, with a final gigantic flood from the Valles Marineris system of troughs, which would have had sufficient head to move fluids across nearly level gradients through the Simud and Tiu channels. -P.Br.

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

    PubMed Central

    Yeoum, Sanggil; Kang, Byungseok; Lee, Jinkyu; Choo, Hyunseung

    2017-01-01

    Collision-free transmission and efficient data transfer between nodes can be achieved through a set of channels in multichannel wireless sensor networks (MWSNs). While using multiple channels, we have to carefully consider channel interference, channel and time slot (resources) optimization, channel switching delay, and energy consumption. Since sensor nodes operate on low battery power, the energy consumed in channel switching becomes an important challenge. In this paper, we propose channel and time slot scheduling for minimal channel switching in MWSNs, while achieving efficient and collision-free transmission between nodes. The proposed scheme constructs a duty-cycled tree while reducing the amount of channel switching. As a next step, collision-free time slots are assigned to every node based on the minimal data collection delay. The experimental results demonstrate that the validity of our scheme reduces the amount of channel switching by 17.5%, reduces energy consumption for channel switching by 28%, and reduces the schedule length by 46%, as compared to the existing schemes. PMID:28471416

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

    PubMed

    Yeoum, Sanggil; Kang, Byungseok; Lee, Jinkyu; Choo, Hyunseung

    2017-05-04

    Collision-free transmission and efficient data transfer between nodes can be achieved through a set of channels in multichannel wireless sensor networks (MWSNs). While using multiple channels, we have to carefully consider channel interference, channel and time slot (resources) optimization, channel switching delay, and energy consumption. Since sensor nodes operate on low battery power, the energy consumed in channel switching becomes an important challenge. In this paper, we propose channel and time slot scheduling for minimal channel switching in MWSNs, while achieving efficient and collision-free transmission between nodes. The proposed scheme constructs a duty-cycled tree while reducing the amount of channel switching. As a next step, collision-free time slots are assigned to every node based on the minimal data collection delay. The experimental results demonstrate that the validity of our scheme reduces the amount of channel switching by 17.5%, reduces energy consumption for channel switching by 28%, and reduces the schedule length by 46%, as compared to the existing schemes.

  19. Measurement of the $s$-channel Single Top Quark Cross Section at the CDF Experiment and Contributions to the Evidence of $$H\\rightarrow bb$$ at the Tevatron

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Liu, Hao

    2014-08-01

    In this thesis, we present the measurement of the s-channel single top quark production cross section. In the cross section measurement we use data generated by protonantiproton collisions at the center-of-mass energy √s = 1.96 TeV and collected by the CDF Run II detector. The total data set corresponds to an integrated luminosity of 9.4 fb -1.

  20. Voltage Sensor Inactivation in Potassium Channels

    PubMed Central

    Bähring, Robert; Barghaan, Jan; Westermeier, Regina; Wollberg, Jessica

    2012-01-01

    In voltage-gated potassium (Kv) channels membrane depolarization causes movement of a voltage sensor domain. This conformational change of the protein is transmitted to the pore domain and eventually leads to pore opening. However, the voltage sensor domain may interact with two distinct gates in the pore domain: the activation gate (A-gate), involving the cytoplasmic S6 bundle crossing, and the pore gate (P-gate), located externally in the selectivity filter. How the voltage sensor moves and how tightly it interacts with these two gates on its way to adopt a relaxed conformation when the membrane is depolarized may critically determine the mode of Kv channel inactivation. In certain Kv channels, voltage sensor movement leads to a tight interaction with the P-gate, which may cause conformational changes that render the selectivity filter non-conductive (“P/C-type inactivation”). Other Kv channels may preferably undergo inactivation from pre-open closed-states during voltage sensor movement, because the voltage sensor temporarily uncouples from the A-gate. For this behavior, known as “preferential” closed-state inactivation, we introduce the term “A/C-type inactivation”. Mechanistically, P/C- and A/C-type inactivation represent two forms of “voltage sensor inactivation.” PMID:22654758

  1. Instream wood in a steep headwater channel: geomorphic significance of large and small wood

    NASA Astrophysics Data System (ADS)

    Galia, Tomáš; Šilhán, Karel; Ruiz-Villanueva, Virginia; Tichavský, Radek

    2016-04-01

    Besides the well-known significance of large wood (LW), also small woody pieces (SW; here defined as pieces with dimensions at least 0.5 m length and 0.05 m diameter), can play an important role in steep narrow headwaters. We inventoried instream wood in the 0.4 km long Mazák headwater channel, Moravskoslezské Beskydy Mts, Czech Republic (2S<0.40 m/m) with very steep adjacent hillslopes (0.6<S<1.1 m/m), where the parameters of wood dimensions, orientation, decay status (four classes), stability (unattached/contact with hillslopes/attached by bed sediments or other wood), % of influenced channel width by a wood, the geomorphic function of a wood (step, wood jam) and % of length of a wood in channel were assessed. The total number of inventoried instream wood was 90 LWs and 199 SWs. In addition, dendrogeomorphic dating of 36 LWs and 17 SWs was performed to obtain residence time of local instream wood and to provide some insights into its mobility. Practically all investigated pieces were European beeches (Fagus sylvatica L.); only two pieces were Norway spruces (Picea abies (L.) Karst.). First results showed an increase in the number of LWs in channel-reaches confined by the steepest adjacent hillslopes (especially at 0.15-0.20 km). Increasing downstream amount of SW most likely reflected transport processes in the stream, and the later deposition of SWs on the lowest channel gradients. Also LWs and SWs in the downstream channel-reaches were more decayed than wood presented in the upper reaches. The orientation of instream wood was connected with its length and stability, and LWs longer than 5 m were usually attached to adjacent hillslopes. Pieces longer than 2 m, which were unattached or were somehow stabilized in the channel bed, had often orientation of 0° or 337°. LWs were mostly unattached in the upstream channel-reaches, while often stabilized by adjacent hillslopes in the middle part. At 0.05-0.10 km, there were also many logs stabilized by

  2. Reliable video transmission over fading channels via channel state estimation

    NASA Astrophysics Data System (ADS)

    Kumwilaisak, Wuttipong; Kim, JongWon; Kuo, C.-C. Jay

    2000-04-01

    Transmission of continuous media such as video over time- varying wireless communication channels can benefit from the use of adaptation techniques in both source and channel coding. An adaptive feedback-based wireless video transmission scheme is investigated in this research with special emphasis on feedback-based adaptation. To be more specific, an interactive adaptive transmission scheme is developed by letting the receiver estimate the channel state information and send it back to the transmitter. By utilizing the feedback information, the transmitter is capable of adapting the level of protection by changing the flexible RCPC (rate-compatible punctured convolutional) code ratio depending on the instantaneous channel condition. The wireless channel is modeled as a fading channel, where the long-term and short- term fading effects are modeled as the log-normal fading and the Rayleigh flat fading, respectively. Then, its state (mainly the long term fading portion) is tracked and predicted by using an adaptive LMS (least mean squares) algorithm. By utilizing the delayed feedback on the channel condition, the adaptation performance of the proposed scheme is first evaluated in terms of the error probability and the throughput. It is then extended to incorporate variable size packets of ITU-T H.263+ video with the error resilience option. Finally, the end-to-end performance of wireless video transmission is compared against several non-adaptive protection schemes.

  3. Martian channels and valleys - Their characteristics, distribution, and age

    NASA Technical Reports Server (NTRS)

    Carr, M. H.; Clow, G. D.

    1981-01-01

    The distribution and ages of Martian channels and valleys, which are generally believed to have been cut by running water, are examined with particular emphasis on the small branching networks referred to as runoff channels or valley networks. Valleys at latitudes from 65 deg S to 65 deg N were surveyed on Viking images at resolutions between 125 and 300 m. Almost all of the valleys are found in the old cratered terrain, in areas characterized by high elevations, low albedos and low violet/red ratios. The networks are deduced to have formed early in the history of the planet, with a formation rate declining rapidly shortly after the decline of the cratering rate 3.9 billion years ago. Two types of outflow channels are distinguished: unconfined, in which broad swaths of terrain are scoured, and confined, in which flow is restricted to discrete channels. Both types start at local sources, and have formed episodically throughout Martian history. Fretted channels, found mainly in two latitude belts characterized by relatively rapid erosion along escarpments, are explained by the lateral enlargement of other channels by mass wasting.

  4. Inhibitory effects of cortisone and hydrocortisone on human Kv1.5 channel currents.

    PubMed

    Yu, Jing; Park, Mi-Hyeong; Jo, Su-Hyun

    2015-01-05

    Glucocorticoids are the primary hormones that respond to stress and protect organisms from dangerous situations. The glucocorticoids hydrocortisone and its dormant form, cortisone, affect the cardiovascular system with changes such as increased blood pressure and cardioprotection. Kv1.5 channels play a critical role in the maintenance of cellular membrane potential and are widely expressed in pancreatic β-cells, neurons, myocytes, and smooth muscle cells of the pulmonary vasculature. We examined the electrophysiological effects of both cortisone and hydrocortisone on human Kv1.5 channels expressed in Xenopus oocytes using a two-microelectrode voltage clamp technique. Both cortisone and hydrocortisone rapidly and irreversibly suppressed the amplitude of Kv1.5 channel current with IC50 values of 50.2±4.2μM and 33.4±3.2μM, respectively, while sustained the current trace shape of Kv1.5 current. The inhibitory effect of cortisone on Kv1.5 decreased progressively from -10mV to +30mV, while hydrocortisone׳s inhibition of the channel did not change across the same voltage range. Both cortisone and hydrocortisone blocked Kv1.5 channel currents in a non-use-dependent manner and neither altered the channel׳s steady-state activation or inactivation curves. These results show that cortisone and hydrocortisone inhibited Kv1.5 channel currents differently, and that Kv1.5 channels were more sensitive to hydrocortisone than to cortisone. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. Quantum mechanical calculations of charge effects on gating the KcsA channel.

    PubMed

    Kariev, Alisher M; Znamenskiy, Vasiliy S; Green, Michael E

    2007-05-01

    A series of ab initio (density functional) calculations were carried out on side chains of a set of amino acids, plus water, from the (intracellular) gating region of the KcsA K(+) channel. Their atomic coordinates, except hydrogen, are known from X-ray structures [D.A. Doyle, J.M. Cabral, R.A. Pfuetzner, A. Kuo, J.M. Gulbis, S.L. Cohen, B.T. Chait, R. MacKinnon, The structure of the potassium channel: molecular basis of K(+) conduction and selectivity, Science 280 (1998) 69-77; R. MacKinnon, S.L. Cohen, A. Kuo, A. Lee, B.T. Chait, Structural conservation in prokaryotic and eukaryotic potassium channels, Science 280 (1998) 106-109; Y. Jiang, A. Lee, J. Chen, M. Cadene, B.T. Chait, R. MacKinnon, The open pore conformation of potassium channels. Nature 417 (2001) 523-526], as are the coordinates of some water oxygen atoms. The 1k4c structure is used for the starting coordinates. Quantum mechanical optimization, in spite of the starting configuration, places the atoms in positions much closer to the 1j95, more tightly closed, configuration. This state shows four water molecules forming a "basket" under the Q119 side chains, blocking the channel. When a hydrated K(+) approaches this "basket", the optimized system shows a strong set of hydrogen bonds with the K(+) at defined positions, preventing further approach of the K(+) to the basket. This optimized structure with hydrated K(+) added shows an ice-like 12 molecule nanocrystal of water. If the water molecules exchange, unless they do it as a group, the channel will remain blocked. The "basket" itself appears to be very stable, although it is possible that the K(+) with its hydrating water molecules may be more mobile, capable of withdrawing from the gate. It is also not surprising that water essentially freezes, or forms a kind of glue, in a nanometer space; this agrees with experimental results on a rather different, but similarly sized (nm dimensions) system [K.B. Jinesh, J.W.M. Frenken, Capillary condensation in

  6. Symmetrization for redundant channels

    NASA Technical Reports Server (NTRS)

    Tulplue, Bhalchandra R. (Inventor); Collins, Robert E. (Inventor)

    1988-01-01

    A plurality of redundant channels in a system each contain a global image of all the configuration data bases in each of the channels in the system. Each global image is updated periodically from each of the other channels via cross channel data links. The global images of the local configuration data bases in each channel are separately symmetrized using a voting process to generate a system signal configuration data base which is not written into by any other routine and is available for indicating the status of the system within each channel. Equalization may be imposed on a suspect signal and a number of chances for that signal to heal itself are provided before excluding it from future votes. Reconfiguration is accomplished upon detecting a channel which is deemed invalid. A reset function is provided which permits an externally generated reset signal to permit a previously excluded channel to be reincluded within the system. The updating of global images and/or the symmetrization process may be accomplished at substantially the same time within a synchronized time frame common to all channels.

  7. Ultrashort Channel Length Black Phosphorus Field-Effect Transistors.

    PubMed

    Miao, Jinshui; Zhang, Suoming; Cai, Le; Scherr, Martin; Wang, Chuan

    2015-09-22

    This paper reports high-performance top-gated black phosphorus (BP) field-effect transistors with channel lengths down to 20 nm fabricated using a facile angle evaporation process. By controlling the evaporation angle, the channel length of the transistors can be reproducibly controlled to be anywhere between 20 and 70 nm. The as-fabricated 20 nm top-gated BP transistors exhibit respectable on-state current (174 μA/μm) and transconductance (70 μS/μm) at a VDS of 0.1 V. Due to the use of two-dimensional BP as the channel material, the transistors exhibit relatively small short channel effects, preserving a decent on-off current ratio of 10(2) even at an extremely small channel length of 20 nm. Additionally, unlike the unencapsulated BP devices, which are known to be chemically unstable in ambient conditions, the top-gated BP transistors passivated by the Al2O3 gate dielectric layer remain stable without noticeable degradation in device performance after being stored in ambient conditions for more than 1 week. This work demonstrates the great promise of atomically thin BP for applications in ultimately scaled transistors.

  8. Mechanisms of Calmodulin Regulation of Different Isoforms of Kv7.4 K+ Channels.

    PubMed

    Sihn, Choong-Ryoul; Kim, Hyo Jeong; Woltz, Ryan L; Yarov-Yarovoy, Vladimir; Yang, Pei-Chi; Xu, Jun; Clancy, Colleen E; Zhang, Xiao-Dong; Chiamvimonvat, Nipavan; Yamoah, Ebenezer N

    2016-01-29

    Calmodulin (CaM), a Ca(2+)-sensing protein, is constitutively bound to IQ domains of the C termini of human Kv7 (hKv7, KCNQ) channels to mediate Ca(2+)-dependent reduction of Kv7 currents. However, the mechanism remains unclear. We report that CaM binds to two isoforms of the hKv7.4 channel in a Ca(2+)-independent manner but that only the long isoform (hKv7.4a) is regulated by Ca(2+)/CaM. Ca(2+)/CaM mediate reduction of the hKv7.4a channel by decreasing the channel open probability and altering activation kinetics. We took advantage of a known missense mutation (G321S) that has been linked to progressive hearing loss to further examine the inhibitory effects of Ca(2+)/CaM on the Kv7.4 channel. Using multidisciplinary techniques, we demonstrate that the G321S mutation may destabilize CaM binding, leading to a decrease in the inhibitory effects of Ca(2+) on the channels. Our study utilizes an expression system to dissect the biophysical properties of the WT and mutant Kv7.4 channels. This report provides mechanistic insights into the critical roles of Ca(2+)/CaM regulation of the Kv7.4 channel under physiological and pathological conditions. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  9. The Psychology of Channeling.

    ERIC Educational Resources Information Center

    Corey, Michael A.

    1988-01-01

    Theoretically analyzes phenomenon of channeling from perspective of C. G. Jung's analytic psychology. Hypothesizes that contact with otherworldly spiritual beings claimed by channelers is actually projected contact with contents of channeler's own unconscious mind. Suggests that channelers seek more constructive ways of contacting their…

  10. Inactivation of A currents and A channels on rat nodose neurons in culture

    PubMed Central

    1989-01-01

    Cultured sensory neurons from nodose ganglia were investigated with whole-cell patch-clamp techniques and single-channel recordings to characterize the A current. Membrane depolarization from -40 mV holding potential activated the delayed rectifier current (IK) at potentials positive to -30 mV; this current had a sigmoidal time course and showed little or no inactivation. In most neurons, the A current was completely inactivated at the -40 mV holding potential and required hyperpolarization to remove the inactivation; the A current was isolated by subtracting the IK evoked by depolarizations from -40 mV from the total outward current evoked by depolarizations from -90 mV. The decay of the A current on several neurons had complex kinetics and was fit by the sum of three exponentials whose time constants were 10- 40 ms, 100-350 ms, and 1-3 s. At the single-channel level we found that one class of channel underlies the A current. The conductance of A channels varied with the square root of the external K concentration: it was 22 pS when exposed to 5.4 mM K externally, the increased to 40 pS when exposed to 140 mM K externally. A channels activated rapidly upon depolarization and the latency to first opening decreased with depolarization. The open time distributions followed a single exponential and the mean open time increased with depolarization. A channels inactivate in three different modes: some A channels inactivated with little reopening and gave rise to ensemble averages that decayed in 10-40 ms; other A channels opened and closed three to four times before inactivating and gave rise to ensemble averages that decayed in 100-350 ms; still other A channels opened and closed several hundred times and required seconds to inactivate. Channels gating in all three modes contributed to the macroscopic A current from the whole cell, but their relative contribution differed among neurons. In addition, A channels could go directly from the closed, or resting, state to the

  11. Artificial phosphorylation sites modulate the activity of a voltage-gated potassium channel

    NASA Astrophysics Data System (ADS)

    Ariyaratne, Amila; Zocchi, Giovanni

    2015-03-01

    The KvAP potassium channel is representative of a family of voltage-gated ion channels where the membrane potential is sensed by a transmembrane helix containing several positively charged arginines. Previous work by Wang and Zocchi [A. Wang and G. Zocchi, PLoS ONE 6, e18598 (2011), 10.1371/journal.pone.0018598] showed how a negatively charged polyelectrolyte attached in proximity to the voltage sensing element can bias the opening probability of the channel. Here we introduce three phosphorylation sites at the same location and show that the response curve of the channel shifts by about 20 mV upon phosphorylation, while other characteristics such as the single-channel conductance are unaffected. In summary, we construct an artificial phosphorylation site which confers allosteric regulation to the channel.

  12. Cardiac metabolic effects of KNa1.2 channel deletion and evidence for its mitochondrial localization.

    PubMed

    Smith, Charles O; Wang, Yves T; Nadtochiy, Sergiy M; Miller, James H; Jonas, Elizabeth A; Dirksen, Robert T; Nehrke, Keith; Brookes, Paul S

    2018-06-04

    Controversy surrounds the molecular identity of mitochondrial K + channels that are important for protection against cardiac ischemia-reperfusion injury. Although K Na 1.2 (sodium-activated potassium channel encoded by Kcn2) is necessary for cardioprotection by volatile anesthetics, electrophysiological evidence for a channel of this type in mitochondria is lacking. The endogenous physiological role of a potential mito-K Na 1.2 channel is also unclear. In this study, single channel patch-clamp of 27 independent cardiac mitochondrial inner membrane (mitoplast) preparations from wild-type (WT) mice yielded 6 channels matching the known ion sensitivity, ion selectivity, pharmacology, and conductance properties of K Na 1.2 (slope conductance, 138 ± 1 pS). However, similar experiments on 40 preparations from Kcnt2 -/- mice yielded no such channels. The K Na opener bithionol uncoupled respiration in WT but not Kcnt2 -/- cardiomyocytes. Furthermore, when oxidizing only fat as substrate, Kcnt2 -/- cardiomyocytes and hearts were less responsive to increases in energetic demand. Kcnt2 -/- mice also had elevated body fat, but no baseline differences in the cardiac metabolome. These data support the existence of a cardiac mitochondrial K Na 1.2 channel, and a role for cardiac K Na 1.2 in regulating metabolism under conditions of high energetic demand.-Smith, C. O., Wang, Y. T., Nadtochiy, S. M., Miller, J. H., Jonas, E. A., Dirksen, R. T., Nehrke, K., Brookes, P. S. Cardiac metabolic effects of K Na 1.2 channel deletion and evidence for its mitochondrial localization.

  13. Functional interactions at the interface between voltage-sensing and pore domains in the Shaker K(v) channel.

    PubMed

    Soler-Llavina, Gilberto J; Chang, Tsg-Hui; Swartz, Kenton J

    2006-11-22

    Voltage-activated potassium (K(v)) channels contain a central pore domain that is partially surrounded by four voltage-sensing domains. Recent X-ray structures suggest that the two domains lack extensive protein-protein contacts within presumed transmembrane regions, but whether this is the case for functional channels embedded in lipid membranes remains to be tested. We investigated domain interactions in the Shaker K(v) channel by systematically mutating the pore domain and assessing tolerance by examining channel maturation, S4 gating charge movement, and channel opening. When mapped onto the X-ray structure of the K(v)1.2 channel the large number of permissive mutations support the notion of relatively independent domains, consistent with crystallographic studies. Inspection of the maps also identifies portions of the interface where residues are sensitive to mutation, an external cluster where mutations hinder voltage sensor activation, and an internal cluster where domain interactions between S4 and S5 helices from adjacent subunits appear crucial for the concerted opening transition.

  14. Bayesian sparse channel estimation

    NASA Astrophysics Data System (ADS)

    Chen, Chulong; Zoltowski, Michael D.

    2012-05-01

    In Orthogonal Frequency Division Multiplexing (OFDM) systems, the technique used to estimate and track the time-varying multipath channel is critical to ensure reliable, high data rate communications. It is recognized that wireless channels often exhibit a sparse structure, especially for wideband and ultra-wideband systems. In order to exploit this sparse structure to reduce the number of pilot tones and increase the channel estimation quality, the application of compressed sensing to channel estimation is proposed. In this article, to make the compressed channel estimation more feasible for practical applications, it is investigated from a perspective of Bayesian learning. Under the Bayesian learning framework, the large-scale compressed sensing problem, as well as large time delay for the estimation of the doubly selective channel over multiple consecutive OFDM symbols, can be avoided. Simulation studies show a significant improvement in channel estimation MSE and less computing time compared to the conventional compressed channel estimation techniques.

  15. Potassium channels in brain mitochondria.

    PubMed

    Bednarczyk, Piotr

    2009-01-01

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

  16. Localization and Molecular Determinants of the Hanatoxin Receptors on the Voltage-Sensing Domains of a K+ Channel

    PubMed Central

    Li-Smerin, Yingying; Swartz, Kenton J.

    2000-01-01

    Hanatoxin inhibits voltage-gated K+ channels by modifying the energetics of activation. We studied the molecular determinants and physical location of the Hanatoxin receptors on the drk1 voltage-gated K+ channel. First, we made multiple substitutions at three previously identified positions in the COOH terminus of S3 to examine whether these residues interact intimately with the toxin. We also examined a region encompassing S1–S3 using alanine-scanning mutagenesis to identify additional determinants of the toxin receptors. Finally, guided by the structure of the KcsA K+ channel, we explored whether the toxin interacts with the peripheral extracellular surface of the pore domain in the drk1 K+ channel. Our results argue for an intimate interaction between the toxin and the COOH terminus of S3 and suggest that the Hanatoxin receptors are confined within the voltage-sensing domains of the channel, at least 20–25 Å away from the central pore axis. PMID:10828242

  17. Regulation of Transient Receptor Potential channels by the phospholipase C pathway

    PubMed Central

    Rohacs, Tibor

    2013-01-01

    Transient Receptor Potential (TRP) channels were discovered while analyzing visual mutants in drosophila. The protein encoded by the transient receptor potential (trp) gene is a Ca2+ permeable cation channel activated downstream of the phospholipase C (PLC) pathway. While searching for homologues in other organisms, a surprisingly large number of mammalian TRP channels were cloned. The regulation of TRP channels is quite diverse, but many of them are either activated downstream of the PLC pathway, or modulated by it. This review will summarize the current knowledge on regulation of TRP channels by the PLC pathway, with special focus on TRPC-s, which can be considered as effectors of the PLC pathway, and the heat and capsaicin sensitive TRPV1, which is modulated by the PLC pathway in a complex manner. PMID:23916247

  18. Constraints on voltage sensor movement in the shaker K+ channel.

    PubMed

    Darman, Rachel B; Ivy, Allison A; Ketty, Vina; Blaustein, Robert O

    2006-12-01

    In nerve and muscle cells, the voltage-gated opening and closing of cation-selective ion channels is accompanied by the translocation of 12-14 elementary charges across the membrane's electric field. Although most of these charges are carried by residues in the S4 helix of the gating module of these channels, the precise nature of their physical movement is currently the topic of spirited debate. Broadly speaking, two classes of models have emerged: those that suggest that small-scale motions can account for the extensive charge displacement, and those that invoke a much larger physical movement. In the most recent incarnation of the latter type of model, which is based on structural and functional data from the archaebacterial K(+) channel KvAP, a "voltage-sensor paddle" comprising a helix-turn-helix of S3-S4 translocates approximately 20 A through the bilayer during the gating cycle (Jiang, Y., A. Lee, J. Chen, V. Ruta, M. Cadene, B.T. Chait, and R. MacKinnon. 2003. Nature. 423:33-41; Jiang, Y., V. Ruta, J. Chen, A. Lee, and R. MacKinnon. 2003. Nature. 423:42-48.; Ruta, V., J. Chen, and R. MacKinnon. 2005. Cell. 123:463-475). We used two methods to test for analogous motions in the Shaker K(+) channel, each examining the aqueous exposure of residues near S3. In the first, we employed a pore-blocking maleimide reagent (Blaustein, R.O., P.A. Cole, C. Williams, and C. Miller. 2000. Nat. Struct. Biol. 7:309-311) to probe for state-dependent changes in the chemical reactivity of substituted cysteines; in the second, we tested the state-dependent accessibility of a tethered biotin to external streptavidin (Qiu, X.Q., K.S. Jakes, A. Finkelstein, and S.L. Slatin. 1994. J. Biol. Chem. 269:7483-7488; Slatin, S.L., X.Q. Qiu, K.S. Jakes, and A. Finkelstein. 1994. Nature. 371:158-161). In both types of experiments, residues predicted to lie near the top of S3 did not exhibit any change in aqueous exposure during the gating cycle. This lack of state dependence argues against

  19. Lightning-channel conditioning

    NASA Astrophysics Data System (ADS)

    Sonnenfeld, R.; da Silva, C. L.; Eack, K.; Edens, H. E.; Harley, J.; McHarg, M.; Contreras Vidal, L.

    2017-12-01

    The concept of "conditioning" has several distinct applications in understanding lightning. It is commonly associated to the greater speed of dart-leaders vs. stepped leaders and the retrace of a cloud-to-ground channel by later return strokes. We will showadditional examples of conditioning: (A) High-speed videos of triggered flashes show "dark" periods of up to 50 ms between rebrightenings of an existing channel. (B) Interferometer (INTF) images of intra-cloud (IC) flashes demonstrate that electric-field "K-changes" correspond to rapid propagation of RF impulses along a previously formed channel separated by up to 20 ms with little RF emission on that channel. (C) Further, INTF images (like the one below) frequently show that the initial IC channel is more branched and "fuzzier'' than its later incarnations. Also, we contrast high-speed video, INTF observations, and spectroscopic measurements with possible physical mechanisms that can explain how channel conditioning guides and facilitates dart leader propagation. These mechanisms include: (1) a plasmochemical effect where electrons are stored in negative ions and released during the dart leader propagation via field-induced detachment; (2) small-amplitude residual currents that can maintain electrical conductivity; and (3) slow heat conduction cooling of plasma owing to channel expansion dynamics.

  20. Two different types of channels exhibiting distinct proton transport behavior in an open-framework aluminophosphate

    NASA Astrophysics Data System (ADS)

    Xue, Chen; Zou, Yang; Liu, Shao-Xian; Ren, Xiao-Ming; Tian, Zheng-Fang

    2018-02-01

    A three-dimensional open-framework aluminophosphate, (NH4)2Al4(PO4)4(HPO4)·H2O (1), shows two types of eight-membered polyhedral ring channels. The lattice water molecules occupy within the channel with (HO)PO3 tetrahedra (channel-I), whilst the ammonium ions reside in another type of channel (channel-II). This aluminophosphate shows superior stability to water and NaOH aqueous solution, but unstable to H2SO4 aqueous solution. The proton conductance of 1 has been investigated under anhydrous condition and various relative humidity, indicating rather low conductivity under anhydrous condition even at elevated temperature (σdc = 9.05 × 10-13 S cm-1 at 343 K and 4.25 × 10-10 S cm-1 even at 473 K), and this situation demonstrates that both the ammonium ions and the protons in (HO)PO3 tetrahedra have quite low mobility. The conductivity of 1 reaches to 4.0 × 10-5 S cm-1 at 299 K, 2.57 × 10-4 S cm-1 at 343 K under 99%RH, respectively. The greatly enhancement of proton conductivity at 99%RH is due to the formation of H-bond between H2O molecules and (HO)PO3 tetrahedra in the channel-I to assist proton hopping process, while the ammonium ions show negligible contribution to enhancement of proton conductivity.

  1. Quantum teleportation through noisy channels with multi-qubit GHZ states

    NASA Astrophysics Data System (ADS)

    Espoukeh, Pakhshan; Pedram, Pouria

    2014-08-01

    We investigate two-party quantum teleportation through noisy channels for multi-qubit Greenberger-Horne-Zeilinger (GHZ) states and find which state loses less quantum information in the process. The dynamics of states is described by the master equation with the noisy channels that lead to the quantum channels to be mixed states. We analytically solve the Lindblad equation for -qubit GHZ states where Lindblad operators correspond to the Pauli matrices and describe the decoherence of states. Using the average fidelity, we show that 3GHZ state is more robust than GHZ state under most noisy channels. However, GHZ state preserves same quantum information with respect to Einstein-Podolsky-Rosen and 3GHZ states where the noise is in direction in which the fidelity remains unchanged. We explicitly show that Jung et al.'s conjecture (Phys Rev A 78:012312, 2008), namely "average fidelity with same-axis noisy channels is in general larger than average fidelity with different-axes noisy channels," is not valid for 3GHZ and 4GHZ states.

  2. Molecular mechanisms underlying pimaric acid-induced modulation of voltage-gated K+ channels.

    PubMed

    Sakamoto, Kazuho; Suzuki, Yoshiaki; Yamamura, Hisao; Ohya, Susumu; Muraki, Katsuhiko; Imaizumi, Yuji

    2017-04-01

    Voltage-gated K + (K V ) channels, which control firing and shape of action potentials in excitable cells, are supposed to be potential therapeutic targets in many types of diseases. Pimaric acid (PiMA) is a unique opener of large conductance Ca 2+ -activated K + channel. Here, we report that PiMA modulates recombinant rodent K V channel activity. The enhancement was significant at low potentials (<0 mV) but not at more positive potentials. Application of PiMA significantly shifted the voltage-activation relationships (V 1/2 ) of rodent K V 1.1, 1.2, 1.3, 1.4, 1.6 and 2.1 channels (K V 1.1-K V 2.1) but K V 4.3 to lower potentials and prolonged their half-decay times of the deactivation (T 1/2D ). The amino acid sequence which is responsible for the difference in response to PiMA was examined between K V 1.1-K V 2.1 and K V 4.3 by site-directed mutagenesis of residues in S5 and S6 segments of Kv1.1. The point mutation of Phe 332 into Tyr mimics the effects of PiMA on V 1/2 and T 1/2D and also abolished the further change by addition of PiMA. The results indicate that PiMA enhances voltage sensitivity of K V 1.1-K V 2.1 channels and suggest that the lipophilic residues including Phe 332 in S5 of K V 1.1-K V 2.1 channels may be critical for the effects of PiMA, providing beneficial information for drug development of K V channel openers. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  3. Comparison between mouse and sea urchin orthologs of voltage-gated proton channel suggests role of S3 segment in activation gating.

    PubMed

    Sakata, Souhei; Miyawaki, Nana; McCormack, Thomas J; Arima, Hiroki; Kawanabe, Akira; Özkucur, Nurdan; Kurokawa, Tatsuki; Jinno, Yuka; Fujiwara, Yuichiro; Okamura, Yasushi

    2016-12-01

    The voltage-gated proton channel, Hv1, is expressed in blood cells, airway epithelium, sperm and microglia, playing important roles in diverse biological contexts including phagocytosis or sperm maturation through its regulation of membrane potential and pH. The gene encoding Hv1, HVCN1, is widely found across many species and is also conserved in unicellular organisms such as algae or dinoflagellates where Hv1 plays role in calcification or bioluminescence. Voltage-gated proton channels exhibit a large variation of activation rate among different species. Here we identify an Hv1 ortholog from sea urchin, Strongylocentrotus purpuratus, SpHv1. SpHv1 retains most of key properties of Hv1 but exhibits 20-60 times more rapid activation kinetics than mammalian orthologs upon heterologous expression in HEK293T cells. Comparison between SpHv1 and mHv1 highlights novel roles of the third transmembrane segment S3 in activation gating of Hv1. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Development of a good-quality speech coder for transmission over noisy channels at 2.4 kb/s

    NASA Astrophysics Data System (ADS)

    Viswanathan, V. R.; Berouti, M.; Higgins, A.; Russell, W.

    1982-03-01

    This report describes the development, study, and experimental results of a 2.4 kb/s speech coder called harmonic deviations (HDV) vocoder, which transmits good-quality speech over noisy channels with bit-error rates of up to 1%. The HDV coder is based on the linear predictive coding (LPC) vocoder, and it transmits additional information over and above the data transmitted by the LPC vocoder, in the form of deviations between the speech spectrum and the LPC all-pole model spectrum at a selected set of frequencies. At the receiver, the spectral deviations are used to generate the excitation signal for the all-pole synthesis filter. The report describes and compares several methods for extracting the spectral deviations from the speech signal and for encoding them. To limit the bit-rate of the HDV coder to 2.4 kb/s the report discusses several methods including orthogonal transformation and minimum-mean-square-error scalar quantization of log area ratios, two-stage vector-scalar quantization, and variable frame rate transmission. The report also presents the results of speech-quality optimization of the HDV coder at 2.4 kb/s.

  5. Targeting mechanisms of high voltage-activated Ca2+ channels.

    PubMed

    Herlitze, Stefan; Xie, Mian; Han, Jing; Hümmer, Alexander; Melnik-Martinez, Katya V; Moreno, Rosa L; Mark, Melanie D

    2003-12-01

    Functional voltage-dependent Ca2+ channel complexes are assembled by three to four subunits: alpha1, beta, alpha2delta subunits (C. Leveque et al., 1994, J. Biol Chem. 269, 6306-6312; M. W. McEnery et al., 1991, Proc. Natl. Acad. Sci. U.S.A. 88, 11095-11099) and at least in muscle cells also y subunits (B. M. Curtis and W. A. Catterall, 1984, Biochemistry 23, 2113-2118). Ca2+ channels mediate the voltage-dependent Ca2+ influx in subcellular compartments, triggering such diverse processes as neurotransmitter release, dendritic action potentials, excitation-contraction, and excitation-transcription coupling. The targeting of biophysically defined Ca2+ channel complexes to the correct subcellular structures is, thus, critical to proper cell and physiological functioning. Despite their importance, surprisingly little is known about the targeting mechanisms by which Ca2+ channel complexes are transported to their site of function. Here we summarize what we know about the targeting of Ca2+ channel complexes through the cell to the plasma membrane and subcellular structures.

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

    PubMed Central

    Njie-Mbye, Ya F.; Opere, Catherine A.; Chitnis, Madhura; Ohia, Sunny E.

    2012-01-01

    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. PMID:22934046

  7. Structural basis of gating of CNG channels.

    PubMed

    Giorgetti, Alejandro; Nair, Anil V; Codega, Paolo; Torre, Vincent; Carloni, Paolo

    2005-03-28

    Cyclic nucleotide-gated (CNG) ion channels, underlying sensory transduction in vertebrate photoreceptors and olfactory sensory neurons, require cyclic nucleotides to open. Here, we present structural models of the tetrameric CNG channel pore from bovine rod in both open and closed states, as obtained by combining homology modeling-based techniques, experimentally derived spatial constraints and structural patterns present in the PDB database. Gating is initiated by an anticlockwise rotation of the N-terminal region of the C-linker, which is then, transmitted through the S6 transmembrane helices to the P-helix, and in turn from this to the pore lumen, which opens up from 2 to 5A thus allowing for ion permeation. The approach, here presented, is expected to provide a general methodology for model ion channels and their gating when structural templates are available and an extensive electrophysiological analysis has been performed.

  8. Analysis by metadynamics simulation of binding pathway of influenza virus M2 channel blockers.

    PubMed

    Sakai, Yuri; Kawaguchi, Atsushi; Nagata, Kyosuke; Hirokawa, Takatsugu

    2018-01-01

    M2 protein of influenza A virus is a proton channel spanning the viral envelope. Activity of this proton channel is required for uncoating of viral particles and equilibrating the pH across the trans Golgi apparatus, which prevents conformational change in hemagglutinin. Amantadine, an anti-influenza A virus drug, inhibits M2 proton channel activity by binding to the channel pore; however, most currently circulating influenza A viruses are amantadine-resistant. The most prevalent resistant mutation is a substitution from Ser31 to Asn31 in M2. Further atomistic analysis of ligand-M2 complexes is needed to provide new approaches for the design of novel M2 channel blockers. Here, the free energy profiles of the binding kinetics of M2 channel blockers were examined by well-tempered metadynamics simulations and it was found that amantadine first binds to Asp24 of S31 M2 and forms a metastable conformation. In contrast, the free energy profiles of adamantyl bromothiophene dual inhibitor with either S31 M2 or N31 M2 are broad funnel-shaped curves, suggesting that adamantyl bromothiophene does not form metastable complexes with M2. The trajectory of well-tempered metadynamics simulations revealed that steric hindrance between adamantyl bromothiophene and S31 M2 interrupts formation of a metastable conformation at Asp24 and that a halogen bond between the bromine atom and N31 is responsible for pulling down the ligand to the channel pore of N31 M2 in the absence of a metastable state. Binding pathways of M2 channel blockers to M2 are here proposed on the basis of these findings; they may provide new approaches to designing further M2 channel blockers. © 2017 The Societies and John Wiley & Sons Australia, Ltd.

  9. A point mutation in the human Slo1 channel that impairs its sensitivity to omega-3 docosahexaenoic acid

    PubMed Central

    Xu, Rong; Hou, Shangwei; Heinemann, Stefan H.; Tian, Yutao

    2013-01-01

    Long-chain polyunsaturated omega-3 fatty acids such as docosahexaenoic acid (DHA) at nanomolar concentrations reversibly activate human large-conductance Ca2+- and voltage-gated K+ (Slo1 BK) channels containing auxiliary β1 or β4 subunits in cell-free patches. Here we examined the action of DHA on the Slo1 channel without any auxiliary subunit and sought to elucidate the biophysical mechanism and the molecular determinants of the DHA sensitivity. Measurements of ionic currents through human Slo1 (hSlo1) channels reveal that the stimulatory effect of DHA does not require activation of the voltage or Ca2+ sensors. Unlike gating of the hSlo1 channel, that of the Drosophila melanogaster Slo1 (dSlo1) channel is unaltered by DHA. Our mutagenesis study based on the differential responses of human and dSlo1 channels to DHA pinpoints that Y318 near the cytoplasmic end of S6 in the hSlo1 channel is a critical determinant of the stimulatory action of DHA. The mutation Y318S in hSlo1, which replaces Y with S as found in dSlo1, greatly diminishes the channel’s response to DHA with a 22-carbon chain whether β1 or β4 is absent or present. However, the responses to α-linolenic acid, an omegea-3 fatty acid with an 18-carbon chain, and to arachidonic acid, an omega-6 fatty acid with a 20-carbon chain, remain unaffected by the mutation. Y318 in the S6 segment of hSlo1 is thus an important determinant of the electrophysiological response of the channel to DHA. Furthermore, the mutation Y318S may prove to be useful in dissecting out the complex lipid-mediated modulation of Slo1 BK channels. PMID:24127525

  10. Drowned reefs and antecedent karst topography, Au'au channel, S.E. Hawaiian Islands

    USGS Publications Warehouse

    Grigg, R.W.; Grossman, E.E.; Earle, S.A.; Gittings, S.R.; Lott, D.; McDonough, J.

    2002-01-01

    During the last glacial maximum (LGM), about 21,000 years ago, the Hawaiian Islands of Maui, Lanai, and Molokai were interconnected by limestone bridges, creating a super-island known as Maui-Nui. Approximately 120 m of sea-level rise during the Holocene Transgression flooded, and then drowned, these bridges separating the islands by inter-island channels. A new multibeam high-resolution bathymetric survey of the channels between the islands, coupled with observations and video-transects utilizing DeepWorker-2000 submersibles, has revealed the existence of numerous drowned reef features including concentric solution basins, solution ridges (rims), sand and sediment plains, and conical-shaped reef pinnacles. The concentric basins contain flat lagoon-like bottoms that are rimmed by steep-sided limestone walls. Undercut notches rim the basins at several depths, marking either sea-level still stands or paleo-lake levels. All of the solution basins shallower than 120 m were subaerial at the LGM, and at one stage or another may have been shallow shoreline lakes. Today, about 70 drowned reef pinnacles are scattered across the Maui-Lanai underwater bridge and all are situated in wave-sheltered positions. Most drowned during the interval between 14,000 and 10,000 years ago when sea-level rise averaged 15 mm/year. Virtually all of the surficial topography in the Au'au Channel today is a product of karst processes accentuated by marginal reef growth during the Holocene. Both the submerged basins and the drowned reefs represent an archive of sea-level and climate history in Hawaii during the late Quaternary.

  11. 47 CFR 15.707 - Permissible channels of operation.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    .... These channels will be identified and protected in the TV bands database(s). (b) Operation on available...) of this section and as determined by a TV bands database in accordance with the interference...

  12. Practical gigahertz quantum key distribution robust against channel disturbance.

    PubMed

    Wang, Shuang; Chen, Wei; Yin, Zhen-Qiang; He, De-Yong; Hui, Cong; Hao, Peng-Lei; Fan-Yuan, Guan-Jie; Wang, Chao; Zhang, Li-Jun; Kuang, Jie; Liu, Shu-Feng; Zhou, Zheng; Wang, Yong-Gang; Guo, Guang-Can; Han, Zheng-Fu

    2018-05-01

    Quantum key distribution (QKD) provides an attractive solution for secure communication. However, channel disturbance severely limits its application when a QKD system is transferred from the laboratory to the field. Here a high-speed Faraday-Sagnac-Michelson QKD system is proposed that can automatically compensate for the channel polarization disturbance, which largely avoids the intermittency limitations of environment mutation. Over a 50 km fiber channel with 30 Hz polarization scrambling, the practicality of this phase-coding QKD system was characterized with an interference fringe visibility of 99.35% over 24 h and a stable secure key rate of 306 k bits/s over seven days without active polarization alignment.

  13. Truthful Channel Sharing for Self Coexistence of Overlapping Medical Body Area Networks

    PubMed Central

    Dutkiewicz, Eryk; Zheng, Guanglou

    2016-01-01

    As defined by IEEE 802.15.6 standard, channel sharing is a potential method to coordinate inter-network interference among Medical Body Area Networks (MBANs) that are close to one another. However, channel sharing opens up new vulnerabilities as selfish MBANs may manipulate their online channel requests to gain unfair advantage over others. In this paper, we address this issue by proposing a truthful online channel sharing algorithm and a companion protocol that allocates channel efficiently and truthfully by punishing MBANs for misreporting their channel request parameters such as time, duration and bid for the channel. We first present an online channel sharing scheme for unit-length channel requests and prove that it is truthful. We then generalize our model to settings with variable-length channel requests, where we propose a critical value based channel pricing and preemption scheme. A bid adjustment procedure prevents unbeneficial preemption by artificially raising the ongoing winner’s bid controlled by a penalty factor λ. Our scheme can efficiently detect selfish behaviors by monitoring a trust parameter α of each MBAN and punish MBANs from cheating by suspending their requests. Our extensive simulation results show our scheme can achieve a total profit that is more than 85% of the offline optimum method in the typical MBAN settings. PMID:26844888

  14. The Natural Plant Product Rottlerin Activates Kv7.1/KCNE1 Channels.

    PubMed

    Matschke, Veronika; Piccini, Ilaria; Schubert, Janina; Wrobel, Eva; Lang, Florian; Matschke, Johann; Amedonu, Elsie; Meuth, Sven G; Strünker, Timo; Strutz-Seebohm, Nathalie; Greber, Boris; Scherkenbeck, Jürgen; Seebohm, Guiscard

    2016-01-01

    Acquired as well as inherited channelopathies are disorders that are caused by altered ion channel function. A family of channels whose malfunction is associated with different channelopathies is the Kv7 K+ channel family; and restoration of normal Kv7 channel function by small molecule modulators is a promising approach for treatment of these often fatal diseases. Here, we show the modulation of Kv7 channels by the natural compound Rottlerin heterologously expressed in Xenopus laevis oocytes and on iPSC cardiomyocytes overexpressing Kv7.1 channels. We show that currents carried by Kv7.1 (EC50 = 1.48 μM), Kv7.1/KCNE1 (EC50 = 4.9 μM), and Kv7.4 (EC50 = 0.148 μM) are strongly enhanced by the compound, whereas Kv7.2, Kv7.2/Kv7.3, and Kv7.5 are not sensitive to Rottlerin. Studies on Kv7.1/KCNE1 mutants and in silico modelling indicate that Rottlerin binds to the R-L3-activator site. Rottlerin mediated activation of Kv7.1/KCNE1 channels might be a promising approach in long QT syndrome. As a proof of concept, we show that Rottlerin shortens cardiac repolarisation in iPSC-derived cardiomyocytes expressing Kv7.1. Rottlerin or an optimized derivative holds a potential as QT interval correcting drug. © 2016 The Author(s) Published by S. Karger AG, Basel.

  15. Use of Small Fluorescent Molecules to Monitor Channel Activity

    NASA Astrophysics Data System (ADS)

    Jones, Sharon; Stringer, Sarah; Naik, Rajesh; Stone, Morley

    2001-03-01

    The Mechanosensitive channel of Large conductance (MscL) allows bacteria to rapidly adapt to changing environmental conditions such as osmolarity. The MscL channel opens in response to increases in membrane tension, which allows for the efflux of cytoplasmic constituents. Here we describe the cloning and expression of Salmonella typhimurium MscL (St-MscL). Using a fluorescence efflux assay, we demonstrate that efflux through the MscL channel during hypoosmotic shock can be monitored using endogenously produced fluorophores. In addition, we observe that thermal stimulation, i.e., heat shock, can also induce efflux through MscL. We present the first evidence of thermal activation of MscL efflux by heat shocking cells expressing the S. typhimurium protein variant. This finding has significant biosensor implications, especially for investigators exploring the use of channel proteins in biosensor applications. Thermal biosensors are relatively unexplored, but would have considerable commercial and military utility.

  16. A Disease Mutation Causing Episodic Ataxia Type I in the S1 Links Directly to the Voltage Sensor and the Selectivity Filter in Kv Channels.

    PubMed

    Petitjean, Dimitri; Kalstrup, Tanja; Zhao, Juan; Blunck, Rikard

    2015-09-02

    The mutation F184C in Kv1.1 leads to development of episodic ataxia type I (EA1). Although the mutation has been said to alter activation kinetics and to lower expression, we show here that the underlying molecular mechanisms may be more complex. Although F184 is positioned in the "peripheral" S1 helix, it occupies a central position in the 3D fold. We show in cut-open oocyte voltage-clamp recordings of gating and ionic currents of the Shaker Kv channel expressed in Xenopus oocytes that F184 not only interacts directly with the gating charges of the S4, but also creates a functional link to the selectivity filter of the neighboring subunit. This link leads to impaired fast and slow inactivation. The effect on fast inactivation is of an allosteric nature considering that fast inactivation is caused by a linked cytosolic ball peptide. The extensive effects of F184C provide a new mechanism underlying EA. Episodic ataxia (EA) is an inherited disease that leads to occasional loss of motor control in combination with variable other symptoms such as vertigo or migraine. EA type I (EA1), studied here, is caused by mutations in a voltage-gated potassium channel that contributes to the generation of electrical signals in the brain. The mechanism by which mutations in voltage-gated potassium channels lead to EA is still unknown and there is no consistent pharmacological treatment. By studying in detail one disease-causing mutation in Kv1.1, we describe a novel molecular mechanism distinct from mechanisms described previously. This mechanism contributes to the understanding of potassium channel function in general and might lead to a better understanding of how EA develops. Copyright © 2015 the authors 0270-6474/15/3512198-09$15.00/0.

  17. A linearization of quantum channels

    NASA Astrophysics Data System (ADS)

    Crowder, Tanner

    2015-06-01

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

  18. Search for s channel single top quark production in pp collisions at $$ \\sqrt{s}=7 $$ and 8 TeV

    DOE PAGES

    Khachatryan, V.; Sirunyan, A. M.; Tumasyan, A.; ...

    2016-09-06

    In this study, a search is presented for single top quark production in the s channel in proton-proton collisions with the CMS detector at the CERN LHC in decay modes of the top quark containing a muon or an electron in the final state. The signal is extracted through a maximum-likelihood fit to the distribution of a multivariate discriminant defined using boosted decision trees to separate the expected signal contribution from background processes. The analysis uses data collected at centre-of-mass energies of 7 and 8 TeV and corresponding to integrated luminosities of 5.1 and 19.7 fb –1, respectively. The measuredmore » cross sections of 7.1 ± 8.1 pb (at 7 TeV) and 13.4 ± 7.3 pb (at 8 TeV) result in a best fit value of 2.0 ± 0.9 for the combined ratio of the measured and expected values. The signal significance is 2.5 standard deviations, and the upper limit on the rate relative to the standard model expectation is 4.7 at 95% confidence level.« less

  19. Search for s channel single top quark production in pp collisions at $$ \\sqrt{s}=7 $$ and 8 TeV

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Khachatryan, V.; Sirunyan, A. M.; Tumasyan, A.

    In this study, a search is presented for single top quark production in the s channel in proton-proton collisions with the CMS detector at the CERN LHC in decay modes of the top quark containing a muon or an electron in the final state. The signal is extracted through a maximum-likelihood fit to the distribution of a multivariate discriminant defined using boosted decision trees to separate the expected signal contribution from background processes. The analysis uses data collected at centre-of-mass energies of 7 and 8 TeV and corresponding to integrated luminosities of 5.1 and 19.7 fb –1, respectively. The measuredmore » cross sections of 7.1 ± 8.1 pb (at 7 TeV) and 13.4 ± 7.3 pb (at 8 TeV) result in a best fit value of 2.0 ± 0.9 for the combined ratio of the measured and expected values. The signal significance is 2.5 standard deviations, and the upper limit on the rate relative to the standard model expectation is 4.7 at 95% confidence level.« less

  20. Mechanically Activated Ion Channels

    PubMed Central

    Ranade, Sanjeev S.; Syeda, Ruhma; Patapoutian, Ardem

    2015-01-01

    Mechanotransduction, the conversion of physical forces into biochemical signals, is an essential component of numerous physiological processes including not only conscious senses of touch and hearing, but also unconscious senses such as blood pressure regulation. Mechanically activated (MA) ion channels have been proposed as sensors of physical force, but the identity of these channels and an understanding of how mechanical force is transduced has remained elusive. A number of recent studies on previously known ion channels along with the identification of novel MA ion channels have greatly transformed our understanding of touch and hearing in both vertebrates and invertebrates. Here, we present an updated review of eukaryotic ion channel families that have been implicated in mechanotransduction processes and evaluate the qualifications of the candidate genes according to specified criteria. We then discuss the proposed gating models for MA ion channels and highlight recent structural studies of mechanosensitive potassium channels. PMID:26402601

  1. Peroxisomal Pex11 is a pore-forming protein homologous to TRPM channels.

    PubMed

    Mindthoff, Sabrina; Grunau, Silke; Steinfort, Laura L; Girzalsky, Wolfgang; Hiltunen, J Kalervo; Erdmann, Ralf; Antonenkov, Vasily D

    2016-02-01

    More than 30 proteins (Pex proteins) are known to participate in the biogenesis of peroxisomes-ubiquitous oxidative organelles involved in lipid and ROS metabolism. The Pex11 family of homologous proteins is responsible for division and proliferation of peroxisomes. We show that yeast Pex11 is a pore-forming protein sharing sequence similarity with TRPM cation-selective channels. The Pex11 channel with a conductance of Λ=4.1 nS in 1.0M KCl is moderately cation-selective (PK(+)/PCl(-)=1.85) and resistant to voltage-dependent closing. The estimated size of the channel's pore (r~0.6 nm) supports the notion that Pex11 conducts solutes with molecular mass below 300-400 Da. We localized the channel's selectivity determining sequence. Overexpression of Pex11 resulted in acceleration of fatty acids β-oxidation in intact cells but not in the corresponding lysates. The β-oxidation was affected in cells by expression of the Pex11 protein carrying point mutations in the selectivity determining sequence. These data suggest that the Pex11-dependent transmembrane traffic of metabolites may be a rate-limiting step in the β-oxidation of fatty acids. This conclusion was corroborated by analysis of the rate of β-oxidation in yeast strains expressing Pex11 with mutations mimicking constitutively phosphorylated (S165D, S167D) or unphosphorylated (S165A, S167A) protein. The results suggest that phosphorylation of Pex11 is a mechanism that can control the peroxisomal β-oxidation rate. Our results disclose an unexpected function of Pex11 as a non-selective channel responsible for transfer of metabolites across peroxisomal membrane. The data indicate that peroxins may be involved in peroxisomal metabolic processes in addition to their role in peroxisome biogenesis. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Mutations in the voltage-sensing domain affect the alternative ion permeation pathway in the TRPM3 channel.

    PubMed

    Held, Katharina; Gruss, Fabian; Aloi, Vincenzo Davide; Janssens, Annelies; Ulens, Chris; Voets, Thomas; Vriens, Joris

    2018-03-31

    Mutagenesis at positively charged amino acids (arginines and lysines) (R1-R4) in the voltage-sensor domain (transmembrane segment (S) 4) of voltage-gated Na + , K + and Ca 2+ channels can lead to an alternative ion permeation pathway distinct from the central pore. Recently, a non-canonical ion permeation pathway was described in TRPM3, a member of the transient receptor potential (TRP) superfamily. The non-canonical pore exists in the native TRPM3 channel and can be activated by co-stimulation of the endogenous agonist pregnenolone sulphate and the antifungal drug clotrimazole or by stimulation of the synthetic agonist CIM0216. Alignment of the voltage sensor of Shaker K + channels with the entire TRPM3 sequence revealed the highest degree of similarity in the putative S4 region of TRPM3, and suggested that only one single gating charge arginine (R2) in the putative S4 region is conserved. Mutagenesis studies in the voltage-sensing domain of TRPM3 revealed several residues in the voltage sensor (S4) as well as in S1 and S3 that are crucial for the occurrence of the non-canonical inward currents. In conclusion, this study provides evidence for the involvement of the voltage-sensing domain of TRPM3 in the formation of an alternative ion permeation pathway. Transient receptor potential (TRP) channels are cationic channels involved in a broad array of functions, including homeostasis, motility and sensory functions. TRP channel subunits consist of six transmembrane segments (S1-S6), and form tetrameric channels with a central pore formed by the region encompassing S5 and S6. Recently, evidence was provided for the existence of an alternative ion permeation pathway in TRPM3, which allows large inward currents upon hyperpolarization independently of the central pore. However, very little knowledge is available concerning the localization of this alternative pathway in the native TRPM3 channel protein. Guided by sequence homology with Shaker K + channels, in which

  3. Rational design and validation of a vanilloid-sensitive TRPV2 ion channel

    PubMed Central

    Yang, Fan; Vu, Simon; Yarov-Yarovoy, Vladimir; Zheng, Jie

    2016-01-01

    Vanilloids activation of TRPV1 represents an excellent model system of ligand-gated ion channels. Recent studies using cryo-electron microcopy (cryo-EM), computational analysis, and functional quantification revealed the location of capsaicin-binding site and critical residues mediating ligand-binding and channel activation. Based on these new findings, here we have successfully introduced high-affinity binding of capsaicin and resiniferatoxin to the vanilloid-insensitive TRPV2 channel, using a rationally designed minimal set of four point mutations (F467S–S498F–L505T–Q525E, termed TRPV2_Quad). We found that binding of resiniferatoxin activates TRPV2_Quad but the ligand-induced open state is relatively unstable, whereas binding of capsaicin to TRPV2_Quad antagonizes resiniferatoxin-induced activation likely through competition for the same binding sites. Using Rosetta-based molecular docking, we observed a common structural mechanism underlying vanilloids activation of TRPV1 and TRPV2_Quad, where the ligand serves as molecular “glue” that bridges the S4–S5 linker to the S1–S4 domain to open these channels. Our analysis revealed that capsaicin failed to activate TRPV2_Quad likely due to structural constraints preventing such bridge formation. These results not only validate our current working model for capsaicin activation of TRPV1 but also should help guide the design of drug candidate compounds for this important pain sensor. PMID:27298359

  4. Phosphorylation regulates the sensitivity of voltage-gated Kv7.2 channels towards phosphatidylinositol-4,5-bisphosphate.

    PubMed

    Salzer, Isabella; Erdem, Fatma Asli; Chen, Wei-Qiang; Heo, Seok; Koenig, Xaver; Schicker, Klaus W; Kubista, Helmut; Lubec, Gert; Boehm, Stefan; Yang, Jae-Won

    2017-02-01

    Phosphatidylinositol-4,5-bisphosphate (PIP 2 ) is a key regulator of many membrane proteins, including voltage-gated Kv7.2 channels. In this study, we identified the residues in five phosphorylation sites and their corresponding protein kinases, the former being clustered within one of four putative PIP 2 -binding domains in Kv7.2. Dephosphorylation of these residues reduced the sensitivity of Kv7.2 channels towards PIP 2 . Dephosphorylation of Kv7.2 affected channel inhibition via M 1 muscarinic receptors, but not via bradykinin receptors. Our data indicated that phosphorylation of the Kv7.2 channel was necessary to maintain its low affinity for PIP 2 , thereby ensuring the tight regulation of the channel via G protein-coupled receptors. The function of numerous ion channels is tightly controlled by G protein-coupled receptors (GPCRs). The underlying signalling mechanisms may involve phosphorylation of channel proteins and participation of phosphatidylinositol-4,5-bisphosphate (PIP 2 ). Although the roles of both mechanisms have been investigated extensively, thus far only little has been reported on their interaction in channel modulation. GPCRs govern Kv7 channels, the latter playing a major role in the regulation of neuronal excitability by determining the levels of PIP 2 and through phosphorylation. Using liquid chromatography-coupled mass spectrometry for Kv7.2 immunoprecipitates of rat brain membranes and transfected cells, we mapped a cluster of five phosphorylation sites in one of the PIP2-binding domains. To evaluate the effect of phosphorylation on PIP 2 -mediated Kv7.2 channel regulation, a quintuple alanine mutant of these serines (S427/S436/S438/S446/S455; A 5 mutant) was generated to mimic the dephosphorylated state. Currents passing through these mutated channels were less sensitive towards PIP 2 depletion via the voltage-sensitive phosphatase Dr-VSP than were wild-type channels. In vitro phosphorylation assays with the purified C-terminus of Kv7

  5. Properties of Single K+ and Cl− Channels in Asclepias tuberosa Protoplasts 1

    PubMed Central

    Schauf, Charles L.; Wilson, Kathryn J.

    1987-01-01

    Potassium and chloride channels were characterized in Asclepias tuberosa suspension cell derived protoplasts by patch voltage-clamp. Whole-cell currents and single channels in excised patches had linear instantaneous current-voltage relations, reversing at the Nernst potentials for K+ and Cl−, respectively. Whole cell K+ currents activated exponentially during step depolarizations, while voltage-dependent Cl− channels were activated by hyperpolarizations. Single K+ channel conductance was 40 ± 5 pS with a mean open time of 4.5 milliseconds at 100 millivolts. Potassium channels were blocked by Cs+ and tetraethylammonium, but were insensitive to 4-aminopyridine. Chloride channels had a single-channel conductance of 100 ± 17 picosiemens, mean open time of 8.8 milliseconds, and were blocked by Zn2+ and ethacrynic acid. Whole-cell Cl− currents were inhibited by abscisic acid, and were unaffected by indole-3-acetic acid and 2,4-dichlorophenoxyacetic acid. Since internal and external composition can be controlled, patch-clamped protoplasts are ideal systems for studying the role of ion channels in plant physiology and development. Images Fig. 5 PMID:16665712

  6. Purified ryanodine receptor from rabbit skeletal muscle is the calcium- release channel of sarcoplasmic reticulum

    PubMed Central

    1988-01-01

    The ryanodine receptor of rabbit skeletal muscle sarcoplasmic reticulum was purified as a single 450,000-dalton polypeptide from CHAPS- solubilized triads using immunoaffinity chromatography. The purified receptor had a [3H]ryanodine-binding capacity (Bmax) of 490 pmol/mg and a binding affinity (Kd) of 7.0 nM. Using planar bilayer recording techniques, we show that the purified receptor forms cationic channels selective for divalent ions. Ryanodine receptor channels were identical to the Ca-release channels described in native sarcoplasmic reticulum using the same techniques. In the present work, four criteria were used to establish this identity: (a) activation of channels by micromolar Ca and millimolar ATP and inhibition by micromolar ruthenium red, (b) a main channel conductance of 110 +/- 10 pS in 54 mM trans Ca, (c) a long- term open state of lower unitary conductance induced by ryanodine concentrations as low as 20 nM, and (d) a permeability ratio PCa/PTris approximately equal to 14. In addition, we show that the purified ryanodine receptor channel displays a saturable conductance in both monovalent and divalent cation solutions (gamma max for K and Ca = 1 nS and 172 pS, respectively). In the absence of Ca, channels had a broad selectivity for monovalent cations, but in the presence of Ca, they were selectively permeable to Ca against K by a permeability ratio PCa/PK approximately equal to 6. Receptor channels displayed several equivalent conductance levels, which suggest an oligomeric pore structure. We conclude that the 450,000-dalton polypeptide ryanodine receptor is the Ca-release channel of the sarcoplasmic reticulum and is the target site of ruthenium red and ryanodine. PMID:2459298

  7. KCNE1 remodels the voltage sensor of Kv7.1 to modulate channel function.

    PubMed

    Wu, Dick; Pan, Hua; Delaloye, Kelli; Cui, Jianmin

    2010-12-01

    The KCNE1 auxiliary subunit coassembles with the Kv7.1 channel and modulates its properties to generate the cardiac I(Ks) current. Recent biophysical evidence suggests that KCNE1 interacts with the voltage-sensing domain (VSD) of Kv7.1. To investigate the mechanism of how KCNE1 affects the VSD to alter the voltage dependence of channel activation, we perturbed the VSD of Kv7.1 by mutagenesis and chemical modification in the absence and presence of KCNE1. Mutagenesis of S4 in Kv7.1 indicates that basic residues in the N-terminal half (S4-N) and C-terminal half (S4-C) of S4 are important for stabilizing the resting and activated states of the channel, respectively. KCNE1 disrupts electrostatic interactions involving S4-C, specifically with the lower conserved glutamate in S2 (Glu(170) or E2). Likewise, Trp scanning of S4 shows that mutations to a cluster of residues in S4-C eliminate current in the presence of KCNE1. In addition, KCNE1 affects S4-N by enhancing MTS accessibility to the top of the VSD. Consistent with the structure of Kv channels and previous studies on the KCNE1-Kv7.1 interaction, these results suggest that KCNE1 alters the interactions of S4 residues with the surrounding protein environment, possibly by changing the protein packing around S4, thereby affecting the voltage dependence of Kv7.1. Copyright © 2010 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  8. Phosphorylation regulates the sensitivity of voltage‐gated Kv7.2 channels towards phosphatidylinositol‐4,5‐bisphosphate

    PubMed Central

    Salzer, Isabella; Erdem, Fatma Asli; Chen, Wei‐Qiang; Heo, Seok; Koenig, Xaver; Schicker, Klaus W.; Kubista, Helmut; Lubec, Gert; Boehm, Stefan

    2016-01-01

    Key points Phosphatidylinositol‐4,5‐bisphosphate (PIP2) is a key regulator of many membrane proteins, including voltage‐gated Kv7.2 channels.In this study, we identified the residues in five phosphorylation sites and their corresponding protein kinases, the former being clustered within one of four putative PIP2‐binding domains in Kv7.2.Dephosphorylation of these residues reduced the sensitivity of Kv7.2 channels towards PIP2.Dephosphorylation of Kv7.2 affected channel inhibition via M1 muscarinic receptors, but not via bradykinin receptors.Our data indicated that phosphorylation of the Kv7.2 channel was necessary to maintain its low affinity for PIP2, thereby ensuring the tight regulation of the channel via G protein‐coupled receptors. Abstract The function of numerous ion channels is tightly controlled by G protein‐coupled receptors (GPCRs). The underlying signalling mechanisms may involve phosphorylation of channel proteins and participation of phosphatidylinositol‐4,5‐bisphosphate (PIP2). Although the roles of both mechanisms have been investigated extensively, thus far only little has been reported on their interaction in channel modulation. GPCRs govern Kv7 channels, the latter playing a major role in the regulation of neuronal excitability by determining the levels of PIP2 and through phosphorylation. Using liquid chromatography‐coupled mass spectrometry for Kv7.2 immunoprecipitates of rat brain membranes and transfected cells, we mapped a cluster of five phosphorylation sites in one of the PIP2‐binding domains. To evaluate the effect of phosphorylation on PIP2‐mediated Kv7.2 channel regulation, a quintuple alanine mutant of these serines (S427/S436/S438/S446/S455; A5 mutant) was generated to mimic the dephosphorylated state. Currents passing through these mutated channels were less sensitive towards PIP2 depletion via the voltage‐sensitive phosphatase Dr‐VSP than were wild‐type channels. In vitro phosphorylation assays with the

  9. Performance Analysis of Iterative Channel Estimation and Multiuser Detection in Multipath DS-CDMA Channels

    NASA Astrophysics Data System (ADS)

    Li, Husheng; Betz, Sharon M.; Poor, H. Vincent

    2007-05-01

    This paper examines the performance of decision feedback based iterative channel estimation and multiuser detection in channel coded aperiodic DS-CDMA systems operating over multipath fading channels. First, explicit expressions describing the performance of channel estimation and parallel interference cancellation based multiuser detection are developed. These results are then combined to characterize the evolution of the performance of a system that iterates among channel estimation, multiuser detection and channel decoding. Sufficient conditions for convergence of this system to a unique fixed point are developed.

  10. Continuum Level Density of a Coupled-Channel System in the Complex Scaling Method

    NASA Astrophysics Data System (ADS)

    Suzuki, R.; Kruppa, A. T.; Giraud, B. G.; Katō, K.

    2008-06-01

    We study the continuum level density (CLD) in the formalism of the complex scaling method (CSM) for coupled-channel systems. We apply the formalism to the ^{4}He = [^{3}H + p] + [^3{He} + n] coupled-channel cluster model where there are resonances at low energy. Numerical calculations of the CLD in the CSM with a finite number of L^{2} basis functions are consistent with the exact result calculated from the S-matrix by solving coupled-channel equations. We also study channel densities. In this framework, the extended completeness relation (ECR) plays an important role.

  11. Relevance of quantum mechanics on some aspects of ion channel function

    PubMed Central

    Roy, Sisir

    2010-01-01

    Mathematical modeling of ionic diffusion along K ion channels indicates that such diffusion is oscillatory, at the weak non-Markovian limit. This finding leads us to derive a Schrödinger–Langevin equation for this kind of system within the framework of stochastic quantization. The Planck’s constant is shown to be relevant to the Lagrangian action at the level of a single ion channel. This sheds new light on the issue of applicability of quantum formalism to ion channel dynamics and to the physical constraints of the selectivity filter. PMID:19520314

  12. Channel adjustments to historical disturbances along the lower Brazos and Sabine Rivers, south-central USA

    NASA Astrophysics Data System (ADS)

    Heitmuller, Franklin T.

    2014-01-01

    Historical channel adjustments are documented and discussed in context with anthropogenic disturbances along two meandering, coastal plain rivers - the lower Brazos and Sabine Rivers in the south-central United States. Hard-copy streamflow-measurement notes of the U.S. Geological Survey were utilized to render historical cross sections (1925-2007) at nine gauging stations, which were complemented with repeat photographs and flood-frequency analysis to assess trajectories of channel change and interpret causative mechanisms. Downstream- and upstream-propagating disturbances caused episodes of channel-bed incision and aggradation at different locations for distinct time periods along both rivers. Incision associated with upstream dams is detected, but channels are compensated downstream with sediment inputs from lateral channel migration and tributaries. In one case, temporary aggradation along the Brazos River at Waco was likely caused by a combination of dam construction and regional soil erosion. Channel-bed incision on the lowermost Brazos River is unrelated to dams, but is associated with instream aggregate extraction, possibly in conjunction with downstream channelization. On the Sabine River, extensive aggradation during the 1930s might be associated with logging activities (1880s-1930s), but whether the cause is pervasive regional-scale hillslope erosion or local-scale mill-site activities is indeterminate. Following passage of this sediment, the river generally recovered to pre-disturbance conditions and has exhibited stability despite a mainstem reservoir. Translation of this sediment slug is attenuated by a transition to a flood-prone, distributary-dominated system downstream of the Holocene-Pleistocene terrace onlap position. Additional findings include cross-channel hingepoints separating thalweg incision from simultaneous point-bar or bank accretion at meander bends, which indicates channel adjustment occurs along non-cohesive beds in preference to

  13. Pharmacology of the human red cell voltage-dependent cation channel; Part I. Activation by clotrimazole and analogues.

    PubMed

    Barksmann, Trine L; Kristensen, Berit I; Christophersen, Palle; Bennekou, Poul

    2004-01-01

    The activation and pharmacological modulation of the nonselective voltage-dependent cation (NSVDC) channel from human erythrocytes were studied. Basic channel activation was achieved by suspending red cells in a low Cl(-) Ringer (2 mM), where a positive membrane potential (V(m) = E(Cl)) immediately developed. Voltage- and time-dependent activation of the NSVDC channel occurred, reaching a cation conductance (g+) of 1.5-2.0 microS cm(-2). In the presence of the classical Gárdos channel blocker clotrimazole (0-50 microM), activation occurred faster, and g+ saturated dose-dependently (EC50 = 14 microM) at a value of about 4 microS cm(-2). The clotrimazole analogues TRAM-34, econazole, and miconazole also stimulated the channel, whereas the chemically more distant Gárdos channel inhibitors nitrendipine and cetiedil had no effects. Although the potency for modulation of the NSVDC channel is much lower than the IC50 value for Gárdos channel inhibition, clotrimazole (and its analogues) constitutes the first chemical class of positive modulators of the NSVDC channel. This may be an important pharmacological "fingerprint" in the identification of the cloned equivalent of the erythrocyte channel.

  14. Lateral movement and stability of channel banks near four highway crossings in southwestern Mississippi

    USGS Publications Warehouse

    Turnipseed, D. Phil

    1994-01-01

    Channel meandering in alluvial streams has caused localized channel instability that has resulted in bridge failure and loss of human life in Mississippi. The U.S. Geological Survey, in coopera- tion with the Mississippi Department of Transpor- tation, conducted a study to develop a better methodology for defining and estimating channel meandering. For this report, river reaches near four bridge sites with current lateral movement of channel banks were selected for study. The lateral movement of channel banks was studied by mapping meanders from aerial photographs taken at various times, evaluating available discharge measurements, and measuring existing channel geometry and soil strength properties at these sites. Rapid, unre- stricted meander cuts and sandy banks are charac- teristic of the sites. Lateral movement was signi- ficant upstream from all four sites, and only one bridge site did not have significant lateral channel-bank movement during the study period. The development of cutbanks and localized channel-bank erosion have caused unstable conditions at three of the sites. Maps of tops of channel indicate significant lateral movement of channel banks upstream and downstream of all four sites and near the bridges at three of four sites. No significant movement occurred at the U.S. Highway 98 crossing of the Bogue Chitto near Tylertown from 1941 to 1991 despite large floods in 1983 and 1990. Slope stability analyses indicated this site to be marginally stable. The maximum lateral movement indicated from maps of tops of channel banks was 680 feet of northward movement of the right (north) bank of the Homochitto River near the State Highway 33 crossing at Rosetta from 1941 to 1983.

  15. Molecular basis of the interaction between gating modifier spider toxins and the voltage sensor of voltage-gated ion channels

    NASA Astrophysics Data System (ADS)

    Lau, Carus H. Y.; King, Glenn F.; Mobli, Mehdi

    2016-09-01

    Voltage-sensor domains (VSDs) are modular transmembrane domains of voltage-gated ion channels that respond to changes in membrane potential by undergoing conformational changes that are coupled to gating of the ion-conducting pore. Most spider-venom peptides function as gating modifiers by binding to the VSDs of voltage-gated channels and trapping them in a closed or open state. To understand the molecular basis underlying this mode of action, we used nuclear magnetic resonance to delineate the atomic details of the interaction between the VSD of the voltage-gated potassium channel KvAP and the spider-venom peptide VSTx1. Our data reveal that the toxin interacts with residues in an aqueous cleft formed between the extracellular S1-S2 and S3-S4 loops of the VSD whilst maintaining lipid interactions in the gaps formed between the S1-S4 and S2-S3 helices. The resulting network of interactions increases the energetic barrier to the conformational changes required for channel gating, and we propose that this is the mechanism by which gating modifier toxins inhibit voltage-gated ion channels.

  16. The pore properties of human nociceptor channel TRPA1 evaluated in single channel recordings

    PubMed Central

    Bobkov, Y.V.; Corey, E.A.; Ache, B.W.

    2011-01-01

    TRPA channels detect stimuli of different sensory modalities, including a broad spectrum of chemosensory stimuli, noxious stimuli associated with tissue damage and inflammation, mechanical stimuli, and thermal stimuli. Despite a growing understanding of potential modulators, agonists, and antagonists for these channels, the exact mechanisms of channel regulation and activation remain mostly unknown or controversial and widely debated. Relatively little is also known about the basic biophysical parameters of both native and heterologously expressed TRPA channels. Here we use conventional single channel inside-out and outside-out patch recording from the human TRPA1 channel transiently expressed in human embryonic kidney 293T cells to characterize the selectivity of the channel for inorganic mono-/divalent and organic monovalent cations in the presence of Allylisothiocyanate (AITC). We show the relative permeability of the hTRPA1 channel to inorganic cations to be: Ca2+(5.1)>Ba2+(3.5)>Mg2+(2.8)>NH4+(1.5)>Li+(1.2)>Na+(1.0)≥K+(0.98)≥Rb+(0.98)>Cs+(0.95); and to organic cations: Na+(1.0)≥Dimethylamine(0.99)>Trimethylamine(0.7)>Tetramethylammonium(0.4)>N-methyl-d-glucamine(0.1). Activation of the hTRPA1 channels by AITC appears to recruit the channels to a conformational state with an increased permeability to large organic cations. The pore of the channels in this state can be characterized as dilated by approximately 1–2.5A. These findings provide important insight into the basic fundamental properties and function of TRPA1 channels in general and human TRPA1 channel in particular. PMID:21195050

  17. Study on statistical models for land mobile satellite channel

    NASA Astrophysics Data System (ADS)

    Wang, Ying; Hu, Xiulin

    2005-11-01

    Mobile terminals in a mobile satellite communication system cause the radio propagation channel to vary with time. So it is necessary to study the channel models in order to estimate the behavior of satellite signal propagation. A lot of research work have been done on the L- and S- bands. With the development of gigabit data transmissions and multimedia applications in recent years, the Ka-band studies gain much attention. Non-geostationary satellites are also in research because of its low propagation delay and low path loss. The future satellite mobile communication systems would be integrated into the other terrestrial networks in order to enable global, seamless and ubiquitous communications. At the same time QoS-technologies are studied to satisfy users' different service classes, such as mobility and resource managements. All the above make a suitable efficient channel model face new challenges. This paper firstly introduces existed channel models and analyzes their respective characteristics. Then we focus on a general model presented by Xie YongJun, which is popular under any environment and describes difference through different parameter values. However we believe that it is better to take multi-state Markov model as category in order to adapt to different environments. So a general model based on Markov process is presented and necessary simulation is carried out.

  18. Rapid Water Permeation Through Carbon Nanomembranes with Sub-Nanometer Channels.

    PubMed

    Yang, Yang; Dementyev, Petr; Biere, Niklas; Emmrich, Daniel; Stohmann, Patrick; Korzetz, Riko; Zhang, Xianghui; Beyer, André; Koch, Sascha; Anselmetti, Dario; Gölzhäuser, Armin

    2018-05-22

    The provision of clean water is a global challenge, and membrane filtration is a key technology to address it. Conventional filtration membranes are constrained by a trade-off between permeance and selectivity. Recently, some nanostructured membranes demonstrated the ability to overcome this limitation by utilizing well-defined carbon nanoconduits that allow a coordinated passage of water molecules. The fabrication of these materials is still very challenging, but their performance inspires research toward nanofabricated membranes. This study reports on molecularly thin membranes with sub-nanometer channels that combine high water selectivity with an exceptionally high permeance. Carbon nanomembranes (CNMs) of ∼1.2 nm thickness are fabricated from terphenylthiol (TPT) monolayers. Scanning probe microscopy and transport measurements reveal that TPT CNMs consist of a dense network of sub-nanometer channels that efficiently block the passage of most gases and liquids. However, water passes through with an extremely high permeance of ∼1.1 × 10 -4 mol·m -2 ·s -1 ·Pa -1 , as does helium, but with a ∼ 2500 times lower flux. Assuming all channels in a TPT CNM are active in mass transport, we find a single-channel permeation of ∼66 water molecules·s -1 ·Pa -1 . This suggests that water molecules translocate fast and cooperatively through the sub-nanometer channels, similar to carbon nanotubes and membrane proteins (aquaporins). CNMs are thus scalable two-dimensional sieves that can be utilized toward energy-efficient water purification.

  19. Domain model for Ca2(+)-inactivation of Ca2+ channels at low channel density.

    PubMed Central

    Sherman, A; Keizer, J; Rinzel, J

    1990-01-01

    The "shell" model for Ca2(+)-inactivation of Ca2+ channels is based on the accumulation of Ca2+ in a macroscopic shell beneath the plasma membrane. The shell is filled by Ca2+ entering through open channels, with the elevated Ca2+ concentration inactivating both open and closed channels at a rate determined by how fast the shell is filled. In cells with low channel density, the high concentration Ca2+ "shell" degenerates into a collection of nonoverlapping "domains" localized near open channels. These domains form rapidly when channels open and disappear rapidly when channels close. We use this idea to develop a "domain" model for Ca2(+)-inactivation of Ca2+ channels. In this model the kinetics of formation of an inactivated state resulting from Ca2+ binding to open channels determines the inactivation rate, a mechanism identical with that which explains single-channel recordings on rabbit-mesenteric artery Ca2+ channels (Huang Y., J. M. Quayle, J. F. Worley, N. B. Standen, and M. T. Nelson. 1989. Biophys. J. 56:1023-1028). We show that the model correctly predicts five important features of the whole-cell Ca2(+)-inactivation for mouse pancreatic beta-cells (Plants, T. D. 1988. J. Physiol. 404:731-747) and that Ca2(+)-inactivation has only minor effects on the bursting electrical activity of these cells. PMID:2174274

  20. Gating Behavior of Endoplasmic Reticulum Potassium Channels of Rat Hepatocytes in Diabetes

    PubMed Central

    Ghasemi, Maedeh; Khodaei, Naser; Salari, Sajjad; Eliassi, Afsaneh; Saghiri, Reza

    2014-01-01

    Background: Defects in endoplasmic reticulum homeostasis are common occurrences in different diseases, such as diabetes, in which the function of endoplasmic reticulum is disrupted. It is now well established that ion channels of endoplasmic reticulum membrane have a critical role in endoplasmic reticulum luminal homeostasis. Our previous studies showed the presence of an ATP-sensitive cationic channel in endoplasmic reticulum. Therefore, in this study, we examined and compared the activities of this channel in control and diabetic rats using single-channel recording techniques. Method: Male Wistar rats were made diabetic for 2 weeks with a single dose injection of streptozotocin (45 mg/kg). Ion channel incorporation of rough endoplasmic reticulum of diabetic hepatocytes into the bilayer lipid membrane allowed the characterization of K+ channel. Results: Ion channel incorporation of rough endoplasmic reticulum vesicles into the bilayer lipid revealed that the channel current-voltage (I-V) relation with a mean slope conductance of 520 ± 19 pS was unaffected in diabetes. Interestingly, the channel Po-voltage relation was significantly lower in diabetic rats at voltages above +30 mV. Conclusion: We concluded that the endoplasmic reticulum cationic channel is involved in diabetes. Also, this finding could be considered as a goal for further therapeutic plans. PMID:24842143

  1. Gating behavior of endoplasmic reticulum potassium channels of rat hepatocytes in diabetes.

    PubMed

    Ghasemi, Maedeh; Khodaei, Naser; Salari, Sajjad; Eliassi, Afsaneh; Saghiri, Reza

    2014-07-01

    Defects in endoplasmic reticulum homeostasis are common occurrences in different diseases, such as diabetes, in which the function of endoplasmic reticulum is disrupted. It is now well established that ion channels of endoplasmic reticulum membrane have a critical role in endoplasmic reticulum luminal homeostasis. Our previous studies showed the presence of an ATP-sensitive cationic channel in endoplasmic reticulum. Therefore, in this study, we examined and compared the activities of this channel in control and diabetic rats using single-channel recording techniques. Male Wistar rats were made diabetic for 2 weeks with a single dose injection of streptozotocin (45 mg/kg). Ion channel incorporation of rough endoplasmic reticulum of diabetic hepatocytes into the bilayer lipid membrane allowed the characterization of K+ channel. Ion channel incorporation of rough endoplasmic reticulum vesicles into the bilayer lipid revealed that the channel current-voltage (I-V) relation with a mean slope conductance of 520 ± 19 pS was unaffected in diabetes. Interestingly, the channel Po-voltage relation was significantly lower in diabetic rats at voltages above +30 mV. We concluded that the endoplasmic reticulum cationic channel is involved in diabetes. Also, this finding could be considered as a goal for further therapeutic plans.

  2. A simple analytical model of coupled single flow channel over porous electrode in vanadium redox flow battery with serpentine flow channel

    NASA Astrophysics Data System (ADS)

    Ke, Xinyou; Alexander, J. Iwan D.; Prahl, Joseph M.; Savinell, Robert F.

    2015-08-01

    A simple analytical model of a layered system comprised of a single passage of a serpentine flow channel and a parallel underlying porous electrode (or porous layer) is proposed. This analytical model is derived from Navier-Stokes motion in the flow channel and Darcy-Brinkman model in the porous layer. The continuities of flow velocity and normal stress are applied at the interface between the flow channel and the porous layer. The effects of the inlet volumetric flow rate, thickness of the flow channel and thickness of a typical carbon fiber paper porous layer on the volumetric flow rate within this porous layer are studied. The maximum current density based on the electrolyte volumetric flow rate is predicted, and found to be consistent with reported numerical simulation. It is found that, for a mean inlet flow velocity of 33.3 cm s-1, the analytical maximum current density is estimated to be 377 mA cm-2, which compares favorably with experimental result reported by others of ∼400 mA cm-2.

  3. Binding site in eag voltage sensor accommodates a variety of ions and is accessible in closed channel.

    PubMed

    Silverman, William R; Bannister, John P A; Papazian, Diane M

    2004-11-01

    In ether-a-go-go K+ channels, voltage-dependent activation is modulated by ion binding to a site located in an extracellular-facing crevice between transmembrane segments S2 and S3 in the voltage sensor. We find that acidic residues D278 in S2 and D327 in S3 are able to coordinate a variety of divalent cations, including Mg2+, Mn2+, and Ni2+, which have qualitatively similar functional effects, but different half-maximal effective concentrations. Our data indicate that ions binding to individual voltage sensors in the tetrameric channel act without cooperativity to modulate activation gating. We have taken advantage of the unique phenotype of Ni2+ in the D274A channel, which contains a mutation of a nonbinding site residue, to demonstrate that ions can access the binding site from the extracellular solution when the voltage sensor is in the resting conformation. Our results are difficult to reconcile with the x-ray structure of the KvAP K+ channel, in which the binding site residues are widely separated, and with the hydrophobic paddle model for voltage-dependent activation, in which the voltage sensor domain, including the S3-S4 loop, is near the cytoplasmic side of the membrane in the closed channel.

  4. n-Channel semiconductor materials design for organic complementary circuits.

    PubMed

    Usta, Hakan; Facchetti, Antonio; Marks, Tobin J

    2011-07-19

    emphasis on structure-property relationships. We then examine the synthesis and properties of carbonyl-functionalized oligomers, which constitute second-generation n-channel oligothiophenes, in both vacuum- and solution-processed FETs. These materials have high carrier mobilities and good air stability. In parallel, exceptionally electron-deficient cyano-functionalized arylenediimide derivatives are discussed as early examples of thermodynamically air-stable, high-performance n-channel semiconductors; they exhibit record electron mobilities of up to 0.64 cm(2)/V·s. Furthermore, we provide an overview of highly soluble ladder-type macromolecular semiconductors as OFET components, which combine ambient stability with solution processibility. A high electron mobility of 0.16 cm(2)/V·s is obtained under ambient conditions for solution-processed films. Finally, examples of polymeric n-channel semiconductors with electron mobilities as high as 0.85 cm(2)/V·s are discussed; these constitute an important advance toward fully printed polymeric electronic circuitry. Density functional theory (DFT) computations reveal important trends in molecular physicochemical and semiconducting properties, which, when combined with experimental data, shed new light on molecular charge transport characteristics. Our data provide the basis for a fundamental understanding of charge transport in high-performance n-channel organic semiconductors. Moreover, our results provide a road map for developing functional, complementary organic circuitry, which requires combining p- and n-channel transistors.

  5. Coherifying quantum channels

    NASA Astrophysics Data System (ADS)

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

    2018-04-01

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

  6. 76 FR 11679 - Drawbridge Operation Regulation; Shark River (South Channel), Belmar, NJ

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-03

    ... Operation Regulation; Shark River (South Channel), Belmar, NJ AGENCY: Coast Guard, DHS. ACTION: Notice of... temporary deviation from the regulations governing the operation of the S71 Bridge across Shark River (South... Bridge, a bascule lift drawbridge, across Shark River (South Channel), at mile 0.8, in Belmar, NJ, has a...

  7. Single-channel 40 Gbit/s digital coherent QAM quantum noise stream cipher transmission over 480 km.

    PubMed

    Yoshida, Masato; Hirooka, Toshihiko; Kasai, Keisuke; Nakazawa, Masataka

    2016-01-11

    We demonstrate the first 40 Gbit/s single-channel polarization-multiplexed, 5 Gsymbol/s, 16 QAM quantum noise stream cipher (QNSC) transmission over 480 km by incorporating ASE quantum noise from EDFAs as well as the quantum shot noise of the coherent state with multiple photons for the random masking of data. By using a multi-bit encoded scheme and digital coherent transmission techniques, secure optical communication with a record data capacity and transmission distance has been successfully realized. In this system, the signal level received by Eve is hidden by both the amplitude and the phase noise. The highest number of masked signals, 7.5 x 10(4), was achieved by using a QAM scheme with FEC, which makes it possible to reduce the output power from the transmitter while maintaining an error free condition for Bob. We have newly measured the noise distribution around I and Q encrypted data and shown experimentally with a data size of as large as 2(25) that the noise has a Gaussian distribution with no correlations. This distribution is suitable for the random masking of data.

  8. External protons destabilize the activated voltage sensor in hERG channels.

    PubMed

    Shi, Yu Patrick; Cheng, Yen May; Van Slyke, Aaron C; Claydon, Tom W

    2014-03-01

    Extracellular acidosis shifts hERG channel activation to more depolarized potentials and accelerates channel deactivation; however, the mechanisms underlying these effects are unclear. External divalent cations, e.g., Ca(2+) and Cd(2+), mimic these effects and coordinate within a metal ion binding pocket composed of three acidic residues in hERG: D456 and D460 in S2 and D509 in S3. A common mechanism may underlie divalent cation and proton effects on hERG gating. Using two-electrode voltage clamp, we show proton sensitivity of hERG channel activation (pKa = 5.6), but not deactivation, was greatly reduced in the presence of Cd(2+) (0.1 mM), suggesting a common binding site for the Cd(2+) and proton effect on activation and separable effects of protons on activation and deactivation. Mutational analysis confirmed that D509 plays a critical role in the pH dependence of activation, as shown previously, and that cooperative actions involving D456 and D460 are also required. Importantly, neutralization of all three acidic residues abolished the proton-induced shift of activation, suggesting that the metal ion binding pocket alone accounts for the effects of protons on hERG channel activation. Voltage-clamp fluorimetry measurements demonstrated that protons shifted the voltage dependence of S4 movement to more depolarized potentials. The data indicate a site and mechanism of action for protons on hERG activation gating; protonation of D456, D460 and D509 disrupts interactions between these residues and S4 gating charges to destabilize the activated configuration of S4.

  9. Valles Marineris and Chryse Outflow Channels

    NASA Image and Video Library

    1998-06-08

    A color image of Valles Marineris, the great canyon and the south Chryse basin-Valles Marineris outflow channels of Mars; north toward top. The scene shows the entire Valles Marineris canyon system, over 3,000 km long and averaging 8 km deep, extending from Noctis Labyrinthus, the arcuate system of graben to the west, to the chaotic terrain to the east and related outflow canyons that drain toward the Chryse basin. Eos and Capri Chasmata (south to north) are two canyons connected to Valles Marineris. Ganges Chasma lies directly north. The chaos in the southeast part of the image gives rise to several outflow channels, Shalbatana, Simud, Tiu, and Ares Valles (left to right), that drained north into the Chryse basin. The mouth of Ares Valles is the site of the Mars Pathfinder lander. This image is a composite of Viking medium-resolution images in black and white and low-resolution images in color; Mercator projection. The image roughly extends from latitude 20 degrees S. to 20 degrees N. and from longitude 15 degrees to 102.5 degrees. The connected chasma or valleys of Valles Marineris may have formed from a combination of erosional collapse and structural activity. Layers of material in the eastern canyons might consist of carbonates deposited in ancient lakes, eolian deposits, or volcanic materials. Huge ancient river channels began from Valles Marineris and from adjacent canyons and ran north. Many of the channels flowed north into Chryse Basin. The south Chryse outflow channels are cut an average of 1 km into the cratered highland terrain. This terrain is about 9 km above datum near Valles Marineris and steadily decreases in elevation to 1 km below datum in the Chryse basin. Shalbatana is relatively narrow (10 km wide) but can reach 3 km in depth. The channel begins at a 2- to 3-km-deep circular depression within a large impact crater, whose floor is partly covered by chaotic material, and ends in Simud Valles. Tiu and Simud Valles consist of a complex of

  10. Properties of an inward rectifying K channel in the membrane of guinea-pig atrial cardioballs.

    PubMed

    Bechem, M; Glitsch, H G; Pott, L

    1983-11-01

    Single channel outward current fluctuations are recorded in excised (outside-out) membrane patches of isolated atrial cells in culture (cardioballs) from hearts of adult guinea-pigs. The ionic channel displays a high selectivity to K ions. Accordingly the reversal potential of the single channel current is close to the K equilibrium potential. The open channel conductance is unaffected by the membrane potential but depends on the K concentration of the outside solution (19.7pS at 2 mM Ko to 30.7pS at 20 mM Ko). The open state probability (Po) of the channel shows a marked voltage dependence. Po amounts to c.0.9 at -40 mV and decreases to c.0.1 at +40 mV. Under the assumption of no channel interaction a macroscopic steady state current voltage relationship is reconstructed from the single channel data. The relationship displays inward-going rectification. The rectification is due to the voltage dependence of Po. The I-V curve displays a negative slope at membrane potentials positive to -15 mV. In bathing solutions containing Ba ions (0.2 mM) Po is reduced by rapid closures which interrupt the open state events. The unit channel conductance is unaffected by Ba ions. The channel block exerted by Ba ions is augmented with increasing membrane hyperpolarization. The results suggest that the channel studied may represent a background K conductance.

  11. Generalized channeled polarimetry.

    PubMed

    Alenin, Andrey S; Tyo, J Scott

    2014-05-01

    Channeled polarimeters measure polarization by modulating the measured intensity in order to create polarization-dependent channels that can be demodulated to reveal the desired polarization information. A number of channeled systems have been described in the past, but their proposed designs often unintentionally sacrifice optimality for ease of algebraic reconstruction. To obtain more optimal systems, a generalized treatment of channeled polarimeters is required. This paper describes methods that enable handling of multi-domain modulations and reconstruction of polarization information using linear algebra. We make practical choices regarding use of either Fourier or direct channels to make these methods more immediately useful. Employing the introduced concepts to optimize existing systems often results in superficial system changes, like changing the order, orientation, thickness, or spacing of polarization elements. For the two examples we consider, we were able to reduce noise in the reconstruction to 34.1% and 57.9% of the original design values.

  12. How well do the rosgen classification and associated "natural channel design" methods integrate and quantify fluvial processes and channel response?

    USGS Publications Warehouse

    Simon, A.; Doyle, M.; Kondolf, M.; Shields, F.D.; Rhoads, B.; Grant, G.; Fitzpatrick, F.; Juracek, K.; McPhillips, M.; MacBroom, J.

    2005-01-01

    Over the past 10 years the Rosgen classification system and its associated methods of "natural channel design" have become synonymous (to many without prior knowledge of the field) with the term "stream restoration" and the science of fluvial geomorphology. Since the mid 1990s, this classification approach has become widely, and perhaps dominantly adopted by governmental agencies, particularly those funding restoration projects. For example, in a request for proposals for the restoration of Trout Creek in Montana, the Natural Resources Conservation Service required "experience in the use and application of a stream classification system and its implementation." Similarly, classification systems have been used in evaluation guides for riparian areas and U.S. Forest Service management plans. Most notably, many highly trained geomorphologists and hydraulic engineers are often held suspect, or even thought incorrect, if their approach does not include reference to or application of a classification system. This, combined with the para-professional training provided by some involved in "natural channel design" empower individuals and groups with limited backgrounds in stream and watershed sciences to engineer wholesale re-patterning of stream reaches using 50-year old technology that was never intended for engineering design. At Level I, the Rosgen classification system consists of eight or nine major stream types, based on hydraulic-geometry relations and four other measures of channel shape to distinguish the dimensions of alluvial stream channels as a function of the bankfull stage. Six classes of the particle size of the boundary sediments are used to further sub-divide each of the major stream types, resulting in 48 or 54 stream types. Aside from the difficulty in identifying bankfull stage, particularly in incising channels, and the issue of sampling from two distinct populations (beds and banks) to classify the boundary sediments, the classification provides a

  13. Monitoring and Mapping Off-Channel Water Quality in the Willamette River, Oregon

    NASA Astrophysics Data System (ADS)

    Buccola, N. L.; Rounds, S. A.; Smith, C.; Anderson, C.; Jones, K.; Mangano, J.; Wallick, R.

    2016-12-01

    The floodplain of the Willamette River in northwestern Oregon includes remnant slower-moving sloughs, side-channels, and alcoves that provide rearing habitat and potential cool-water sources for native cold-water fish species, such as the federally threatened Chinook salmon. The mapping and characterization of the hydraulics and water sources of these off-channel areas is the first step toward protecting and restoring these resources for future generations. A primary focus of this study is to determine how flow management can increase the habitat value of these off-channel areas, especially during summer low-flow periods when water temperatures in the main channel regularly exceed lethal temperatures for salmonids. The U.S. Geological Survey, in cooperation with U.S. Army Corps of Engineers and Oregon State University, has been measuring the characteristics of off-channel water quality in the Willamette River under a variety of water levels in summer 2015-16. About 30 diverse off-channel sites within the Willamette floodplain are being monitored and compared with conditions in the main channel. Hourly water temperature, conductivity, and dissolved oxygen (DO) data are being collected at a subset of these sites. Some deep off-channel pools have substantial, consistent cool-water inflows that can dominate locally, allowing them to function as cold-water refuges for salmonids at varying mainstem Willamette flows. Other sloughs have varying characteristics due to intermittent connections to the main channel, depending on river levels. A vibrant community of algae and aquatic macrophytes often coincide with thick layers of fine sediment or organic detritus near the bed, producing low DO zones (<5 mg/L) in many slower-moving off-channel areas. We propose some preliminary hydro-geomorphic categories to better explain cool inflows as sourced from regional groundwater aquifers or localized subsurface river features. A better understanding of the processes governing the

  14. Performance evaluation of multi-channel wireless mesh networks with embedded systems.

    PubMed

    Lam, Jun Huy; Lee, Sang-Gon; Tan, Whye Kit

    2012-01-01

    Many commercial wireless mesh network (WMN) products are available in the marketplace with their own proprietary standards, but interoperability among the different vendors is not possible. Open source communities have their own WMN implementation in accordance with the IEEE 802.11s draft standard, Linux open80211s project and FreeBSD WMN implementation. While some studies have focused on the test bed of WMNs based on the open80211s project, none are based on the FreeBSD. In this paper, we built an embedded system using the FreeBSD WMN implementation that utilizes two channels and evaluated its performance. This implementation allows the legacy system to connect to the WMN independent of the type of platform and distributes the load between the two non-overlapping channels. One channel is used for the backhaul connection and the other one is used to connect to the stations to wireless mesh network. By using the power efficient 802.11 technology, this device can also be used as a gateway for the wireless sensor network (WSN).

  15. Distinct modes of perimembrane TRP channel turnover revealed by TIR-FRAP.

    PubMed

    Ghosh, Debapriya; Segal, Andrei; Voets, Thomas

    2014-11-19

    Transient Receptor Potential (TRP) channels form a broadly expressed and functionally diverse family of cation channels involved in various (patho)physiological processes. Whereas the mechanisms that control opening of TRP channels have been extensively studied, little is known about the transport processes of TRP channels to and within the plasma membrane. Here we used Total Internal Reflection--Fluorescence Recovery after Photobleaching (TIR-FRAP) to selectively visualize and bleach the fluorescently labeled TRP channels TRPV2 and TRPM4 in close proximity of the glass-plasma membrane interface, allowing detailed analysis of their perimembrane dynamics. We show that recovery of TRPM4 occurs via 200-nm diameter transport vesicles, and demonstrate the full fusion of such vesicles with the plasma membrane. In contrast, TRPV2 recovery proceeded mainly via lateral diffusion from non-bleached areas of the plasma membrane. Analysis of the two-dimensional channel diffusion kinetics yielded 2D diffusion coefficients ranging between 0.1 and 0.3 μm(2)/s, suggesting that these TRP channels move relatively unrestricted within the plasma membrane. These data demonstrate distinct modes of TRP channel turnover at the plasma membrane and illustrate the usefulness of TIR-FRAP to monitor these processes with high resolution.

  16. Performance Analysis of Hybrid PON (WDM-TDM) with Equal and Unequal Channel Spacing

    NASA Astrophysics Data System (ADS)

    Sharma, Ramandeep; Dewra, Sanjeev; Rani, Aruna

    2016-06-01

    In this hybrid WDM-TDM PON has been evaluated and compared the downstream wavelengths with equal and unequal channel spacing at 5 Gbit/s per wavelength in the scenario of triple play services with 128 optical network units (ONUs). The triple play services: data, voice and video signals are transmitted up to 50 km distance having Q factor of 6.68 and BER of 3.64e-012 with unequal channel spacing and 45 km distance having Q factor of 6.33 and BER of 2.40e-011 with equal channel spacing in downstream direction. It has been observed that downstream wavelengths with unequal channel spacing provide better results than equal channel spacing.

  17. Structural basis for the selective permeability of channels made of communicating junction proteins

    PubMed Central

    Ek-Vitorin, Jose F.; Burt, Janis M.

    2012-01-01

    The open state(s) of gap junction channels is evident from their permeation by small ions in response to an applied intercellular (transjunctional/transchannel) voltage gradient. That an open channel allows variable amounts of current to transit from cell-to-cell in the face of a constant intercellular voltage difference indicates channel open/closing can be complete or partial. The physiological significance of such open state options is, arguably, the main concern of junctional regulation. Because gap junctions are permeable to many substances, it is sensible to inquire whether and how each open state influences the intercellular diffusion of molecules as valuable as, but less readily detected than current-carrying ions. Presumably, structural changes perceived as shifts in channel conductivity would significantly alter the transjunctional diffusion of molecules whose limiting diameter approximates the pore’s limiting diameter. Moreover, changes in junctional permeability to some molecules might occur without evident changes in conductivity, either at macroscopic or single channel level. Open gap junction channels allow the exchange of cytoplasmic permeants between contacting cells by simple diffusion. The identity of such permeants, and the functional circumstances and consequences of their junctional exchange presently constitute the most urgent (and demanding) themes of the field. Here, we consider the necessity for regulating this exchange, the possible mechanism(s) and structural elements likely involved in such regulation, and how regulatory phenomena could be perceived as changes in chemical vs. electrical coupling; an overall reflection on our collective knowledge of junctional communication is then applied to suggest new avenues of research. PMID:22342665

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

    PubMed

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

    2017-01-01

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

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

    PubMed Central

    Bennion, David H.; Roseman, Edward F.; Holbrook, Christopher M.; Boase, James C.; Chiotti, Justin A.; Thomas, Michael V.; Wills, Todd C.; Drouin, Richard G.; Kessel, Steven T.; Krueger, Charles C.

    2017-01-01

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

  20. G-protein mediates voltage regulation of agonist binding to muscarinic receptors: effects on receptor-Na/sup +/ channel interaction

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Cohen-Armon, M.; Garty, H.; Sokolovsky, M.

    1988-01-12

    The authors previous experiments in membranes prepared from rat heart and brain led them to suggest that the binding of agonist to the muscarinic receptors and to the Na/sup +/ channels is a coupled event mediated by guanine nucleotide binding protein(s) (G-protein(s)). These in vitro findings prompted us to employ synaptoneurosomes from brain stem tissue to examine (i) the binding properties of (/sup 3/H) acetylcholine at resting potential and under depolarization conditions in the absence and presence of pertussis toxin; (ii) the binding of (/sup 3/H)batrachotoxin to Na/sup +/ channel(s) in the presence of the muscarinic agonists; and (iii) muscarinicallymore » induced /sup 22/Na/sup +/ uptake in the presence and absence of tetrodotoxin, which blocks Na/sup +/ channels. The findings indicate that agonist binding to muscarinic receptors is voltage dependent, that this process is mediated by G-protein(s), and that muscarinic agonists induce opening of Na/sup +/channels. The latter process persists even after pertussis toxin treatment, indicating that it is not likely to be mediated by pertussis toxin sensitive G-protein(s). The system with its three interacting components-receptor, G-protein, and Na/sup +/ channel-is such that at resting potential the muscarinic receptor induces opening of Na/sup +/ channels; this property may provide a possible physiological mechanism for the depolarization stimulus necessary for autoexcitation or repetitive firing in heart or brain tissues.« less

  1. Temperature sensitivity of ligand-gated ion channels: ryanodine receptor case

    NASA Astrophysics Data System (ADS)

    Iaparov, B. I.; Moskvin, A. S.; Solovyova, O. E.

    2017-11-01

    Temperature influences all biochemical processes, in particular, excitation-contraction coupling(ECC) in cardiac cells. In this work we propose a theoretical explanation of temperature effects on an isolated ryanodine receptor calcium release channel (RyR channel) within the electron-conformational (EC) model. We show that the EC model with an Arrhenius-like temperature dependence of the “internal” and “external” frictions and a specific thermosensitivity of the tunnelling “open ↔ closed” transitions can provide both qualitative and quantitative description of the temperature effects for isolated RyR channels. Interestingly that a small change of the activation energy for the “internal” friction can make an ion channel either heat-inhibited or heat-activated while the “external” friction doesn’t play a key role in temperature sensitivity: neglect of “external” friction doesn’t change the channel’s temperature sensitivity qualitatively.

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

    NASA Astrophysics Data System (ADS)

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

    2017-12-01

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

  3. Inhibition of single Shaker K channels by kappa-conotoxin-PVIIA.

    PubMed Central

    Naranjo, David

    2002-01-01

    kappa-Conotoxin-PVIIA (kappa-PVIIA) is a 27-residue basic (+4) peptide from the venom of the predator snail Conus purpurascens. A single kappa-PVIIA molecule interrupts ion conduction by binding to the external mouth of Shaker K channels. The blockade of Shaker by kappa-PVIIA was studied at the single channel level in membrane patches from Xenopus oocytes. The amplitudes of blocked and closed events were undistinguishable, suggesting that the toxin interrupts ion conduction completely. Between -20 and 40 mV kappa-PVIIA increased the latency to the first opening by one order of magnitude in a concentration-independent fashion. Because kappa-PVIIA has higher affinity for the closed channels at high enough concentration to block >90% of the resting channels, the dissociation rate could be estimated from the analysis of the first latency. At 0 mV, the dissociation rate was 20 s(-1) and had an effective valence of 0.64. The apparent closing rate increased linearly with [kappa-PVIIA] indicating an association rate of 56 microM(-1) s(-1). The toxin did not modify the fraction of null traces. This result suggests that the structural rearrangements in the external mouth contributing to the slow inactivation preserve the main geometrical features of the toxin-receptor interaction. PMID:12023223

  4. N- and P-type Ca2+ channels are involved in acetylcholine release at a neuroneuronal synapse: only the N-type channel is the target of neuromodulators.

    PubMed Central

    Fossier, P; Baux, G; Tauc, L

    1994-01-01

    Cholinergic transmission in an identified neuro-neuronal synapse of the Aplysia buccal ganglion was depressed by application of a partially purified extract of the funnel-web-spider venom (FTx) or of its synthetic analog (sFTx). This specific blocker of voltage-dependent P-type Ca2+ channels did not interfere with the effect of the N-type Ca2+ channel blocker omega-conotoxin, which could further decrease synaptic transmission after a previous application of FTx. Similar results were obtained when the reversal order of application of these two Ca2+ channel blockers was used. Both P- and N-type Ca2+ currents trigger acetylcholine release in the presynaptic neuron. The neuromodulatory effects of FMRF-amide, histamine, and buccalin on transmitter release disappeared after the blockade of the N-type Ca2+ channels but remained still effective in the presence of FTx. These results indicate that only N-type Ca2+ channels appear to be sensitive to the neuromodulators we have identified. PMID:7910963

  5. N- and P-type Ca2+ channels are involved in acetylcholine release at a neuroneuronal synapse: only the N-type channel is the target of neuromodulators.

    PubMed

    Fossier, P; Baux, G; Tauc, L

    1994-05-24

    Cholinergic transmission in an identified neuro-neuronal synapse of the Aplysia buccal ganglion was depressed by application of a partially purified extract of the funnel-web-spider venom (FTx) or of its synthetic analog (sFTx). This specific blocker of voltage-dependent P-type Ca2+ channels did not interfere with the effect of the N-type Ca2+ channel blocker omega-conotoxin, which could further decrease synaptic transmission after a previous application of FTx. Similar results were obtained when the reversal order of application of these two Ca2+ channel blockers was used. Both P- and N-type Ca2+ currents trigger acetylcholine release in the presynaptic neuron. The neuromodulatory effects of FMRF-amide, histamine, and buccalin on transmitter release disappeared after the blockade of the N-type Ca2+ channels but remained still effective in the presence of FTx. These results indicate that only N-type Ca2+ channels appear to be sensitive to the neuromodulators we have identified.

  6. Constraints on Voltage Sensor Movement in the Shaker K+ Channel

    PubMed Central

    Darman, Rachel B.; Ivy, Allison A.; Ketty, Vina; Blaustein, Robert O.

    2006-01-01

    In nerve and muscle cells, the voltage-gated opening and closing of cation-selective ion channels is accompanied by the translocation of 12–14 elementary charges across the membrane's electric field. Although most of these charges are carried by residues in the S4 helix of the gating module of these channels, the precise nature of their physical movement is currently the topic of spirited debate. Broadly speaking, two classes of models have emerged: those that suggest that small-scale motions can account for the extensive charge displacement, and those that invoke a much larger physical movement. In the most recent incarnation of the latter type of model, which is based on structural and functional data from the archaebacterial K+ channel KvAP, a “voltage-sensor paddle” comprising a helix-turn-helix of S3–S4 translocates ∼20 Å through the bilayer during the gating cycle (Jiang, Y., A. Lee, J. Chen, V. Ruta, M. Cadene, B.T. Chait, and R. MacKinnon. 2003. Nature. 423:33–41; Jiang, Y., V. Ruta, J. Chen, A. Lee, and R. MacKinnon. 2003. Nature. 423:42–48.; Ruta, V., J. Chen, and R. MacKinnon. 2005. Cell. 123:463–475). We used two methods to test for analogous motions in the Shaker K+ channel, each examining the aqueous exposure of residues near S3. In the first, we employed a pore-blocking maleimide reagent (Blaustein, R.O., P.A. Cole, C. Williams, and C. Miller. 2000. Nat. Struct. Biol. 7:309–311) to probe for state-dependent changes in the chemical reactivity of substituted cysteines; in the second, we tested the state-dependent accessibility of a tethered biotin to external streptavidin (Qiu, X.Q., K.S. Jakes, A. Finkelstein, and S.L. Slatin. 1994. J. Biol. Chem. 269:7483–7488; Slatin, S.L., X.Q. Qiu, K.S. Jakes, and A. Finkelstein. 1994. Nature. 371:158–161). In both types of experiments, residues predicted to lie near the top of S3 did not exhibit any change in aqueous exposure during the gating cycle. This lack of state dependence argues

  7. Voltage-Gated Calcium Channels

    NASA Astrophysics Data System (ADS)

    Zamponi, Gerald Werner

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

  8. Scale dependant compensational stacking of channelized sedimentary deposits

    NASA Astrophysics Data System (ADS)

    Wang, Y.; Straub, K. M.; Hajek, E. A.

    2010-12-01

    Compensational stacking, the tendency for sediment transport system to preferentially fill topographic lows, thus smoothing out topographic relief is a concept used in the interpretation of the stratigraphic record. Recently, a metric was developed to quantify the strength of compensation in sedimentary basins by comparing observed stacking patterns to what would be expected from simple, uncorrelated stacking. This method uses the rate of decay of spatial variability in sedimentation between picked depositional horizons with increasing vertical stratigraphic averaging distance. We explore how this metric varies as a function of stratigraphic scale using data from physical experiments, stratigraphy exposed in outcrops and numerical models. In an experiment conducted at Tulane University’s Sediment Dynamics Laboratory, the topography of a channelized delta formed by weakly cohesive sediment was monitored along flow-perpendicular transects at a high temporal resolution relative to channel kinematics. Over the course of this experiment a uniform relative subsidence pattern, designed to isolate autogenic processes, resulted in the construction of a stratigraphic package that is 25 times as thick as the depth of the experimental channels. We observe a scale-dependence on the compensational stacking of deposits set by the system’s avulsion time-scale. Above the avulsion time-scale deposits stack purely compensationally, but below this time-scale deposits stack somewhere between randomly and deterministically. The well-exposed Ferris Formation (Cretaceous/Paleogene, Hanna Basin, Wyoming, USA) also shows scale-dependant stratigraphic organization which appears to be set by an avulsion time-scale. Finally, we utilize simple object-based models to illustrate how channel avulsions influence compensation in alluvial basins.

  9. Potassium channels cloned from neuroblastoma cells display slowly inactivating outward currents in Xenopus oocytes.

    PubMed

    Ito, Y; Yokoyama, S; Higashida, H

    1992-05-22

    Messenger RNAs (mRNAs) specific for NGK1 and NGK2 potassium channels were synthesized from complementary DNAs (cDNAs) that had been cloned from mouse neuroblastoma x rat glioma hybrid NG108-15 cells. Outward pottasium currents were evoked by 5 s depolarizing voltage commands in Xenopus oocytes injected with NGK1- or NGK2-specific mRNAs. The NGK1 or NGK2 currents showed different activation and inactivation kinetics, and different pharmacological sensitivities. The threshold potential for activation of the NGK2 current (-14 mV) was more positive than that for the NGK1 (-36 mV). The NGK2 current showed faster inactivation during a 5 s depolarizing pulse than did the NGK1 current. Inactivation was best fit by time constants of 0.37, 1.5 and 19 s for the NGK2 current and 4.4 and 19 s for NGK1. Extracellularly applied tetraethylammonium chloride (TEA) was 1000 times more potent on the NGK2 current than the NGK1 current. Furthermore we examined outward current following co-injection of an equal amount of mRNAs for NGK1 and NGK2. The timecourse of inactivation differed from either alone or from a simple sum of the two individual currents. TEA sensitivity could not be explained by summation of the two homomultimeric channels. These findings suggest that both NGK1 and NGK2 proteins assemble to form heteromultimeric K+ channels in addition to homomultimeric K+ channels. NGK2 channels and the heteromultimeric channels may be responsible for the native transient outward current with slow inactivation in NG108-15 hybrid cells.

  10. Regulation of Na+ channel inactivation by the DIII and DIV voltage-sensing domains.

    PubMed

    Hsu, Eric J; Zhu, Wandi; Schubert, Angela R; Voelker, Taylor; Varga, Zoltan; Silva, Jonathan R

    2017-03-06

    Functional eukaryotic voltage-gated Na + (Na V ) channels comprise four domains (DI-DIV), each containing six membrane-spanning segments (S1-S6). Voltage sensing is accomplished by the first four membrane-spanning segments (S1-S4), which together form a voltage-sensing domain (VSD). A critical Na V channel gating process, inactivation, has previously been linked to activation of the VSDs in DIII and DIV. Here, we probe this interaction by using voltage-clamp fluorometry to observe VSD kinetics in the presence of mutations at locations that have been shown to impair Na V channel inactivation. These locations include the DIII-DIV linker, the DIII S4-S5 linker, and the DIV S4-S5 linker. Our results show that, within the 10-ms timeframe of fast inactivation, the DIV-VSD is the primary regulator of inactivation. However, after longer 100-ms pulses, the DIII-DIV linker slows DIII-VSD deactivation, and the rate of DIII deactivation correlates strongly with the rate of recovery from inactivation. Our results imply that, over the course of an action potential, DIV-VSDs regulate the onset of fast inactivation while DIII-VSDs determine its recovery. © 2017 Hsu et al.

  11. Direct Interaction between the Voltage Sensors Produces Cooperative Sustained Deactivation in Voltage-gated H+ Channel Dimers*

    PubMed Central

    Okuda, Hiroko; Yonezawa, Yasushige; Takano, Yu; Okamura, Yasushi; Fujiwara, Yuichiro

    2016-01-01

    The voltage-gated H+ channel (Hv) is a voltage sensor domain-like protein consisting of four transmembrane segments (S1–S4). The native Hv structure is a homodimer, with the two channel subunits functioning cooperatively. Here we show that the two voltage sensor S4 helices within the dimer directly cooperate via a π-stacking interaction between Trp residues at the middle of each segment. Scanning mutagenesis showed that Trp situated around the original position provides the slow gating kinetics characteristic of the dimer's cooperativity. Analyses of the Trp mutation on the dimeric and monomeric channel backgrounds and analyses with tandem channel constructs suggested that the two Trp residues within the dimer are functionally coupled during Hv deactivation but are less so during activation. Molecular dynamics simulation also showed direct π-stacking of the two Trp residues. These results provide new insight into the cooperative function of voltage-gated channels, where adjacent voltage sensor helices make direct physical contact and work as a single unit according to the gating process. PMID:26755722

  12. Molecular analysis of the Na+ channel blocking actions of the novel class I anti-arrhythmic agent RSD 921.

    PubMed

    Pugsley, M K; Goldin, A L

    1999-05-01

    RSD 921 is a novel, structurally unique, class I Na+ channel blocking drug under development as a local anaesthetic agent and possibly for the treatment of cardiac arrhythmias. The effects of RSD 921 on wild-type heart, skeletal muscle, neuronal and non-inactivating IFMQ3 mutant neuronal Na+ channels expressed in Xenopus laevis oocytes were examined using a two-electrode voltage clamp. RSD 921 produced similarly potent tonic block of all three wild-type channel isoforms, with EC50 values between 35 and 47 microM, whereas the EC50 for block of the IFMQ3 mutant channel was 110+5.5 microM. Block of Na+ channels by RSD 921 was concentration and use-dependent, with marked frequency-dependent block of heart channels and mild frequency-dependent block of skeletal muscle, wild-type neuronal and IFMQ3 mutant channels. RSD 921 produced a minimal hyperpolarizing shift in the steady-state voltage-dependence of inactivation of all three wild-type channel isoforms. Open channel block of the IFMQ3 mutant channel was best fit with a first order blocking scheme with k(on) equal to 0.11+/-0.012x10(6) M(-1) s(-1) and k(off) equal to 12.5+/-2.5 s(-1), resulting in KD of 117+/-31 microM. Recovery from open channel block occurred with a time constant of 14+/-2.7 s(-1). These results suggest that RSD 921 preferentially interacts with the open state of the Na+ channel, and that the drug may produce potent local anaesthetic or anti-arrhythmic action under conditions of shortened action potentials, such as during anoxia or ischaemia.

  13. A complicated complex: Ion channels, voltage sensing, cell membranes and peptide inhibitors.

    PubMed

    Zhang, Alan H; Sharma, Gagan; Undheim, Eivind A B; Jia, Xinying; Mobli, Mehdi

    2018-04-21

    Voltage-gated ion channels (VGICs) are specialised ion channels that have a voltage dependent mode of action, where ion conduction, or gating, is controlled by a voltage-sensing mechanism. VGICs are critical for electrical signalling and are therefore important pharmacological targets. Among these, voltage-gated sodium channels (Na V s) have attracted particular attention as potential analgesic targets. Na V s, however, comprise several structurally similar subtypes with unique localisations and distinct functions, ranging from amplification of action potentials in nociception (e.g. Na V 1.7) to controlling electrical signalling in cardiac function (Na V 1.5). Understanding the structural basis of Na V function is therefore of great significance, both to our knowledge of electrical signalling and in development of subtype and state selective drugs. An important tool in this pursuit has been the use of peptides from animal venoms as selective Na V modulators. In this review, we look at peptides, particularly from spider venoms, that inhibit Na V s by binding to the voltage sensing domain (VSD) of this channel, known as gating modifier toxins (GMT). In the first part of the review, we look at the structural determinants of voltage sensing in VGICs, the gating cycle and the conformational changes that accompany VSD movement. Next, the modulation of the analgesic target Na V 1.7 by GMTs is reviewed to develop bioinformatic tools that, based on sequence information alone, can identify toxins that are likely to inhibit this channel. The same approach is also used to define VSD sequences, other than that from Na V 1.7, which are likely to be sensitive to this class of toxins. The final section of the review focuses on the important role of the cellular membrane in channel modulation and also how the lipid composition affects measurements of peptide-channel interactions both in binding kinetics measurements in solution and in cell-based functional assays. Copyright © 2018

  14. Interaction of the BKCa channel gating ring with dendrotoxins

    PubMed Central

    Takacs, Zoltan; Imredy, John P; Bingham, Jon-Paul; Zhorov, Boris S; Moczydlowski, Edward G

    2014-01-01

    Two classes of small homologous basic proteins, mamba snake dendrotoxins (DTX) and bovine pancreatic trypsin inhibitor (BPTI), block the large conductance Ca2+-activated K+ channel (BKCa, KCa1.1) by production of discrete subconductance events when added to the intracellular side of the membrane. This toxin-channel interaction is unlikely to be pharmacologically relevant to the action of mamba venom, but as a fortuitous ligand-protein interaction, it has certain biophysical implications for the mechanism of BKCa channel gating. In this work we examined the subconductance behavior of 9 natural dendrotoxin homologs and 6 charge neutralization mutants of δ-dendrotoxin in the context of current structural information on the intracellular gating ring domain of the BKCa channel. Calculation of an electrostatic surface map of the BKCa gating ring based on the Poisson-Boltzmann equation reveals a predominantly electronegative surface due to an abundance of solvent-accessible side chains of negatively charged amino acids. Available structure-activity information suggests that cationic DTX/BPTI molecules bind by electrostatic attraction to site(s) on the gating ring located in or near the cytoplasmic side portals where the inactivation ball peptide of the β2 subunit enters to block the channel. Such an interaction may decrease the apparent unitary conductance by altering the dynamic balance of open versus closed states of BKCa channel activation gating. PMID:25483585

  15. An Embedded, Eight Channel, Noise Canceling, Wireless, Wearable sEMG Data Acquisition System With Adaptive Muscle Contraction Detection.

    PubMed

    Ergeneci, Mert; Gokcesu, Kaan; Ertan, Erhan; Kosmas, Panagiotis

    2018-02-01

    Wearable technology has gained increasing popularity in the applications of healthcare, sports science, and biomedical engineering in recent years. Because of its convenient nature, the wearable technology is particularly useful in the acquisition of the physiological signals. Specifically, the (surface electromyography) sEMG systems, which measure the muscle activation potentials, greatly benefit from this technology in both clinical and industrial applications. However, the current wearable sEMG systems have several drawbacks including inefficient noise cancellation, insufficient measurement quality, and difficult integration to customized applications. Additionally, none of these sEMG data acquisition systems can detect sEMG signals (i.e., contractions), which provides a valuable environment for further studies such as human machine interaction, gesture recognition, and fatigue tracking. To this end, we introduce an embedded, eight channel, noise canceling, wireless, wearable sEMG data acquisition system with adaptive muscle contraction detection. Our design consists of two stages, which are the sEMG sensors and the multichannel data acquisition unit. For the first stage, we propose a low cost, dry, and active sEMG sensor that captures the muscle activation potentials, a data acquisition unit that evaluates these captured multichannel sEMG signals and transmits them to a user interface. In the data acquisition unit, the sEMG signals are processed through embedded, adaptive methods in order to reject the power line noise and detect the muscle contractions. Through extensive experiments, we demonstrate that our sEMG sensor outperforms a widely used commercially available product and our data acquisition system achieves 4.583 dB SNR gain with accuracy in the detection of the contractions.

  16. Alcohol modulation of BK channel gating depends on β subunit composition

    PubMed Central

    Kuntamallappanavar, Guruprasad

    2016-01-01

    In most mammalian tissues, Ca2+i/voltage-gated, large conductance K+ (BK) channels consist of channel-forming slo1 and auxiliary (β1–β4) subunits. When Ca2+i (3–20 µM) reaches the vicinity of BK channels and increases their activity at physiological voltages, β1- and β4-containing BK channels are, respectively, inhibited and potentiated by intoxicating levels of ethanol (50 mM). Previous studies using different slo1s, lipid environments, and Ca2+i concentrations—all determinants of the BK response to ethanol—made it impossible to determine the specific contribution of β subunits to ethanol action on BK activity. Furthermore, these studies measured ethanol action on ionic current under a limited range of stimuli, rendering no information on the gating processes targeted by alcohol and their regulation by βs. Here, we used identical experimental conditions to obtain single-channel and macroscopic currents of the same slo1 channel (“cbv1” from rat cerebral artery myocytes) in the presence and absence of 50 mM ethanol. First, we assessed the role five different β subunits (1,2,2-IR, 3-variant d, and 4) in ethanol action on channel function. Thus, two phenotypes were identified: (1) ethanol potentiated cbv1-, cbv1+β3-, and cbv1+β4-mediated currents at low Ca2+i while inhibiting current at high Ca2+i, the potentiation–inhibition crossover occurring at 20 µM Ca2+i; (2) for cbv1+β1, cbv1+wt β2, and cbv1+β2-IR, this crossover was shifted to ∼3 µM Ca2+i. Second, applying Horrigan–Aldrich gating analysis on both phenotypes, we show that ethanol fails to modify intrinsic gating and the voltage-dependent parameters under examination. For cbv1, however, ethanol (a) drastically increases the channel’s apparent Ca2+ affinity (nine-times decrease in Kd) and (b) very mildly decreases allosteric coupling between Ca2+ binding and channel opening (C). The decreased Kd leads to increased channel activity. For cbv1+β1, ethanol (a) also decreases Kd

  17. Local anesthetics disrupt energetic coupling between the voltage-sensing segments of a sodium channel.

    PubMed

    Muroi, Yukiko; Chanda, Baron

    2009-01-01

    Local anesthetics block sodium channels in a state-dependent fashion, binding with higher affinity to open and/or inactivated states. Gating current measurements show that local anesthetics immobilize a fraction of the gating charge, suggesting that the movement of voltage sensors is modified when a local anesthetic binds to the pore of the sodium channel. Here, using voltage clamp fluorescence measurements, we provide a quantitative description of the effect of local anesthetics on the steady-state behavior of the voltage-sensing segments of a sodium channel. Lidocaine and QX-314 shifted the midpoints of the fluorescence-voltage (F-V) curves of S4 domain III in the hyperpolarizing direction by 57 and 65 mV, respectively. A single mutation in the S6 of domain IV (F1579A), a site critical for local anesthetic block, abolished the effect of QX-314 on the voltage sensor of domain III. Both local anesthetics modestly shifted the F-V relationships of S4 domain IV toward hyperpolarized potentials. In contrast, the F-V curve of the S4 domain I was shifted by 11 mV in the depolarizing direction upon QX-314 binding. These antagonistic effects of the local anesthetic indicate that the drug modifies the coupling between the voltage-sensing domains of the sodium channel. Our findings suggest a novel role of local anesthetics in modulating the gating apparatus of the sodium channel.

  18. Screen channel liquid acquisition device outflow tests in liquid hydrogen

    NASA Astrophysics Data System (ADS)

    Hartwig, J. W.; Chato, D. J.; McQuillen, J. B.; Vera, J.; Kudlac, M. T.; Quinn, F. D.

    2014-11-01

    This paper presents experimental design and test results of the recently concluded 1-g inverted vertical outflow testing of two 325 × 2300 full scale liquid acquisition device (LAD) channels in liquid hydrogen (LH2). One of the channels had a perforated plate and internal cooling from a thermodynamic vent system (TVS) to enhance performance. The LADs were mounted in a tank to simulate 1-g outflow over a wide range of LH2 temperatures (20.3-24.2 K), pressures (100-350 kPa), and flow rates (0.010-0.055 kg/s). Results indicate that the breakdown point is dominated by liquid temperature, with a second order dependence on mass flow rate through the LAD. The best performance is always achieved in the coldest liquid states for both channels, consistent with bubble point theory. Higher flow rates cause the standard channel to break down relatively earlier than the TVS cooled channel. Both the internal TVS heat exchanger and subcooling the liquid in the propellant tank are shown to significantly improve LAD performance.

  19. Screen Channel Liquid Acquisition Device Outflow Tests in Liquid Hydrogen

    NASA Technical Reports Server (NTRS)

    Hartwig, Jason W.; Chato, David J.; McQuillen, J. B.; Vera, J.; Kudlac, M. T.; Quinn, F. D.

    2013-01-01

    This paper presents experimental design and test results of the recently concluded 1-g inverted vertical outflow testing of two 325x2300 full scale liquid acquisition device (LAD) channels in liquid hydrogen (LH2). One of the channels had a perforated plate and internal cooling from a thermodynamic vent system (TVS) to enhance performance. The LADs were mounted in a tank to simulate 1-g outflow over a wide range of LH2 temperatures (20.3 - 24.2 K), pressures (100 - 350 kPa), and flow rates (0.010 - 0.055 kg/s). Results indicate that the breakdown point is dominated by liquid temperature, with a second order dependence on mass flow rate through the LAD. The best performance is always achieved in the coldest liquid states for both channels, consistent with bubble point theory. Higher flow rates cause the standard channel to break down relatively earlier than the TVS cooled channel. Both the internal TVS heat exchanger and subcooling the liquid in the propellant tank are shown to significantly improve LAD performance.

  20. Channel plate for DNA sequencing

    DOEpatents

    Douthart, R.J.; Crowell, S.L.

    1998-01-13

    This invention is a channel plate that facilitates data compaction in DNA sequencing. The channel plate has a length, a width and a thickness, and further has a plurality of channels that are parallel. Each channel has a depth partially through the thickness of the channel plate. Additionally an interface edge permits electrical communication across an interface through a buffer to a deposition membrane surface. 15 figs.

  1. Small Landslides in Aram-Ares Channel, Mars

    NASA Astrophysics Data System (ADS)

    Kraal, E. R.; Shoup, J.

    2014-12-01

    An east-west channel (located at 341°E and 3°N) connects Aram Chaos to Ares Valles. The valley is approximately 80 km long, 12 km wide, and 1.5 km deep. The channel is filled with a series of slope failures or landslides that form lobate aprons covering the valley floor. Preliminary studies of the valley on the north wall of the valley (south facing) characterized 6 landslides using gridded MOLA topography from JMARS, including area, drop height and run out distance. These relatively small landslides have surface areas ranging from 5.6 to 55 km2. Their aprons run out ~ 10 km, often covering the entire width of the valley floor. Drop height was measured using both maximum and minimum estimates due to resolution limits of the topography and ranged from 1200 to 2200 meters. Using the drop height and run out distance, we determine the coefficient of friction and maximum velocity for two of the landslides using previously established landslide equations based on physical properties. The coefficient of friction for the landslide events ranged from 0.5 to 1.5, which corresponds to a maximum landslide velocity of 87 m/s2 to 96 m/s2. The variations in the coefficients may be due to landslides size, relative size, or possible volatile or ice content. Preliminary geomorphic surface mapping is currently under way to identify the relationship between the aprons and the channel floor, relative age of the landslides, and other characteristics. Initial analysis indicates the channel floor and depositional aprons have experienced deflation and eolian processes and aprons have a variable level of erosion indicating that the landslides did not form during a single event.

  2. Voltage-gated Proton Channels

    PubMed Central

    DeCoursey, Thomas E.

    2014-01-01

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

  3. A new mechanism of voltage-dependent gating exposed by KV10.1 channels interrupted between voltage sensor and pore.

    PubMed

    Tomczak, Adam P; Fernández-Trillo, Jorge; Bharill, Shashank; Papp, Ferenc; Panyi, Gyorgy; Stühmer, Walter; Isacoff, Ehud Y; Pardo, Luis A

    2017-05-01

    Voltage-gated ion channels couple transmembrane potential changes to ion flow. Conformational changes in the voltage-sensing domain (VSD) of the channel are thought to be transmitted to the pore domain (PD) through an α-helical linker between them (S4-S5 linker). However, our recent work on channels disrupted in the S4-S5 linker has challenged this interpretation for the KCNH family. Furthermore, a recent single-particle cryo-electron microscopy structure of K V 10.1 revealed that the S4-S5 linker is a short loop in this KCNH family member, confirming the need for an alternative gating model. Here we use "split" channels made by expression of VSD and PD as separate fragments to investigate the mechanism of gating in K V 10.1. We find that disruption of the covalent connection within the S4 helix compromises the ability of channels to close at negative voltage, whereas disconnecting the S4-S5 linker from S5 slows down activation and deactivation kinetics. Surprisingly, voltage-clamp fluorometry and MTS accessibility assays show that the motion of the S4 voltage sensor is virtually unaffected when VSD and PD are not covalently bound. Finally, experiments using constitutively open PD mutants suggest that the presence of the VSD is structurally important for the conducting conformation of the pore. Collectively, our observations offer partial support to the gating model that assumes that an inward motion of the C-terminal S4 helix, rather than the S4-S5 linker, closes the channel gate, while also suggesting that control of the pore by the voltage sensor involves more than one mechanism. © 2017 Tomczak et al.

  4. A new mechanism of voltage-dependent gating exposed by KV10.1 channels interrupted between voltage sensor and pore

    PubMed Central

    Fernández-Trillo, Jorge; Bharill, Shashank; Panyi, Gyorgy; Stühmer, Walter; Isacoff, Ehud Y.

    2017-01-01

    Voltage-gated ion channels couple transmembrane potential changes to ion flow. Conformational changes in the voltage-sensing domain (VSD) of the channel are thought to be transmitted to the pore domain (PD) through an α-helical linker between them (S4–S5 linker). However, our recent work on channels disrupted in the S4–S5 linker has challenged this interpretation for the KCNH family. Furthermore, a recent single-particle cryo-electron microscopy structure of KV10.1 revealed that the S4–S5 linker is a short loop in this KCNH family member, confirming the need for an alternative gating model. Here we use “split” channels made by expression of VSD and PD as separate fragments to investigate the mechanism of gating in KV10.1. We find that disruption of the covalent connection within the S4 helix compromises the ability of channels to close at negative voltage, whereas disconnecting the S4–S5 linker from S5 slows down activation and deactivation kinetics. Surprisingly, voltage-clamp fluorometry and MTS accessibility assays show that the motion of the S4 voltage sensor is virtually unaffected when VSD and PD are not covalently bound. Finally, experiments using constitutively open PD mutants suggest that the presence of the VSD is structurally important for the conducting conformation of the pore. Collectively, our observations offer partial support to the gating model that assumes that an inward motion of the C-terminal S4 helix, rather than the S4–S5 linker, closes the channel gate, while also suggesting that control of the pore by the voltage sensor involves more than one mechanism. PMID:28360219

  5. Search for the X b and other hidden-beauty states in the π +π -Υ(1S) channel at ATLAS

    DOE PAGES

    Aad, G.; Abbott, B.; Abdallah, J.; ...

    2014-12-02

    This Letter presents a search for a hidden-beauty counterpart of the X(3872) in the mass ranges of 10.05–10.31 GeV and 10.40–11.00 GeV, in the channel X b → π +π -Υ (1S)(→ μ +μ -), using 16.2 fb -1 of √s = 8 TeV pp collision data collected by the ATLAS detector at the LHC. No evidence for new narrow states is found, and upper limits are set on the product of the X b cross section and branching fraction, relative to those of the Υ(2S), at the 95% confidence level using the CL S approach. These limits range frommore » 0.8% to 4.0%, depending on mass. For masses above 10.1 GeV, the expected upper limits from this analysis are the most restrictive to date. As a result, searches for production of the Υ (1 3D J), Υ(10860), and Υ(11020) states also reveal no significant signals« less

  6. Search for the X b and other hidden-beauty states in the π +π -Υ(1S) channel at ATLAS

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Aad, G.; Abbott, B.; Abdallah, J.

    This Letter presents a search for a hidden-beauty counterpart of the X(3872) in the mass ranges of 10.05–10.31 GeV and 10.40–11.00 GeV, in the channel X b → π +π -Υ (1S)(→ μ +μ -), using 16.2 fb -1 of √s = 8 TeV pp collision data collected by the ATLAS detector at the LHC. No evidence for new narrow states is found, and upper limits are set on the product of the X b cross section and branching fraction, relative to those of the Υ(2S), at the 95% confidence level using the CL S approach. These limits range frommore » 0.8% to 4.0%, depending on mass. For masses above 10.1 GeV, the expected upper limits from this analysis are the most restrictive to date. As a result, searches for production of the Υ (1 3D J), Υ(10860), and Υ(11020) states also reveal no significant signals« less

  7. Competitive photodissociation channels in jet-cooled HNCO: Thermochemistry and near-threshold predissociation

    NASA Astrophysics Data System (ADS)

    Zyrianov, M.; Droz-Georget, Th.; Sanov, A.; Reisler, H.

    1996-11-01

    The photoinitiated unimolecular decomposition of jet-cooled HNCO has been studied following S1(1A″)←S0(1A') excitation near the thresholds of the spin-allowed dissociation channels: (1) H(2S)+NCO(X2Π) and (2) NH(a1Δ)+CO(X1Σ+), which are separated by 4470 cm-1. Photofragment yield spectra of NCO(X2Π) and NH (a1Δ) were obtained in selected regions in the 260-220 nm photolysis range. The NCO(X2Π)yield rises abruptly at 38 380 cm-1 and the spectrum exhibits structures as narrow as 0.8 cm-1 near the threshold. The linewidths increase only slowly with photolysis energy. The jet-cooled absorption spectrum near the channel (1) threshold [D0(H+NCO)] was obtained using two-photon excitation via the S1 state, terminating in a fluorescent product. The absorption spectrum is similar to the NCO yield spectrum, and its intensity does not diminish noticeably above D0(H+NCO), indicating that dissociation near threshold is slow. The NCO product near threshold is cold, as is typical of a barrierless reaction. NH (a1Δ) products appear first at 42 840 cm-1, but their yield is initially very small, as evidenced also by the insignificant decrease in the NCO yield in the threshold region of channel (2). The NH (a1Δ) yield increases faster at higher photolysis energies and the linewidths increase as well. At the channel (2) threshold, the NH (a1Δ) product is generated only in the lowest rotational level, J=2, and rotational excitation increases with photolysis energy. We propose that in the range 260-230 nm, HNCO (S1) undergoes radiationless decay terminating in S0/T1 followed by unimolecular reaction. Decompositions via channels (1) and (2) proceed without significant exit channel barriers. At wavelengths shorter than 230 nm, the participation of an additional, direct pathway cannot be ruled out. The jet-cooled photofragment yield spectra allow the determination, with good accuracy, of thermochemical values relevant to HNCO decomposition. The following heats of formation are

  8. Properties and function of KCNQ1 K+ channels isolated from the rectal gland of Squalus acanthias.

    PubMed

    Kerst, G; Beschorner, U; Unsöld, B; von Hahn, T; Schreiber, R; Greger, R; Gerlach, U; Lang, H J; Kunzelmann, K; Bleich, M

    2001-10-01

    KCNQ1 (KVLQT1) K+ channels play an important role during electrolyte secretion in airways and colon. KCNQ1 was cloned recently from NaCl-secreting shark rectal glands. Here we study the properties and regulation of the cloned sKVLQT1 expressed in Xenopus oocytes and Chinese hamster ovary (CHO) cells and compare the results with those obtained from in vitro perfused rectal gland tubules (RGT). The expression of sKCNQ1 induced voltage-dependent, delayed activated K+ currents, which were augmented by an increase in intracellular cAMP and Ca2+. The chromanol derivatives 293B and 526B potently inhibited sKCNQ1 expressed in oocytes and CHO cells, but had little effect on RGT electrolyte transport. Short-circuit currents in RGT were activated by alkalinization and were decreased by acidification. In CHO cells an alkaline pH activated and an acidic pH inhibited 293B-sensitive KCNQ1 currents. Noise analysis of the cell-attached basolateral membrane of RGT indicated the presence of low-conductance (<3 pS) K+ channels, in parallel with other K+ channels. sKCNQ1 generated similar small-conductance K+ channels upon expression in CHO cells and Xenopus oocytes. The results suggest the presence of low-conductance KCNQ1 K+ channels in RGT, which are probably regulated by changes in intracellular cAMP, Ca2+ and pH.

  9. The antiparasitic isoxazoline A1443 is a potent blocker of insect ligand-gated chloride channels.

    PubMed

    Ozoe, Yoshihisa; Asahi, Miho; Ozoe, Fumiyo; Nakahira, Kunimitsu; Mita, Takeshi

    2010-01-01

    A structurally unique isoxazoline class compound, A1443, exhibits antiparasitic activity against cat fleas and dog ticks comparable to that of the commercial ectoparasiticide fipronil. This isoxazoline compound inhibits specific binding of the gamma-aminobutyric acid (GABA) receptor channel blocker [(3)H]4'-ethynyl-4-n-propylbicycloorthobenzoate (EBOB) to housefly-head membranes, with an IC(50) value of 455pM. In contrast, the IC(50) value in rat-brain membranes is>10muM. To study the mode of action of this isoxazoline, we utilized MdGBCl and MdGluCl cDNAs, which encode the subunits of housefly GABA- and glutamate-gated chloride channels, respectively. Two-electrode voltage clamp electrophysiology was used to confirm that A1443 blocks GABA- and glutamate-induced chloride currents in Xenopus oocytes expressing MdGBCl or MdGluCl channels, with IC(50) values of 5.32 and 79.9 nM, respectively. Blockade by A1443 was observed in A2'S-MdGBCl and S2'A-MdGluCl mutant channels at levels similar to those of the respective wild-types, and houseflies expressing A2'S-MdGBCl channels were as susceptible to A1443 as standard houseflies. These findings indicate that A1443 is a novel and specific blocker of insect ligand-gated chloride channels. Copyright 2009 Elsevier Inc. All rights reserved.

  10. Ultrasonic alignment of bio-functionalized magnetic beads and live cells in PDMS micro-fluidic channel.

    PubMed

    Islam, Afroja T; Siddique, Ariful H; Ramulu, T S; Reddy, Venu; Eu, Young-Jae; Cho, Seung Hyun; Kim, CheolGi

    2012-12-01

    In this work, we demonstrated the alignment of polystyrene latex microspheres (diameter of 1 ~45 μm), bio-functionalized superparamagnetic beads (diameter 2.8 μm), and live cells (average diameter 1 ~2 μm) using an ultrasonic standing wave (USW) in a PDMS microfluidic channel (330 μm width) attached on a Si substrate for bio-medical applications. To generate a standing wave inside the channel, ultrasound of 2.25 MHz resonance frequency (for the channel width) was applied by two ultrasound transducers installed at both sides of the channel which caused the radiation force to concentrate the micro-particles at the single pressure nodal plane of USW. By increasing the frequency to the next resonance condition of the channel, the particles were concentrated in dual nodal planes. Migration time of the micro-particles towards the single nodal plane was recorded as 108 s, 17 s, and 115 s for polystyrene particles of 2 μm diameter, bio-functionalized magnetic beads, and live cells, respectively. These successful alignments of the bio-functionalized magnetic beads along the desired part of the channel can enhance the performance of a sensor which is applicable for the bio-hybrid system and the alignment of live cells without any damage can be used for sample pre-treatment for the application of lab-on-a-chip type bioassays.

  11. KCa2 and KCa3 Channels in Learning and Memory Processes, and Neurodegeneration

    PubMed Central

    Kuiper, Els F. E.; Nelemans, Ad; Luiten, Paul; Nijholt, Ingrid; Dolga, Amalia; Eisel, Uli

    2012-01-01

    Calcium-activated potassium (KCa) channels are present throughout the central nervous system as well as many peripheral tissues. Activation of KCa channels contribute to maintenance of the neuronal membrane potential and was shown to underlie the afterhyperpolarization (AHP) that regulates action potential firing and limits the firing frequency of repetitive action potentials. Different subtypes of KCa channels were anticipated on the basis of their physiological and pharmacological profiles, and cloning revealed two well defined but phylogenetic distantly related groups of channels. The group subject of this review includes both the small conductance KCa2 channels (KCa2.1, KCa2.2, and KCa2.3) and the intermediate-conductance (KCa3.1) channel. These channels are activated by submicromolar intracellular Ca2+ concentrations and are voltage independent. Of all KCa channels only the KCa2 channels can be potently but differentially blocked by the bee-venom apamin. In the past few years modulation of KCa channel activation revealed new roles for KCa2 channels in controlling dendritic excitability, synaptic functioning, and synaptic plasticity. Furthermore, KCa2 channels appeared to be involved in neurodegeneration, and learning and memory processes. In this review, we focus on the role of KCa2 and KCa3 channels in these latter mechanisms with emphasis on learning and memory, Alzheimer’s disease and on the interplay between neuroinflammation and different neurotransmitters/neuromodulators, their signaling components and KCa channel activation. PMID:22701424

  12. Controlled injection using a channel pinch in a plasma-channel-guided laser wakefield accelerator

    NASA Astrophysics Data System (ADS)

    Liu, Jiaqi; Zhang, Zhijun; Liu, Jiansheng; Li, Wentao; Wang, Wentao; Yu, Changhai; Qi, Rong; Qin, Zhiyong; Fang, Ming; Wu, Ying; Feng, Ke; Ke, Lintong; Wang, Cheng; Li, Ruxin

    2018-06-01

    Plasma-channel-guided laser plasma accelerators make it possible to drive high-brilliance compact radiation sources and have high-energy physics applications. Achieving tunable internal injection of the electron beam (e beam) inside the plasma channel, which realizes a tunable radiation source, is a challenging method to extend such applications. In this paper, we propose the use of a channel pinch, which is designed as an initial reduction followed by an expansion of the channel radius along the plasma channel, to achieve internal controlled off-axis e beam injection in a channel-guided laser plasma accelerator. The off-axis injection is triggered by bubble deformation in the expansion region. The dynamics of the plasma wake is explored, and the trapping threshold is found to be reduced radially in the channel pinch. Simulation results show that the channel pinch not only triggers injection process localized at the pinch but also modulates the parameters of the e beam by adjusting its density profile, which can additionally accommodate a tunable radiation source via betatron oscillation.

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

    PubMed

    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. Piezo channels and GsMTx4: Two milestones in our understanding of excitatory mechanosensitive channels and their role in pathology.

    PubMed

    Suchyna, Thomas M

    2017-11-01

    Discovery of Piezo channels and the reporting of their sensitivity to the inhibitor GsMTx4 were important milestones in the study of non-selective cationic mechanosensitive channels (MSCs) in normal physiology and pathogenesis. GsMTx4 had been used for years to investigate the functional role of cationic MSCs, especially in muscle tissue, but with little understanding of its target or inhibitory mechanism. The sensitivity of Piezo channels to bilayer stress and its robust mechanosensitivity when expressed in heterologous systems were keys to determining GsMTx4's mechanism of action. However, questions remain regarding Piezo's role in muscle function due to the non-selective nature of GsMTx4 inhibition toward membrane mechanoenzymes and the implication of MCS channel types by genetic knockdown. Evidence supporting Piezo like activity, at least in the developmental stages of muscle, is presented. While the MSC targets of GsMTx4 in muscle pathology are unclear, its muscle protective effects are clearly demonstrated in two recent in situ studies on normal cardiomyocytes and dystrophic skeletal muscle. The muscle protective function may be due to the combined effect of GsMTx4's inhibitory action on cationic MSCs like Piezo and TRP, and its potentiation of repolarizing K + selective MSCs like K2P and SAKCa. Paradoxically, the potent in vitro action of GsMTx4 on many physiological functions seems to conflict with its lack of in situ side-effects on normal animal physiology. Future investigations into cytoskeletal control of sarcolemma mechanics and the suspected inclusion of MSCs in membrane micro/nano sized domains with distinct mechanical properties will aide our understanding of this dichotomy. Published by Elsevier Ltd.

  15. Chaotic behavior of channeling particles.

    PubMed

    Chen, Ling; Kaloyeros, Alain E.; Wang, Guang-Hou

    1994-03-01

    Channeling describes the collimated motion of energetic charged particles along the lattice plane or axis in a crystal. The energetic particles are steered through the channels formed by strings of atomic constituents in the lattice. In the case of planar channeling, the motion of a charged particle between the atomic planes can be periodic or quasiperiodic, such as a simple oscillatory motion in the transverse direction. In practice, however, the periodic motion of the channeling particles can be accompanied by an irregular, chaotic behavior. In this paper, the Moliere potential, which is considered as a good analytical approximation for the interaction of channeling particles with the rows of atoms in the lattice, is used to simulate the channeling behavior of positively charged particles in a tungsten (100) crystal plane. By appropriate selection of channeling parameters, such as the projectile energy E(0) and incident angle psi(0), the transition of channeling particles from regular to chaotic motion is demonstrated. It is argued that the fine structures that appear in the angular scan channeling experiments are due to the particles' chaotic motion.

  16. Tunable dual-channel filter based on the photonic crystal with air defects.

    PubMed

    Zhao, Xiaodan; Yang, Yibiao; Wen, Jianhua; Chen, Zhihui; Zhang, Mingda; Fei, Hongming; Hao, Yuying

    2017-07-01

    We propose a tuning filter containing two channels by inserting a defect layer (Air/Si/Air/Si/Air) into a one-dimensional photonic crystal of Si/SiO 2 , which is on the symmetry of the defect. Two transmission peaks (1528.98 and 1564.74 nm) appear in the optical communication S-band and C-band, and the transmittance of these two channels is up to 100%. In addition, this design realizes multi-channel filtering to process large dynamic range or multiple independent signals in the near-infrared band by changing the structure. The tuning range will be enlarged, and the channels can be moved in this range through the easy control of air thickness and incident angle.

  17. Optimization of the Solution-Based Indium-Zinc Oxide/Zinc-Tin Oxide Channel Layer for Thin-Film Transistors.

    PubMed

    Lim, Kiwon; Choi, Pyungho; Kim, Sangsub; Kim, Hyunki; Kim, Minsoo; Lee, Jeonghyun; Hyeon, Younghwan; Koo, Kwangjun; Choi, Byoungdeog

    2018-09-01

    Double stacked indium-zinc oxide (IZO)/zinc-tin oxide (ZTO) active layers were employed in amorphous-oxide-semiconductor thin-film transistors (AOS TFTs). Channel layers of the TFTs were optimized by varying the molarity of ZTO back channel layers (0.05, 0.1, 0.2, 0.3 M) and the electrical properties of IZO/ZTO double stacked TFTs were compared to single IZO and ZTO TFTs with varying the molarity and molar ratio. On the basis of the results, IZO/ZTO (0.1 M) TFTs showed the excellent electrical properties of saturation mobility (13.6 cm2/V·s), on-off ratio (7×106), and subthreshold swing (0.223 V/decade) compared to ZTO (0.1 M) of 0.73 cm2/V · s, 1 × 107, 0.416 V/decade and IZO (0.04 M) of 0.10 cm2/V · s, 5 × 106, 0.60 V/decade, respectively. This may be attributed to diffusing Sn into front layer during annealing process. In addition, with varying molarity of ZTO back channel layer, from 0.1 M to 0.3 M ZTO back channel TFTs, electrical properties and positive bias stability deteriorated with increasing molarity of back channel layer because of increasing total trap states. On the other hand, 0.05 M ZTO back channel TFT had inferior electrical properties than that of 0.1 M ZTO back channel TFT. It was related to back channel effect because of having thin thickness of channel layer. Among these devices, 0.1 M ZTO back channel TFT had a lowest total trap density, outstanding electrical properties and stability. Therefore, we recommended IZO/ZTO (0.1 M) TFT as a promising channel structure for advanced display applications.

  18. Synergistic Malaria Parasite Killing by Two Types of Plasmodial Surface Anion Channel Inhibitors

    PubMed Central

    Pain, Margaret; Fuller, Alexandra W.; Basore, Katherine; Pillai, Ajay D.; Solomon, Tsione; Bokhari, Abdullah A. B.; Desai, Sanjay A.

    2016-01-01

    Malaria parasites increase their host erythrocyte’s permeability to a broad range of ions and organic solutes. The plasmodial surface anion channel (PSAC) mediates this uptake and is an established drug target. Development of therapies targeting this channel is limited by several problems including interactions between known inhibitors and permeating solutes that lead to incomplete channel block. Here, we designed and executed a high-throughput screen to identify a novel class of PSAC inhibitors that overcome this solute-inhibitor interaction. These new inhibitors differ from existing blockers and have distinct effects on channel-mediated transport, supporting a model of two separate routes for solute permeation though PSAC. Combinations of inhibitors specific for the two routes had strong synergistic action against in vitro parasite propagation, whereas combinations acting on a single route produced only additive effects. The magnitude of synergism depended on external nutrient concentrations, consistent with an essential role of the channel in parasite nutrient acquisition. The identified inhibitors will enable a better understanding of the channel’s structure-function and may be starting points for novel combination therapies that produce synergistic parasite killing. PMID:26866812

  19. Elucidation of pyrethroid and DDT receptor sites in the voltage-gated sodium channel.

    PubMed

    Zhorov, Boris S; Dong, Ke

    2017-05-01

    DDT and pyrethroid insecticides were among the earliest neurotoxins identified to act on voltage-gated sodium channels. In the 1960s, equipped with, at the time, new voltage-clamp techniques, Professor Narahashi and associates provided the initial evidence that DDT and allethrin (the first commercial pyrethroid insecticide) caused prolonged flow of sodium currents in lobster and squid giant axons. Over the next several decades, continued efforts by Prof. Narahashi's group as well as other laboratories led to a comprehensive understanding of the mechanism of action of DDT and pyrethroids on sodium channels. Fast forward to the 1990s, genetic, pharmacological and toxicological data all further confirmed voltage-gated sodium channels as the primary targets of DDT and pyrethroid insecticides. Modifications of the gating kinetics of sodium channels by these insecticides result in repetitive firing and/or membrane depolarization in the nervous system. This mini-review focuses on studies from Prof. Narahashi's pioneer work and more recent mutational and computational modeling analyses which collectively elucidated the elusive pyrethroid receptor sites as well as the molecular basis of differential sensitivities of insect and mammalian sodium channels to pyrethroids. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Roughness characteristics of natural channels

    USGS Publications Warehouse

    Barnes, Harry Hawthorne

    1967-01-01

    Color photographs and descriptive data are presented for 50 stream channels for which roughness coefficients have been determined. All hydraulic computations involving flow in open channels require an evaluation of the roughness characteristics of the channel. In the absence of a satisfactory quantitative procedure this evaluation remains chiefly an art. The ability to evaluate roughness coefficients must be developed through experience. One means of gaining this experience is by examining and becoming acquainted with the appearance of some typical channels whose roughness coefficients are known. The photographs and data contained in this report represent a wide range of channel conditions. Familiarity with the appearance, geometry, and roughness characteristics of these channels will improve the engineer's ability to select roughness coefficients for other channels .

  1. Bidirectional optical subassembly-shaped 20-Gbit/s compact single-mode four-channel wavelength-division multiplexing optical modules for optical multimedia interfaces

    NASA Astrophysics Data System (ADS)

    Lim, Kwon-Seob; Yu, Hong-Yeon; Park, Hyoung-Jun; Kang, Hyun Seo; Jang, Jae-Hyung

    2016-06-01

    Low-cost single-mode four-channel optical transmitter and receiver modules using the wavelength-division multiplexing (WDM) method have been developed for long-reach fiber optic applications. The single-mode four-channel WDM optical transmitter and receiver modules consist of two dual-wavelength optical transmitter and receiver submodules, respectively. The integration of two channels in a glass-sealed transistor outline-can package is an effective way to reduce cost and size and to extend the number of channels. The clear eye diagrams with more than about 6 dB of the extinction ratio and the minimum receiver sensitivity of lower than -16 dBm at a bit error rate of 10-12 have been obtained for the transmitter and receiver modules, respectively, at 5 Gbps/channel. The 4K ultrahigh definition contents have been transmitted over a 1-km-long single-mode fiber using a pair of proposed four-channel transmitter optical subassembly and receiver optical subassembly.

  2. Polyester modification of the mammalian TRPM8 channel protein: Implications for structure and function

    PubMed Central

    Bikard, Yann; Chen, Wei; Liu, Tong; Li, Hong; Jendrossek, Dieter; Cohen, Alejandro; Pavlov, Evgeny; Rohacs, Tibor; Zakharian, Eleonora

    2013-01-01

    SUMMARY The TRPM8 ion channel is expressed in sensory neurons and is responsible for sensing environmental cues such as cold temperatures and chemical compounds, including menthol and icilin. The channel functional activity is regulated by various physical and chemical factors, and is likely to be pre-conditioned by its molecular composition. Our studies indicate that TRPM8 channel forms a structural-functional complex with the polyester, poly-(R)-3hydroxybutyrate (PHB). We identified by mass spectrometry a number of PHB-modified peptides in the N-terminus of the TRPM8 protein and in its extracellular S3–S4 linker. Removal of PHB by enzymatic hydrolysis, and site-directed mutagenesis of both the serine residues that serve as covalent anchors for PHB and adjacent hydrophobic residues that interact with the methyl groups of the polymer, resulted in significant inhibition of TRPM8 channel activity. We conclude that the TRPM8 channel undergoes post-translational modification by PHB and that this modification is required for its normal function. PMID:23850286

  3. Amortization does not enhance the max-Rains information of a quantum channel

    NASA Astrophysics Data System (ADS)

    Berta, Mario; Wilde, Mark M.

    2018-05-01

    Given an entanglement measure E, the entanglement of a quantum channel is defined as the largest amount of entanglement E that can be generated from the channel, if the sender and receiver are not allowed to share a quantum state before using the channel. The amortized entanglement of a quantum channel is defined as the largest net amount of entanglement E that can be generated from the channel, if the sender and receiver are allowed to share an arbitrary state before using the channel. Our main technical result is that amortization does not enhance the entanglement of an arbitrary quantum channel, when entanglement is quantified by the max-Rains relative entropy. We prove this statement by employing semi-definite programming (SDP) duality and SDP formulations for the max-Rains relative entropy and a channel’s max-Rains information, found recently in Wang et al (arXiv:1709.00200). The main application of our result is a single-letter, strong converse, and efficiently computable upper bound on the capacity of a quantum channel for transmitting qubits when assisted by positive-partial-transpose preserving (PPT-P) channels between every use of the channel. As the class of local operations and classical communication (LOCC) is contained in PPT-P, our result establishes a benchmark for the LOCC-assisted quantum capacity of an arbitrary quantum channel, which is relevant in the context of distributed quantum computation and quantum key distribution.

  4. Kinship structures create persistent channels for language transmission.

    PubMed

    Lansing, J Stephen; Abundo, Cheryl; Jacobs, Guy S; Guillot, Elsa G; Thurner, Stefan; Downey, Sean S; Chew, Lock Yue; Bhattacharya, Tanmoy; Chung, Ning Ning; Sudoyo, Herawati; Cox, Murray P

    2017-12-05

    Languages are transmitted through channels created by kinship systems. Given sufficient time, these kinship channels can change the genetic and linguistic structure of populations. In traditional societies of eastern Indonesia, finely resolved cophylogenies of languages and genes reveal persistent movements between stable speech communities facilitated by kinship rules. When multiple languages are present in a region and postmarital residence rules encourage sustained directional movement between speech communities, then languages should be channeled along uniparental lines. We find strong evidence for this pattern in 982 individuals from 25 villages on two adjacent islands, where different kinship rules have been followed. Core groups of close relatives have stayed together for generations, while remaining in contact with, and marrying into, surrounding groups. Over time, these kinship systems shaped their gene and language phylogenies: Consistently following a postmarital residence rule turned social communities into speech communities. Copyright © 2017 the Author(s). Published by PNAS.

  5. Kinetics of veratridine action on Na channels of skeletal muscle

    PubMed Central

    Sutro, JB

    1986-01-01

    Veratridine bath-applied to frog muscle makes inactivation of INa incomplete during a depolarizing voltage-clamp pulse and leads to a persistent veratridine-induced Na tail current. During repetitive depolarizations, the size of successive tail currents grows to a plateau and then gradually decreases. When pulsing is stopped, the tail current declines to zero with a time constant of approximately 3 s. Higher rates of stimulation result in a faster build-up of the tail current and a larger maximum value. I propose that veratridine binds only to open channels and, when bound, prevents normal fast inactivation and rapid shutting of the channel on return to rest. Veratridine-modified channels are also subject to a "slow" inactivation during long depolarizations or extended pulse trains. At rest, veratridine unbinds with a time constant of approximately 3 s. Three tests confirm these hypotheses: (a) the time course of the development of veratridine-induced tail currents parallels a running time integral of gNa during the pulse; (b) inactivating prepulses reduce the ability to evoke tails, and the voltage dependence of this reduction parallels the voltage dependence of h infinity; (c) chloramine-T, N-bromoacetamide, and scorpion toxin, agents that decrease inactivation in Na channels, each greatly enhance the tail currents and alter the time course of the appearance of the tails as predicted by the hypothesis. Veratridine-modified channels shut during hyperpolarizations from -90 mV and reopen on repolarization to -90 mV, a process that resembles normal activation gating. Veratridine appears to bind more rapidly during larger depolarizations. PMID:2419478

  6. Enhancement mode GaN-based multiple-submicron channel array gate-recessed fin metal-oxide-semiconductor high-electron mobility transistors

    NASA Astrophysics Data System (ADS)

    Lee, Ching-Ting; Wang, Chun-Chi

    2018-04-01

    To study the function of channel width in multiple-submicron channel array, we fabricated the enhancement mode GaN-based gate-recessed fin metal-oxide-semiconductor high-electron mobility transistors (MOS-HEMTs) with a channel width of 450 nm and 195 nm, respectively. In view of the enhanced gate controllability in a narrower fin-channel structure, the transconductance was improved from 115 mS/mm to 151 mS/mm, the unit gain cutoff frequency was improved from 6.2 GHz to 6.8 GHz, and the maximum oscillation frequency was improved from 12.1 GHz to 13.1 GHz of the devices with a channel width of 195 nm, compared with the devices with a channel width of 450 nm.

  7. Structure of a prokaryotic sodium channel pore reveals essential gating elements and an outer ion binding site common to eukaryotic channels

    PubMed Central

    Shaya, David; Findeisen, Felix; Abderemane-Ali, Fayal; Arrigoni, Cristina; Wong, Stephanie; Nurva, Shailika Reddy; Loussouarn, Gildas; Minor, Daniel L.

    2013-01-01

    Voltage-gated sodium channels (NaVs) are central elements of cellular excitation. Notwithstanding advances from recent bacterial NaV (BacNaV) structures, key questions about gating and ion selectivity remain. Here, we present a closed conformation of NaVAe1p, a pore-only BacNaV derived from NaVAe1, a BacNaV from the arsenite oxidizer Alkalilimnicola ehrlichei found in Mono Lake, California, that provides insight into both fundamental properties. The structure reveals a pore domain in which the pore-lining S6 helix connects to a helical cytoplasmic tail. Electrophysiological studies of full-length BacNaVs show that two elements defined by the NaVAe1p structure, an S6 activation gate position and the cytoplasmic tail ‘neck’, are central to BacNaV gating. The structure also reveals the selectivity filter ion entry site, termed the ‘outer ion’ site. Comparison with mammalian voltage-gated calcium channel (CaV) selectivity filters, together with functional studies shows that this site forms a previously unknown determinant of CaV high affinity calcium binding. Our findings underscore commonalities between BacNaVs and eukaryotic voltage-gated channels and provide a framework for understanding gating and ion permeation in this superfamily. PMID:24120938

  8. Structure of a prokaryotic sodium channel pore reveals essential gating elements and an outer ion binding site common to eukaryotic channels.

    PubMed

    Shaya, David; Findeisen, Felix; Abderemane-Ali, Fayal; Arrigoni, Cristina; Wong, Stephanie; Nurva, Shailika Reddy; Loussouarn, Gildas; Minor, Daniel L

    2014-01-23

    Voltage-gated sodium channels (NaVs) are central elements of cellular excitation. Notwithstanding advances from recent bacterial NaV (BacNaV) structures, key questions about gating and ion selectivity remain. Here, we present a closed conformation of NaVAe1p, a pore-only BacNaV derived from NaVAe1, a BacNaV from the arsenite oxidizer Alkalilimnicola ehrlichei found in Mono Lake, California, that provides insight into both fundamental properties. The structure reveals a pore domain in which the pore-lining S6 helix connects to a helical cytoplasmic tail. Electrophysiological studies of full-length BacNaVs show that two elements defined by the NaVAe1p structure, an S6 activation gate position and the cytoplasmic tail "neck", are central to BacNaV gating. The structure also reveals the selectivity filter ion entry site, termed the "outer ion" site. Comparison with mammalian voltage-gated calcium channel (CaV) selectivity filters, together with functional studies, shows that this site forms a previously unknown determinant of CaV high-affinity calcium binding. Our findings underscore commonalities between BacNaVs and eukaryotic voltage-gated channels and provide a framework for understanding gating and ion permeation in this superfamily. © 2013. Published by Elsevier Ltd. All rights reserved.

  9. Modeling, Real-Time Estimation, and Identification of UWB Indoor Wireless Channels

    DOE PAGES

    Olama, Mohammed M.; Djouadi, Seddik M.; Li, Yanyan; ...

    2013-01-01

    Stochastic differential equations (SDEs) are used to model ultrawideband (UWB) indoor wireless channels. We show that the impulse responses for time-varying indoor wireless channels can be approximated in a mean-square sense as close as desired by impulse responses that can be realized by SDEs. The state variables represent the inphase and quadrature components of the UWB channel. The expected maximization and extended Kalman filter are employed to recursively identify and estimate the channel parameters and states, respectively, from online received signal strength measured data. Both resolvable and nonresolvable multipath received signals are considered and represented as small-scaled Nakagami fading. Themore » proposed models together with the estimation algorithm are tested using UWB indoor measurement data demonstrating the method’s viability and the results are presented.« less

  10. Double-stranded helical twisted beta-sheet channels in crystals of gramicidin S grown in the presence of trifluoroacetic and hydrochloric acids.

    PubMed

    Llamas-Saiz, Antonio L; Grotenbreg, Gijsbert M; Overhand, Mark; van Raaij, Mark J

    2007-03-01

    Gramicidin S is a nonribosomally synthesized cyclic decapeptide antibiotic with twofold symmetry (Val-Orn-Leu-D-Phe-Pro)(2); a natural source is Bacillus brevis. Gramicidin S is active against Gram-positive and some Gram-negative bacteria. However, its haemolytic toxicity in humans limits its use as an antibiotic to certain topical applications. Synthetically obtained gramicidin S was crystallized from a solution containing water, methanol, trifluoroacetic acid and hydrochloric acid. The structure was solved and refined at 0.95 A resolution. The asymmetric unit contains 1.5 molecules of gramicidin S, two trifluoroacetic acid molecules and ten water molecules located and refined in 14 positions. One gramicidin S molecule has an exact twofold-symmetrical conformation; the other deviates from the molecular twofold symmetry. The cyclic peptide adopts an antiparallel beta-sheet secondary structure with two type II' beta-turns. These turns have the residues D-Phe and Pro at positions i + 1 and i + 2, respectively. In the crystals, the gramicidin S molecules line up into double-stranded helical channels that differ from those observed previously. The implications of the supramolecular structure for several models of gramicidin S conformation and assembly in the membrane are discussed.

  11. Conformational rearrangements in the transmembrane domain of CNGA1 channels revealed by single-molecule force spectroscopy

    NASA Astrophysics Data System (ADS)

    Maity, Sourav; Mazzolini, Monica; Arcangeletti, Manuel; Valbuena, Alejandro; Fabris, Paolo; Lazzarino, Marco; Torre, Vincent

    2015-05-01

    Cyclic nucleotide-gated (CNG) channels are activated by binding of cyclic nucleotides. Although structural studies have identified the channel pore and selectivity filter, conformation changes associated with gating remain poorly understood. Here we combine single-molecule force spectroscopy (SMFS) with mutagenesis, bioinformatics and electrophysiology to study conformational changes associated with gating. By expressing functional channels with SMFS fingerprints in Xenopus laevis oocytes, we were able to investigate gating of CNGA1 in a physiological-like membrane. Force spectra determined that the S4 transmembrane domain is mechanically coupled to S5 in the closed state, but S3 in the open state. We also show there are multiple pathways for the unfolding of the transmembrane domains, probably caused by a different degree of α-helix folding. This approach demonstrates that CNG transmembrane domains have dynamic structure and establishes SMFS as a tool for probing conformational change in ion channels.

  12. Gating of the two-pore cation channel AtTPC1 in the plant vacuole is based on a single voltage-sensing domain.

    PubMed

    Jaślan, D; Mueller, T D; Becker, D; Schultz, J; Cuin, T A; Marten, I; Dreyer, I; Schönknecht, G; Hedrich, R

    2016-09-01

    The two-pore cation channel TPC1 operates as a dimeric channel in animal and plant endomembranes. Each subunit consists of two homologous Shaker-like halves, with 12 transmembrane domains in total (S1-S6, S7-S12). In plants, TPC1 channels reside in the vacuolar membrane, and upon voltage stimulation, give rise to the well-known slow-activating SV currents. Here, we combined bioinformatics, structure modelling, site-directed mutagenesis, and in planta patch clamp studies to elucidate the molecular mechanisms of voltage-dependent channel gating in TPC1 in its native plant background. Structure-function analysis of the Arabidopsis TPC1 channel in planta confirmed that helix S10 operates as the major voltage-sensing site, with Glu450 and Glu478 identified as possible ion-pair partners for voltage-sensing Arg537. The contribution of helix S4 to voltage sensing was found to be negligible. Several conserved negative residues on the luminal site contribute to calcium binding, stabilizing the closed channel. During evolution of plant TPC1s from two separate Shaker-like domains, the voltage-sensing function in the N-terminal Shaker-unit (S1-S4) vanished. © 2016 German Botanical Society and The Royal Botanical Society of the Netherlands.

  13. Multi-country Survey Revealed Prevalent and Novel F1534S Mutation in Voltage-Gated Sodium Channel (VGSC) Gene in Aedes albopictus.

    PubMed

    Xu, Jiabao; Bonizzoni, Mariangela; Zhong, Daibin; Zhou, Guofa; Cai, Songwu; Li, Yiji; Wang, Xiaoming; Lo, Eugenia; Lee, Rebecca; Sheen, Roger; Duan, Jinhua; Yan, Guiyun; Chen, Xiao-Guang

    2016-05-01

    Aedes albopictus is an important dengue vector because of its aggressive biting behavior and rapid spread out of its native home range in Southeast Asia. Pyrethroids are widely used for adult mosquito control, and resistance to pyrethroids should be carefully monitored because vector control is the only effective method currently available to prevent dengue transmission. The voltage-gated sodium channel gene is the target site of pyrethroids, and mutations in this gene cause knockdown resistance (kdr). Previous studies reported various mutations in the voltage-gated sodium channel (VGSC) gene, but the spatial distribution of kdr mutations in Ae. albopictus has not been systematically examined, and the association between kdr mutation and phenotypic resistance has not been established. A total of 597 Ae. albopictus individuals from 12 populations across Asia, Africa, America and Europe were examined for mutations in the voltage-gated sodium channel gene. Three domains for a total of 1,107 bp were sequenced for every individual. Two populations from southern China were examined for pyrethroid resistance using the World Health Organization standard tube bioassay, and the association between kdr mutations and phenotypic resistance was tested. A total of 29 synonymous mutations were found across domain II, III and IV of the VGSC gene. Non-synonymous mutations in two codons of the VGSC gene were detected in 5 populations from 4 countries. A novel mutation at 1532 codon (I1532T) was found in Rome, Italy with a frequency of 19.7%. The second novel mutation at codon 1534 (F1534S) was detected in southern China and Florida, USA with a frequency ranging from 9.5-22.6%. The WHO insecticide susceptibility bioassay found 90.1% and 96.1% mortality in the two populations from southern China, suggesting resistance and probable resistance. Positive association between kdr mutations with deltamethrin resistance was established in these two populations. Two novel kdr mutations, I1532T

  14. The role of cystic fibrosis transmembrane conductance regulator phenylalanine 508 side chain in ion channel gating

    PubMed Central

    Cui, Liying; Aleksandrov, Luba; Hou, Yue-Xian; Gentzsch, Martina; Chen, Jey-Hsin; Riordan, John R; Aleksandrov, Andrei A

    2006-01-01

    Cystic fibrosis transmembrane conductance regulator (CFTR) is an ion channel employing the ABC transporter structural motif. Deletion of a single residue (Phe508) in the first nucleotide-binding domain (NBD1), which occurs in most patients with cystic fibrosis, impairs both maturation and function of the protein. However, substitution of the Phe508 with small uncharged amino acids, including cysteine, is permissive for maturation. To explore the possible role of the phenylalanine aromatic side chain in channel gating we introduced a cysteine at this position in cysless CFTR, enabling its selective chemical modification by sulfhydryl reagents. Both cysless and wild-type CFTR ion channels have identical mean open times when activated by different nucleotide ligands. Moreover, both channels could be locked in an open state by introducing an ATPase inhibiting mutation (E1371S). However, the introduction of a single cysteine (F508C) prevented the cysless E1371S channel from maintaining the permanently open state, allowing closing to occur. Chemical modification of cysless E1371S/F508C by sulfhydryl reagents was used to probe the role of the side chain in ion channel function. Specifically, benzyl-methanethiosulphonate modification of this variant restored the gating behaviour to that of cysless E1371S containing the wild-type phenylalanine at position 508. This provides the first direct evidence that a specific interaction of the Phe508 aromatic side chain plays a role in determining the residency time in the closed state. Thus, despite the fact that this aromatic side chain is not essential for CFTR folding, it is important in the ion channel function. PMID:16484308

  15. Channel morphology [Chapter 5

    Treesearch

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

    2012-01-01

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

  16. Dynamics of the EAG1 K+ channel selectivity filter assessed by molecular dynamics simulations.

    PubMed

    Bernsteiner, Harald; Bründl, Michael; Stary-Weinzinger, Anna

    2017-02-26

    EAG1 channels belong to the KCNH family of voltage gated potassium channels. They are expressed in several brain regions and increased expression is linked to certain cancer types. Recent cryo-EM structure determination finally revealed the structure of these channels in atomic detail, allowing computational investigations. In this study, we performed molecular dynamics simulations to investigate the ion binding sites and the dynamical behavior of the selectivity filter. Our simulations suggest that sites S2 and S4 form stable ion binding sites, while ions placed at sites S1 and S3 rapidly switched to sites S2 and S4. Further, ions tended to dissociate away from S0 within less than 20 ns, due to increased filter flexibility. This was followed by water influx from the extracellular side, leading to a widening of the filter in this region, and likely non-conductive filter configurations. Simulations with the inactivation-enhancing mutant Y464A or Na + ions lead to trapped water molecules behind the SF, suggesting that these simulations captured early conformational changes linked to C-type inactivation. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  17. A robotic multi-channel platform for interstitial photodynamic therapy

    PubMed Central

    Sharikova, Anna V.; Finlay, Jarod C.; Dimofte, Andreea; Zhu, Timothy C.

    2015-01-01

    A custom-made robotic multichannel platform for interstitial photodynamic therapy (PDT) and diffuse optical tomography (DOT) was developed and tested in a phantom experiment. The system, which was compatible with the operating room (OR) environment, had 16 channels for independent positioning of light sources and/or isotropic detectors in separate catheters. Each channel’s motor had an optical encoder for position feedback, with resolution of 1.5 mm, and a maximum speed of 5 cm/s. Automatic calibration of detector positions was implemented using an optical diode beam that defined the starting position of each motor, and by means of feedback algorithms controlling individual channels. As a result, the accuracy of zero position of 0.1 mm for all channels was achieved. We have also employed scanning procedures where detectors automatically covered the appropriate range around source positions. Thus, total scan time for a typical optical properties (OP) measurement throughout the phantom was about 1.5 minutes with point sources. The OP were determined based on the measured light fluence rates. These enhancements allow a tremendous improvement of treatment quality for a bulk tumor compared to the systems employed in previous clinical trials. PMID:25914794

  18. A Flow-Channel Analysis for the Mars Hopper

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    W. Spencer Cooley

    The Mars Hopper is an exploratory vehicle designed to fly on Mars using carbon dioxide from the Martian atmosphere as a rocket propellant. The propellent gasses are thermally heated while traversing a radioisotope ther- mal rocket (RTR) engine’s core. This core is comprised of a radioisotope surrounded by a heat capacitive material interspersed with tubes for the propellant to travel through. These tubes, or flow channels, can be manu- factured in various cross-sectional shapes such as a special four-point star or the traditional circle. Analytical heat transfer and computational fluid dynamics (CFD) anal- yses were performed using flow channels withmore » either a circle or a star cross- sectional shape. The nominal total inlet pressure was specified at 2,805,000 Pa; and the outlet pressure was set to 2,785,000 Pa. The CO2 inlet tem- perature was 300 K; and the channel wall was 1200 K. The steady-state CFD simulations computed the smooth-walled star shape’s outlet temper- ature to be 959 K on the finest mesh. The smooth-walled circle’s outlet temperature was 902 K. A circle with a surface roughness specification at 0.01 mm gave 946 K and at 0.1 mm yielded 989 K. The The effects of a slightly varied inlet pressure were also examined. The analytical calculations were based on the mass flow rates computed in the CFD simulations and provided significantly higher outlet temperature results while displaying the same comparison trends. Research relating to the flow channel heat transfer studies was also done. Mathematical methods to geometrically match the cross-sectional areas of the circle and star, along with a square and equilateral triangle, were derived. A Wolfram Mathematica 8 module was programmed to analyze CFD results using Richardson Extrapolation and calculate the grid convergence index (GCI). A Mathematica notebook, also composed, computes and graphs the bulk mean temperature along a flow channel’s length while the user dynam- ically provides the

  19. Identification of Intracellular β-Barrel Residues Involved in Ion Selectivity in the Mechanosensitive Channel of Thermoanaerobacter tengcongensis

    PubMed Central

    Song, Yingcai; Zhang, Bing; Guo, Fei; Yang, Maojun; Li, Yang; Liu, Zhi-Qiang

    2017-01-01

    The mechanosensitive channel of small conductance (MscS) is a bacterial membrane pore that senses membrane tension and protects cells from lysis by releasing osmolytes. MscS is a homoheptameric channel with a cytoplasmic domain with seven portals and a β-barrel opening to the cytoplasm. TtMscS, an MscS channel from Thermoanaerobacter tengcongensis, is an anion-selective channel. A previous study from our laboratory has defined the crucial role of β-barrel in the anion selectivity of TtMscS (Zhang et al., 2012). However, the mechanistic details by which the β-barrel determines anion selectivity remain unclear. Here, using mutagenesis and patch-clamp recordings, we investigated the function and structural correlations between β-barrels and the anion selectivity of TtMscS at the atomic level. Our results indicated that mutation of V274, a residue at the center of the inner wall of the β-barrel in TtMscS, caused the anion selectivity of TtMscS reverse to cation selectivity. Moreover, the electrostatic potential (T272) and physical size (L276) of residues in the inner wall of β-barrel also determine the anion selectivity of TtMscS. In summary, the present study confirmed that the β-barrel region of TtMscS acts as a “selective filter” that renders TtMscS anion selectivity. PMID:29118717

  20. Capacities of quantum amplifier channels

    NASA Astrophysics Data System (ADS)

    Qi, Haoyu; Wilde, Mark M.

    2017-01-01

    Quantum amplifier channels are at the core of several physical processes. Not only do they model the optical process of spontaneous parametric down-conversion, but the transformation corresponding to an amplifier channel also describes the physics of the dynamical Casimir effect in superconducting circuits, the Unruh effect, and Hawking radiation. Here we study the communication capabilities of quantum amplifier channels. Invoking a recently established minimum output-entropy theorem for single-mode phase-insensitive Gaussian channels, we determine capacities of quantum-limited amplifier channels in three different scenarios. First, we establish the capacities of quantum-limited amplifier channels for one of the most general communication tasks, characterized by the trade-off between classical communication, quantum communication, and entanglement generation or consumption. Second, we establish capacities of quantum-limited amplifier channels for the trade-off between public classical communication, private classical communication, and secret key generation. Third, we determine the capacity region for a broadcast channel induced by the quantum-limited amplifier channel, and we also show that a fully quantum strategy outperforms those achieved by classical coherent-detection strategies. In all three scenarios, we find that the capacities significantly outperform communication rates achieved with a naive time-sharing strategy.

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